title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Infectious complications following endoscopic retrograde cholangiopancreatography: an automated surveillance system for detecting postprocedure bacteremia. | We have developed an automated surveillance system to detect bloodstream infection (BSI) occurring after endoscopic retrograde cholangiopancreatography (ERCP). We retrospectively applied this automated surveillance tool to all patients who underwent ERCP at out institution between July 2004 and April 2006 to determine the baseline rates of BSI after ERCP and identify the epidemiology of the pathogens. A total of 2052 ERCPs were performed during the study period; 46 BSIs occurred within 30 days after ERCP (overall rate of post-ERCP BSI, 2.24/100 procedures). The most commonly isolated organisms were Enterobacteriaceae (n = 18; 29%) and enterococci (n = 14; 22%). Because invasive procedures are performed in various outpatient and inpatient settings, novel methods are needed to conduct effective surveillance for infection. | 18,926,314 |
Instrument processing with lauryl dimethyl benzyl ammonium bromide: a challenge for patient safety. | The quaternary ammonium compound (QUAT) lauryl dimethyl benzyl ammonium bromide (LDBAB) is commercialized in the Caribbean, Central, and South America under label claims to sterilize medical and dental instruments in 30 minutes or less. But QUAT formulations are classified as low-level disinfectants with no sporicidal activity or tuberculocidal efficacy. This study evaluated the presumptive sporicidal and tuberculocidal activities of 2 LDBAB formulations with label claims of high-level disinfectant action used widely in the Americas. In this study, sporicidal activity was evaluated against a challenge inoculum of 10(6)Bacillus atrophaeus spores. Tuberculocidal activity was evaluated against Mycobacterium tuberculosis H37Rv using the quantitative suspension test described in European Standard EN14348:2005. Tested at the recommended product concentrations indicated on their respective labels, both LDBAB solutions failed to demonstrate sporicidal activity and tuberculocidal efficacy. These findings underscore the need for public health authorities, as well as medical and dental professionals, to correctly identify LDBAB as a low-level disinfectant and avoid its use in instrument processing, a practice that may endanger lives. | 18,926,316 |
The influence of triage systems and triage scores on timeliness of ED analgesic administration. | The aim of the study was to examine the association between triage scoring systems and triage priority scores on time to initial emergency department (ED) analgesic administration. An observational, multicenter, prospective, cohort study was conducted at 20 US and Canadian EDs. Centers from the United States used the Emergency Severity Index triage system or 1 of 3 unvalidated triage systems. Canadian centers used the Canadian Triage and Acuity Scale. Patients aged 8 years or older who presented to the ED with a chief complaint of moderate to severe pain (>3 on a 10-point numerical rating scale) and who were ultimately discharged home were eligible for study enrollment. Triage score, triage system, pain rating on arrival, and time of initial analgesic administration were recorded. Among 842 enrolled subjects, 506 (60%) received an analgesic while in the ED. Lower-acuity patients consistently waited longer for analgesics. On multivariate modeling, presenting pain intensity, total time spent in the ED, white ethnicity, and triage system were associated with time to initial analgesic administration. Emergency departments using the Canadian Triage and Acuity Scale triage system exhibited the lowest rates of analgesic use and displayed longer median times to initial analgesic administration. Although there were some differences between triage systems, all sites and systems demonstrated unacceptably long times to analgesic provision. Many patients with moderate to severe pain received no analgesic during their ED stay. Future studies should examine whether ED overcrowding impacts timeliness of analgesic administration and identify specific strategies to improve pain management practices in this challenging environment. | 18,926,342 |
Hypertension in the ED: still an unrecognized problem. | Hypertension is prevalent in the general population. Emergency Department (ED) follow-up studies show persistence of blood pressure elevations in up to 50% of patients, and ED screening for hypertension has been recommended. Blood pressure elevations are often ignored or attributed to pain or anxiety. Our purpose was to document the incidence and recognition of hypertension in the ED and to assess its relation to pain scores and age. This was a retrospective study. Patients presenting to the ED during a 1-month period were included. Age, blood pressure, and pain scores were reviewed. Discharge instructions and diagnoses were assessed as to whether blood pressure was recognized or follow-up was recommended. There were 2821 patients. Fifteen percent were less than 18 years old. Twenty-six percent had an elevated blood pressure (40% of pediatric patients). There was no correlation between the distribution of pain scores in either children or adults. There was almost no recognition of the problem. Follow-up for elevated blood pressure was recommended in only 4%. Of these, only 46% actually received follow-up. Twenty-four percent of patients with elevated blood pressure received follow-up for other reasons. Blood pressure was still elevated in 47%. Hypertension was a common problem in our patient population. Elevated blood pressure readings were almost uniformly ignored or unrecognized, particularly in children. There was no correlation of elevated blood pressure readings and acute pain scores. Elevated blood pressure readings should not be attributed solely to anxiety or acute pain on presentation. | 18,926,352 |
Constrictive pericarditis after cardiac transplantation: a case report and literature review. | We present a patient who was found to have constrictive pericarditis 6 months after cardiac allograft transplantation. The many invasive and non-invasive diagnostic procedures that were undertaken are reviewed, as is the gross pathology seen during surgery. In addition, the entity of constriction in the transplant patient is placed in context by an examination of the previous literature. | 18,926,409 |
MR urography: technique and results for the evaluation of urinary obstruction in the pediatric population. | MR urography has the potential to revolutionize imaging of the urinary tract in both adults and children, because of its ability to provide an unprecedented level of anatomic information and quantitative functional evaluation of each kidney. MR urography can now provide useful assessment of obstructive uropathy and may provide predictive information about which children will benefit from surgery. It has the potential to identify parameters that indicate a significant obstruction as opposed to self-limited hydronephrosis. Further technical developments in the field will produce greater insights into the pathophysiology of not only urologic disorders but also disorders of the kidney itself. | 18,926,428 |
The PROTECT pilot study: a randomized, placebo-controlled, dose-finding study of the adenosine A1 receptor antagonist rolofylline in patients with acute heart failure and renal impairment. | Rolofylline, an adenosine A(1) receptor antagonist, facilitates diuresis and preserves renal function in patients with acute heart failure (AHF) with renal impairment. Although not powered around any specific hypothesis, this pilot study was designed to identify an efficacious dose while refining inclusion criteria and end points. A total of 301 patients hospitalized for AHF with an estimated creatinine clearance of 20 to 80 mL/min and elevated natriuretic peptide levels were enrolled within 24 hours of presentation to placebo or rolofylline 10, 20, or 30 mg administered as 4-hour infusions for 3 days in addition to intravenously administered loop diuretics. Post hoc analyses for end points chosen for subsequent Phase III studies were performed. Compared with placebo, rolofylline produced trends toward greater proportions of patients with marked or moderately improved dyspnea and fewer patients with worsening heart failure or renal function. Serum creatinine increased in patients receiving placebo and remained stable or tended to decrease in those receiving rolofylline. On day 14 the absolute differences between placebo and rolofylline for change in creatinine increased with increasing rolofylline dose, reflecting the lesser increase in creatinine in rolofylline-treated patients (r = -0.12, P = .030). Treatment with 30 mg, the dose selected for the pivotal trials, was associated with a trend toward reduced 60-day mortality or readmission for cardiovascular or renal cause (hazard ratio, 0.55; 95% confidence interval, 0.28-1.04). These results demonstrate that adenosine A(1) receptor blockade with rolofylline can prevent renal impairment in patients with AHF and may positively affect acute symptoms and 60-day outcome. A 2000-patient trial of this agent is now under way. | 18,926,433 |
Mesohepatectomy as an option for the treatment of central liver tumors. | Despite substantial improvements in intra- and postoperative management of extended hemihepatectomy as the curative option for treatment of central liver tumors, the high morbidity and mortality rates accompanying the procedure still represent major obstacles. Mesohepatectomy preserves up to 35% more functional liver tissue than extended hepatectomy, but it has not been widely applied, perhaps because of its complexity as a resection method. Forty-eight consecutive patients (29 men and 19 women) with centrally located liver tumors underwent mesohepatectomy. Peri- and postoperative morbidity and mortality rates were prospectively evaluated and analyzed. Mean age of the patients was 60.7 years. Indications for mesohepatectomy were liver metastasis (n = 29), hepatocellular carcinoma (n = 5), gallbladder carcinoma (n = 4), cholangiocellular carcinoma (n = 4), hemangioma (n = 2), and other benign diseases (n = 4). Mean operative time was 238 minutes (range 65 to 480 minutes) and mean intraoperative blood loss was 1,120 mL (range 100 to 5,000 mL). Mean amount of intraoperative red blood cells and fresh frozen plasma transfusion was 3.6 U (range 1 to 12 U) and 3.8 U (range 2 to 14 U), respectively. Mean postoperative hospitalization was 15.8 days (range 6 to 104 days). Postoperative surgical complications were seen in 18.8% of patients (n = 9) and included liver failure (n = 1), intraabdominal abscess (n = 1), bilioma or bile leakage (n = 4), hemorrhage and hematoma (n = 2), peritonitis because of intestinal perforation (n = 1), and wound infection (n = 1). One patient (2%) died in the early postoperative phase from portal vein bleeding and disseminated intravascular coagulation, followed by liver failure. Compared with extended liver resection, mesohepatectomy clearly leads to less parenchymal loss. Although it is a technically difficult operation and requires special attention to prevent surgical complications, it is justified in selected patients with centrally located tumors and is a feasible and safe alternative to extended liver resection. | 18,926,451 |
What is the quality of surgery-related information on the internet? Lessons learned from a standardized evaluation of 10 common operations. | Although there is high-quality information on the Internet, it is difficult for patients to identify high-quality Web sites from those with inaccurate or misleading information. Our goal was to determine specific characteristics of Web search results that yield high-quality information and can be discerned easily by patients. A validated rating system was used to evaluate surgical Web sites for appropriateness and adequacy. Web sites were identified using three search term types (technical, descriptive, and layperson) for 10 common surgical procedures. The top three sponsored (paid) and unsponsored (unpaid) Web site matches were identified. The search and analysis were repeated 1 month later. One hundred forty-five Web sites were retrieved: 90 unsponsored and 55 sponsored. Unsponsored sites had higher mean composite scores than sponsored Web sites (50.6% versus 25%, p < 0.0001). Searches using layperson terms had lower mean composite scores compared with those using technical terms (36.9% versus 47.5%, p < 0.02). Professional Web sites had the highest mean composite scores (66.3%); legal Web sites had the lowest (6.3%). On regression analysis, unsponsored Web sites were associated with higher composite scores (p < 0.0001); number 1 match results (p < 0.02) and using layperson search terms (p < 0.052) were associated with lower mean composite scores. Repeat search results demonstrated no significant differences, except number 3 match results were no longer significant. To optimize patients' Web searches, surgeons should recommend unsponsored sites; suggest professional society sites, if available; and provide technical search terms. But information on some topics, such as risks of not undergoing surgery, remains poor and requires discussion between the surgeon and patient. | 18,926,463 |
Molecular and biochemical mechanisms in maize endosperm development: the role of pyruvate-Pi-dikinase and Opaque-2 in the control of C/N ratio. | A combined transcriptomic, proteomic and metabolic analysis provided an overview of the main changes occurring in gene expression during maize kernel development. It allowed identifying genes expressed at each developmental stage and the shift occurring from one stage to the other. A major change occurred at the transition from lag phase where final grain size is established to grain filling where starch and protein are accumulated in the endosperm storage tissue. Although the expression of enzymes involved in storage product synthesis is dominant in the accumulation phase, the proportion of protein destination and protein synthesis gene products is still important. Detailed proteomic analysis of metabolism shows an upsurge of the pyruvate-Pi-dikinase (PPDK) in the late filing period (21 DAP onwards) that is interpreted as a switch in the starch/protein balance. This hypothesis is based on biochemical arguments involving the negative effect of PPi on the ADP-glucose pyrophosphorylase (Agpase), a key-enzyme of starch synthesis, and the role of phosphoenolpyruvate (PEP) in aromatic amino acid synthesis. It is substantiated by the data on the Opaque-2 gene encoding a transcription factor with pleiotropic effect affecting lysine content and carbohydrate metabolism, thus acting indirectly on starch/amino acid ratio. The direct effect of O2 on PPDK gene expression provides a clue for explaining the competition between C and N metabolisms. This epistatic relationship between PPDK and O2 is further supported by quantitative and association genetics. | 18,926,491 |
Metatarsals in the estimation of stature in South Africans. | To date, only one study has investigated the potential of metatarsals in the estimation of stature for forensic purposes. The morphology of these bones from clinical and paleontological perspectives is well researched in different parts of the world including South Africa. The present study aimed at assessing the usefulness of metatarsals of South Africans in the estimation of stature. For this study, 226 complete skeletons obtained from the Raymond A. Dart Collection were used in the formulation of univariate and multivariate regression equations from six linear measurements of metatarsals. The standard error of estimate for these equations was lower than that obtained for fragments of long bones and other skeletal elements studied so far for stature estimation in South Africans with the exception of intact long bones. Therefore, regression equations presented in this study can provide a reliable estimate of stature in cases where intact long bones are not available for forensic analysis. | 18,926,502 |
Tonsillitis and sudden childhood death. | Critical reduction in upper airway diameter may result from tonsillar enlargement due to infection or from associated abscess formation. Other potentially lethal complications include hemorrhage and disseminated sepsis. Two cases are reported to illustrate features of specific cases: Case 1: a 12-year-old girl who exsanguinated from a pharyngocarotid fistula caused by a retropharyngeal abscess due to acute tonsillitis, and Case 2: a 17-year-old girl who asphyxiated from an aspirated blood clot following tonsillectomy. While most cases of acute tonsillitis resolve without sequelae, occasional cases may be associated with a lethal outcome. Massive hemorrhage may occur due to erosion of tonsillar vessels or subjacent larger vessels, or it may follow surgical extirpation of the tonsils. The autopsy assessment of cases where there has been possible lethal tonsillar pathology requires review of the presenting history and possible operative procedures, with careful dissection of Waldeyer's ring, adjacent soft tissues and major vessels. Presentations may not be straightforward and there may be misleading histories of epistaxis, hemoptysis, hematemesis and even melena. | 18,926,504 |
Atypical wound of entry and unusual presentation in a fatal stab injury. | Stab wounds encountered in medico-legal autopsies are usually caused by sharp pointed weapons. Peculiarities of the wound of entry in stab wounds, for example due to the hilt of the weapon, movement of the weapon and sometimes by the hand of the assailant holding the weapon are often described in literature. We report an unusual presentation in a fatal stab injury wherein a single atypical external wound was associated with multiple internal injuries to the organs. The exact cause of such peculiarities can never be accurately determined, rather that can be speculated upon at the time of the autopsy and recorded for the purpose of academic interest. | 18,926,506 |
Vertebral arterial injury due to fatal dog bites. | Dog bite-related injuries and fatalities are major public health problem worldwide. The authors present a case of a Japanese Tosa-dog bite-related fatality in an old woman who died from a vertebral arterial laceration with the C5 vertebral fracture. This was an uncommon type of injury that dog bites injured the vertebral artery only without damage to carotid artery. The identity of the Tosa-dog as an offending dog in this case was unsuccessful by a DNA analysis. Then the detection of the offending dog was made by comparisons of the dental casts of the dog with the victim's wounds. This case report describes making dental cast of the dog, and statistical data on dog-bite incidents in Japan. | 18,926,508 |
Traumatic degloving lesion of male external genitalia. | Injury to the male external genitalia is relatively uncommon when compared with other parts of the human body. Trauma to external genitalia could result from accidents involving motor vehicles, power farm machinery, gun shot and stab injuries. We present a rare case of traumatic degloving injury of male external genitalia associated with partial penile amputation and loss of both testes sparing the internal abdominal and pelvic organs, resulting from run over by a heavy vehicle tyre. | 18,926,510 |
Predictors of changes in body image concerns of Chinese adolescents. | This nine-month prospective study tested the extent to which risk factors implicated in recent accounts of body dissatisfaction predicted changes in body image concerns of adolescent boys and girls in China. A sample of 593 Chinese adolescents (217 boys, 376 girls) completed measures of weight esteem, appearance esteem and physical stature concern in addition to demographics, internalization of attractiveness ideals, negative affect, and appearance pressure, teasing, and comparison at baseline and nine-month follow-up. For girls, initial levels of social comparison, and internalized attractiveness ideals predicted decreases in body esteem over time. Time 1 negative affect contributed to changes in both appearance esteem and weight esteem for boys. Baseline level of stature concerns and reported height were the only predictors of later stature concerns within each sex. In sum, this study suggests specific factors previously implicated in Western accounts also have utility for understanding body image concerns of adolescents in China. | 18,926,567 |
Use of anti-diabetic drugs and glycaemic control in type 2 diabetes-tThe Hong Kong Diabetes Registry. | In this report, we examined the usage of anti-diabetic treatments including oral anti-diabetic drug (OAD) and/or insulin and their combination from baseline data of a consecutive cohort of 7549 Chinese type 2 diabetic subjects in the Hong Kong Diabetes Registry. Pattern of usage of anti-diabetic treatment and corresponding glycemic control was analyzed. OAD failure was defined as the need to add insulin to maintain glycemic target (glycated hemoglobin, HbA(1c) level<7%) with or without continuation of OAD. There were 4109 [54.4%] women and 3440 [45.6%] men (age: median 57.0 years; range 13-92 years). The mean HbA(1c) level was 7.7+/-1.8% with 39.7% attaining glycemic target. Long disease duration was associated with more complex regimens and the respective rates of OAD failure requiring insulin use were 23.7%, 39.3%, 57.1% and 75.9% in those with disease duration <5 years, 5-9.9 years, 10-19.9 years and > or =20 years (p<0.001). In conclusion, in a clinic-based type 2 diabetic population, 39.7% attained glycemic target with HbA(1c)<7%. Long disease duration and complexity of treatment regimens were associated with suboptimal glycemic control. Early intensification of therapy and system improvement are needed to enhance the effectiveness of these drugs in clinical practice. | 18,926,583 |
Pregnancy-associated acute liver disease and acute viral hepatitis: differentiation, course and outcome. | Pregnant women with acute viral hepatitis (VH) and those with pregnancy associated acute liver disease (PAALD) including acute fatty liver disease of pregnancy, hemolysis elevated liver enzyme and low platelet syndrome present with similar clinical features and liver tests abnormalities. Accurate differentiation between the two groups is critical to expedite early delivery in the latter and prevent progressive liver damage. There is scant data in the literature to differentiate between PAALD and VH. We studied the clinical variables, hematological, biochemical and viral serological tests of 87 consecutive pregnant patients with jaundice from 2000 to 2003. There were 46 and 41 patients in PAALD and VH group, respectively. Two-thirds in VH group were due to hepatitis E. Univariate analysis identified hypertension, encephalopathy, oliguria, ascites, serum creatinine, and low platelets as significantly more common in the PAALD group. Multivariate analysis and recursive partitioning identified hypertension and ascites as predictors of PAALD with excellent predictive ability and c value of 0.92. Mortality was 41% in PAALD and 7.5% in VH. Increased bilirubin and oliguria were predictors of mortality in PAALD. Presence of ascites and hypertension differentiates PAALD from VH and should prompt early delivery. Mortality due to hepatitis E is low. | 18,926,590 |
Forty years of atmospheric radiocarbon monitoring around Bohunice nuclear power plant, Slovakia. | Radiocarbon variations in the atmospheric CO(2) with attenuating amplitudes and decreasing mean values with typical maxima in summer and minima in winter have been observed since 1967 in two localities of Slovakia, in Bratislava and Zlkovce, situated about 60 km NE from Bratislava, only 5 km from the Bohunice Nuclear Power Plant (NPP). The (14)C record in Bratislava has been influenced mainly by fossil CO(2) emissions, in contrast to the Zlkovce record which has been more variable, as it has clearly been affected by operation of the Bohunice NPP. However, during specific meteorological conditions with NE transport of air masses to Bratislava, the effect of the Bohunice NPP has been visible in Bratislava as well. Maximum (14)C concentrations (up to 120% above a natural background) were observed around A1 NPP which used CO(2) with admixture of air as a cooling agent. The (14)C concentrations around four pressurized light water reactors were up to 30% above the background. The Delta(14)C values in the heavily polluted atmosphere of Bratislava were up to 10% and at Zlkovce up to 5% lower than the European clean air represented by the Jungfraujoch Delta(14)C data. Later the Delta(14)C values were similar at both sites, and from 2003 they were close to the European clean air levels. The observed Delta(14)C behaviour in the atmosphere provides a unique evidence of decreased fossil fuel CO(2) emissions in the region, as well as the long-term effect of the Bohunice NPP on the Bratislava and Zlkovce stations. The estimated annual radiation doses to the local public due to digestion of radiocarbon contaminated food have been estimated to be around 3 microSv. | 18,926,606 |
Water management in Angkor: human impacts on hydrology and sediment transportation. | The city of Angkor, capital of the Khmer empire from the 9th to 15th century CE, is well known for its impressive temples, but recent research has uncovered an extensive channel network stretching across over 1000 km2. The channel network with large reservoirs (termed baray) formed the structure of the city and was the basis for its water management. The annual long dry season associated with the monsoon climate has challenged water management for centuries, and the extensive water management system must have played an important role in the mitigation of such marked seasonality. However, by changing the natural water courses with off-take channels the original catchments were also reshaped. Moreover, severe problems of erosion and sedimentation in human built channels evolved and impacted on the whole water management system. This paper describes the present hydrology of the area and discusses the impacts of water management on hydrology during the Angkor era. The paper, moreover, attempts to summarise lessons that could be learnt from Angkorian water management that might apply to present challenges within the field. | 18,926,615 |
Characterization study of heavy metal-bearing phases in MSW slag. | Slag products derived from the pyrolysis/melting and plasma/melting treatment of municipal solid waste (MSW) in Japan were examined for the characterization study of heavy metal-bearing phases using petrographic techniques. Detailed microscopic observations revealed that the shapes of heavy metal-rich inclusions are generally spherical to semi-spherical and their sizes range from submicron to scarcely large size spheres (over 100 microm). The experiments (both optical microscopy and electron probe microanalysis) indicated that Fe and Cu participate in mutual substitution and different proportions, and form mainly two-phase Fe-Cu alloys that bound in the silicate glass. This alloy characterizes the composition of more than 80% of the metal-rich inclusions. Other metals and non-metals (such as Pb, Ni, Sb, Sn, P, Si, Al and S) with variable amounts and uneven distributions are also incorporated in the Fe-Cu alloy. In average, the bulk concentration of heavy metals in samples from pyrolysis/melting type is almost six times greater than samples treated under plasma/arc processing. The observations also confirmed that slag from pyrolysis origin contains remarkably higher concentration of metallic inclusions than slag from plasma treatment. In the latter, the metallic compounds are separately tapped from molten slag during the melting treatment that might lead to the generation of safer slag product for end users from environmental viewpoint. | 18,926,624 |
Decolourization and mineralization of commercial reactive dyes by using homogeneous and heterogeneous Fenton and UV/Fenton processes. | The oxidative decolourization and mineralization of three reactive dyes in separately prepared aqueous solutions C.I. Reactive Yellow 3 (RY3), C.I. Reactive Blue 2 (RB2) and C.I. Reactive Violet 2 (RV2) by using homogeneous and heterogeneous Fenton and UV/Fenton processes have been investigated. The effects of H(2)O(2), Fe(2+) and Fe(0) concentrations, Fe(2+)/H(2)O(2) and Fe(0)/H(2)O(2) molar ratios at pH 3 and T=23+/-1 degrees C have been studied. Optimal operational conditions for the efficient degradation of all three dye solutions (100 mg L(-1)) were found to be Fe(2+)/H(2)O(2)=0.5mM/20mM and Fe(0)/H(2)O(2)=2mM/1mM. The experimental results showed that the homogeneous Fenton process employing UV irradiation was the most effective. By using this process, the high levels of mineralization (78-84%) and decolourization (95-100%) were achieved. Pseudo-first-order degradation rate constants were obtained from the batch experimental data. | 18,926,634 |
Suppressive effect of mirtazapine on the HPA system in acutely depressed women seems to be transient and not related to antidepressant action. | Impaired regulation of the hypothalamus-pituitary-adrenocortical (HPA) system is a consistent finding among patients with depression, which can be most sensitively detected with the combined dexamethasone (dex)/corticotrophin releasing hormone (CRH) test. The majority of patients with acute depression shows an exaggerated plasma corticotrophin (ACTH) and cortisol response to this test that normalizes gradually during successful antidepressant therapy. In contrast, persistently high HPA-responses to this challenge are prognostically less favorable. It has been recently questioned, whether this observation applies also to treatment with the atypical antidepressant mirtazapine, as patients treated with this drug showed a distinct attenuation of the endocrine response to the dex/CRH test already after 1 week of treatment. In the present study, we investigated whether the attenuating effect of mirtazapine on the HPA system is an acute pharmacological reaction disappearing after physiological adaptation or whether this effect is related to the antidepressant action of the drug. We examined plasma ACTH and cortisol responses to the dex/CRH test in acutely depressed inpatients treated either with mirtazapine (n=55) or a monoamine reuptake inhibitor (n=105) according to doctor's choice and compared the test results with healthy controls (n=40). Patients treated with monoamine reuptake inhibitors received either selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA) or the combined serotonin and noradrenalin reuptake inhibitor venlafaxine. We found increased plasma ACTH and cortisol responses to the dex/CRH test in depressed patients compared with healthy controls, but also significantly (p=.017) attenuated plasma cortisol secretion in the mirtazapine group compared to the group of monoamine reuptake inhibitor treated patients. This effect was not significant in male patients. Furthermore this effect was independent of the psychopathological state, but depended on treatment duration. Patient treatment with mirtazapine for up to 7 days resulted in dex/CRH test outcome that was indistinguishable from controls. This effect, however waned as it was not observable in patients treated for a longer period. These results suggest that short-term administration of mirtazapine has immediate but only transient suppressive effects on the HPA system predominantly in women. Our results confirm that dex/CRH tests can be used as predictors of clinical course also under mirtazapine treatment. | 18,926,641 |
Association between CARD15/NOD2 gene polymorphisms and paratuberculosis infection in cattle. | Paratuberculosis represents a major problem in farmed ruminants and at the present is considered a potential zoonosis. The disease is caused by Mycobacterium avium subsp. paratuberculosis, and susceptibility to infection is suspected to have a genetic component. Caspase recruitment domain 15 (CARD15) gene encodes for a cytosolic protein implicated in bacterial recognition during innate immunity. Crohn's disease (CD) is an idiopathic inflammatory bowel disease in humans comparable in many features to bovine paratuberculosis involving an abnormal mucosal immune response. The association between mutations in the CARD15 gene and increased risk of Crohn's disease has been described. The objective of this candidate gene case-control study was to characterize the distribution of three polymorphisms in the bovine CARD15 gene and test their association with paratuberculosis infection in cattle. Three previously reported single nucleotide polymorphisms (E2[-32] intron 1; 2197/C733R and 3020/Q1007L) were screened for the study population (431 adult cows). The statistical analysis resulted in significant differences in allelic frequencies between cases and controls for SNP2197/C733R (P<0.001), indicating a significant association between infection and variant allele. In the analysis of genotypes, a significant association was also found between SNP2197/C733R and infection status (P<0.0001); cows with the heterozygous genotype were 3.35 times more likely to be infected than cows with the reference genotype (P=0.01). Results suggest a role for CARD15 gene in the susceptibility of cattle to paratuberculosis infection. These data contribute to the understanding of paratuberculosis, suggest new similarities with Crohn's disease and provide new information for the control of bovine paratuberculosis. | 18,926,647 |
Vascular endothelial growth factor in neonates with perinatal asphyxia. | Vascular endothelial growth factor (VEGF) is a polypeptide growth factor that is activated by tissue hypoxia. The role of VEGF in perinatal asphyxia in human neonates is yet to be clarified. In infants who develop moderate to severe acute hypoxic ischemic encephalopathy (HIE) it is crucial to clearly understand physiologic and biochemical changes that accompany HIE before a novel treatment can be developed. To assess VEGF in cord blood of infants suffering from perinatal asphyxia, and to determine whether an association exists between increased concentrations of VEGF and the risk for development of encephalopathy. We prospectively studied 40 full term infants; of them 20 infants suffered from perinatal asphyxia, and 20 control infants of comparable age and sex. We obtained cord blood samples from all subjects immediately after delivery. Neurological examination and grading of HIE were performed during the first day of life. Birth weight, gestational age and gender did not differ between the control (n=20) and asphyxia (n=20) groups. Within the asphyxia group four infants developed HIE; one with severe encephalopathy who died shortly after birth, while the other three infants had moderate HIE. Concentrations of VEGF were increased in infants with asphyxia when compared to controls (P0.001). Within the asphyxia group, infants with HIE had significantly increased concentrations of VEGF when compared to non-HIE asphyxiated infants (P=0.008). In the logistic regression model, VEGF inversely correlated with pH and PO(2) in cord blood, and Apgar scores at 1min, while it did not associate with gestational age and birth weight. This study indicates that VEGF is increased in cord blood of neonates following birth asphyxia, and that VEGF is specifically most increased in infants who later developed encephalopathy. Further studies are required to determine the role of VEGF in brain insult. Such studies will help determine whether a therapeutic role for VEGF or VEGF inhibitors can exist for HIE infants. | 18,926,648 |
[Exocrin pancreatic deficiency revealing an alpha-1-antitrypsin deficiency]. | There are genetic mutations taking part in the physiopathology of pancreatitis. The role of alpha-1-antitrypsin (AAT) deficiency in this pathology is debated. We report the case of a 60-year-old man with a pancreatic exocrine insufficiency. He was diagnosed with AAT deficiency. The phenotype was Pi SZ, with genotyping confirmation. The place of AAT deficiency in the midst of pancreatic diseases should be further studied. | 18,926,650 |
Complications of percutaneous transhepatic biliary drainage in patients with dilated and nondilated intrahepatic bile ducts. | Percutaneous transhepatic biliary drainage (PTBD) have been described as an effective technique to obtain biliary access. Between January 1996 and December 2006, a total of 419 consecutive patients with endoscopically inaccessible bile ducts underwent PTBD. The current retrospective study evaluated success and complication rates of this invasive technique. PTBD was successful in 410/419 patients (97%). The success rate was equal in patients with dilated and nondilated bile ducts (p=0.820). In 39/419 patients (9%) procedure related complications could be observed. Major complications occurred in 17/419 patients (4%). Patients with nondilated intrahepatic bile ducts had significantly higher complication rates compared to patients with dilated intrahepatic bile ducts (14.5% vs. 6.9%, respectively [p=0.022]). Procedure related deaths were observed in 3 patients (0.7%). In conclusion, percutaneous transhepatic biliary drainage is an effective procedure in patients with dilated and nondilated intrahepatic bile ducts. However, patients with nondilated intrahepatic bile ducts showed a higher risk for procedure related complications. | 18,926,655 |
1,6-O,O-diacetylbritannilactones inhibits IkappaB kinase beta-dependent NF-kappaB activation. | To determine the chemical constituents responsible for pharmacological effects of Inula britannica-F., three specific sesquiterpene lactones in Inula britannica were isolated from chloroform extract and identified, including britannilactone (BL), 1-O-acetylbritannilactone (ABLO), and 1,6-O,O-diacetylbritannilactone (ABLOO). Electrophoretic mobility shift assay (EMSA) was performed to detect the nuclear translocation of nuclear factor-kappaB (NF-kappaB) p65. The expressions of IkappaBalpha, pIkappaBalpha, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), IkappaB kinase alpha/beta (IKKalpha/beta) and NF-kappaB kinase (NIK) were detected by Western blot and RT-PCR. We found that acetyl side groups enhanced the inhibitory action of the agents on LPS/IFN-gamma-induced iNOS and COX-2 expression. Their inhibiting activity was positive correlation with the acetyl side group number. The effects of LPS/IFN-gamma were reversed by ABLOO, and BL without acetyl side groups showed only a weak inhibitory action. Further study indicated that ABLOO markedly inhibited the phosphorylation of IKKbeta down to based level, but not IKKalpha, corresponding with decreased in IkappaBalpha degradation and phosphorylation induced by LPS/IFN-gamma, resulting in the suppression of NF-kappaB nuclear translocation and activity. These results suggest that the acetyl moieties add to the lipophilicity, and consequently enhance cellular penetration, so that ABLOO possess the most anti-inflammatory effect and may be a potent lead structure for the development of therapeutic and cytokine-suppressing remedies valuable for the treatment of various inflammatory diseases. | 18,926,678 |
Inhibitory mechanisms of Agaricus blazei Murill on the growth of prostate cancer in vitro and in vivo. | Agaricus blazei Murill (A. blazei) has been conventionally used as a health food for the prevention of cancer. However, little is known about the direct effects and action mechanisms of A. blazei on human prostate cancer. In the present study, the effects of A. blazei on the growth of human prostate cancer were examined in vitro and in vivo. A. blazei, especially the broth fraction, inhibited cell proliferation in both androgen-dependent and androgen-independent prostate cancer cell lines. The broth of A. blazei induced lactate dehydrogenase leakage in three cancer cell lines, whereas the activities of caspase 3 and the DNA fragmentation were enhanced the most in androgen-independent PC3 cells. The protein expressions of apoptosis-related molecules were elevated by the broth of A. blazei in PC3 cells. Oral supplementation with the broth of A. blazei (with the higher ratio of beta-glucan) significantly suppressed tumor growth without inducing adverse effects in severe combined immunodeficient mice with PC3 tumor xenograft. Tumor xenografts from A. blazei-fed mice showed decreased proliferating cell nuclear antigen-positive cells and reduced tumor microvessel density. Based on these results, we found that the broth of A. blazei may directly inhibit the growth of prostate cancer cell via an apoptotic pathway and suppress prostate tumor growth via antiproliferative and antiangiogenic mechanisms. We therefore suggest that A. blazei might have potential therapeutic use in the prevention and treatment of human prostate cancer. | 18,926,679 |
Green and black tea extracts inhibit HMG-CoA reductase and activate AMP kinase to decrease cholesterol synthesis in hepatoma cells. | Recent studies have demonstrated that green and black tea consumption can lower serum cholesterol in animals and in man, and suppression of hepatic cholesterol synthesis is suggested to contribute to this effect. To evaluate this hypothesis, we measured cholesterol synthesis in cultured rat hepatoma cells in the presence of green and black tea extracts and selected components. Green and black tea decreased cholesterol synthesis by up to 55% and 78%, respectively, as measured by a 3-h incorporation of radiolabeled acetate. Inhibition was much less evident when radiolabeled mevalonate was used, suggesting that the inhibition was mediated largely at or above the level of HMG-CoA reductase. Both extracts directly inhibited HMG-CoA reductase when added to microsomal preparations, although the extent of inhibition was considerably less than the decrease in cholesterol synthesis observed in whole cells. As HMG-CoA reductase activity also can be decreased by enzyme phosphorylation by AMP kinase, the phosphorylation state of HMG-CoA reductase and AMP kinase, which is activated by phosphorylation, was determined in lysates from cells treated with tea extracts. Both extracts increased AMP-kinase phosphorylation and HMG-CoA reductase phosphorylation by 2.5- to 4-fold, but with different time courses: maximal phosphorylation with green tea was evident within 30 min of treatment, whereas with black tea phosphorylation was slower to develop, with maximal phosphorylation occurring > or =3 hours after treatment. These results suggest that both green and black tea decrease cholesterol synthesis in whole cells by directly inhibiting HMG-CoA reductase and by promoting its inactivation by AMP kinase. | 18,926,682 |
5-Caffeoylquinic acid and caffeic acid orally administered suppress P-selectin expression on mouse platelets. | Caffeic acid and 5-caffeoylquinic acid are naturally occurring phenolic acid and its quinic acid ester found in plants. In this article, potential effects of 5-caffeoylquinic acid and caffeic acid on P-selectin expression were investigated due to its significant involvement in platelet activation. First, the effects of 5-caffeoylquinic acid and caffeic acid on cyclooxygenase (COX) enzymes were determined due to their profound involvement in regulating P-selectin expression on platelets. At the concentration of 0.05 microM, 5-caffeoylquinic acid and caffeic acid were both able to inhibit COX-I enzyme activity by 60% (P<.013) and 57% (P<.017), respectively. At the same concentration, 5-caffeoylquinic acid and caffeic acid were also able to inhibit COX-II enzyme activity by 59% (P<.012) and 56% (P<.015), respectively. As expected, 5-caffeoylquinic acid and caffeic acid were correspondingly able to inhibit P-selectin expression on the platelets by 33% (P<.011) and 35% (P<.018), at the concentration of 0.05 microM. In animal studies, 5-caffeoylquinic acid and caffeic acid orally administered to mice were detected as intact forms in the plasma. Also, P-selectin expression was respectively reduced by 21% (P<.016) and 44% (P<.019) in the plasma samples from mice orally administered 5-caffeoylquinic acid (400 microg per 30 g body weight) and caffeic acid (50 microg per 30 g body weight). These data suggest that both 5-caffeoylquinic acid and caffeic acid orally administered can be absorbed and suppress P-selectin expression on mouse platelets. | 18,926,684 |
The fairness of PAYT systems: some guidelines for decision-makers. | Although the whole idea behind the PAYT approach is to develop a fairer system of waste charges than currently used, there still remains a number of issues that need to be considered when designing any given application of the PAYT principle, bearing in mind the variety of possible PAYT systems and the set of factors that influence their implementation. We assume that the perception of the system's fairness affects acceptance and thus participation, in the sense that the higher the perceived fairness the higher will be the acceptance of the system and, therefore, the higher the participation will be. Consequently, when it comes to analysing the acceptance of the implementation of a PAYT system or its effective functioning, waste management decision-makers should be interested in making sure that the system is perceived as fair in order to ensure a high participation rate. In addition, from a social point of view, decision-makers and politicians may be interested in the consequences of the operation of the system for other social values and in its impacts on particular groups of participants. This presentation examines the conditions for fairness and the considerations that should be taken into account so as to design a fair PAYT system in a specific municipality. | 18,926,689 |
On-chip impedimetric detection of bacteriophages in dairy samples. | Bacteriophage infection of starter cultures constitutes a major problem in the dairy fermentation industry, which may bring about important economic losses. In this study, a rapid detection method of bacteriophages was developed based on analysis of impedance changes occurred upon infection of a host-biofilm established onto metal microelectrodes. Bacteriophage PhiX174 and Escherichia coli WG5 were chosen as models for bacteriophage and host strain, respectively, because of their easiness of manipulation. Impedimetric changes occurring at the microelectrode surface, caused by bacteriophage infection and subsequent lysis of the host strain, were monitored over a 6-h period after the initial inoculation of phages by non-faradic impedance spectroscopy (IS) in PBS and milk samples. Analysis of data was performed by two different approaches: (1) the equivalent circuit modelling theory, where a decrease in the magnitude of both the double layer and the biofilm capacitances due to the bacteriophage infection process was recorded, and (2) analysis of the impedance value, specially the impedance imaginary component (Z(i)) at selected frequencies. Z(i) is related to the capacitance of the circuit and also showed a decrease with respect to the control sample (without bacteriophages). The simplicity of the assay and the possibility of miniaturization of the system as well as its wide application, being able of detecting any bacteriophage as long as a suitable bacterial host is available, increase the number of applications to which this system could be used for. | 18,926,694 |
Synthesis of Arabino glycosyl triazoles as potential inhibitors of mycobacterial cell wall biosynthesis. | A series of arabino glycosyl triazoles with varying hydrophobic groups were synthesised as putative mimics of decaprenolphosphoarabinose (DPA) as potential inhibitors of mycobacterial cell wall biosynthesis. Biological testing against Mycobacterium bovis BCG revealed low to moderate anti-mycobacterial activity, with strong dependence on the identity of the hydrophobic side chain. | 18,926,698 |
Pituitary apoplexy associated with acute cerebral infarct. | We describe a case of pituitary apoplexy associated with acute cerebral infarction. A review of the literature regarding the pathogenesis of cerebral infarction in the presence of pituitary apoplexy is presented and management options proposed. | 18,926,706 |
Double edge redox-implications for the interaction between endogenous thiols and copper ions: In vitro studies. | The present study investigated the redox-consequences of the interaction between various endogenous thiols (RSH)-glutathione, cysteine, homocysteine, gamma-glutamyl-cysteine, and cysteinyl-glycine- and Cu(2+) ions, in terms of their free radical-scavenging, ascorbate-oxidizing and O2(*-)-generating properties of the resulting mixtures. Upon a brief incubation (3-30 min) with Cu(2+), the free radical-scavenging properties (towards ABTS(*)(+) and DPPH(*)) and thiol-titratable groups of the RSH added to the mixtures decreased significantly. Remarkably, both effects were only partial, even in the presence of a large molar Cu(2+)-excess, and were unaffected despite increasing the incubation time. At equimolar concentrations, the RSH/Cu(2+) mixtures led to the formation of (EPR paramagnetic) Cu(II)-complexes that were time-stable and ascorbate-reducible, but redox-inactive towards oxygen. In turn, at a slight molar thiol-excess (3:1), the mixtures resulted in the formation of time-stable Cu(I)-complexes (EPR silent) that were unreactive towards ascorbate and oxygen. The only exception was seen for the thiol, glutathione, whose mixture with Cu(2+) mixture displayed a O2(*-)-generating capacity (cytochrome c- and lucigenin-reduction). The data indicate that, depending on their molar ratio, the interaction between Cu(2+) and the tested thiols would give place to mixtures containing either: (i) time-stable and ascorbate-reducible Cu(II)-complexes which display free radical-scavenging properties, or (ii) time-stable but redox-inactive towards oxygen Cu(I)-complexes. Among the latter, the only exception was that of glutathione. | 18,926,709 |
Novel piperidinylpyrimidine derivatives as inhibitors of HIV-1 LTR activation. | Piperidinylpyrimidine derivatives, previously prepared as inhibitors of TNF-alpha production, were evaluated for their inhibitory activity against HIV-1 LTR activation. Some of these derivatives inhibited activation of HIV-1 LTR-directed CAT gene expression induced by PMA in Jurkat cells. In this report, we describe SAR in this series of compounds and show that the 3,4-methylenedioxybenzoyl (piperonyloyl) group on the nitrogen of piperidine and lipophilic substitution at the C(6)-position of pyrimidine are important for this inhibitory activity. Some of the synthesized compounds also inhibited HIV-1 LTR transactivation induced by viral protein Tat. These results suggest that piperidinylpyrimidines are useful as potent AIDS therapeutics that directly inhibit HIV-1 LTR activation and indirectly suppress TNF-alpha production. | 18,926,711 |
Statistics for clinical nursing practice: an introduction. | Difficulty in understanding statistics is one of the most frequently reported barriers to nurses applying research results in their practice. Yet the amount of nursing research published each year continues to grow, as does the expectation that nurses will undertake practice based on this evidence. Critical care nurses do not need to be statisticians, but they do need to develop a working knowledge of statistics so they can be informed consumers of research and so practice can evolve and improve. For those undertaking a research project, statistical literacy is required to interact with other researchers and statisticians, so as to best design and undertake the project. This article is the first in a series that guides critical care nurses through statistical terms and concepts relevant to their practice. | 18,926,715 |
Ionized o-, m-, and p-difluorobenzene dissociate through ring-opened intermediates: a TPEPICO investigation. | Threshold photoelectron photoion coincidence (TPEPICO) experiments have shown that o-, m-, and p-difluorobenzene ions dissociate via a common, ring-opened intermediate and not via ionized p-difluorobenzene. Rice-Ramsperger-Kassel-Marcus (RRKM) modeling of the experimental breakdown curves yields activation energies for the initial isomerization of 4.48 +/- 0.05, 4.55 +/- 0.05, and 4.68 +/- 0.05 eV for o-, m-, and p-difluorobenzene, respectively. These values place each ion at a similar absolute energy and thus similar transition states. A large positive DeltaS(double dagger) for each ion (ca 100 J K(-1) mol(-1)) suggests a ring-opened structure for these transition states. | 18,926,721 |
Maxillary first molar with aberrant canal configuration: a report of 3 cases. | The prognosis for endodontic treatment in teeth exhibiting morphological aberrations is unfavorable if the clinician fails to recognize extra root canals. This report demonstrates 3 clinical cases of maxillary first molars that presented 2 canals in the palatal root merging at the apical third (Vertucci's type II canal morphology), a pattern that is rare and seldom encountered. | 18,926,731 |
Radiopacity and histological assessment of Portland cement plus bismuth oxide. | The present study evaluated the subcutaneous connective tissue reactions and the radiopacity of MTA, Portland cement (PC), and Portland cement plus bismuth oxide (BO). Forty rats were divided into 5 groups (n = 8 per group): A1: Control (empty capsule); A2: Pro-Root MTA; A3: PC; A4: PC + BO 1:1; and A5: PC + BO 2:1. Polyethylene tubes were filled with the test materials and standardized radiographic images were taken. Histological evaluation was done after 7 and 60 days. Student t test and Fisher's test were used in the statistical analysis (P < .05). The radiopacity of the materials were in decreasing order: A2 > A4 > A5 > A3. No differences were found for the tissue response in the 2 experimental periods. A positive correlation between BO concentration and radiopacity of PC was determined. The histological evaluation suggests that all studied materials were biocompatible at 7 and 60 days. | 18,926,734 |
Enhanced spectral resolution by high-dimensional NMR using the filter diagonalization method and "hidden" dimensions. | High-dimensional (HD) NMR spectra have poorer digital resolution than low-dimensional (LD) spectra, for a fixed amount of experiment time. This has led to "reduced-dimensionality" strategies, in which several LD projections of the HD NMR spectrum are acquired, each with higher digital resolution; an approximate HD spectrum is then inferred by some means. We propose a strategy that moves in the opposite direction, by adding more time dimensions to increase the information content of the data set, even if only a very sparse time grid is used in each dimension. The full HD time-domain data can be analyzed by the filter diagonalization method (FDM), yielding very narrow resonances along all of the frequency axes, even those with sparse sampling. Integrating over the added dimensions of HD FDM NMR spectra reconstitutes LD spectra with enhanced resolution, often more quickly than direct acquisition of the LD spectrum with a larger number of grid points in each of the fewer dimensions. If the extra-dimensions do not appear in the final spectrum, and are used solely to boost information content, we propose the moniker hidden-dimension NMR. This work shows that HD peaks have unmistakable frequency signatures that can be detected as single HD objects by an appropriate algorithm, even though their patterns would be tricky for a human operator to visualize or recognize, and even if digital resolution in an HD FT spectrum is very coarse compared with natural line widths. | 18,926,747 |
Orally administered microencapsulated lysozyme downregulates serum AGE and reduces the severity of early-stage diabetic nephropathy. | Diabetic nephropathy is the leading cause of end-stage kidney disease in developed countries and is related to chronic hyperglycaemia. The increased production and tissue deposition of advanced glycation end products (AGE) are known to play a major role in the pathogenesis of diabetic kidney damage. This study was undertaken to determine if lysozyme (LZ), microencapsulated in orally administrable chitosan-coated alginate microspheres (MS), is effective against the early changes seen in the initial stages of diabetic nephropathy. LZ-containing MS (MSLZ) and an equivalent dose (equidose) of nonencapsulated LZ were given as oral treatments. LZ was administered to Wistar rats for seven weeks after diabetes induction with streptozotocin. The results showed that microencapsulated LZ treatment significantly reduced the concentration of serum AGE in the circulation and their deposition in the kidneys. Likewise, MSLZ significantly prevented the development of microalbuminuria compared with untreated diabetic rats. Furthermore, MSLZ significantly prevented the development of glomerular and renal hypertrophy as well as overexpression of AGE receptors (RAGE). An equidose of free LZ had little or no effect whatsoever. Our study supports a relationship between serum AGE and nephropathy in diabetes, and suggests that orally administered microencapsulated LZ can exert kidney-protective activity in a diabetic animal model. | 18,926,757 |
Successful non-operative management of an iatrogenic recto-urethral fistula in a 13-year-old boy. | Here we present a case of successful non-operative management of an iatrogenic recto-urethral fistula in a 13-year-old boy. The fistula was created when urethroscopic repair of a urethral stricture was attempted. Due to the anatomy of the lesion and previous urinary diversion, it was deemed possible to spare this patient diverting colostomy or surgical repair of the fistula. The result was successful closure of the fistula, which was confirmed on retrograde urethrogram. While we do not support the routine use of non-operative management for recto-urethral fistulas we have demonstrated that there are circumstances where it can be safely applied. | 18,926,776 |
Detection of chitinase activity by 2-aminobenzoic acid labeling of chito-oligosaccharides. | Chitinases are hydrolases capable of hydrolyzing the abundant natural polysaccharide chitin. Next to artificial fluorescent substrates, more physiological chito-oligomers are commonly used in chitinase assays. Analysis of chito-oligosaccharides products is generally accomplished by UV detection. However, the relatively poor sensitivity poses a serious limitation. Here we report on a novel, much more sensitive assay for the detection of chito-oligosaccharide reaction products released by chitinases, based on fluorescent detection, following chemical labeling by 2-aminobenzoic acid. Comparison with existing UV-based assays, shows that the novel assay offers the same advantages yet allows detection of chito-oligosaccharides in the low picomolar range. | 18,926,793 |
Biochemical characterization of human epidermal retinol dehydrogenase 2. | The mRNA encoding a putative human enzyme named Epidermal Retinol Dehydrogenase 2 (RDH-E2) was found to be significantly elevated in psoriatic skin [Y. Matsuzaka, K. Okamoto, H. Tsuji, T. Mabuchi, A. Ozawa, G. Tamiya, H. Inoko, Identification of the hRDH-E2 gene, a novel member of the SDR family, and its increased expression in psoriatic lesion, Biochem. Biophys. Res. Commun. 297 (2002) 1171-1180]. This finding led the authors to propose that RDH-E2 may be involved in the pathogenesis of psoriasis through its potential role in retinoic acid biosynthesis and stimulation of keratinocyte proliferation. However, enzymatic activity for RDH-E2 has never been demonstrated. RDH-E2 is a member of the short-chain dehydrogenase/reductase (SDR) superfamily of proteins, and is most closely related to the group of SDRs comprised of both NAD(+)- and NADP(+)-dependent enzymes with activities toward retinoid and steroid substrates. In this study, we began the characterization of RDH-E2 protein in order to determine whether it might play a role in retinoic acid biosynthesis. The results of this study show that, similarly to other SDR-type retinol dehydrogenases, RDH-E2 appears to be associated with the membranes of endoplasmic reticulum. Furthermore, RDH-E2 expressed in Sf9 insect cells as a fusion to the C-terminal His(6)-tag and purified using Ni(2+)-affinity chromatography recognizes all-trans-retinol and all-trans-retinaldehyde as substrates and exhibits a strong preference for NAD(+)/NADH as cofactors. Specific activity of RDH-E2 toward all-trans-retinoids is much lower than that of other retinoid-active SDRs, such as human RoDH4 or RDH10. The preference for NAD(+) suggests that RDH-E2 is likely to function in the oxidative direction in vivo, further supporting its potential role in the oxidation of retinol to retinaldehyde for retinoic acid biosynthesis in human keratinocytes. | 18,926,804 |
TGIF, a homeodomain transcription factor, regulates retinal progenitor cell differentiation. | TG-interacting factor (TGIF) is a TALE homeodomain protein expressed predominantly in the central nervous system and functions as a transcriptional repressor. Several mutations in TGIF have been identified in patients with holoprosencephaly, the most common congenital malformation of the developing human forebrain. However, the precise role of TGIF in neural development is not well understood. We found that TGIF was expressed strongly in the mouse retina during early stages of development, and that its expression gradually decreased as retinal development progressed. In vitro explant cultures of mouse retina mimic the in vivo development of retinal subtypes. Forced expression of TGIF using a retrovirus in explant culture induced the differentiation of amacrine cells from retinal progenitor cells. A TGIF paralog, TGIF2, showed a similar transition in expression during retinal development, and TGIF2 also promoted amacrine cell differentiation in a retinal explant culture system. However, no apparent difference between wild-type and TGIF-knockout mouse retina was observed, suggesting that TGIF and TGIF2 function redundantly in that tissue. Forced expression of TGIF homeodomain (HD)-EnR (repressing) rather than TGIF HD-VP16 (activating) resulted in a phenotype similar to that induced by wild-type TGIF, suggesting that TGIFs may act as transcriptional repressors to induce amacrine genesis. | 18,926,818 |
Histone-deacetylase inhibition reverses atrial arrhythmia inducibility and fibrosis in cardiac hypertrophy independent of angiotensin. | Atrial fibrosis influences the development of atrial fibrillation (AF), particularly in the setting of structural heart disease where angiotensin-inhibition is partially effective for reducing atrial fibrosis and AF. Histone-deacetylase inhibition reduces cardiac hypertrophy and fibrosis, so we sought to determine if the HDAC inhibitor trichostatin A (TSA) could reduce atrial fibrosis and arrhythmias. Mice over-expressing homeodomain-only protein (HopX(Tg)), which recruits HDAC activity to induce cardiac hypertrophy were investigated in 4 groups (aged 14-18 weeks): wild-type (WT), HopX(Tg), HopX(Tg) mice treated with TSA for 2 weeks (TSA-HopX) and wild-type mice treated with TSA for 2 weeks (TSA-WT). These groups were characterized using invasive electrophysiology, atrial fibrosis measurements, atrial connexin immunocytochemistry and myocardial angiotensin II measurements. Invasive electrophysiologic stimulation, using the same attempts in each group, induced more atrial arrhythmias in HopX(Tg) mice (48 episodes in 13 of 15 HopX(Tg) mice versus 5 episodes in 2 of 15 TSA-HopX mice, P<0.001; versus 9 episodes in 2 of 15 WT mice, P<0.001; versus no episodes in any TSA-WT mice, P<0.001). TSA reduced atrial arrhythmia duration in HopX(Tg) mice (1307+/-289 ms versus 148+/-110 ms, P<0.01) and atrial fibrosis (8.1+/-1.5% versus 3.9+/-0.4%, P<0.001). Atrial connexin40 was lower in HopX(Tg) compared to WT mice, and TSA normalized the expression and size distribution of connexin40 gap junctions. Myocardial angiotensin II levels were similar between WT and HopX(Tg) mice (76.3+/-26.0 versus 69.7+/-16.6 pg/mg protein, P=NS). Therefore, it appears HDAC-inhibition reverses atrial fibrosis, connexin40 remodeling and atrial arrhythmia vulnerability independent of angiotensin II in cardiac hypertrophy. | 18,926,829 |
A network approach to modeling population aggregation and genetic control of pest insects. | Historically, models of the invasion and biological control of insect pests have omitted heterogeneities in the spatial structure of the targeted populations. In this study, we use stochastic network simulations to examine explicitly population heterogeneity as a function of landscape structure and insect behavior. We show that when insects are distributed non-randomly across a heterogeneous landscape, control can be significantly hindered. However, when insect populations are clustered as a result of limited dispersal, genetic control efficiency can be enhanced. In developing the model, we relax a key assumption of previous theoretical studies of genetic control: that released genetic control insects remain homogenously distributed irrespective of the spatial structure of the wild type populations. Here, this behavior (termed the 'coverage proportion') is parameterized and its properties are explored. We show that landscape heterogeneity and limited dispersal have little effect on the critical coverage proportion necessary for control. | 18,926,837 |
A population-coding model of attention's influence on contrast response: Estimating neural effects from psychophysical data. | Human psychophysics and monkey physiology studies have shown that attention modulates early vision - contrast sensitivity and processing. But how can we bridge the effects of attention on perceptual performance to their neural underpinnings? Here we implement a population-coding model that estimates attentional effects on population contrast response given psychophysical data. Model results show that whereas endogenous (sustained, voluntary) attention changes population contrast-response via contrast gain, exogenous (transient, involuntary) attention changes population contrast-response via response gain. | 18,926,845 |
Episodic-like and procedural memory impairments in histamine H1 Receptor knockout mice coincide with changes in acetylcholine esterase activity in the hippocampus and dopamine turnover in the cerebellum. | We investigated episodic-like (ELM) and procedural memory (PM) in histamine H1 receptor knockout (H1R-KO) mice. In order to relate possible behavioral deficits to neurobiological changes, we examined H1R-KO and wild-type (WT) mice in terms of acetylcholine esterase (AChE) activity in subregions of the hippocampus and AChE and tyrosine hydroxylase (TH) expression in the striatum. Furthermore, we analyzed acetylcholine (ACh), 5-HT and dopamine (DA) levels, including metabolites, in the cerebellum of H1R-KO and WT mice. The homozygous H1R-KO mice showed impaired ELM as compared with the heterozygous H1R-KO and WT mice. The performance of homozygous H1R-KO mice in the ELM task was primarily driven by familiarity-based memory processes. While the homozygous H1R-KO mice performed similar to the heterozygous H1R-KO and WT mice during the acquisition of a PM, as measured with an accelerating rotarod, after a retention interval of 7 days their performance was impaired relative to the heterozygous H1R-KO and WT mice. These findings suggest that, both, ELM and long-term PM are impaired in the homozygous H1R-KO mice. Neurochemical assays revealed that the H1R-KO mice had significantly lower levels of AChE activity in the dentate gyrus (DG) and CA1 subregions of the hippocampus as compared with the WT mice. The homozygous H1R-KO mice also displayed significantly reduced dihydroxyphenylacetic acid (DOPAC) levels and a reduced DOPAC/DA ratio in the cerebellum, suggesting that the DA turnover in the cerebellum is decelerated in homozygous H1R-KO mice. In conclusion, homozygous H1R-KO mice display severe long-term memory deficits in, both, ELM and PM, which coincide with changes in AChE activity in the hippocampus as well as DA turnover in the cerebellum. The importance of these findings for Alzheimer's (AD) and Parkinson's disease (PD) is discussed. | 18,926,883 |
Descending pathways from activated locus coeruleus/subcoeruleus following unilateral hindpaw inflammation in the rat. | We have previously shown that the descending pathways from the locus coeruleus (LC)/subcoeruleus (SC) to the spinal cord are activated during peripheral inflammation, and that activation of this coeruleospinal system decreases development of hyperalgesia. Anatomical evidence suggests that the descending modulation system from the LC/SC should be active bilaterally during inflammation when the LC/SC either ipsilateral or contralateral to the site of inflammation is activated. In the present study, the development of hyperalgesia following the induction of unilateral hindpaw inflammation was compared between rats with either bilateral or unilateral lesions of the LC/SC and rats with a sham operation. Four hours after carrageenan injection, in the inflamed paw, paw withdrawal latencies (PWLs) to thermal stimuli of the bilateral LC/SC-lesioned rats were significantly shorter than those of the unilateral LC/SC-lesioned and the sham-operated rats, whereas the decreased PWLs of the unilateral LC/SC-lesioned rats were equivalent to those of the sham-operated rats. A difference in PWL between the bilateral and the unilateral LC/SC-lesioned rats was not observed in the contralateral non-inflamed paw. The result suggests that in the LC/SC both ipsilateral and contralateral to the inflamed paw, only neurons which project to the dorsal horn ipsilateral to the inflamed paw were activated following peripheral inflammation. | 18,926,888 |
Determination of the human brainstem respiratory control network and its cortical connections in vivo using functional and structural imaging. | This study combined functional and structural magnetic resonance imaging techniques, optimized for the human brainstem, to investigate activity in brainstem respiratory control centres in a group of 12 healthy human volunteers. We stimulated respiration with carbon dioxide (CO(2)), and utilized novel methodology to separate its vascular from its neuronal effects upon the blood oxygen level dependent (BOLD) signal. In the brainstem we observed activity in the dorsal rostral pons (representing the Kölliker-Fuse/parabrachial (KF/PB) nuclei and locus coeruleus), the inferior ventral pons and the dorsal and lateral medulla. These areas of activation correspond to respiratory nuclei identified in recent rodent studies. Our results also reveal functional participation of the anteroventral (AV), ventral posterolateral (VPL) ventrolateral thalamic nuclei, and the posterior putamen in the response to CO(2) stimulation, suggesting that these centres may play a role in gating respiratory information to the cortex. As the functional imaging plane was limited to the brainstem and adjacent subcortical areas, we employed diffusion tractography to further investigate cortical connectivity of the thalamic activations. This revealed distinct connectivity profiles of these thalamic activations suggesting subdivision of the thalamus with regards to respiratory control. From these results we speculate that the thalamus plays an important role in integrating respiratory signals to and from the brainstem respiratory centres. | 18,926,913 |
Phylogenetics and biogeography of the broad-nosed bats, genus Platyrrhinus (Chiroptera: Phyllostomidae). | The Neotropical broad-nosed bats, genus Platyrrhinus, represent a well-defined monophyletic group of 14 recognized species. A recent study of morphological characters confirmed Platyrrhinus monophyly and species diagnosis, but offered little support to their intra-specific relationships. We conducted phylogenetic analyses of the genus, using dense taxonomic sampling in combination with four gene sequences representing both mitochondrial and nuclear DNA transmission systems. Our aim was to elucidate the phylogenetic structure among species, using the resulting 3341 bp of DNA. Maximum parsimony, maximum likelihood, and Bayesian inference analyses produced similar topologies that confirm the monophyly of the genus Platyrrhinus and strongly support many previously unrecognized groups. Paraphyly of Platyrrhinus helleri and the unclear position of P. brachycephalus in the clades were also apparent in the data. Our biogeographical analysis suggests a Brazilian Shield origin for Platyrrhinus, followed by subsequent radiations of lineages in the Amazon Basin and Andes. Secondary dispersal from Amazonian and Andean centers is responsible for the Platyrrhinus inhabiting the Guianan Shield and the Pacific lowlands and Central America, respectively. | 18,926,914 |
Lactobacillus-mediated inhibition of clinical toxic shock syndrome Staphylococcus aureus strains and its relation to acid and peroxide production. | The inhibitory activities of 39 strains representing 20 different species of Lactobacillus toward a menstrual toxic shock syndrome (TSS) Staphylococcus aureus archetype strain MN8 were investigated. Nearly every strain (38 of 39) produced an inhibitory effect under both aerobic and anaerobic conditions when assayed on agar medium. In addition, the MN8 inhibition was conserved against at least 10 other clinical TSS S. aureus isolates and, interestingly, required actively growing cultures of Lactobacillus (verified with a two-well co-culture system in broth medium). This general uniform inhibition could be ameliorated by organic buffer (PIPES) supplied in the growth medium and, with only one exception, MRS medium adjusted with non-organic acid (HCl) failed to support growth of TSS strains at or below pH 5.5. By comparison, the vast majority of lactobacilli in this study decreased culture pH to a range of 4-5. Hydrogen peroxide production by the lactobacilli was also assessed and verified by two different methodologies revealing a broad spectrum of phenotypes that, contrary to reports touting its effectiveness, did not seem to correspond with our inhibition studies. Furthermore, resistances to peroxide by MN8, other TSS strains, and a subset of lactobacilli used in this study were nearly identical whereas the S. aureus collection was slightly more sensitive to racemic lactic acid than the lactobacilli. Collectively, these data suggest that the underlying inhibition toward Staphylococcus is generally conserved in Lactobacillus sp. and is related to a common factor in this genus involving promotion of acidic conditions. | 18,926,917 |
Quality of life in seizure-free patients with epilepsy on monotherapy. | Epilepsy is a multifaceted chronic disorder which has diverse and complex effects on the well-being of the patient. Although it is evident that seizure type and frequency play a critical role in the quality of life (QOL) of patients with epilepsy, it is less clear what the major determinants are that influence QOL in seizure-free patients receiving monotherapy. The aim of this study was to evaluate demographic, clinical, and socioeconomic factors influencing the QOL of seizure-free patients receiving monotherapy. All participants were patients from four medical centers who had epilepsy, were on monotherapy, and had been seizure-free for at least 1 year. Responders completed three questionnaires on demographic and clinical information, QOL, and antiepileptic drug (AED) side effects during routine follow-up visits in the epilepsy clinics. We present the data of 103 patients: 59 females (57.3%), mean age 37.75+/-13.66 years. Treatment side effects and unemployment (p<0.0001, p=0.037, respectively) were significant predictors for poor overall QOL, whereas age, gender, education, family status, comorbidity, seizure type, age of seizure onset, and epilepsy duration did not significantly affect overall QOL. There was no significant difference in side effects and QOL between patients receiving older versus newer AEDs. Ninety-four (92.2%) patients reported experiencing at least one side effect of AEDs when queried about specific symptoms, while only 11 (10.7%) patients replied affirmatively when asked whether they experienced "any" side effects. The most common side effects involved the central nervous system. In conclusion, this study reveals that the most significant factor influencing the QOL in seizure-free patients on monotherapy is AED side effects. QOL is a crucial component in the clinical care of patients with epilepsy, and physicians should take the time to ask specific questions on side effects of AEDs. | 18,926,930 |
Alkaline mineral water lowers bone resorption even in calcium sufficiency: alkaline mineral water and bone metabolism. | Dietary acid charge enhances bone loss. Bicarbonate or alkali diet decreases bone resorption in humans. We compared the effect of an alkaline mineral water, rich in bicarbonate, with that of an acid one, rich in calcium only, on bone markers, in young women with a normal calcium intake. This study compared water A (per litre: 520 mg Ca, 291 mg HCO(3)(-), 1160 mg SO(4)(-), Potential Renal Acid load (PRAL) +9.2 mEq) with water B (per litre: 547 mg Ca, 2172 mg HCO(3)(-), 9 mg SO(4)(-), PRAL -11.2 mEq). 30 female dieticians aged 26.3 yrs (SD 7.3) were randomized into two groups, followed an identical weighed, balanced diet (965 mg Ca) and drank 1.5 l/d of the assigned water. Changes in blood and urine electrolytes, C-telopeptides (CTX), urinary pH and bicarbonate, and serum PTH were measured after 2 and 4 weeks. The two groups were not different at baseline, and showed a similar increase in urinary calcium excretion. Urinary pH and bicarbonate excretion increased with water B, but not with water A. PTH (p=0.022) and S-CTX (p=0.023) decreased with water B but not with water A. In calcium sufficiency, the acid calcium-rich water had no effect on bone resorption, while the alkaline water rich in bicarbonate led to a significant decrease of PTH and of S-CTX. | 18,926,940 |
Testing the "epidemiologic paradox" of birth outcomes among Asian immigrant women in Hsin-Chu County, Taiwan. | Taiwan saw an increase in immigration during the last decade. This retrospective study investigated whether immigrant status confers a protective effect on birth outcomes and whether this effect varies across racial/ethnic subgroups in Hsin-Chu County, Taiwan. A total of 30,770 singleton birth certificates from January 1, 2002 to July 31, 2007 were analyzed using ANOVA and logistic regression. Outcomes included low birth weight (LBW, < 2500 g), high birth weight (HBW, > 4000 g), preterm birth (< 37 weeks) and stillbirth. Covariates included maternal age, year of delivery, mode of delivery, medical care institution, infant sex and congenital birth defects. Five models were designed for various analyses. The reference categories included non-immigrant, non-aboriginal Taiwanese and non-Chinese-speaking immigrants. Preterm rate ranged from 6.3% among mainland Chinese to 13.5% among aboriginal Taiwanese. LBW rate ranged from 4.3% among mainland Chinese to 17.3% among aboriginal Taiwanese. HBW rate ranged from 1.2% among aboriginal Taiwanese to 3.4% among mainland Chinese. Stillbirth rate ranged from 0.2% among Indonesians to 0.7% among aboriginal Taiwanese. Adjusted odds ratio (OR) was lower among mainland Chinese (preterm OR, 0.77; LBW OR, 0.62) but higher among aboriginal Taiwanese (preterm OR, 1.79; LBW OR, 2.68; stillbirth OR, 2.92). HBW rate was significantly higher (OR, 1.84) among mainland Chinese. Chinese-speaking immigrants showed significant differences in LBW (OR, 0.57) and HBW (OR, 1.62) compared with non-Chinese-speaking immigrants. An epidemiologic paradox and heterogeneity of birth outcomes were observed among immigrants in this study. However, aboriginal Taiwanese constituted the subgroup with the highest risk. Further research is needed to identify the determinants of birth outcomes. | 18,926,945 |
Answers to questions posed during daily patient care are more likely to be answered by UpToDate than PubMed. | UpToDate and PubMed are popular sources for medical information. Data regarding the efficiency of PubMed and UpToDate in daily medical care are lacking. The purpose of this observational study was to describe the percentage of answers retrieved by these information sources, comparing search results with regard to different medical topics and the time spent searching for an answer. A total of 40 residents and 30 internists in internal medicine working in an academic medical center searched PubMed and UpToDate using an observation portal during daily medical care. The information source used for searching and the time needed to find an answer to the question were recorded by the portal. Information was provided by searchers regarding the topic of the question, the situation that triggered the question, and whether an answer was found. We analyzed 1305 patient-related questions sent to PubMed and/or UpToDate between October 1, 2005 and March 31, 2007 using our portal. A complete answer was found in 594/1125 (53%) questions sent to PubMed or UpToDate. A partial or full answer was obtained in 729/883 (83%) UpToDate searches and 152/242 (63%) PubMed searches (P < .001). UpToDate answered more questions than PubMed on all major medical topics, but a significant difference was detected only when the question was related to etiology (P < .001) or therapy (P = .002). Time to answer was 241 seconds (SD 24) for UpToDate and 291 seconds (SD 7) for PubMed. Specialists and residents in internal medicine generally use less than 5 minutes to answer patient-related questions in daily care. More questions are answered using UpToDate than PubMed on all major medical topics. | 18,926,978 |
Is attention needed for word identification? Evidence from the Stroop paradigm. | One of the most robust findings in attention research is that the time to name a color is lengthened markedly in the presence of an irrelevant word that spells a different color name: the Stroop effect. The Stroop effect is found even when the word is physically separated from the color, apparently indicating that words can be read outside the focus of spatial attention. The present study critically evaluated this claim. We employed several stringent measures within a Stroop paradigm to prevent participants from attending to the irrelevant words (e.g., limiting exposure duration to prevent attention capture). Nonetheless, residual Stroop effects were obtained for both color words and semantic associates (e.g., sky to blue). These data suggest that lexical processing can sometimes occur outside the focus of spatial attention. | 18,926,987 |
The role of valence and frequency in the emotional Stroop task. | People are generally slower to name the color of emotion-laden words than they are to name that of emotionally neutral words. However, an analysis of this emotional Stroop effect (Larsen, Mercer, & Balota, 2006) indicates that the emotion-laden words used are sometimes longer, have lower frequencies, and have smaller orthographic neighborhoods than the emotionally neutral words. This difference in word characteristics raises the possibility that the emotional Stroop effect is partly caused by lexical rather than by emotional aspects of the stimuli-a conclusion supported by the finding that reaction times to name the color of low-frequency words are longer than those for high-frequency words (Burt, 2002). To examine the relative contributions of valence and frequency in color naming, we had 64 participants complete an experiment in which each of these variables was manipulated in a 3 x 2 factorial design; length, orthographic neighborhood density, and arousal were balanced. The data indicate that valence and word frequency interact in contributing to the emotional Stroop effect. | 18,926,988 |
State-trace analysis of the effects of a visual illusion on saccade amplitudes and perceptual judgments. | Visual illusions often appear to have a larger influence on subjective judgments than on visuomotor behavior. Although this effect has been taken as evidence for multiple estimates of stimulus size in the visual brain, dissociations between subjective judgments and visuomotor measures can frequently be reconciled with a single-estimate model. To circumvent this difficulty, we used state-trace analysis in a pair of experiments to examine the effects of the Müller-Lyer illusion on subjective length estimates, voluntary saccade amplitudes, and reflexive saccade amplitudes. All dependent measures were affected by the illusion. However, state-trace analyses revealed nonmonotonic relationships among all three variables, a pattern inconsistent with the possibility of a single underlying estimate of stimulus size. | 18,926,997 |
On suppressing unwanted cues via randomization. | In certain perceptual discrimination tasks, a change in a particular stimulus variable can be perceived as changes along multiple perceptual dimensions. If the study is primarily concerned with a particular perceptual dimension or cue, it is important that the experimenter keep the influences of the other unwanted but correlated perceptual cues under control. One way to accomplish this objective is to randomize the stimuli along the stimulus dimensions primarily associated with these unwanted cues, making them unreliable as a basis for the discrimination. This theoretical note presents a mathematical proof that a uniform randomization is the most effective way of suppressing unwanted cues. | 18,927,020 |
Influence of hand position on the near effect in 3-D attention. | Voluntary reorienting of attention in real depth situations is characterized by an attentional bias to locations nearer the viewer once attention is deployed to a spatially cued object in depth. Previously, this effect (initially referred to as the near effect) was attributed to access of a 3-D viewer-centered spatial representation for guiding attention in 3-D space. The aim of this study was to investigate whether the near effect could have been associated with the position of the response hand, which was always near the viewer in previous studies that investigated endogenous attentional shifts in real depth. In Experiment 1, the response hand was placed at either the near or far target depth in a depth-cuing task. Placing the response hand at the far target depth abolished the near effect, but failed to bias spatial attention to the far location. Experiment 2 showed that the response hand effect was not modulated by the presence of an additional (passive) hand, whereas Experiment 3 confirmed that attentional prioritization of the passive hand was not masked by the influence of the responding hand on spatial attention in Experiment 2. The pattern of results is most consistent with the idea that response preparation can modulate spatial attention within a 3-D viewer-centered spatial representation. | 18,927,021 |
Indirect assessment of visual working memory for simple and complex objects. | Previous research has shown that visual search performance is modulated by the current contents in visual working memory (VWM), even when the contents of VWM are irrelevant to the search task. For example, visual search is faster when the target--rather than a distractor--is surrounded by a shape currently held in VWM. This study uses the modulation of visual search by VWM to investigate properties of VWM. Participants wereasked to remember the color or the shape of novel polygons whose "goodness" of figure varied according to Garner's (1962) rotation and reflection transformation principle. During the memory retention interval, participants searched for a tilted line among vertical lines embedded inside colored polygons. Search was faster when the target--rather than a distractor--was enclosed by the remembered polygons. The congruity effect diminished with increasing memory load and decreasing figure goodness. We conclude that congruity effects in visual search can indirectly assess VWM representation strength. | 18,927,031 |
What is the impact of the explicit knowledge of sequence regularities on both deterministic and probabilistic serial reaction time task performance? | The aim of this study was to explore the role of prior explicit sequence knowledge by comparing its influence on serial reaction time (SRT) performance with either a deterministic or a probabilistic sequence. The results confirm that, with a deterministic sequence, preliminary explicit learning improves SRT performance. On the other hand, with a probabilistic sequence, the results show no advantage for SRT performance in explicit-learning conditions. In addition, by using the process dissociation procedure (Jacoby, 1991), we show that performance on a subsequent generation task was more sustained by controlled processes for participants in the explicit-learning conditions than for those in the incidental condition. On the whole, these results, showing that the influence of explicit knowledge can be suppressed in certain specific conditions, are consistent with the intervention of both implicit and explicit mechanisms in SRT tasks, and the results also show that their relative influence can be modulated by the particular demands of the task. | 18,927,043 |
Dominance and context effects on activation of alternative homophone meanings. | Two eyetracking-during-listening experiments showed frequency and context effects on fixation probability for pictures representing multiple meanings of homophones. Participants heard either an imperative sentence instructing them to look at a homophone referent (Experiment 1) or a declarative sentence that was either neutral or biased toward the homophone's subordinate meaning (Experiment 2). At homophone onset in both experiments, the participants viewed four pictures: (1) a referent of one homophone meaning, (2) a shape competitor for a nonpictured homophone meaning, and (3) two unrelated filler objects. In Experiment 1, meaning dominance affected looks to both the homophone referent and the shape competitor. In Experiment 2, as compared with neutral contexts, subordinate-biased contexts lowered the fixation probability for shape competitors of dominant meanings, but shape competitors still attracted more looks than would be expected by chance. We discuss the consistencies and discrepancies of these findings with the selective access and reordered access theories of lexical ambiguity resolution. | 18,927,045 |
RT distribution analysis of category congruence effects with masked primes. | In the number magnitude decision task ("Is the number bigger/smaller than 5?"), response to a target (e.g., 3) is faster following a masked prime congruent with the target (e.g., 1) than it is following an incongruent prime (e.g., 9). This category congruence effect has been reported to be "interference-dominant" relative to a neutral prime (e.g., the # sign, the number 5) on the basis of the analysis of mean response time (RT). Using RT distribution analysis as well as mean RTs, we identified two bases for this pattern. One relates to the choice of neutral baseline: The # prime, unlike the digit prime, does not factor in the cost of perceptual transition between the prime and target, and therefore underestimates facilitation and overestimates the interference effect. The second basis of the interference-dominant pattern is a disproportionate slowdown of congruent trials in the slow RT bins. Furthermore, this slowdown is greater for primes that had been used as targets than it is with "novel" primes that have not been responded to as targets. We interpret the results as suggesting that the category congruence effect has two components with different time courses-one based on stimulus-response mapping, and the other on semantic categorization. | 18,927,046 |
Flattening generalization gradients, context, and perceptual learning. | The present research investigated the effects of physical context change and perceptual learning on generalization. In a video game, participants learned to suppress their mouse-clicking behavior in the presence of one stimulus (AX). Generalization was observed between the AX stimulus and another stimulus (BX) that was designed to be similar. When testing was conducted in a context different from that in which AX was used in training, responding to AX was attenuated, and responding to BX was enhanced. That is, the generalization gradient flattened. The latter effect was only evident in groups for which generalization had been reduced through a preexposure manipulation believed to produce perceptual learning. Experiment 2 demonstrated that the increase in generalization observed in the first experiment was due to the context change between the preexposure and test rather than to a change between the conditioning and test contexts. Implications for flattening generalization gradients and mechanisms of perceptual learning are discussed. | 18,927,051 |
Effects of reinforcer delay and variability in a successive-encounters procedure. | Pigeons responded in a successive-encounters procedure that consisted of a search period, a choice period, and a handling period. The search period was either a fixed-interval or a mixed-interval schedule presented on the center key of a three-key chamber. Upon completion of the search period, the center key was turned off and the two side keys were lit. A pigeon could either accept a delay followed by food (by pecking the right key) or reject this option and return to the search period (by pecking the left key). During the choice period, a red right key represented the long alternative (a long handling delay followed by food), and a green right key represented the short alternative (a short handling delay followed by food). The experiment consisted of a series of comparisons for which optimal diet theory predicted no changes in preference for the long alternative (because the overall rates of reinforcement were unchanged), whereas the hyperbolic-decay model predicted changes in preference (because the delays to the next possible reinforcer were varied). In all comparisons, the results supported the predictions of the hyperbolic-decay model, which states that the value of a reinforcer is inversely related to the delay between a choice response and reinforcer delivery. | 18,927,053 |
Sources and levels of potentially toxic elements in the biodegradable fraction of autoclaved non-segregated household waste and its compost/digestate. | Waste that reflected the average UK composition of household waste was treated by autoclaving at the three set pressure/temperature levels of 2.7 bar/130 degrees C, 6.2 bar/160 degrees C and 15.5 bar/200 degrees C. The biodegradable fraction of the autoclaved household waste (;floc') was manually separated by screening and underwent characterization for its Cd, Cr, Cu, Pb, Hg, Ni, and Zn content. Autoclaving did not guarantee the production of compost/digestate that met the UK specification for compost, BSi PAS100, without restrictions being made on the composition of the waste feedstock. Results indicate that the levels of Zn and Cd associated with floc materials alone could lead to compost limit values being exceeded. For all other potentially toxic elements (PTEs), the estimated excessive (i.e. above levels of compliance) PTEs levels for compost/digestate were mainly due to external (i.e. non-floc) materials, primarily electronic/electrical waste. Batteries may have also contributed to the high levels of Zn and Hg. In this study, for all PTEs examined, with the exception of Cd and Zn, autoclaving had a performance comparable to that of the most effective mechanical biological treatment systems. | 18,927,061 |
Site selection of sanitary landfills on the small island of Mauritius using the analytical hierarchy process multi-criteria method. | This paper focuses on the application of a multi-criteria analysis methodology - the analytical hierarchy process - for the locating of a sanitary landfill on the small island of Mauritius. Four candidate sites were assessed using three main criteria (environmental, technical and socio-economic) and twenty-one sub-criteria. Scores were assigned to each criterion and sub-criterion by stakeholders in the solid waste sector, based on the impact assessment of each site so as to obtain their relative importance. The analytical hierarchy process was then applied, which involved the combination of the weights obtained at the different stages of pair-wise comparisons. The candidate sites were finally ranked to obtain the optimum site. Because of political factors, the second best ranked site was chosen by the authorities for the location of a new landfill on the island. This technique provides a realistic approach for use by small island developing states such as Mauritius for choosing and justifying to all stakeholders the best location for a sanitary landfill site or any other waste management site. | 18,927,063 |
Multiplex immunoassay for serological diagnosis of Mycobacterium bovis infection in cattle. | Efforts to develop a better diagnostic assay for bovine tuberculosis have shown that the sensitivity and specificity of an assay can be improved by the use of two or more antigens. As reported here, we developed a multiplex chemiluminescent immunoassay that can simultaneously detect antibody activity to 25 antigens in a single well in a 96-well plate array format. The chemiluminescent signal is captured with a digital imaging system and analyzed with a macro program that tracks each serum for its pattern of antibody activity for Mycobacterium bovis antigens. The comparison of sera from 522 infected and 1,489 uninfected animals showed that a sensitivity of 93.1% and a specificity of 98.4% can be achieved with a combination of antigens. The assay system is rapid and can be automated for use in a centralized laboratory. | 18,927,068 |
The risk of monozygotic twins after assisted reproductive technology: a systematic review and meta-analysis. | It is estimated that there is at least a 2-fold rise in the incidence of monozygotic twinning after assisted reproductive technology compared with natural conception. This can result in adverse pregnancy outcomes. We searched MEDLINE, EMBASE and SCISEARCH for studies that estimated the risk of monozygotic twinning and its association with any particular assisted reproductive technique. Monozygotic twinning was defined by ultrasound or Weinberg criteria. A meta-analysis of the proportion of monozygotic twins was performed using both fixed and random effects models. The search revealed 37 publications reporting on the incidence of monozygotic twins after assisted reproductive techniques. Twenty-seven studies met the inclusion criteria and were included in the meta-analysis. The summary incidence of monozygotic twins after assisted conception was 0.9% (0.8-0.9%). The incidence of monozygotic twins in natural conception is 0.4%. Blastocyst transfer and intracytoplasmic sperm injection are associated with 4.25 and 2.25 times higher risk of monozygotic twins. The risk of monozygotic twins in assisted conception is 2.25 times higher than the natural conceptions. Larger studies reporting on monozygotic twinning following single-embryo transfer or after post-natal confirmation of zygosity with DNA analysis are warranted before definitive conclusions can be drawn and guidelines produced. In order to provide adequate pre-conceptional counselling, it is important to monitor the incidence of monozygotic twins in both natural and assisted conceptions. We suggest building a national multiple pregnancy database based on accurate diagnosis of zygosity. | 18,927,071 |
Ethnic differences in participation in flexible sigmoidoscopy screening in the UK. | The aim of the study was to examine ethnic differences in participation in colorectal cancer screening by flexible sigmoidoscopy (FS). It assessed both intentions to be screened and actual screening uptake, and considered whether demographic, health and psychosocial factors mediated the ethnic differences. The setting of this study follows a subset of participants from the UK FS Trial. A postal questionnaire assessed ethnicity, demographic characteristics, health, attitudes to screening and FS screening intentions. Data on screening intentions were available for 17,333 adults aged 55-64 years (Sample 1). Screening uptake was recorded in a subsample of 4303 respondents who were subsequently randomized to receive an invitation to screening (Sample 2). Screening intentions in Sample 1 were equally high across all the ethnic groups (>80% [13,724/17,042] reported they were interested). In contrast, attendance (Sample 2) was considerably lower among Asians (54% [43/79]) compared with White (69% [2843/4123]) or Black (80% [33/41]) respondents. Multivariate analysis showed that potential explanatory factors, including socioeconomic deprivation, poor health and fearful and fatalistic attitudes did not account for the lower screening attendance among Asians. Further research is required to identify explanations for the gap between intentions and behaviour in UK Asians if any future FS screening programme is to be introduced equitably. | 18,927,095 |
French colorectal cancer screening pilot programme: results of the first round. | In France, a national pilot population-based screening programme on colorectal cancer was set up in 2002. In 2006, 23 French districts were included, targeting a population of more than five million people. This programme offers biennial screening using the fecal occult blood test (FOBT) to average risk subjects aged between 50 and 74 years. People receive a letter inviting them to consult their GPs, who in turn provide the FOBT. People with a positive test result are proposed a full colonoscopy. The results of the programme's first-round performance indicators are presented. The monitoring centre collected data from GPs and gastroenterologists on follow-up and colonoscopy results for people who were screened positive. Data were transferred to the French Institute for Public Health Surveillance (InVS) for the analysis. The overall participation rate for the 19 districts having completed a first screening round reached 42%. The overall positive test rate was 2.7%. In the eight districts with comprehensive follow-up data for the first round, 86% of colonoscopies were completed after a positive test. A total of 1615 people were diagnosed with cancer, and 4612 people with adenoma. The cancer detection rate reached 2.3/1000 [corrected] it was higher in men than in women (3.4/1000 [corrected] versus 1.4/1000) [corrected] and increased with age. Forty-three percent of invasive detected cancers were stage I, 24% stage II, 23% had lymph node involvement and 10% presented with distant metastasis. These results suggest that indicators are consistent with international references. During 2007-2008, the programme coverage will be progressively extended, and all 99 French districts should be actively involved in its implementation. | 18,927,097 |
miROrtho: computational survey of microRNA genes. | MicroRNAs (miRNAs) are short, non-protein coding RNAs that direct the widespread phenomenon of post-transcriptional regulation of metazoan genes. The mature approximately 22-nt long RNA molecules are processed from genome-encoded stem-loop structured precursor genes. Hundreds of such genes have been experimentally validated in vertebrate genomes, yet their discovery remains challenging, and substantially higher numbers have been estimated. The miROrtho database (http://cegg.unige.ch/mirortho) presents the results of a comprehensive computational survey of miRNA gene candidates across the majority of sequenced metazoan genomes. We designed and applied a three-tier analysis pipeline: (i) an SVM-based ab initio screen for potent hairpins, plus homologs of known miRNAs, (ii) an orthology delineation procedure and (iii) an SVM-based classifier of the ortholog multiple sequence alignments. The web interface provides direct access to putative miRNA annotations, ortholog multiple alignments, RNA secondary structure conservation, and sequence data. The miROrtho data are conceptually complementary to the miRBase catalog of experimentally verified miRNA sequences, providing a consistent comparative genomics perspective as well as identifying many novel miRNA genes with strong evolutionary support. | 18,927,110 |
Identification of a common variant at the NOS1AP locus strongly associated to QT-interval duration. | QT-interval prolongation is an electrophysiologic phenomenon associated with sudden cardiac death. The QT-interval in the general population is approximately 35% heritable. In genome-wide association studies, a common variant (rs10494366T > G) within the nitric oxide synthase 1 adaptor protein (NOS1AP) gene was identified and consistently associated with QT-interval duration. Yet, the causal variant remains unclear. Therefore, we performed fine mapping of the association of the NOS1AP locus with QT-interval within the Rotterdam Study, a population-based, prospective cohort study of individuals of > or =55 years of age. First, we tested the association of single-nucleotide polymorphisms (SNPs) in or within +/-100 kb of the NOS1AP gene with QT-interval duration, using sex-specific unstandardized residuals after regression on age and RR-interval, in 385 individuals using the combined set of SNPs present in the Affymetrix 500k and Illumina 550k chip arrays. Subsequently, we examined correspondence of the association signals in 4606 individuals using the Illumina 550k array. A C-to-T SNP at chromosome 1 position 160300514 (rs12143842, T-allele frequency = 24%) was associated with a QT-interval duration increase of 4.4 ms per additional T-allele (P = 4.4 x 10(-28)). For comparison, the most strongly associated variant to date, rs10494366T > G, was associated with a 3.5 ms increase (P = 1.6 x 10(-23)) per additional G-allele. None of the inferred haplotypes showed a stronger effect than the individual rs12143842C > T SNP. In conclusion, we found rs12143842 6 kb upstream distance of NOS1AP to be more strongly associated to QT-interval duration than rs10494366T > G. Functional analysis of this marker is warranted. | 18,927,126 |
Mannose-binding lectin-2 genotypes and recurrent late pregnancy losses. | Low levels of mannose-binding lectin (MBL) predispose to various infectious and inflammatory disorders and have been reported to be associated with recurrent early miscarriages. Recurrent late pregnancy losses (RLPL) in the second trimester is a rare but devastating syndrome where maternal rather than fetal causes are likely to play a stronger role than in early recurrent miscarriage. We identified 75 patients with at least two late losses of pregnancies with apparently normal fetuses between gestational week 14 and 30 among patients with recurrent pregnancy losses referred to our clinic. Polymorphisms in the MBL2 gene associated with plasma MBL levels were investigated in all patients and in 104 women with two or more children and no miscarriages. The patients were divided into three groups: one with clinical signs of cervical insufficiency, one positive for the lupus anticoagulant (LAC) and an idiopathic group. Among all patients with RLPL, 26.7% had MBL2 genotypes associated with MBL deficiency compared with 12.5% in controls [odds ratio (OR) 2.55; 95% confidence interval (CI) 1.17-5.52; P < 0.02]. Among patients with clinical signs of cervical insufficiency or the LAC, the frequency of genotypes associated with MBL deficiency was not significantly increased. However, among 38 patients with idiopathic RLPL, 36.8% carried low-producing MBL2 genotypes, which was significantly more than in controls (OR 4.08, 95% CI 1.70-9.83, P = 0.001). MBL deficiency is strongly associated with idiopathic RLPL. This may point towards a role for excessive inflammatory disturbances as a cause of the syndrome. | 18,927,129 |
Deliberate self-harm in children and adolescents: a qualitative study exploring the needs of parents and carers. | Deliberate Self-harm (DSH) is a serious public health problem and is becoming more prevalent among young people in Ireland. Research tends to focus on the DSH patient. However, parental involvement is recognized as an important factor in their child's prognosis. This study aimed to describe parents' and carers' experiences of self-harm in their child in order to identify their support needs. A focus group methodology was used to generate qualitative data. Representative participants whose children had engaged in suicidal behaviour were recruited from the Paediatric Emergency, Child and Adolescent Mental Health Teams and Family Support Services. Twenty-five participants attended the focus group meeting. A transcript-based conceptual analysis was conducted to identify and explore emerging themes. Participants expressed the need for support; information about suicidal behaviour in young people; skills for parenting an adolescent; and advice on managing further incidents. Parents described significant difficulties in family communication, in parent-child relationships, and in the area of discipline following self-harm. These findings support current research that identifies the need for service development and information for parents/carers of young people who self-harm. | 18,927,136 |
The development of motor coordination in Drosophila embryos. | We used non-invasive muscle imaging to study the onset of motor activity and emergence of coordinated movement in Drosophila embryos. Earliest movements are myogenic, and neurally controlled muscle contractions first appear with the onset of bursting activity 17 hours after egg laying. Initial episodes of activity are poorly organised and coordinated crawling sequences only begin to appear after a further hour of bursting. Thus, network performance improves during this first period of activity. The embryo continues to exhibit bursts of crawling-like sequences until shortly before hatching, while other reflexes also mature. Bursting does not begin as a reflex response to sensory input but appears to reflect the onset of spontaneous activity in the motor network. It does not require GABA-mediated transmission, and, by using a light-activated channel to excite the network, we demonstrate activity-dependent depression that may cause burst termination. | 18,927,150 |
An epidemiological study of football (soccer) injuries in Benin City, Nigeria. | The increase in popularity of soccer and expectations from players make significant numbers of soccer injuries conceivable. Concerns have been expressed about the demand placed on the modern-day footballer and translation of these physical and mental demands into injuries. Despite the popularity and importance of the game of soccer in Benin, no detailed study on the occurrence of soccer injury has been carried out. The study sets out to describe and assess the determinants and effects of soccer injuries. Seven clubs (196 players) from the premiership, professional, national and state amateur clubs were studied using a descriptive cross-sectional study design. A pre-designed semi-structured questionnaire and key informants interview guide were used for data collection. Descriptive and inferential statistics were used in the analysis, with significant levels generally taken at 5% level of significance. A total of 196 players sustained 204 injuries with a prevalence rate of 81.6%. More injuries were recorded during matches (46.1%) than during training (36.8%). Injuries occurring by body contact constituted 62.3% of the total injuries. The ankle (25%) was the most affected site, followed by the knee (20.1%), while sprain injury (33.3%) and strain (13.2%) were the commonest injury types. Moderate injury (28.9%) was the highest form of severity recorded. Recurrent injury accounted for 38.8% of injuries, occurring more in training (44.9%) than in matches (36.7%). A greater percentage (86.8%) of the injuries were traumatic in nature, with tackling (44.6%) being the commonest mechanism. Defenders (34.3%) and strikers (31.4%) had higher injury occurrence. The association between the player's role and the mechanism of injury was significant (p = 0.02), while that between weather condition and injury type was very significant (p = 0.004). Moreover, the association between experience and mechanism of injury was extremely significant (p<0.001). The study also shows that injury has economic, physical and psychological impacts on players. A prevalence rate of 81.6% was recorded. Sprain was the leading injury type, while the ankle was the most affected anatomical site. Factors such as weather, previous injury, experience, role, and activity tend to influence injury occurrence. Soccer injury also has economic, physical and psychological implications. It is therefore recommended that preventive measures such as adequate treatment of injuries, full rehabilitation after injuries, use of protective equipment, appropriate exercises and warm-ups, continual team education on injury managements and skill improvement, etc., be utilised and enforced to protect this group of sport workers. | 18,927,169 |
Acceptance of repeat population-based voluntary counselling and testing for HIV in rural Malawi. | To examine the acceptance of repeat population-based voluntary counselling and testing (VCT) for HIV in rural Malawi. Behavioural and biomarker data were collected in 2004 and 2006 from approximately 3000 adult respondents. In 2004, oral swab specimens were collected and analysed using ELISA and confirmatory Western blot tests, while finger-prick rapid testing was done in 2006. We used cross-tabulations with chi(2) tests and significance tests of proportions to determine the statistical significance of differences in acceptance of VCT by year, individual characteristics and HIV risk. First, over 90% of respondents in each round accepted the HIV test, despite variations in testing protocols. Second, the percentage of individuals who obtained their test results significantly increased from 67% in 2004, when the results were provided in randomly selected locations several weeks after the specimens were collected, to 98% in 2006 when they were made available immediately within the home. Third, whereas there were significant variations in the sociodemographic and behavioural profiles of those who were successfully contacted for a second HIV test, this was not the case for those who accepted repeat VCT. This suggests that variations in the success of repeat testing might come from contacting the individuals rather than from accepting the test or knowing the results. Repeat HIV testing at home by trained healthcare workers from outside the local area, and with either saliva or blood, is almost universally acceptable in rural Malawi and, thus, likely to be acceptable in similar contexts. | 18,927,181 |
Pace of change in coronary heart disease mortality in Finland, Ireland and the United Kingdom from 1985 to 2006. | Finland, Ireland and the United Kingdom have the highest rates of coronary heart disease (CHD) mortality among EU-15 countries. This study examines the pace of change in CHD mortality in these countries from 1985-2006. The percentage change in 5-year average all age, under 65 and 65 years and over age standardized mortality rates from 1985-89 to 2002-06 was calculated for each country. Joinpoint regression analysis was used to analyse age standardized mortality rates to identify points (years) where the slope of the linear trend changed significantly. The pace of change in the CHD mortality rate was measured using annual percentage change (APC). The percentage change in 5-year age standardized (under 65) CHD mortality rates was similar in Finland and the UK for both genders whereas in Ireland the rate of change was greater, especially for females. The percentage change in >/=65 year and all age rates was between 8.2% and 12.4% lower for Finnish males, and between 11.6% and 13% lower for Finnish females compared to their Irish and UK counterparts. There were different turning points in the downward trend in CHD mortality across the three countries varying from 1991-2003. The APC in CHD mortality after the turning point was greatest for Irish males (all age = -7.3%, under 65 = -8.2% and 65 and over = -7.1%), and Irish females (under 65 = -7.2%). We have identified differing pace of decline in three countries with similar burden of disease and successful national strategies to control CHD. | 18,927,185 |
Bacterial-mucosal interactions in inflammatory bowel disease: an alliance gone bad. | The complex interaction of genetic, microbial, and environmental factors may result in continuous activation of the mucosal immune system leading to inflammatory bowel disease (IBD). Most present treatments for IBD involve altering or suppressing the aberrant immune response; however, the role of the intestinal microbiota in the pathophysiology of IBD is becoming more evident. The epithelial layer is essential for the proper functioning of the gastrointestinal tract, and its increased permeability to the luminal antigens may lead to the inflammatory processes and mucosal damage observed in IBD. Factors affecting the efficacy of the epithelial barrier include presence of pathogenic bacteria (e.g., Helicobacter spp.), presence of probiotic bacteria, availability of selected nutrients, and others. Defective function of the mucosal barrier might facilitate the contact of bacterial antigens and adjuvants with innate and adaptive immune cells to generate prolonged inflammatory responses. This review will briefly describe the complex structure of the epithelial barrier in the context of bacterial-mucosal interactions observed in human IBD and mouse models of colitis. | 18,927,210 |
Characterization and putative role of a type I gonadotropin-releasing hormone in the cephalochordate amphioxus. | GnRH, originally isolated from mammalian hypothalamus, is a key player in the control of vertebrate reproduction. Employing reverse-phase chromatography, we purified a peptide of relative molecular mass of 1182.60 Da from the cephalochordate amphioxus Branchiostoma lanceolatum. We found that its amino acid sequence (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH(2)) was identical to that of mammalian GnRH. The highest concentrations (4.04 +/- 0.3 microg/g tissue), localized in the anterior part of the body, occurred in November, a time when amphioxus gonads prepare for the seasonal spawning. Furthermore, the biological activity of amphioxus GnRH was investigated by examining its capability to elicit LH release from the rodent pituitary gland. The origins of GnRH can be traced back to the origins of chordates. The seasonal variations of amphioxus GnRH also suggest an ancient role of this peptide in the control of reproduction in chordates, even before the evolution of a proper pituitary gland. | 18,927,217 |
Sequencing and analysis of approximately 40,000 soybean cDNA clones from a full-length-enriched cDNA library. | A large collection of full-length cDNAs is essential for the correct annotation of genomic sequences and for the functional analysis of genes and their products. We obtained a total of 39,936 soybean cDNA clones (GMFL01 and GMFL02 clone sets) in a full-length-enriched cDNA library which was constructed from soybean plants that were grown under various developmental and environmental conditions. Sequencing from 5' and 3' ends of the clones generated 68 661 expressed sequence tags (ESTs). The EST sequences were clustered into 22,674 scaffolds involving 2580 full-length sequences. In addition, we sequenced 4712 full-length cDNAs. After removing overlaps, we obtained 6570 new full-length sequences of soybean cDNAs so far. Our data indicated that 87.7% of the soybean cDNA clones contain complete coding sequences in addition to 5'- and 3'-untranslated regions. All of the obtained data confirmed that our collection of soybean full-length cDNAs covers a wide variety of genes. Comparative analysis between the derived sequences from soybean and Arabidopsis, rice or other legumes data revealed that some specific genes were involved in our collection and a large part of them could be annotated to unknown functions. A large set of soybean full-length cDNA clones reported in this study will serve as a useful resource for gene discovery from soybean and will also aid a precise annotation of the soybean genome. | 18,927,222 |
Pharmacokinetics of novel atrial-selective antiarrhythmic agent vernakalant hydrochloride injection (RSD1235): influence of CYP2D6 expression and other factors. | Vernakalant hydrochloride injection (RSD1235) is a relatively atrial-selective antiarrhythmic agent that converts atrial fibrillation rapidly to sinus rhythm. The pharmacokinetics of vernakalant were explored in healthy volunteers and in patients with atrial fibrillation or atrial flutter in 4 clinical studies. Key pharmacokinetic parameters analyzed were the maximum plasma concentration and the area under the plasma concentration-time curve. Vernakalant exhibited linear pharmacokinetics over the dose range of 0.1 mg/kg to 5.0 mg/kg in healthy subjects, and generally showed dose proportionality in patients with atrial fibrillation or atrial flutter who received 1 or 2 vernakalant infusions. Vernakalant was metabolized rapidly via 4-O-demethylation by cytochrome P450 (CYP)2D6 to its major metabolite RSD1385, which then circulated predominantly as an inactive glucuronide conjugate. In most patients, the maximum plasma concentration of RSD1385 glucuronide exceeded that of vernakalant. Unconjugated RSD1385 was found at low levels in all patients demonstrating either a cytochrome P450 CYP2D6 "extensive metabolizer" or "poor metabolizer" phenotype or genotype; however, CYP2D6 poor metabolizers had even lower levels of unconjugated RSD1385. The impact of CYP2D6 metabolizer status on vernakalant exposure was explored in patients with atrial fibrillation or atrial flutter who received a therapeutic regimen (3 mg/kg initially via 10-minute intravenous infusion followed by a second 2 mg/kg 10-minute infusion if atrial fibrillation persisted after a 15-minute observation period). In the subset that received 2 vernakalant infusions, there was little difference in vernakalant maximum plasma concentration or area under the plasma concentration-time curve from the start of the first infusion to 90 minutes between CYP2D6 poor metabolizers and extensive metabolizers or between those who did or did not receive concomitant CYP2D6-inhibitor medications. Gender, age, and renal function did not have a clinically significant influence on the pharmacokinetics of vernakalant. These results suggest that an assessment of CYP2D6 expression may not be needed when vernakalant is administered acutely and intravenously to patients with atrial fibrillation. | 18,927,241 |
Bone biopsy of the parasymphyseal pubic bone region in athletes with chronic groin injury demonstrates new woven bone formation consistent with a diagnosis of pubic bone stress injury. | There is little scientific evidence available regarding the pathologic basis for chronic groin injury in athletes, a known difficult clinical problem. Histological analysis of the superior pubic ramus in athletes with diagnosed chronic groin injury may reveal the nature of the pathologic process. Case series; Level of evidence, 4. Ten athletes with a diagnosis of chronic groin injury by clinical criteria (at least 6 weeks of pain) and magnetic resonance imaging criteria (unequivocal increase in T2 signal intensity) underwent bone biopsy of the superior pubic ramus. The biopsy site was located in the parasymphyseal region in the area of increased magnetic resonance image signal intensity. Histologic analysis of the specimens was then undertaken. Evidence of new woven bone was seen in all biopsy specimens. Signs of old bony injury were seen in 8 of the 10 specimens. There was no evidence of inflammation or osteonecrosis. Histologic analysis of bone biopsy specimens taken from the parasymphyseal pubic bone region with magnetic resonance imaging T2-weighted increased signal intensity of athletes diagnosed by clinical and magnetic resonance imaging criteria as having chronic groin injury demonstrates new woven bone formation. This is consistent with the athlete having a bone stress injury that may contribute significantly to athletic groin pain. | 18,927,251 |
Family involvement in inpatient care in Taiwan. | This descriptive, cross-sectional survey study illustrates the roles for and motives of being a family visitor to accompany a hospitalized loved one during hospitalization in a Taiwanese hospital. Family visitors were approached by research assistants on a random basis in acute inpatient units. Among the 1,034 participants, 91% were relatives. About 80.0% of them were present to attend to the patient's physical care, 61.0% to offer psychological support, and 63.5% to express their desire to learn more about the patient's medical condition and illness in time. Their primary motives included fulfilling one of their responsibilities, coming to help voluntarily, showing filial piety for their parent, and being afraid that the patient could not obtain appropriate care. The family involvement culture in Taiwan may have placed pressure on family members to be present at the bedside and contributed to families' psychological and financial burden. | 18,927,262 |
Activation of the RAF/mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase pathway mediates apoptosis induced by chelerythrine in osteosarcoma. | Chelerythrine, a widely used broad-range protein kinase C inhibitor, induces apoptosis in many cell types. In this study, the mechanism of chelerythrine-induced apoptosis in osteosarcoma was investigated. Signaling pathways activated by chelerythrine in osteosarcoma were detected by Western blots. Impacts of RAF/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK MAPK on apoptosis and cell survival were studied using genetic approaches and pharmacologic pathway-specific inhibitors. Osteosarcoma cells underwent apoptosis rapidly after treatment with chelerythrine. Three parallel MAPKs pathways, including the ERKs, c-Jun NH(2) kinases, and p38, were activated by chelerythrine in a dose-dependent and time-dependent fashion. For the ERKs, the activation was evident at the earliest time point tested (2 minutes) and sustained for >4 hours. Introduction of a dominant-negative H-RAS mutant (17N) partially attenuated ERK activation and delayed the onset of apoptosis induced by chelerythrine. The ERK activation and apoptotic effects of chelerythrine were greatly abrogated by the pharmaceutical inhibitors of MEK, but not by those of c-Jun NH(2) kinase or p38. Moreover, osteosarcoma cells were sensitized to chelerythrine by transient transfection with wild-type MEK1 or constitutively active MEK1 and became resistant with dominant-negative MEK1. Other protein kinase C inhibitors, including GF109203X or Gö6976, did not cause ERK activation or apoptosis in the same timeframe tested. In osteosarcoma, chelerythrine-induced apoptosis is mediated through activation of the RAF/MEK/ERK pathway. These findings suggest that activating the ERK MAPK, as opposed to inhibiting it, may be a therapeutic strategy in osteosarcoma. | 18,927,278 |
Antiapoptotic activity of autocrine interleukin-22 and therapeutic effects of interleukin-22-small interfering RNA on human lung cancer xenografts. | Non-small cell lung carcinoma (NSCLC) is one of most common malignant diseases and usually is resistant against apoptosis-inducing chemotherapy. This study is to explore the antiapoptotic mechanisms of interleukin (IL)-22 in human lung cancer. Nineteen cases with stage I to III NSCLC were collected to determine the expression of IL-22. Stable transfection of human IL-22 cDNA into A549 and PG cells and transfection of IL-22-RNA interference (RNAi) into these cancer cell lines were done to reveal the molecular mechanisms of IL-22. It was found that IL-22 was highly expressed in primary tumor tissue, malignant pleural effusion, and serum of patients with NSCLC. IL-22R1 mRNA was also detected in lung cancer tissues as well as lung cancer cell lines. Overexpression of IL-22 protected lung cancer cell lines from serum starvation-induced and chemotherapeutic drug-induced apoptosis via activation of STAT3 and its downstream antiapoptotic proteins such as Bcl-2 and Bcl-xL and inactivation of extracellular signal-regulated kinase 1/2. Exposure to blocking antibodies against IL-22R1 or transfection with the IL-22-RNAi plasmid in vitro resulted in apoptosis of these lung cancer cells via STAT3 and extracellular signal-regulated kinase 1/2 pathways. Furthermore, an in vivo xenograft study showed that administration of IL-22-RNAi plasmids significantly inhibited the human tumor cell growth in BALB/c nude mice. Our study indicates that autocrine production of IL-22 contributes to human lung cancer cell survival and resistance to chemotherapy through the up-regulation of antiapoptotic proteins. | 18,927,282 |
DNA double-strand break repair of blood lymphocytes and normal tissues analysed in a preclinical mouse model: implications for radiosensitivity testing. | Radiotherapy is an effective cancer treatment, but a few patients suffer severe radiation toxicities in neighboring normal tissues. There is increasing evidence that the variable susceptibility to radiation toxicities is caused by the individual genetic predisposition, by subtle mutations, or polymorphisms in genes involved in cellular responses to ionizing radiation. Double-strand breaks (DSB) are the most deleterious form of radiation-induced DNA damage, and DSB repair deficiencies lead to pronounced radiosensitivity. Using a preclinical mouse model, the highly sensitive gammaH2AX-foci approach was tested to verify even subtle, genetically determined DSB repair deficiencies known to be associated with increased normal tissue radiosensitivity. By enumerating gammaH2AX-foci in blood lymphocytes and normal tissues (brain, lung, heart, and intestine), the induction and repair of DSBs after irradiation with therapeutic doses (0.1-2 Gy) was investigated in repair-proficient and repair-deficient mouse strains in vivo and blood samples irradiated ex vivo. gammaH2AX-foci analysis allowed to verify the different DSB repair deficiencies; even slight impairments caused by single polymorphisms were detected similarly in both blood lymphocytes and solid tissues, indicating that DSB repair measured in lymphocytes is valid for different and complex organs. Moreover, gammaH2AX-foci analysis of blood samples irradiated ex vivo was found to reflect repair kinetics measured in vivo and, thus, give reliable information about the individual DSB repair capacity. gammaH2AX analysis of blood and tissue samples allows to detect even minor genetically defined DSB repair deficiencies, affecting normal tissue radiosensitivity. Future studies will have to evaluate the clinical potential to identify patients more susceptible to radiation toxicities before radiotherapy. | 18,927,295 |
Cyclin D1-specific cytotoxic T lymphocytes are present in the repertoire of cancer patients: implications for cancer immunotherapy. | Cyclin D1, a key cell cycle regulator, is overexpressed in multiple types of cancer. Such tumor-associated genes may be useful targets for cancer immunotherapy. Nevertheless, it had previously been suggested that efficient T cells recognizing cyclin D1-derived epitopes are absent from the repertoire because of thymic deletion. We attempted to induce autologous CTL from healthy donors and patients with cyclin D1-overexpressing tumors using a highly efficient T-cell expansion system based on CD40-activated B cells as antigen-presenting cells. Cyclin D1-derived, HLA-A*0201-restricted epitopes were predicted by multiple computer algorithms, screened in HLA-A2-binding assays, and used for T-cell stimulation. The generated CTL lines and clones were analyzed by IFN-gamma enzyme-linked immunosorbent spot assay or cytolysis assay. After screening, at least two naturally processed and presented HLA-A*0201-binding cyclin D1 epitopes were identified. CTL specific for these epitopes could be successfully generated from HLA-A2(+) donors. T cells efficiently recognized target cells pulsed with the cognate peptide and cyclin D1-expressing tumor cell lines in an HLA-A*0201-restricted manner. More importantly, HLA-A*0201-matched, primary cyclin D1(+) tumor cells were efficiently recognized by cyclin D1-specific CTL. These CTL could be generated from patients with mantle cell lymphoma and cyclin D1(+) colon cancer. These results underscore that cyclin D1 needs to be considered as a target for broad-based antitumor immunotherapy. | 18,927,298 |
Phase I pharmacokinetic and pharmacodynamic study of LAQ824, a hydroxamate histone deacetylase inhibitor with a heat shock protein-90 inhibitory profile, in patients with advanced solid tumors. | To determine the safety, maximum tolerated dose, and pharmacokinetic-pharmacodynamic profile of a histone deacetylase inhibitor, LAQ824, in patients with advanced malignancy. LAQ824 was administered i.v. as a 3-h infusion on days 1, 2, and 3 every 21 days. Western blot assays of peripheral blood mononuclear cell lysates and tumor biopsies pretherapy and posttherapy evaluated target inhibition and effects on heat shock protein-90 (HSP90) client proteins and HSP72. Thirty-nine patients (22 male; median age, 53 years; median Eastern Cooperative Oncology Group performance status 1) were treated at seven dose levels (mg/m(2)): 6 (3 patients), 12 (4 patients), 24 (4 patients), 36 (4 patients), 48 (4 patients), 72 (19 patients), and 100 (1 patient). Dose-escalation used a modified continual reassessment method. Dose-limiting toxicities were transaminitis, fatigue, atrial fibrillation, raised serum creatinine, and hyperbilirubinemia. A patient with pancreatic cancer treated at 100 mg/m(2) died on course one at day 18 with grade 3 hyperbilirubinemia and neutropenia, fever, and acute renal failure. The area under the plasma concentration curve increased proportionally with increasing dose; median terminal half-life ranged from 8 to 14 hours. Peripheral blood mononuclear cell lysates showed consistent accumulation of acetylated histones posttherapy from 24 mg/m(2); higher doses resulted in increased and longer duration of pharmacodynamic effect. Changes in HSP90 client protein and HSP72 levels consistent with HSP90 inhibition were observed at higher doses. No objective response was documented; 3 patients had stable disease lasting up to 14 months. Based on these data, future efficacy trials should evaluate doses ranging from 24 to 72 mg/m(2). LAQ824 was well tolerated at doses that induced accumulation of histone acetylation, with higher doses inducing changes consistent with HSP90 inhibition. | 18,927,309 |
IL12RB2 and ABCA1 genes are associated with susceptibility to radiation dermatitis. | Severe acute radiation dermatitis is observed in approximately 5% to 10% of patients who receive whole-breast radiotherapy. Several factors, including treatment-related and patient-oriented factors, are involved in susceptibility to severe dermatitis. Genetic factors are also thought to be related to a patient's susceptibility to severe dermatitis. To elucidate genetic polymorphisms associated with a susceptibility to radiation-induced dermatitis, a large-scale single-nucleotide polymorphism (SNP) analysis using DNA samples from 156 patients with breast cancer was conducted. Patients were selected from more than 3,000 female patients with early breast cancer who received radiotherapy after undergoing breast-conserving surgery. The dermatitis group was defined as patients who developed dermatitis at a National Cancer Institute Common Toxicity Criteria grade of > or =2. For the SNP analysis, DNA samples from each patient were subjected to the genotyping of 3,144 SNPs covering 494 genes. SNPs that mapped to two genes, ABCA1 and IL12RB2, were associated with radiation-induced dermatitis. In the ABCA1 gene, one of these SNPs was a nonsynonymous coding SNP causing R219K (P = 0.0065). As for the IL12RB2 gene, the strongest association was observed at SNP-K (rs3790568; P = 0.0013). Using polymorphisms of both genes, the probability of severe dermatitis was estimated for each combination of genotypes. These analyses showed that individuals carrying a combination of genotypes accounting for 14.7% of the Japanese population have the highest probability of developing radiation-induced dermatitis. Our results shed light on the mechanisms responsible for radiation-induced dermatitis. These results may also contribute to the individualization of radiotherapy. | 18,927,311 |
JC virus infection in colorectal neoplasia that develops after liver transplantation. | Liver transplant recepients (LTRs) have an increased risk of colorectal neoplasia. The mechanism responsible for this is unknown. JCV encodes for TAg and has been implicated in colorectal carcinogenesis. We hypothesized that the use of immunosuppression in LTRs facilitates activation of JCV and is responsible for the increased risk of neoplasia. JCV TAg DNA and protein expression were determined in normal colonic epithelium (n = 15) and adenomatous polyps (n = 26) from LTRs and compared with tissue samples from control patients (normal colon, n = 21; adenomas, n = 40). Apoptosis and proliferation were determined by M30 and Ki-67 immunoreactivity, respectively. JCV TAg DNA was found in 10 of 15 (67%) of normal colonic mucosa from LTRs compared with 5 of 21 (24%) of control normal mucosa (P = 0.025). JCV TAg DNA was detected in 16 of 26 (62%) of the adenomas from LTRs and in 20 of 40 (50%) of control adenomas. JCV TAg protein was expressed in 13 of 26 (50%) adenomas from LTRs versus 2 of 40 (5%) of adenomas from controls (P < 0.001). In adenomas from LTRs, the mean proliferative activity was higher compared with controls (60.3 +/- 3.2% versus 42.7 +/- 2.8%, P < 0.001), whereas mean apoptotic indices were lower in LTRs (0.29 +/- 0.08% versus 0.39 +/- 0.06%, P = 0.05). The presence of JCV in the colorectal mucosa and adenomas from LTRs, in concert with the use of immunosuppressive agents, suggests that JCV may undergo reactivation, and the subsequent TAg protein expression might explain the increased risk of colorectal neoplasia in LTRs. | 18,927,316 |
Use of adrenomedullin derivatives for molecular imaging of pulmonary circulation. | Currently, there is no low-molecular-weight agent for imaging of the pulmonary circulation. Adrenomedullin (AM) is a peptide predominantly cleared by the pulmonary circulation through specific endothelial receptors. We developed human AM derivatives radiolabeled with 99mTc and evaluated their biodistribution, plasma kinetics, and utility as pulmonary vascular imaging agents. Two derivatives radiolabeled with 99mTc were evaluated: the natural cyclic form of the peptide, to which the chelator diethylenetriaminepentaacetic acid was added (C-DTPA-AM), and the linear form, which allows direct labeling (L-AM). The compounds were injected into dogs, and the activities of the tracers in blood and in organs were determined with a nuclear medicine camera. Single-pass pulmonary clearance was measured by the indicator dilution technique. The capacity to image perfusion defects was evaluated after surgical pulmonary artery ligation. Both derivatives were rapidly cleared from plasma, with elimination half-lives of 42 and 32 min for C-DTPA-AM and L-AM, respectively. The lungs retained most of the activity after 30 min; this activity was higher (P = 0.02) for L-AM (42% +/- 5% [mean +/- SEM]) than for C-DTPA-AM (27% +/- 1%). Lung activity slowly declined over time but was maintained after 2 h at approximately 20% for both tracers. The single-pass pulmonary clearance of plasma L-AM was 414 +/- 85 mL/min. There was a higher level of urinary excretion of L-AM than of C-DTPA-AM. After pulmonary artery ligation, perfusion defects were easily detectable by external imaging. AM derivatives are promising compounds for molecular imaging of the pulmonary circulation. L-AM displayed higher levels of initial lung retention and of kidney excretion. | 18,927,321 |
Nuclear imaging and minimally invasive surgery in the management of hyperparathyroidism. | Primary hyperparathyroidism is the most common cause of hypercalcemia, and the treatment is primarily surgical. Because of biochemical screening, more patients now present with asymptomatic primary hyperparathyroidism, and consensus guidelines have been developed for the treatment of these patients. There is now considerable interest in minimally invasive approaches to the treatment of hyperparathyroidism. Sestamibi scanning as a localizing study, used in combination with anatomic imaging and intraoperative rapid parathyroid hormone assays, has enabled focused surgical approaches. Patients with localizing studies that indicate a single parathyroid adenoma are candidates for such approaches, including unilateral neck exploration, minimally invasive single-gland exploration, or endoscopic exploration instead of the traditional approach of bilateral neck exploration. Nuclear imaging is also critical to the successful management of patients with persistent or recurrent hyperparathyroidism. | 18,927,330 |
Surface sites for engineering allosteric control in proteins. | Statistical analyses of protein families reveal networks of coevolving amino acids that functionally link distantly positioned functional surfaces. Such linkages suggest a concept for engineering allosteric control into proteins: The intramolecular networks of two proteins could be joined across their surface sites such that the activity of one protein might control the activity of the other. We tested this idea by creating PAS-DHFR, a designed chimeric protein that connects a light-sensing signaling domain from a plant member of the Per/Arnt/Sim (PAS) family of proteins with Escherichia coli dihydrofolate reductase (DHFR). With no optimization, PAS-DHFR exhibited light-dependent catalytic activity that depended on the site of connection and on known signaling mechanisms in both proteins. PAS-DHFR serves as a proof of concept for engineering regulatory activities into proteins through interface design at conserved allosteric sites. | 18,927,392 |
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