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Practicability of a tooth rescue concept--the use of a tooth rescue box.
Healing following replantation of avulsed teeth is dependent upon short unphysiologic periods during the extraalveolar phase. A commercially available tooth rescue box was developed and distributed at schools in Hessen, a state in Germany. Aim of the study was to evaluate the availability times of rescue boxes and the storage periods of rescued teeth within the boxes. Two thousand one hundred tooth rescue boxes together with a questionnaire were distributed predominantly at schools. In case of usage of a box, the questionnaire should be filled out by patients and dentists and sent back for evaluation. One hundred seventy-two (8.2%) questionnaires were sent back. Eighteen questionnaires were incomplete. In the remaining 154 tooth rescue boxes, a total of 201 avulsed teeth and tooth crown fragments were rescued. When accidents occurred near a stored rescue box, the availability time was short (median: 5 min). It was significantly longer (median: 35 min) when the location of the accident was distant to a stored box. Storage of avulsed teeth in the tooth rescue box was longer (median: 2 h) than storage of fractured crown fragments (median: 1 h). Lay people (teachers, pupils) used the rescue boxes correctly without professional help or even advice through telephone. The usage of the tooth rescue box seemed to be self-explanatory and plausible to lay persons, very short availability times resulted when accidents occurred near stored boxes. Thus, an excellent healing prognosis can be anticipated after replantation. The storage periods of avulsed teeth before the commencement of treatment exceed by far the periods that are acceptable for alternative but unphysiologic media (saline, saliva, milk). It is concluded that tooth rescue boxes should be distributed at locations prone to tooth traumas (schools, kindergartens, sporting facilities, public pools) to enhance the prognosis of avulsed teeth. Emergency units (hospitals, ambulances) should be equipped with tooth rescue boxes as well as every dentist. Tooth rescue boxes are recommended for families with children.
18,721,341
Basketball players' experience of dental injury and awareness about mouthguard in China.
The objective of the present study was to describe the occurrence of orofacial, particularly dental injuries in basketball, and to survey the athletes' awareness concerning the use of mouthguards during basketball training and competition. A pilot questionnaire was designed and tested with basketball players. Two hundred and thirty-six male athletes were surveyed. Seventy-seven players were professional players. Exactly 80.6% professionals and 37.7% semi-professional athletes had an experience of oral soft tissue laceration and dental injuries in basketball practice. The difference between the two groups is significant. The incidence of dental and oral injuries was related to the length of training time. About 59% of the athletes ranked the risk of orofacial and dental injury in basketball as medium. Although the awareness of mouthguards among the basketball players was very high (80.1%), only one of them had used the custom-made mouthguard. Most of the athletes gained the knowledge about mouthguards from foreign players (33.5%), media (24.8%) and teammates/classmates (24.3%). The influence of dentists was very weak. Athletes should be informed about the high risk of oral injuries when participating in contact sports. Dentists should play a more significant role in the program of promoting mouthguard use to prevent the occurrence of oral injury in sport participation.
18,721,342
Pattern of traumatic dental injuries in children attending the University Dental Hospital, Sri Lanka.
The aim of this study was to determine the pattern of traumatic dental injuries in children seeking care at the Division of Paediatric Dentistry, the Dental Hospital, University of Peradeniya, Sri Lanka. The sample consisted of patients attending the Division Paediatric Dentistry, University Dental Hospital for traumatic dental injuries between February 2003 and May 2006. The data were collected by means of an interviewer administered questionnaire to parent/guardian and a clinical examination. A total of 197 children aged between 2 and 17 years had sought treatment for 304 traumatized teeth. Half of the patients had sought treatment more than 1 month after the trauma occurred. The most frequent cause for dental trauma was a fall (89%) whilst compromised aesthetics was the most common reason for seeking care (48%). Maxillary central incisors were the most affected teeth. Of the permanent teeth, 49% had sustained uncomplicated fractures involving only the enamel and dentine. Pulp therapy ranging from pulpotomy to root canal treatment was the treatment of choice for most of the traumatized permanent teeth (46%). In the deciduous teeth, a fracture involving enamel, dentine and the pulp was the most common (35%). As there was a considerable delay in seeking care for these injuries, it is recommended that educational programs be conducted for parents to create awareness about the importance of immediate management of traumatized teeth.
18,721,351
A modified method of mouthguard fabrication for orthodontic patients.
Orthodontic appliances are one of the major risk factors for traumatic injuries during sports events. As it is difficult to take precise impressions with orthodontic appliances, fabricated custom-made mouthguards (MGs) often have poor retention or are too tight causing the disturbance of orthodontic treatments. The purpose of this article is to describe a method for custom-made MG fabrication using sheet and tube materials, with which better MG retention and rigidity as well as pressure control to the orthodontic appliances can be easily achieved.
18,721,352
A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction.
Feline immunodeficiency virus (FIV) targets helper T cells by attachment of the envelope glycoprotein (Env) to CD134, a subsequent interaction with CXCR4 then facilitating the process of viral entry. As the CXCR4 binding site is not exposed until CD134-binding has occurred then the virus is protected from neutralising antibodies targeting the CXCR4-binding site on Env. Prototypic FIV vaccines based on the FL4 strain of FIV contain a cell culture-adapted strain of FIV Petaluma, a CD134-independent strain of FIV that interacts directly with CXCR4. In addition to a characteristic increase in charge in the V3 loop homologue of FIVFL4, we identified two mutations in potential sites for N-linked glycosylation in the region of FIV Env analogous to the V1-V2 region of HIV and SIV Env, T271I and N342Y. When these mutations were introduced into the primary GL8 and CPG41 strains of FIV, the T271I mutation was found to alter the nature of the virus-CD134 interaction; primary viruses carrying the T271I mutation no longer required determinants in cysteine-rich domain (CRD) 2 of CD134 for viral entry. The T271I mutation did not confer CD134-independent infection upon GL8 or CPG41, nor did it increase the affinity of the CXCR4 interaction, suggesting that the principal effect was targeted at reducing the complexity of the Env-CD134 interaction.
18,721,458
Gene Vector Analysis (Geneva): a unified method to detect differentially-regulated gene sets and similar microarray experiments.
Microarray experiments measure changes in the expression of thousands of genes. The resulting lists of genes with changes in expression are then searched for biologically related sets using several divergent methods such as the Fisher Exact Test (as used in multiple GO enrichment tools), Parametric Analysis of Gene Expression (PAGE), Gene Set Enrichment Analysis (GSEA), and the connectivity map. We describe an analytical method (Geneva: Gene Vector Analysis) to relate genes to biological properties and to other similar experiments in a uniform way. This new method works on both gene sets and on gene lists/vectors as input queries, and can effectively query databases consisting of sets of biologically related sets, or of results from other microarray experiments. We also present an improvement to the null model estimate by using the empirical background distribution drawn from previous experiments. We validated Geneva by rediscovering a number of previous findings, and by finding significant relationships within microarrays in the GEO repository. Provided a reasonable corpus of previous experiments is available, this method is more accurate than the class label permutation model, especially for data sets with limited number of replicates. Geneva is, moreover, computationally faster because the background distributions can be precomputed. We also provide a standard evaluation data set based on 5 pairs of related experiments that should share similar functional relationships and 28 pairs of unrelated experiments from GEO. Discovering relationships amongst GEO data sets has implications for drug repositioning, and understanding relationships between diseases and drugs.
18,721,468
The Hordaland Women's Cohort: a prospective cohort study of incontinence, other urinary tract symptoms and related health issues in middle-aged women.
Urinary incontinence (UI) is a prevalent symptom in middle-aged women, but data on incidence is limited and rarely reported. In order to analyze incidence, remission, or development patterns of severity and types of UI, we have established a 15-year prospective cohort (1997-2012). The Cohort is based on the national collection of health data gathered from county studies (CONOR). Hordaland Health Study (HUSK) is one of them from Hordaland County. Each of the county studies may have local sub-studies and our Cohort is one of them. The Cohort included women aged 40-45 in order to have a broad approach to women's health including UI and other lower urinary tract symptoms (LUTS). A one fifth random sampling from HUSK was used to create the Cohort in 1997-1999. For the necessary sample size a preliminary power calculation, based on a 70% response rate at inclusion and 5% annual attrition rates was used. The Cohort is planned to collect data through questionnaires every second year for the 15-year period from 1997-2012. The Cohort represents a relatively large random sample (N = 2,230) of about 15% of the total population of women born between 1953-57 in the county of Hordaland. Our data shows that the cohort population is very similar to the source population. The baseline demographic, social and medical characteristics of the Cohort are compared with the rest of women in HUSK (N = 7,746) and there were no significant differences between them except for the level of education (P = 0.001) and yearly income (P = 0.018), which were higher in the Cohort population. Urological characteristics of participants from the Cohort (N = 1,920) were also compared with the other participants (N = 3,400). There were no significant statistical differences except for somewhat more urinary continence (P = 0.04), more stress incontinence (P = 0.048) and smaller amount of leakage (P = 0.015) in the Cohort. In conclusion, the Cohort is population-based, with little selection bias, and thus is a rather unique study for investigating UI and LUTS in comparison with many other projects with similar purposes.
18,721,479
Usefulness of paradoxical systolic blood pressure increase after exercise as a predictor of cardiovascular mortality.
Exercise treadmill testing (ETT) is a well-accepted examination for patients with suspected coronary artery disease (CAD), and exercise induced ST-segment deviation is commonly used for CAD detection. However, recent evidence shows that systolic blood pressure (SBP) changes during and after exercise were associated with CAD severity, risk of acute myocardial infarction and stroke, new-onset hypertension, and even cardiovascular mortality. We retrospectively assessed 3,054 patients referred for ETT in 1996. Blood pressure and heart rate were recorded at rest, during peak exercise, and 1 and 3 min after exercise. SBP at 3 min of recovery equal to or higher than that at 1-min of recovery was defined as paradoxical SBP increase. These patients were categorized into 4 groups according to ETT ST-segment change and postexercise SBP change. After 10 years of follow-up, 346 patients (11%) died, with 129 (4%) dying from cardiovascular disease (CVD). Among the 4 groups, patients with ischemic ST-segment change and paradoxical SBP increase were associated with a higher risk for mortality, with odds ratios of 1.86 (95% confidence interval 1.31 to 2.65) for all-cause mortality and 3.18 (95% confidence interval 1.94 to 5.20) for CVD mortality, respectively. Patients with isolated paradoxical SBP increase still had a higher risk of CVD mortality (odds ratio 1.80, 95% confidence interval 1.70 to 3.04), even after controlling other cardiovascular risk factors. In subgroup analysis of 346 mortality subjects, patients with ischemic ST-segment change and paradoxical SBP increase would be more likely to die from CVD. In conclusion, compared with ischemic ST-segment change, paradoxical SBP increase after exercise is an important and significant predictor of CVD mortality.
18,721,505
Bartonella species detection in captive, stranded and free-ranging cetaceans.
We present prevalence of Bartonella spp. for multiple cohorts of wild and captive cetaceans. One hundred and six cetaceans including 86 bottlenose dolphins (71 free-ranging, 14 captive in a facility with a dolphin experiencing debility of unknown origin, 1 stranded), 11 striped dolphins, 4 harbor porpoises, 3 Risso's dolphins, 1 dwarf sperm whale and 1 pygmy sperm whale (all stranded) were sampled. Whole blood (n = 95 live animals) and tissues (n = 15 freshly dead animals) were screened by PCR (n = 106 animals), PCR of enrichment cultures (n = 50 animals), and subcultures (n = 50 animals). Bartonella spp. were detected from 17 cetaceans, including 12 by direct extraction PCR of blood or tissues, 6 by PCR of enrichment cultures, and 4 by subculture isolation. Bartonella spp. were more commonly detected from the captive (6/14, 43%) than from free-ranging (2/71, 2.8%) bottlenose dolphins, and were commonly detected from the stranded animals (9/21, 43%; 3/11 striped dolphins, 3/4 harbor porpoises, 2/3 Risso's dolphins, 1/1 pygmy sperm whale, 0/1 dwarf sperm whale, 0/1 bottlenose dolphin). Sequencing identified a Bartonella spp. most similar to B. henselae San Antonio 2 in eight cases (4 bottlenose dolphins, 2 striped dolphins, 2 harbor porpoises), B. henselae Houston 1 in three cases (2 Risso's dolphins, 1 harbor porpoise), and untyped in six cases (4 bottlenose dolphins, 1 striped dolphin, 1 pygmy sperm whale). Although disease causation has not been established, Bartonella species were detected more commonly from cetaceans that were overtly debilitated or were cohabiting in captivity with a debilitated animal than from free-ranging animals. The detection of Bartonella spp. from cetaceans may be of pathophysiological concern.
18,721,502
Cost of preimplantation cardiac imaging in patients referred for a primary-prevention implantable cardioverter-defibrillator.
Recent guidelines have focused on ejection fraction cut-off values to determine eligibility for primary-prevention implantable cardioverter-defibrillators (ICDs). Clinical trials that led to the guidelines used varying techniques for ejection fraction assessment, including echocardiography and multigated acquisition (MUGA) scan. A prospective cohort study to determine the economic attractiveness of repeated echocardiography and MUGA scanning during the evaluation process of patients referred for consideration of a primary-prevention ICD was undertaken. From January 2005 to December 2006, data were collected for patients aged >18 years with ejection fraction <30% referred for a primary-prevention ICD based on referral assessment of heart function in any form. Costs based on the 2006 Ontario Health Insurance Plan fee schedule were determined for clinical assessment, echocardiography, MUGA scanning, and ICD implantation in patients who remained eligible based on MUGA ejection fraction. The 100 patients (age 61.1 +/- 10.2 years; 78 men) assessed for primary-prevention ICD implantation had an ejection fraction of 28.9 +/- 12.3% using MUGA scan. Thirty-one of 100 patients (31%) had an ejection fraction >30% and were no longer eligible for an ICD. Although imaging increased preimplantation cost from dollars 130 to dollars 536 per patient, averted inappropriate ICDs decreased the overall per-patient cost from dollars 20,914 to dollars 14,877. Despite an additional testing cost of dollars 40,599, the overall cost savings was dollars 603,722 in the 100 patients, with a cost savings of dollars 6,037 per patient. In conclusion, verification of ejection fraction identified a significant proportion of patients who were not eligible for an ICD.
18,721,517
Relation of serum heat shock protein 60 level to severity and prognosis in chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.
Heat shock protein (HSP) 60 is induced by a variety of stressors, including oxidative stress and inflammation, and it plays a protective role against stress-induced cardiomyocyte injury. Recently, it has been reported that HSP 60 exists in the circulation. Chronic heart failure (CHF) is characterized by systemic abnormalities, and the myocardium is exposed to various stressors. However, the clinical significance of serum HSP 60 has not been examined in CHF. Therefore, the purpose of this study was to examine whether HSP 60 is correlated with the severity of CHF and whether HSP 60 can predict clinical outcomes in patients with CHF. Serum HSP 60 levels were measured in 112 patients with CHF and 62 control subjects. Serum HSP 60 levels were higher in patients with CHF than in control subjects and increased with advancing New York Heart Association functional class. There were 37 cardiac events during a mean follow-up period of 569 +/- 476 days (range 17 to 1,986). Serum HSP 60 levels were higher in patients with cardiac events than in event-free patients. Patients were divided into 4 groups on the basis of HSP 60 level. Cox proportional-hazards regression analysis and Kaplan-Meier analysis revealed that the fourth quartile was associated with the greatest risk for cardiac events. In conclusion, serum HSP 60 level was related to the severity of CHF and associated with a high risk for adverse cardiac events in patients CHF.
18,721,521
Effect of alcohol septal ablation in patients with hypertrophic cardiomyopathy on the electrocardiographic pattern.
Alcohol septal ablation (ASA) of patients with hypertrophic cardiomyopathy (HC) allows study of the electrocardiographic effects of myocardial necrosis confined to the base of the interventricular septum, a rare event in atherothrombotic coronary artery disease. Eighty-four consecutive patients were studied after ASA for HC. After excluding 20 with pacing before ASA and 6 with no available preprocedure electrocardiograms, the electrocardiograms of the remaining 58 patients were compared with those of 58 consecutive patients with anterior ST elevation myocardial infarctions who underwent primary intervention for left anterior descending coronary artery (LAD) occlusions. In 25 patients, the occlusions were proximal to the first septal perforator, and in 33 patients, the occlusions were more distal. All electrocardiograms were analyzed with respect to conduction abnormalities and ST-segment changes. Patients with HC developed right bundle branch block significantly more often than those with LAD occlusions (50% vs 14%, p = 0.001) Moreover, patients with HC required postprocedure pacing more frequently (14% vs 2%, p <0.05). A distinctive pattern of ST displacement was found. There was more frequent ST depression in leads I and aVF and greater ST elevation in lead V(1) in patients who underwent ASA, indicating a greater tendency toward a rightward direction than was true in patients with LAD occlusions. In conclusion, in addition to more frequent right bundle branch block after ASA, a distinctive a characteristic pattern of ST-segment deviation similar to but distinct from that produced by proximal LAD occlusion appeared.
18,721,524
Absence of TGFBR1 and TGFBR2 mutations in patients with bicuspid aortic valve and aortic dilation.
Mutations in the genes encoding transforming growth factor-beta receptor types I and II (TGFBR1 and TGFBR2, respectively) are commonly identified in patients with Loeys-Dietz syndrome, as well as some patients with Marfan's syndrome or familial thoracic aortic aneurysms and dissections. This suggests that there is considerable phenotypic heterogeneity associated with mutations in these genes. Because bicuspid aortic valve (BAV) is a congenital heart defect in patients with Loeys-Dietz syndrome, this study was conducted to investigate whether variants in TGFBR1 or TGFBR2 are responsible for sporadic BAV. Analysis of these genes in 35 patients with BAVs identified only known single-nucleotide polymorphisms or novel synonymous or intronic substitutions. In conclusion, mutations in TGFBR1 and TGFBR2 rarely cause sporadic BAV.
18,721,526
Study of binding and denaturation dynamics of IgG and anti-IgG using dual color fluorescence correlation spectroscopy.
In this article, we present a systematic study on IgG and Fab fragment of anti-IgG molecules using fluorescence auto- and cross-correlation spectroscopy to investigate their diffusion characteristics, binding kinetics, and the effect of small organic molecule, urea on their binding. Through our analysis, we found that the diffusion coefficient for IgG and Fab fragment of anti-IgG molecules were 37+/-2 microm2s(-1) and 56+/-2 microm2s(-1), respectively. From the binding kinetics study, the respective forward (k(a)) and backward (k(d)) reaction rates were (5.25+/-0.25)x10(6)M(-1)s(-1) and 0.08+/-0.005 s(-1), respectively and the corresponding dissociation binding constant (K(D)) was 15+/-2 nM. We also found that urea inhibits the binding of these molecules at 4M concentration due to denaturation.
18,721,546
Coronary artery bypass grafting with or without surgical ventricular restoration: a comparison.
Coronary artery bypass grafting (CABG) is an effective treatment for ischemic cardiomyopathy. However, patients with ventricular enlargement are known to have inferior outcomes. We assessed whether surgical ventricular restoration (SVR) with CABG (SVR + CABG) leads to improved outcomes versus CABG alone for patients with ischemic cardiomyopathy and ventricular enlargement. We conducted a case-control study comparing patients with ischemic cardiomyopathy and ejection fraction less than 0.35 who underwent SVR + CABG versus CABG alone from June 2002 to December 2005. Patients who underwent SVR + CABG were compared with control patients who met criteria for SVR + CABG by ventriculogram or echocardiogram but received CABG alone. End points included survival, rehospitalization for heart failure, and New York Heart Association class. During the study period 120 patients underwent SVR + CABG (n = 62) versus CABG alone (n = 58). Patients in the SVR + CABG group were younger (60 versus 64 years; p = 0.04) and more likely to be New York Heart Association class III or IV preoperatively (98% versus 86%; p = 0.01). Operative mortality was similar between groups (6.4% versus 5.2%; p = 1.00). Ejection fraction was similar preoperatively (0.22 versus 0.24; p = 0.31) and postoperatively (0.34 versus 00.32; p = 0.40). The SVR + CABG patients experienced fewer rehospitalizations for heart failure (24% [13 of 54] versus 55% [24 of 44]; p = 0.006) but had similar 4-year survival (p = 0.60). At follow-up, 80% (50 of 62) of SVR + CABG versus 57% (27 of 47) of CABG alone patients improved to New York Heart Association class I or II (p = 0.01). Patients with ischemic cardiomyopathy and ventricular enlargement experience similar early survival after SVR + CABG or CABG alone. However, SVR + CABG resulted in fewer rehospitalizations and better improvements in New York Heart Association class. Surgical ventricular restoration with CABG should be offered to eligible patients with ischemic cardiomyopathy and ventricular enlargement.
18,721,565
Right heart dysfunction after left ventricular assist device implantation: a comparison of the pulsatile HeartMate I and axial-flow HeartMate II devices.
Right heart dysfunction confers significant morbidity and mortality after left ventricular assist device implantation and historically occurs in as many as a third of patients. It is unknown whether newer axial flow pumps have a different impact on postimplant right heart dysfunction. We compared the incidence of right heart dysfunction after implantation of the pulsatile HeartMate I (XVE) and the continuous flow HeartMate II left ventricular assist device. We retrospectively reviewed patients who underwent HeartMate I or HeartMate II implantation between June 2000 and March 2007. Right heart dysfunction was defined as inotropic/vasodilator support for 14 or more consecutive days or the need for a right ventricular assist device, or both. Seventy-seven patients underwent HeartMate implantation; 43 received a HeartMate I and 34 received a HeartMate II, for a mean left ventricular assist device support time of 202 and 160 days, respectively. Operative mortality was lower for HeartMate II patients (28% versus 15%; p = 0.26). The HeartMate II patients had lower preoperative right ventricular stroke work index. Pulmonary vascular resistance index, right ventricular stroke work index, and pulmonary and right atrial pressures improved and were similar between groups postoperatively. Overall, right heart dysfunction developed in 35% of HeartMate I patients (15 of 43) and 41% of HeartMate II patients (14 of 34; p = 0.63). Fewer HeartMate II patients (2) than HeartMate I patients (5) required 7 or more days of epinephrine, whereas more HeartMate II patients (7) than HeartMate I patients (5) required 7 or more days of milrinone. Six HeartMate I and 3 HeartMate II patients required right ventricular assist device implantation for right heart failure. Survival was similar (p = 0.7) between groups at, respectively, 3 (63% versus 62%), 6 (58% versus 58%), and 12 months (49% versus 48%). Right heart dysfunction is a persistent clinical problem after left ventricular assist device placement. We report the first study comparing the incidence of right heart dysfunction after HeartMate I versus HeartMate II implantation. Although the incidence of right heart dysfunction was similar, fewer HeartMate II patients required right ventricular assist device placement and fewer required pure inotropic support for right heart failure.
18,721,570
Arrhythmia surgery in patients with and without congenital heart disease.
Arrhythmia surgery has favorably impacted the clinical course of debilitating atrial and ventricular arrhythmias in patients with and without congenital heart disease. This study reviews arrhythmia mechanisms and documents long-term outcome of patients undergoing arrhythmia operations alone or associated with congenital heart repairs. The analysis excludes Fontan conversion patients. Between 1987 and 2007, arrhythmia operations were done in 11 patients without associated congenital heart disease and in 89 along with congenital heart repairs. Mean age was 15.9 +/- 12.5 years (range, 7 days-48 years); 7 were infants (mean age, 23 +/- 16 days). Resternotomy was performed in 65 (65%). Two functional ventricles were present in 67 patients; 33 had 1 functional ventricle. Arrhythmias included macro-reentrant atrial tachycardia in 45, atrial fibrillation in 11, accessory connections in 19, atrioventricular nodal reentry tachycardia in 6, focal atrial tachycardia in 6, and ventricular tachycardia in 13. Operative mortality was 3 (3.0%) due to advanced associated congenital heart disease. There were 4 late deaths (4.0%) and 2 late cardiac transplants (2.0%). Freedom from arrhythmia recurrence at 1 and 10 years was 94% and 85% for atrial arrhythmias, and 85% and 68% for ventricular arrhythmias, respectively. Successful surgical therapy for atrial arrhythmias can be performed safely with a high freedom from recurrence rate in patients with and without associated congenital heart disease. Surgical ablation for ventricular arrhythmias is less predictive. Complexity of the underlying congenital heart disease and hemodynamic status may contribute to potential arrhythmia recurrence or new onset arrhythmia manifestation.
18,721,574
The treatment of patients with stage IIIA non-small cell lung cancer from N2 disease: who returns to the surgical arena and who survives.
Stage IIIA non-small cell lung (NSCLC) from N2 disease is common, but represents a heterogeneous group of patients. Predictors of who completes their neoadjuvant chemoradiotherapy and undergoes subsequent surgical resection are unknown. This retrospective cohort study used a prospective database. Patients who had biopsy-proven, nonbulky N2 disease underwent neoadjuvant chemoradiotherapy and were restaged or resected, or both. There were 402 patients, and 326 (81%) completed their neoadjuvant therapy. Only 198 (50%) returned for definitive pathologic restaging, and 149 (37%) underwent thoracotomy for attempted resection. Predictors of who returned to the surgical arena were age (< 70), multiple node involvement, and response to neoadjuvant therapy. The 5-year survival was 8% for the 253 patients who did not return for restaging but was 47% for the 149 patients who underwent thoracotomy (p < 0.001). The 5-year survival for selected subgroups of patients who underwent complete resection was 42% for the 14 patients who had unsuspected recalcitrant N2 disease, 49% for the 65 patients who had a partial response, and 53% for the 34 patients who had a complete response. Only 37% of patients with favorable, nonbulky, biopsy-proven N2 disease actually complete their neoadjuvant therapy, undergo restaging, and then return for attempted resection. Only 28% undergo complete resection. However, in this highly selected subset of patients, the 5-year survival is 47% or better if partial or complete pathologic response is achieved. Therefore, surgical resection remains a viable treatment for selected patients with favorable N2 NSCLC.
18,721,582
Radiotracer-guided thoracoscopic resection is a cost-effective technique for the evaluation of subcentimeter pulmonary nodules.
Excisional biopsy of small subcentimeter pulmonary nodules can be difficult using standard thoracoscopic techniques and may require thoracotomy. Radiotracer-guided thoracoscopic resection (RGTR) was developed to facilitate resection of intraparenchymal subcentimeter pulmonary nodules. Decision analysis, used to model cost and effectiveness, is useful to compare treatment options. We hypothesize that RGTR strategy is more cost-effective compared with thoracotomy for subcentimeter pulmonary nodules. The cost-effectiveness of RGTR versus thoracotomy for evaluating highly suspicious subcentimeter pulmonary nodules was examined with a decision analysis model (Fig 1). A 40-patient institutional cohort who underwent RGTR was used to estimate probabilities and costs of the two treatment options within the model. Effectiveness was estimated using 5-year, stage-specific cancer survival and population survival curves. The Society of Thoracic Surgeons General Thoracic Database was queried obtaining mortality estimates for thoracotomy and thoracoscopic wedge resections. These were used to adjust the 5-year survival estimates of patients with benign disease. Sensitivity analyses determined model robustness and the thresholds at which the most cost-effective strategy changed. Radiotracer-guided thoracoscopic resection was 95% successful with no mortality. The average cost-to-effectiveness ratio of RGTR strategy was $27,887 versus $32,271 for thoracotomy. Sensitivity analyses demonstrated that the thoracotomy strategy was more cost-effective if the estimated cost of RGTR increased by 33% or the estimated cost-effectiveness of thoracotomy decreased by 14% or more. Radiotracer-guided thoracoscopic resection was more cost-effective as long as the probability of success was greater than 44%. Decision analysis is a useful tool to evaluate treatment options for thoracic surgeons, and RGTR is a more cost-effective strategy than thoracotomy for subcentimeter pulmonary nodules.
18,721,586
One-session treatment of specific phobias: a detailed description and review of treatment efficacy.
One-Session Treatment (OST) is a form of massed exposure therapy for the treatment of specific phobias. OST combines exposure, participant modeling, cognitive challenges, and reinforcement in a single session, maximized to three hours. Clients are gradually exposed to steps of their fear hierarchy using therapist-directed behavioral experiments. Although there are several studies in the literature examining the efficacy of OST, little has been done to summarize this research. In the following review, research on and empirical support for OST are reviewed with an emphasis on the types of stimuli, samples, and methodologies utilized. Research generally supports OST's efficacy, although replication by independent examiners using adult and child samples is needed using more rigorous comparisons (e.g., psychological placebo or other treatments). Overall, OST continues to be a promising treatment for specific phobias; however, a great deal more investigation is needed to identify mechanisms of change, mediators, and moderators.
18,721,635
The role of interdependence and perceived similarity in depressed affect contagion.
This study hypothesized that perceived similarity significantly impacts depressed affect contagion only for individuals with highly interdependent self-construals. Baseline self-construal and affect were measured. Then, after reading a vignette about a depressed or nondepressed target, affect and perceived similarity were assessed. Participants reading the depressed vignette reported higher negative affect than participants reading the nondepressed vignette. Positive affect did not differ between the two conditions. For participants exposed to the depressed vignette, the hypothesized interaction between perceived similarity and interdependence significantly predicted positive affect. It appears that participants with more interdependent self-construals were more likely to "catch" the low positive affect displayed by the depressed target only if they perceived themselves as highly similar to the target.
18,721,641
Sexually transmitted infections and pelvic inflammatory disease in women.
Sexually transmitted infections (STIs) are an important public health challenge in the United States. Primary care clinicians can contribute to decreasing these largely preventable causes of morbidity and mortality by integrating routine screening, testing, counseling, treatment, and partner management of STIs into their practice. Newer tests for chlamydia and gonorrhea that can be performed on urine specimens allow screening without a pelvic examination. The most recent edition of the Centers for Disease Control and Prevention sexually transmitted disease treatment guidelines provides an evidence-based, reliable, and convenient set of recommendations for treating and caring for patients who have STIs.
18,721,654
Breast disease: benign and malignant.
Breast diseases, both benign and malignant, are common. Typically, young women present with more benign pathologies; however, breast malignancies can occur in young women, especially in those harboring mutations in the BRCA genes, other inherited genetic syndromes associated with increased risk of breast cancer, or familial predisposition for breast cancer. In all women aged 40 and over presenting with abnormalities of the breast, a primary breast cancer should be ruled out because it is the leading cancer among women in developed countries.
18,721,655
Inactivation kinetics of inoculated Escherichia coli O157:H7, Listeria monocytogenes and Salmonella Poona on whole cantaloupe by chlorine dioxide gas.
The objectives of this study were to examine inactivation kinetics of inoculated Escherichia coli O157:H7, Listeria monocytogenes and Salmonella Poona inoculated onto whole cantaloupe and treated with ClO(2) gas at different concentrations (0.5, 1.0, 1.5, 3.0 and 5.0 mg l(-1)) for different times (0, 2.0, 4.0, 6.0, 8.0 and 10.0 min). The effect of ClO(2) gas on the quality and shelf life of whole cantaloupe was also evaluated during storage at 22 degrees C for 12 days. A 100 microl inoculation of each targeted organism was spotted onto the surface (5 cm(2)) of cantaloupe rind (approximately 8-9 log CFU 5 cm(-2)) separately, air dried (60 min), and then treated with ClO(2) gas at 22 degrees C and 90-95% relative humidity for 10 min. Surviving bacterial populations on cantaloupe surfaces were determined using a membrane transferring method with a non-selective medium followed by a selective medium. The inactivation kinetics of E. coli O157:H7, L. monocytogenes and S. Poona were determined using nonlinear kinetics (Weibull model). A 3 log CFU reduction of E. coli O157:H7, L. monocytogenes and S. Poona were achieved with 5.0 mg l(-1) ClO(2) gas for 5.5, 4.2 and 1.5 min, respectively. A 5l og CFU reduction of S. Poona was achieved with 5.0 and 3.0 mg l(-1) ClO(2) gas for 6 and 8 min, respectively. A 4.6 and 4.3 log reduction was achieved after treatment with 5.0 mg l(-1) ClO(2) gas at 10 min for E. coli O157:H7 and L. monocytogenes, respectively. Treatment with 5.0 mg l(-1) ClO(2) gas significantly (p<0.05) reduced the initial microflora (mesophilic bacteria, psychrotrophic bacteria, and yeasts and molds) on cantaloupe by more than 2 log CFU cm(-2) and kept them significantly (p<0.05) lower than the untreated control during storage at 22 degrees C for 12 days. Treatment with ClO(2) gas did not significantly (p>0.05) affect the color of whole cantaloupe and extended the shelf life to 9 days compared to 3 days for the untreated control, when stored at ambient temperature (22 degrees C).
18,721,673
Intraspecific genetic diversity of lactic acid bacteria from malolactic fermentation of Cencibel wines as derived from combined analysis of RAPD-PCR and PFGE patterns.
Three molecular techniques, randomly amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR), pulsed field gel electrophoresis (PFGE) and differential display-polymerase chain reaction (DD-PCR) have been used to assess the intraspecific diversity of the lactic microbiota responsible for spontaneous malolactic fermentation (MLF) in Cencibel wines made at a cellar in Castilla-La Mancha (Spain). The results indicate that RAPD-PCR and PFGE are of value in typing this microbiota. Better discrimination was achieved by RAPD-PCR. Reproducibility using DD-PCR was not good, which makes this method unsuitable. Combined numerical analysis of the patterns obtained from RAPD-PCR and PFGE allowed a better discrimination; this would therefore be a suitable tool to discriminate the diversity of bacterial communities like those found in MLF of wines. Genetic diversity data from combined numerical analysis suggest that there is considerable microbial diversity within MLF of Cencibel wines, with some genotypes coinciding in the two vinifications analysed.
18,721,686
Delayed-onset isolated central Descemet membrane blister detachment following phacoemulsification.
We report 2 patients who developed delayed-onset isolated central Descemet membrane (DM) blister-like detachment following phacoemulsification. The detachments were not associated with a DM tear or inadvertent injection of fluid under DM, and no fluid tracks from the periphery were present. When the detachments failed to resolve spontaneously over several months, intracameral air or C(3)F(8) gas was injected. In 1 patient, a therapeutic paracentral puncture in DM was also performed to facilitate escape of the entrapped fluid. Although a small residual detachment (confirmed by optical coherence tomography) remained in both cases, the visual acuity improved to 20/25 in 1 patient and 20/30 in the other. We think these unique focal detachments in DM may be associated with an underlying preexisting weakness in the DM attachment to the stroma.
18,721,728
Validation of a composite scoring scheme in the diagnosis of folate deficiency in a pediatric and adolescent dialysis cohort.
Laboratory indices are often poorly diagnostic of folate deficiency (FD). Compared with iron depletion in hemodialysis (HD) populations, the impact of FD is less appreciated. The composite scoring of hematologic indices of FD may facilitate a prompt and accurate diagnosis, and enhance operational research on folic acid therapy. Our objectives were to (1) validate composite scores of folate diagnostic indices, and (2) determine the reliability index of the diagnostic tool. A cohort of 30 subjects, with a mean age of 16 (SD +/- 3.2 years), on HD and erythropoietin (EPO) for a minimum of 3 months was studied. After a baseline hematologic assessment, routine folates were administered for 6 months. Composite FD scores (FDS) of baseline mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), random distribution width (RDW), and hemoglobin were determined. Validation and reliability statistics were then analyzed, using the quantitative change in red blood cell folate/plasma homocysteine, or EPO requirement after 6 months of folate use, as diagnostic criteria. The mean FDS for FD and non-FD subsets were 3.0 +/- 1.3 and 1.4 +/- 0.9, respectively (analysis of variance; P = .0001). The correlation coefficient, r(2), between FD total and FDS was 0.61 (P = .001), and the coefficient between 2 (weekly) values of RDW, MCV, MCH, and MCHC was >0.84 (P = .0001). Scoring tools derived from the first (P = .002) and second (P = .01) halves of the laboratory indices remained discriminatory for the FD and non-FD groups. Baseline serum folate is poorly specific for FD, whereas FD score >or=3 had sensitivity, specificity, and positive and negative predictive values close to 90%. Composite scoring of erythrocyte indices was predictive of the FD diagnosis, as defined by the quantitative response of red blood cell folate, homocysteine, and EPO dose to folate therapeutic intervention. The diagnostic items yielded a high reliability coefficient. The FDS scheme is a potential tool for the diagnosis and surveillance of FD, particularly in at-risk populations (e.g., dialysis subjects).
18,721,738
GFP family: structural insights into spectral tuning.
Proteins homologous to green fluorescent protein (GFP) span most of the visible spectrum, offering indispensable tools for live cell imaging. Structural transformations, such as posttranslational autocatalytic and photo-induced modifications, chromophore isomerization, and rearrangements in its environment underlie the unique capacity of these proteins to tune their own optical characteristics. A better understanding of optical self-tuning mechanisms would assist in the engineering of more precisely adapted variants and in expanding the palette of GFP-like proteins to the near-infrared region. The latest advances in this field shed light upon multiple features of protein posttranslational chemistry, and establish some important basic principles about the interplay of structure and spectral properties in the GFP family.
18,721,746
Response to pneumococcal (PNCRM7) and haemophilus influenzae conjugate vaccines (HIB) in pediatric and adult recipients of an allogeneic hematopoietic cell transplantation (alloHCT).
Young children and allogeneic hematopoietic cell transplantation (HCT) recipients respond poorly to polysaccharide antigens, rendering them susceptible to severe infections because of encapsulated bacteria. This study evaluated the responses of 127 HCT patients, median age 23.0 years, vaccinated with PNCRM7 and Haemophilus influenzae (HIB) conjugate, 2 conjugate vaccines highly immunogenic in healthy children. Median time to vaccination was 1.1 years after HCT. Sixty-two percent of patients responded to PNCRM7 (45 of 51 children, 34 of 76 adults, P < .001). Overall response to HIB was 86%, including 77% of PNCRM7 nonresponders. Although PNCRM7 response was adversely affected by older age (P < .001), individuals > or =50 years old responded significantly better if vaccinated following acquisition of specific minimal milestones of immune competence, CD4 >200/microL, IgG >500 mg/dL, PHA within 60% lower limit of normal (11 of 19 versus 0 of 8, P < .006). A similar trend was observed in patients with limited chronic graft-versus-host disease (cGVHD). In all patients, higher levels of circulating CD4(+)CD45RA cells correlated with improved PNCRM7 response. These data demonstrate that PNCRM7 is immunogenic in allogeneic HCT patients, including older adults, but suggest that vaccination at fixed intervals after HCT, irrespective of immune competence, may limit its effectiveness. Prospective, multicenter trials assessing the best strategy to administer this vaccine and its impact on pneumococcal infections following transplantation are warranted.
18,721,765
Twenty years of unrelated donor bone marrow transplantation for pediatric acute leukemia facilitated by the National Marrow Donor Program.
The National Marrow Donor Program (NMDP) has facilitated unrelated donor hematopoietic cell transplants for more than 20 years. In this time period, there have been many changes in clinical practice, including improvements in HLA typing and supportive care, and changes in the source of stem cells. Availability of banked unrelated donor cord blood (incorporated into the NMDP registry in 2000) as a source of stem cells has become an important option for children with leukemia, offering the advantages of immediate availability for children with high-risk disease, the need for a lesser degree of HLA match, and expanding access for those with infrequent HLA haplotypes. Overall survival (OS) in children with acute leukemia transplanted with unrelated donor bone marrow (BM) is markedly better in more recent years, largely attributable to less treatment-related mortality (TRM). Within this cohort, 2-year survival was markedly better for patients with acute lymphoblastic leukemia (ALL) in first complete response (CR1) (74%) versus second complete response (CR2) (62%) or more advanced disease (33%). Similar findings are observed with patients with AML, suggesting earlier referral to bone marrow transplant (BMT) is optimal for survival. Notably, this improvement over time was not observed in unmodified peripheral blood stem cell (PBSC) recipients, suggesting unmodified PBSC may not be the optimal stem cell source for children.
18,721,776
Transgenic analyses of TGIF family proteins in Drosophila imply their role in cell growth.
TG-interacting factors (TGIFs) belong to a family of TALE-homeodomain proteins including TGIF, TGIF2, and TGIF2LX/Y (TGIF2 like on X or Y chromosome) in human. They potentially play important functions in various tissues during development. Mutations in TGIF are frequently associated with malformation of forebrain and facial structures; TGIF2 proteins are over-expressed in many ovarian cancer cell lines; and TGIF2LX/Y are specifically expressed in adult testis. The molecular functions of these proteins have been investigated mostly in cultured cells. TGIF and TGIF2 have been found as transcriptional repressors that modulate TGF-beta signaling. However, these findings are far from sufficient to explain their mutant phenotypes or expression patterns, and the functions of TGIF2LX/Y have never been reported. Here we use Drosophila as a model system to explore the functions of TGIF family proteins in vivo. We observed in fly tissues such as fat body, epithelia, and neuronal cells, that expressing human TGIF2 or human TGIF2LX generally inhibited cell growth in size and number. Co-expressing Drosophila Myc, Cyclin E, or human c-MycS partially rescued the growth inhibition induced by human TGIFs, whereas activated insulin pathway signaling did not. Taken together, we provide in vivo evidence for the potential functions of human TGIF2 and TGIF2LX in growth control. Additionally, we confirmed that Drosophila TGIFs are transcriptional activators by assaying their activities in spermatogenesis.
18,721,782
Intermittent L-DOPA treatment differentially alters synaptotagmin 4 and 7 gene expression in the striatum of hemiparkinsonian rats.
Long-term use of L-DOPA in Parkinson's disease (PD) is frequently associated with side effects that are reflected in changed neurotransmitter/neuropeptide secretion in basal ganglia. These side effects could be connected with synaptotagmins (syts) because syts are involved in regulation of membrane trafficking. We have previously reported that acute L-DOPA treatment upregulated the expression of Syt 4 and Syt 7 mRNAs in hypersensitive striatum of 6-OHDA rat model for PD. Here we investigate whether intermittent L-DOPA treatment that produces behavior sensitization affects the Syt 1, Syt 2, Syt 4, Syt 7 and Syt 10 mRNAs in striatum of 6-OHDA rats killed 4 and 12 h after the last L-DOPA injection. We verified behavioral sensitization by increased intensity of contralateral turning. 6-OHDA lesion caused Syt 2 mRNA downregulation and Syt 10 mRNA upregulation in striatum, but failed to alter Syt 4, Syt 7 and Syt 1 mRNAs. Acute l-DOPA induced an increase of Syt 4 and Syt 7 mRNAs in the denervated striatum leaving the levels of Syt 1, Syt 2 and Syt 10 mRNAs unaffected. Intermittent L-DOPA treatment did not alter Syt 1, Syt 2 and Syt 10 mRNA striatal levels, suggesting that 6-OHDA-induced Syt 2 and Syt 10 mRNA changes reflect a persistent striatal abnormality caused by dopamine depletion. On contrary, intermittent L-DOPA treatment downregulated Syt 4 mRNA and prolonged the elevation of Syt 7 mRNA in the denervated striatum. We conclude that Syt 4 and Syt 7 might be specifically involved in striatal plasticity caused by repeated L-DOPA administration that accompanies sensitization.
18,721,798
The effects of maternal corticosterone levels on offspring behavior in fast- and slow-growth garter snakes (Thamnophis elegans).
During embryonic development, viviparous offspring are exposed to maternally circulating hormones. Maternal stress increases offspring exposure to corticosterone and this hormonal exposure has the potential to influence developmental, morphological and behavioral traits of the resulting offspring. We treated pregnant female garter snakes (Thamnophis elegans) with low levels of corticosterone after determining both natural corticosterone levels in the field and pre-treatment levels upon arrival in the lab. Additional measurements of plasma corticosterone were taken at days 1, 5, and 10 during the 10-day exposure, which occurred during the last third of gestation (of 4-month gestation). These pregnant snakes were from replicate populations of fast- and slow-growth ecotypes occurring in Northern California, with concomitant short and long lifespans. Field corticosterone levels of pregnant females of the slow-growth ecotype were an order of magnitude higher than fast-growth dams. In the laboratory, corticosterone levels increased over the 10 days of corticosterone manipulation for animals of both ecotypes, and reached similar plateaus for both control and treated dams. Despite similar plasma corticosterone levels in treated and control mothers, corticosterone-treated dams produced more stillborn offspring and exhibited higher total reproductive failure than control dams. At one month of age, offspring from fast-growth females had higher plasma corticosterone levels than offspring from slow-growth females, which is opposite the maternal pattern. Offspring from corticosterone-treated mothers, although unaffected in their slither speed, exhibited changes in escape behaviors and morphology that were dependent upon maternal ecotype. Offspring from corticosterone-treated fast-growth females exhibited less anti-predator reversal behavior; offspring from corticosterone-treated slow-growth females exhibited less anti-predator tail lashing behavior.
18,721,809
A molecular model for persister in E. coli.
Like many other bacteria, Escherichia coli remain as tiny viable individuals named persisters after being exposed to an antibiotic. These persisters are believed to be phenotypic heterogeneous one rather than mutants, because their progenies are as susceptible to antibiotics as their ancestors. Recently, two persister-related genes (hipB/hipA) were confirmed to belong to a toxin-antitoxin (TA) module. Their control circuit was believed to be responsible for generation of the persister subpopulation. For the well-studied TA module, we build a simple genetic regulation model to explain the phenotypic heterogeneity. We find that a sole double-negative feedback loop is not enough to explain the phenotypic heterogeneity; the cooperation mechanisms in HipB and HipA are indispensable. Moreover, our model illustrates an important persister-related experimental phenomenon: the emergence of the persister depends on the growth rate in continuous culture.
18,721,814
Adenoviral delivery of soluble VEGF receptor 1 (sFlt-1) inhibits experimental autoimmune encephalomyelitis in dark Agouti (DA) rats.
Previous studies have shown that vascular endothelial growth factor (VEGF) expression is up-regulated in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), a model for MS, and may exacerbate the disease. However, it remains unknown whether anti-VEGF modalities could serve as a potential treatment for such central nervous system (CNS) autoimmune diseases. We constructed a recombinant adenoviral vector carrying FLAG-tagged sFlt-1(1-3) (the first three extracellular domains of Flt-1, the hVEGF receptor-1). Intramuscular transfection of the recombinant adenoviral vector suppressed VEGF-induced inflammatory cell infiltration in matrigel plugs. When given intracerebrally to EAE rats, recombinant sFlt-1(1-3) adenoviral vector significantly reduced disease severity compared to untreated rats. sFlt-1(1-3) gene transfer blocked VEGF and greatly reduced the number of cells that express VEGF and ED1-positive cells in CNS in EAE rats. This study demonstrates that sFlt-1(1-3) gene transfer into the brain ameliorates the severity of EAE by inhibiting monocyte recruitment in the CNS of dark Agouti rats.
18,721,816
Native glycine receptor subtypes and their physiological roles.
The glycine receptor chloride channel (GlyR), a member of the pentameric Cys-loop ion channel receptor family, mediates inhibitory neurotransmission in the spinal cord, brainstem and retina. They are also found presynaptically, where they modulate neurotransmitter release. Functional GlyRs are formed from a total of five subunits (alpha1-alpha4, beta). Although alpha subunits efficiently form homomeric GlyRs in recombinant expression systems, homomeric alpha1, alpha3 and alpha4 GlyRs are weakly expressed in adult neurons. In contrast, alpha2 homomeric GlyRs are abundantly expressed in embryonic neurons, although their numbers decline sharply by adulthood. Numerous lines of biochemical, biophysical, pharmacological and genetic evidence suggest the majority of glycinergic neurotransmission in adults is mediated by heteromeric alpha1beta GlyRs. Immunocytochemical co-localisation experiments suggest the presence of alpha2beta, alpha3beta and alpha4beta GlyRs at synapses in the adult mouse retina. Immunocytochemical and electrophysiological evidence also implicates alpha3beta GlyRs as important mediators of glycinergic inhibitory neurotransmission in nociceptive sensory neuronal circuits in peripheral laminae of the spinal cord dorsal horn. It is yet to be determined why multiple GlyR synaptic subtypes are differentially distributed in these and possibly other locations. The development of pharmacological agents that can discriminate strongly between different beta subunit-containing GlyR isoforms will help to address this issue, and thereby provide important insights into a variety of central nervous system functions including retinal signal processing and spinal pain mechanisms. Finally, agents that selectively potentiate different GlyR isoforms may be useful as therapeutic lead compounds for peripheral inflammatory pain and movement disorders such as spasticity.
18,721,822
Ultrasound-guided near-nerve neurography for early evaluation of nerve regeneration.
For early assessment of axonal outgrowth after trauma, the nerve is surgically exposed to enable compound nerve action potential (CNAP) recordings across the lesion site. Near-nerve neurography, with needle electrodes placed transcutaneously near the nerve, could be a minimally invasive alternative if the needle placement procedure and low reproducibility are improved. We developed ultrasound-guided near-nerve neurography, which facilitates needle placement, and assessed its potential for evaluating nerve regeneration. Measurements were performed at varying times after crush lesion of the peroneal nerve of 25 rabbits. To test if ultrasound-guided near-nerve signals could be measured prior to muscle reinnervation, they were compared with recordings of compound muscle action potentials. A comparison with conventional intra-operative CNAP recordings was made by measuring nerve signal amplitude with both techniques and by assessing reproducibility. In all cases where intra-operative signals could be measured, near-nerve signals were also detected. Compound nerve activity could be recorded after 5 weeks, whereas compound muscle activity appeared after approximately 8 weeks. Reproducibility was slightly better for near-nerve than for intra-operative recordings. We conclude that ultrasound-guided near-nerve neurography is able to assess nerve regeneration well before compound muscle activity can be detected. Its accuracy and reproducibility are similar to those of conventional intra-operative recordings.
18,721,825
FISH-eyed and genome-wide views on the spatial organisation of gene expression.
Eukaryotic cells store their genome inside a nucleus, a dedicated organelle shielded by a double lipid membrane. Pores in these membranes allow the exchange of molecules between the nucleus and cytoplasm. Inside the mammalian cell nucleus, roughly 2 m of DNA, divided over several tens of chromosomes is packed. In addition, protein and RNA molecules functioning in DNA-metabolic processes such as transcription, replication, repair and the processing of RNA fill the nuclear space. While many of the nuclear proteins freely diffuse and display a more or less homogeneous distribution across the nuclear interior, some appear to preferentially cluster and form foci or bodies. A non-random structure is also observed for DNA: increasing evidence shows that selected parts of the genome preferentially contact each other, sometimes even at specific sites in the nucleus. Currently a lot of research is dedicated to understanding the functional significance of nuclear architecture, in particular with respect to the regulation of gene expression. Here we will evaluate evidence implying that the folding of DNA is important for transcriptional control in mammals and we will discuss novel high-throughput techniques expected to further boost our knowledge on nuclear organisation.
18,721,832
BioTimer Assay, a new method for counting Staphylococcus spp. in biofilm without sample manipulation applied to evaluate antibiotic susceptibility of biofilm.
The medical device-related infections are frequently a consequence of Staphylococcus biofilm, a lifestyle enhancing bacterial resistance to antibiotics. Antibiotic susceptibility tests are usually performed on planktonic forms of clinical isolates. Some methods have been developed to perform antibiotic susceptibility tests on biofilm. However, none of them counts bacterial inoculum. As antibiotic susceptibility is related to bacterial inoculum, the test results could be mistaken. Here, a new method, BioTimer Assay (BTA), able to count bacteria in biofilm without any manipulation of samples, is presented. Moreover, the BTA method is applied to analyze antibiotic susceptibility of six Staphylococcus strains in biofilm and to determine the number of viable bacteria in the presence of sub-inhibitory doses of four different antibiotics. To validate BTA, the new method was compared to reference methods both for counting and antibiotic susceptibility tests. A high agreement between BTA and reference methods is found on planktonic forms. Therefore, BTA was employed to count bacteria in biofilm and to analyze biofilm antibiotic susceptibility. Results confirm the high resistance to antibiotics of Staphylococcus biofilm. Moreover, BTA counts the number of viable bacteria in the presence of sub-inhibitory doses of antibiotics. The results show that the number of viable bacteria depends on sub-inhibitory doses, age of biofilm and type of antibiotic. In particular, differently to gentamicin and ampicillin, sub-inhibitory doses of ofloxacin and azithromycin reduce the number of viable bacteria at lower extent in young than in old biofilm. In conclusion, BTA is a reliable, rapid, easy-to-perform, and versatile method, and it can be considered a useful tool to analyze antibiotic susceptibility of Staphylococcus spp. in biofilm.
18,721,833
Exaggerated feedback control decreases brain serotonin concentration and elicits hyperactivity in a rat model of diet-restriction-induced anorexia nervosa.
5-Hydroxytryptamine (5-HT; serotonin) system is the major neurotransmitter system of interest in research on anorexia nervosa (AN). The AN patients show extreme dieting weight loss, hyperactivity and low basal levels of 5-hydroxyindoleacetic acid (5-HIAA), a major metabolite of 5-HT in the cerebrospinal fluid (CSF). Studies on animal models show that diet restriction (DR) decreases 5-HT metabolism in the brain and hypothalamus which is not necessarily associated with a decrease in the availability of essential amino acid tryptophan (TRP) the precursor of serotonin. To further investigate the mechanism involved in DR-induced decreases of 5-HT the present study uses 8-hydroxy-(2-di-n-propylamino) tetralin (8-OH-DPAT), a selective 5-HT-1A agonist, as a probe to monitor the responsiveness of negative feedback control over 5-HT metabolism. Effects of DR and of 8-OHDPAT on TRP, 5-HT and 5-HIAA concentrations are determined in the hypothalamus, a region of the brain known to role in the regulation of appetite. Animals of DR group given access to food 2h daily for 6 days exhibited 21.6% decrease in the body weight compared to freely feeding (FF) controls. The levels of TRP in the plasma and of 5-HT in the hypothalamus decreased. No effect was found on the levels of TRP in the hypothalamus. 8-OH-DPAT-induced decreases of 5-HT and 5-HIAA were greater in DR than FF group. 8-OH-DPAT-induced hyperactivity was also greater in DR than FF group. The results show that DR-induced decreases of 5-HT are due to an increase in the responsiveness of negative feedback control over 5-HT and not due to smaller availability of TRP. DR-induced increase in activity and 8-OH-DPAT-induced greater hyperactivity in DR than FF group may also be due to exaggerated negative feedback control over 5-HT. It is suggested that drugs decreasing the responsiveness of negative feedback control over 5-HT may be of use for the treatment and prevention of AN in under weight patients on restricted diet.
18,721,836
Patterns of mood changes throughout the reproductive cycle in healthy women without premenstrual dysphoric disorders.
The cyclic nature of female reproductive function is a natural part of life accompanied by changes in several physical and psychological phenomena. The aim of our study was to investigate the fluctuation of psychological symptoms throughout the female reproductive cycle in healthy, non-PMDD (premenstrual dysphoric disorder) women. 63 psychiatrically healthy, non-PMDD women with normal regular menstrual cycles and not using hormonal contraceptive methods participated in the study. Participants completed the PRISM (Prospective Record of the Impact and Severity of Menstrual Symptoms) calendar every night for three cycles and in addition they completed several other psychometric measures (Symptom Distress Checklist-SCL-51, State Trait Anxiety Inventory-STAI, Zung Self-rating Depression Scale-ZSDS, Eating Attitude Test-EAT, Mind and Body Cathexis Scale) at three predefined days of the first cycle. Based on an at least 66% increase in physical symptoms from the late follicular to the late luteal phase on the PRISM, subjects were assigned to luteal phase physical symptoms (LPPS) and no luteal phase physical symptoms (nonLPPS) groups. The association of psychometric scores with timing within the cycle and with physical symptoms was analysed. Significant changes in psychometric scores over time were observed for STAI state anxiety, SCL anxiety, SCL somatization, SCL depression, SCL obsessive-compulsive, SCL interpersonal sensitivity, SCL total, and ZSDS. A significant timexLPPS grouping interaction emerged in case of the SCL somatization subscale and the ZSDS. LPPS grouping was associated with only the interpersonal sensitivity subscale of the SCL51. Our results indicate that there is a significant increase in psychological symptoms related to neuroticism and depression from the late follicular to the late luteal phase in a healthy, non-PMDD female population. Although our results may not have direct clinical significance, since the statistically significant increases in psychometric scores are still small, it is an important finding that there is a consistent pattern observable in the fluctuation of psychological symptoms accompanying the female reproductive cycle.
18,721,843
Association between BDNF Val66Met polymorphism and trait depression is mediated via resting EEG alpha band activity.
A functional polymorphism of the brain-derived neurotrophic factor, BDNF Val66Met, is associated with risk for major depression alongside impairments in memory and selective attention. This study aims to identify the mediating neural mechanisms in links between BDNF and depression using highly heritable electroencephalographic (EEG) recordings. In 305 healthy subjects, BDNF Val66Met genotypes were compared in terms of trait depression, neural function (EEG during a resting state) and cognitive performance. The mediating effects of the EEG brain imaging endophenotypes were also examined using structural equation (path) modeling. A genotype-endophenotype-phenotype path model showed that Met homozygosity predicted elevated working memory commission errors and altered EEG activity; that is elevated relative theta and delta power coupled with reduced alpha power. In turn, reduced EEG alpha activity mediated the relationship between the Met/Met genotype and trait depression. These findings demonstrate the utility of an integrative endophenotype approach. They suggest that the BDNF Met/Met homozygote has a direct impact on memory systems, but impacts trait depression via the secondary effects of neural changes.
18,721,847
Lacunarity as a novel measure of cancer cells behavior.
An important goal in many branches of science, especially in molecular biology and medicine is the quantitative analysis of the structures and their morphology. The morphology can be analyzed in many ways, in particular by the fractal analysis. Apart from the fractal dimension, an important part of the fractal analysis is the lacunarity measurement which, roughly speaking, characterizes the distribution of gaps in the fractal: a fractal with high lacunarity has large gaps. In this paper, we present an extension of the lacunarity measure to objects with nonregular shapes that enables us to provide a successful discrimination of cancer cell lines. The cell lines differ in the shape of vacuole (the gaps in their body) which is perfectly suited for the lacunarity analysis.
18,721,854
Staphylococcal enterotoxin B causes differential expression of Rnd3 and RhoA in renal proximal tubule epithelial cells while inducing actin stress fiber assembly and apoptosis.
Staphylococcal enterotoxin B (SEB) is a toxic shock-inducing agent produced by Staphylococcus aureus. The hallmark of SEB-induced lethal shock is acute vasodilation leading to severe hypotension. Animal studies reveal that approximately 70% of intravenously administered toxin localizes to renal proximal tubule epithelial cells (RPTEC). This evidence, together with the well-documented role of the kidney in regulation of vascular tone, suggests that molecular events induced in RPTEC by SEB may contribute to the blood pressure dysregulation seen in enterotoxic shock. In an attempt to elucidate these molecular mechanisms, differential display was performed on SEB-treated and untreated RPTEC, and 32 differentially expressed transcripts (DETs) were identified. One of the down-regulated DETs matched the sequence for Rnd3, which normally inhibits Rho protein function. Consistent with Rnd3 down-regulation, message for RhoA was shown to increase upon SEB exposure, and actin stress fiber formation was dramatically increased. Further, SEB-exposed cells showed both increased enzymatic activity of caspase-3 and an increase in the percentage of apoptotic cells. Taken together, these results support the hypothesis that RPTEC undergo apoptosis upon exposure to SEB. Furthermore, these data implicate the involvement of the Rho family proteins in the molecular signaling pathway induced by SEB in RPTEC.
18,721,871
Vaidurya: a multiple-ontology, concept-based, context-sensitive clinical-guideline search engine.
We designed and implemented a generic search engine (Vaidurya), as part of our Digital clinical-Guideline Library (DeGeL) framework. Two search methods were implemented in addition to full-text search: (1) concept-based search, which relies on pre-indexing the guidelines in a clinically meaningful fashion, and (2) context-sensitive search, which relies on first semi-structuring the guidelines according to a given ontology, then searching for terms within specific labeled text segments. The Vaidurya engine is fully functional and is used within the DeGeL system. We describe the Vaidurya ontological and algorithmic framework; we also briefly summarize the results of a detailed evaluation in the clinical-guideline domain, demonstrating that both concept-based and context-sensitive ontology-independent search are highly feasible and significantly improve on free text search retrieval performance. We conclude by analyzing the limitations and advantages of the approach, and the steps that we have started to take to extend it based on user feedback.
18,721,900
Overview: the neurochemistry of respiratory control.
This special issue of Respiratory Physiology and Neurobiology surveys a broad range of topics focused on the neurochemical control of breathing. A variety of approaches have integrated the neurochemistry of breathing with the physiology of individual neurons, with the neuroanatomy of brainstem and forebrain respiratory circuits, and with the clinical pathology of respiratory disorders all of which has been fueled by the ongoing explosion of information in the molecular biology of the nervous system. Accordingly, substantial progress has identified neurotransmitters, neuromodulators, receptors, signaling cascades, trophic factors, hormones, and genes mediating normal and pathological breathing. Dynamic changes in the neurochemistry of breathing are addressed with respect to brainstem development, environmental challenges such as intermittent or chronic hypoxia, and as a function of the sleep-wake cycle. Respiratory disruption has also been identified in an increasing variety of genetic-based disorders and remarkable progress has been made in determining the affected genes and their mutations that negatively impact respiration.
18,721,910
Aberrant expression of ovary determining gene FOXL2 in the testis and juvenile granulosa cell tumor in children.
FOXL2 is the earliest known marker of ovarian differentiation in mammals. It is involved in ovarian somatic cell differentiation and further follicle maintenance. FOXL2 is not implicated in determination of the male gonad and it is absent in the testis. We investigated whether the rare JGCTT (juvenile granulose cell tumor of the testis), named for its histological similarity to ovarian tumor, could be the first illustration of aberrant expression of this ovary determining gene in the human testis. Between 1990 and 2004, 3 boys with JGCTT were reported from the TGM95 database of the French Society for Childhood Cancer and from 8 pediatric endocrinology centers. Orchiectomy was performed in these patients. Immunohistochemistry of FOXL2, and co-immunofluorescence of FOXL2 and SOX9 were performed on tumor sections. Testicular tumor cells showed aberrant expression of FOXL2, which resembled normal ovarian granulosa cells. The localization of FOXL2 expression was nuclear without any cytoplasmic sequestration, suggesting that FOXL2 had biological activity. Conversely SOX9, which is present in the nucleus of normal testicular cells, was sequestered in the cytoplasm of granulosa tumor cells or markedly under expressed in the nuclei. In this case of residual SOX9 nuclear expression the expression of FOXL2 and SOX9 was mutually exclusive. To our knowledge we report the first human model of aberrant intratesticular expression of an ovary determining gene along with the extinction of SOX9 and the transdifferentiation of a testicular cell into a granulosa tumor cell.
18,721,930
Management of urachal remnants in early childhood.
Generally, it is recommended that all urachal remnants be excised to avoid recurrent disease and possible malignant transformation later in life. However, spontaneous resolution with no need for further intervention has been reported. We reviewed the experience with urachal remnants at a single institution and evaluated which patients could be treated nonoperatively and which required surgical intervention. We reviewed the medical records and radiographic studies of all patients with urachal remnants from January 1999 to January 2007. Patients were analyzed according to initial presentation, imaging findings and treatment. Serial clinical examinations and radiographic imaging were used to follow patients. An external urachal sinus was found in 9 patients (39.1%) and 1 was surgically excised. Of the 12 urachal cysts (52.2%) 9 ultimately required surgical excision, of which 6 were infected initially. A patent urachus was found in 2 patients, which resolved during an observation period. Radiographic imaging and/or physical examination diagnosed all remnants initially and confirmed complete resolution during followup. Eight of the 10 urachal remnants (80.0%) that resolved developed in patients younger than 6 months. Various accompanying urogenital anomalies were found in 8 patients (34.8%). A small urachal remnant, especially at birth, may be viewed as physiological. Urachal remnants in patients younger than 6 months are likely to resolve with nonoperative management. However, if symptoms persist or the urachal remnant fails to resolve after 6 months of age, it should be excised to prevent recurrent infections.
18,721,938
Development and validation of the fecal incontinence and constipation quality of life measure in children with spina bifida.
Fecal incontinence and constipation in children with spina bifida are recognized to impact quality of life. Most disease specific quality of life instruments on fecal incontinence target adults and/or children without neuropathic bowel. We developed an instrument to evaluate bowel function and its impact on quality of life in children with spina bifida and their caregivers. A 51-item questionnaire termed the FIC QOL (Fecal Incontinence and Constipation Quality of Life) survey was developed from expert opinion, patient interviews, and modification of previously published adult and pediatric studies for nonneuropathic bowel dysfunction. The items are divided into 7 quality of life factor groupings, including bowel program, dietary management, symptoms, travel and socialization, family relationships, caregiver emotional impact and financial impact. The questionnaire was given to caregivers of children with and without spina bifida. Discriminant validity was evaluated by comparing the spina bifida and control groups. Test-retest reliability was evaluated by having 41 patients complete 2 surveys within 4 to 6 weeks. Comparing questionnaires from 92 index patients and 52 controls showed a statistically significant difference for all 7 quality of life factor groupings. The FIC QOL instrument objectively demonstrated the negative impact of fecal incontinence and constipation on quality of life in these families. Comparing 82 questionnaires at 2 time points demonstrated the reliability of all FIC QOL questions. The FIC QOL instrument provides a valid and reliable measure of the effect of fecal incontinence and constipation on the quality of life of caregivers and their children with spina bifida.
18,721,959
Construction of a natural looking inverted umbilicus for bladder exstrophy.
Most attempts to create an umbilicus in the exstrophy abdomen eventually leave the end result of a flat scar rather than an inverted structure. We describe a technique that allows the creation of a better looking inverted umbilicus. A total of 19 patients between 5 days and 7 years old underwent umbilicoplasty. At the apex of the vertical midline wound the skin and superficial fascia are elevated off the anterior rectus sheath well beyond the top of the skin incision. The skin edge at the most superior apex of the wound is sutured to the linea alba, thereby inverting the skin and fixing it to the sheath. Two skin flaps based superiorly are cut from the margin of the inverted skin. The flaps are then rotated medial and sutured to the linea alba to form the base of the new umbilicus. The superficial fascia inferior to the umbilicus is opposed and the skin edges are approximated. A total of 18 patients had bladder exstrophy and 1 had cloacal exstrophy. Of the patients 11 underwent bladder/cloacal exstrophy closure, 3 underwent epispadias repair, 3 underwent bladder neck repair, and 2 underwent bladder augmentation and continent cutaneous diversion. Mean +/- SD followup was 6 +/- 4 months. The technique allowed the creation of an inverted umbilicus in all patients. None experienced infection or dehiscence. The cosmetic result obtained was excellent and durable. We recommend the creation of an inverted umbilicus in the exstrophy population at bladder closure or later in life if umbilicoplasty is required.
18,721,975
[Piezosurgery for genioglossal advancement in treatment of obstructive sleep apnea syndrome].
The tongue is a frequent cause of upper airway obstruction in obstructive sleep apnea syndrome. The genioglossi muscles are the front-most muscles of the tongue, attached to the geniotubercle on the inner cortical of the mandibular symphisis. The collapsibility of the tongue can be managed with genioglossus advancement. Piezo surgery can decrease the risk of apical dental lesion. The perfect depth control during osteotomy and absence of soft tissue lesion considerably limit the risks of oral floor lesion.
18,721,994
Homologous recombination evidence in human and swine influenza A viruses.
Dynamic gene mutation and the reassortment of genes have been considered as the key factors responsible for influenza A virus virulence and host tropism change. This study reports several significant evidence demonstrating that homologous recombination also takes place between influenza A viruses in human and swine lineages. Moreover, in a mosaic descended from swine H1N1 subtype and human H2N2, we found that its minor putative parent might be a derivative from the human cold-adapted vaccine lineage, which suggests that live vaccine is capable of playing a role in genetic change of influenza A virus via recombination with circulating viruses. These results would be important for knowing the molecular mechanism of mammal influenza A virus heredity and evolution.
18,721,995
SATB1 is required for CD8 coreceptor reversal.
Intrathymic signals induce the differentiation of immature CD4(+)CD8(+) double positive (DP) thymocytes into mature CD4(+) or CD8(+) single positive (SP) T cells. The transcriptional mechanism by which CD8 lineage is determined is not fully understood. The best evidence, which favors the kinetic signaling/coreceptor reversal model, indicates that signaled DP thymocytes terminate CD8 transcription prior to their subsequent re-initiation of CD8 transcription and ultimate differentiation into CD8SP T cells. We and others have shown that CD8 lineage commitment is severely perturbed in mice in which expression of the transcription factor SATB1 is either conventionally knocked out or T cell-specifically knocked down. Here, we demonstrate that, as with normal thymocytes, cultured SATB1-deficient DP thymocytes inactivate CD8 coreceptor transcription following receipt of signals (PMA plus ionomycin) that mimic TCR-mediated positive selection. However, this terminated CD8 transcription is not re-initiated by signals (IL-7) conducive to CD8 differentiation in SATB1-deficient DP. We show that SATB1 specifically binds to a cis-regulatory element within the CD8 enhancer (E8(III)) known to be required for coreceptor reversal. A requirement in CD8 coreceptor reversal identifies SATB1 as an essential trans-regulator of CD8 lineage fate, whose action may be mediated via recruitment to the E8(III) DP enhancer.
18,722,016
The association of social support at work and in private life with mental health and antidepressant use: the Health 2000 Study.
Social support is assumed to protect mental health, but it is not known whether low social support at work increases the risk of common mental disorders or antidepressant medication. This study, carried out in Finland 2000-2003, examined the associations of low social support at work and in private life with DSM-IV depressive and anxiety disorders and subsequent antidepressant medication. Social support was measured with self-assessment scales in a cohort of 3429 employees from a population-based health survey. A 12-month prevalence of depressive or anxiety disorders was examined with the Composite International Diagnostic Interview (CIDI), which encompasses operationalized criteria for DSM-IV diagnoses and allows the estimation of DSM-IV diagnoses for major mental disorders. Purchases of antidepressants in a 3-year follow-up were collected from the nationwide pharmaceutical register of the Social Insurance Institution. Low social support at work and in private life was associated with a 12-month prevalence of depressive or anxiety disorders (adjusted odds ratio 2.02, 95% CI 1.48-2.82 for supervisory support, 1.65, 95% CI 1.05-2.59 for colleague support, and 1.62, 95% CI 1.12-2.36 for private life support). Work-related social support was also associated with subsequent antidepressant use. This study used a cross-sectional analysis of DSM-IV mental disorders. The use of purchases of antidepressant as an indicator of depressive and anxiety disorders can result in an underestimation of the actual mental disorders. Low social support, both at work and in private life, is associated with DSM-IV mental disorders, and low social support at work is also a risk factor for mental disorders treated with antidepressant medication.
18,722,019
Medicine access and utilization in a population covered by primary health care in Brazil.
To describe medicine utilization and access in a population covered by the Family Health Program (PSF) in Brazil. Cross-sectional study with a random sample of 2988 individuals living in areas covered by 45 PSF clinics. Medicine utilization in the 15 days prior to the interview was assessed, as well as lack of access to medicines (proportion of people with medicines needed but not used), and lack of free access through the PSF (proportion of medicines used which had to be purchased). Overall, 54.5% (95% CI 50.6; 58.4) of individuals used at least one medicine in the 15-day period and 3.6% reported failing to use a needed medicine. Of all medicines used, 41.5% were paid for out-of-pocket (25.5% among the poorest families), and 51.0% were obtained for free from the PSF. Almost 90% of the medicines prescribed by PSF physicians were provided for free by the PSF. Although medicine access was high, individuals paid out-of-pocket for a substantial proportion of the medicines used. Lack of availability in PSF facilities and prescribing by non-PSF providers seem to contribute to the need for out-of-pocket purchases, and thus can be targeted for improvement through PSF policies.
18,722,031
Supported Cu(II) polymer catalysts for aqueous phenol oxidation.
Supported Cu(II) polymer catalysts were used for the catalytic oxidation of phenol at 30 degrees C and atmospheric pressure using air and H(2)O(2) as oxidants. Heterogenisation of homogeneous Cu(II) catalysts was achieved by adsorption of Cu(II) salts onto polymeric matrices (poly(4-vinylpyridine), Chitosan). The catalytic active sites were represented by Cu(II) ions and showed to conserve their oxidative activity in heterogeneous catalysis as well as in homogeneous systems. The catalytic deactivation was evaluated by quantifying released Cu(II) ions in solution during oxidation, from where Cu-PVP(25) showed the best leaching levels no more than 5 mg L(-1). Results also indicated that Cu-PVP(25) had a catalytic activity (56% of phenol conversion when initial Cu(II) catalytic content was 200 mg L(Reaction)(-1)) comparable to that of commercial catalysts (59% of phenol conversion). Finally, the balance between activity and copper leaching was better represented by Cu-PVP(25) due to the heterogeneous catalytic activity had 86% performance in the heterogeneous phase, and the rest on the homogeneous phase, while Cu-PVP(2) had 59% and CuO/gamma-Al(2)O(3) 68%.
18,722,052
[Routine use of extended-release clarithromycin tablets for short-course treatment of acute exacerbations of non-severe COPD].
This study was designed to confirm, in routine clinical practice conditions, the success rates and safety of extended-release clarithromycin tablets in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD), according to the usual empirical criteria in routine clinical practice. An open-label, pharmacoepidemiological, clinical study in community practice was performed with 180 practitioners. The bacterial origin was suspected when sputum was obviously purulent. Seven hundred and nineteen adult patients with acute exacerbation of mild or moderately severe COPD were included. A favorable clinical course of the exacerbation was observed in 92.5% of cases, with resolution of frankly purulent sputum in 99% of cases, associated with good tolerance. These results confirm the value of extended-release clarithromycin tablets as first-line treatment for presumed bacterial exacerbation of mild or moderately severe, stable COPD according to the Société de pathologie infectieuse de langue française consensus.
18,722,065
Qualitative and quantitative analysis of four species of Curcuma rhizomes using twice development thin layer chromatography.
The rhizomes of Curcuma phaeocaulis, Curcuma kwangsiensis, Curcuma wenyujin and Curcuma longa are used as Ezhu or Jianghuang in traditional Chinese medicine for a long time. Due to their similar morphological characters, it is difficult to distinguish their origins of raw materials used in clinic. In this study, a simple, rapid and reliable twice development TLC method was developed for qualitative and quantitative analysis of the four species of Curcuma rhizomes. The chromatography was performed on silica gel 60F(254) plate with chloroform-methanol-formic acid (80:4:0.8, v/v/v) and petroleum ether-ethyl acetate (90:10, v/v) as mobile phase for twice development. The TLC markers were colorized with 1% vanillin-H(2)SO(4) solution. The four species of Curcuma were easily discriminated based on their characteristic TLC profiles, and simultaneous quantification of eight compounds, including bisdemethoxycurcumin, demethoxycurcumin, curcumine, curcumenol, curcumol, curdione, furanodienone and curzerene, in Curcuma were also performed densitometrically at lambda(scan)=518nm and lambda(reference)=800 nm. The investigated compounds had good linearity (r(2)>0.9905) within test ranges. Therefore, the developed TLC method can be used for quality control of Curcuma rhizomes.
18,722,068
Presenting health risk information in different formats: the effect on participants' cognitive and emotional evaluation and decisions.
Effective communication of health risks plays an important role in enabling patients to make adequate decisions. There is little--though contradictory--evidence to indicate which format is most effective for communicating risks, and which risk format is preferred by counselees. In an experiment, subjects were presented health scenarios and risk information in different formats (percentages, frequencies, and population figures) and asked to evaluate the risks and make a decision based on these. Different risk formats had different effects on respondents' evaluation of the health risks presented. Contrary to our expectation, population figures were not evaluated as being the easiest format for all decision problems. Population figures were shown to have the biggest affective impact, and risks presented as population figures were also evaluated as significantly greater than the risks presented in other formats. The format of the presented risks influenced their decision in only one out of four decision-making situations, although in a second situation there was a similar trend. This study suggests that the risk format plays a role in the decision-making process, although it remains unclear which format is the most effective in terms of understanding. More experimental studies based on a theoretical analysis of the factors that promote effective risk communication are needed in the general population as well as in clinical settings with patients actually experiencing the risks and making the decisions.
18,722,073
Audit and feedback using the brief Decision Support Analysis Tool (DSAT-10) to evaluate nurse-standardized patient encounters.
To evaluate the brief Decision Support Analysis Tool (DSAT-10) for auditing the quality of nurse-standardized patient encounters, structuring feedback for nurses, and testing instrument reliability. A systematic process was used to develop standardized patient scenarios, pilot-test scenarios, calibrate DSAT-10 coders, analyze taped telephone encounters using DSAT-10, and provide feedback. Inter-rater reliability was calculated using coder agreement, kappa, and intra-class correlation coefficients. Six scenarios portrayed patients' decisional uncertainty from either: pressure from others (n=2), unclear values (n=2), or inadequate information (n=2). Scenarios were easy to use over the telephone, produced realistic role performance, and were practical for audio-recording interactions. DSAT-10 analysis of 76 nurse-standardized patient encounters revealed nurses' strengths (e.g., information provision) and their limitations (e.g., lack of discussion of values and/or support needs). Scores discriminated between trained and untrained nurses. The kappa coefficient over all items was 0.55 (95% CI: 0.49, 0.61) with higher agreement for encounters involving trained nurses (0.62; 95% CI: 0.43, 0.80). Auditing nurse-standardized patient encounters using DSAT-10 and providing feedback to nurses was feasible. Although DSAT-10 items had adequate inter-rater reliability and discriminated between trained/untrained nurses, some items were problematic. Providing feedback on nurse encounters with standardized patients experiencing uncertainty has the potential to enhance nurses' decision support skills.
18,722,074
Adapting Washington Circle performance measures for public sector substance abuse treatment systems.
The Washington Circle, a group focused on developing and disseminating performance measures for substance abuse services, developed three such measures for private health plans. In this article, we explore whether these measures are appropriate for meeting measurement goals in the public sector and feasible to calculate in the public sector using data collected for administrative purposes by state and local substance abuse and/or mental health agencies. Working collaboratively, 12 states specified revised measures and 6 states pilot tested them. Two measures were retained from the original specifications: initiation of treatment and treatment engagement. Additional measures were focused on continuity of care after assessment, detoxification, residential or inpatient care. These data demonstrate that state agencies can calculate performance measures from routinely available information and that there is wide variability in these indicators. Ongoing research is needed to examine the reasons for these results, which might include lack of patient interest or commitment, need for quality improvement efforts, or financial issues.
18,722,075
The fidelity of treatment delivery can be assessed in treatment outcome studies: a successful illustration from behavioral medicine.
Treatment outcome studies ought to assess the fidelity of their treatments, including treatment delivery, but practical guidelines and examples for this are lacking. Based on general recommendations in available literature, this study proposes and illustrates the design and application of a Method of Assessing Treatment Delivery (MATD) in a behavioral medicine trial comparing two treatments for chronic low back pain. In designing MATD, two experts identified several feasible treatment elements. Agreement between the experts in classifying these elements into five categories (essential and unique, essential but not unique, unique but not essential, compatible, prohibited) was assessed. In applying MATD, treatment recordings were evaluated by two independent raters, who coded the (non)-occurrence of MATD elements and who categorized each session as belonging to one of the two treatments. MATDs content validity was supported by adequate agreement between the experts' classifications of the treatment elements. MATDs interrater reliability was good. Comprehensive illustrations of designing and applying MATD may encourage the verification of treatment delivery as a partial reflection of treatment fidelity in forthcoming treatment outcome studies.
18,722,086
Direct electrochemistry of hemoglobin on carbonized titania nanotubes and its application in a sensitive reagentless hydrogen peroxide biosensor.
Carbonized TiO(2) nanotubes (TNT/C) prepared by carbonization with organic polymers possess advantages combined from high conductivity of carbon and nanostructure of TiO(2) nanotubes. The material was used as a supporting matrix to immobilize a redox protein, hemoglobin (Hb), to explore its direct electron transfer ability. The apparent heterogeneous electron transfer rate constant (k(ET)) of Hb on TNT/C is 108s(-1), which is much higher than that in the reported works, demonstrating excellent direct electrochemistry behavior. The TNT/C-Hb modified glassy carbon electrode (GCE) demonstrates significant electrocatalytic activity for reduction of hydrogen peroxide with a small apparent Michaelis-Menten constant (87.5 microM). The TNT/C-Hb based H(2)O(2) sensor has a low detection limit (0.92 microM), fast response time (3s) and high dynamic response range (10(-6) to 10(-4)M), a much better performance than the reported works. These results demonstrate that a direct electrochemistry behavior can be significantly enhanced through simple carbon coating on a nanostructured material for higher reaction surface area and better conductivity. This work suggests that Hb-immobilized TNT/C has potential applications in a sensitive H(2)O(2) sensor.
18,722,103
Expression of integrin-linked kinase and its binding partners in chondrosarcoma: association with prognostic significance.
Integrin-linked kinase (ILK) and its binding partners alpha-parvin, beta-parvin, Mig-2 and Migfilin are important components of the cell-matrix adhesions implicated in cell motility, growth, survival and ultimately carcinogenesis. Herein, we investigated immunohistochemically the expression of these molecules in cartilaginous neoplasms and explored their involvement in chondrosarcoma pathobiology and behaviour. Our analyses revealed that ILK, alpha-parvin, beta-parvin and Mig-2 are expressed in the majority of chondrosarcomas but in a small proportion of enchondromas, implying that these proteins might have a role in the development and progression of chondrogenic neoplasms. Moreover, our findings highlight the possibilities that ILK might serve as biological marker that could accurately predict a high-grade tumour and that Mig-2 may function as a promising prognostic indicator of high-risk patients.
18,722,108
Is robotic surgery appropriate for vascular procedures? Report of 100 aortoiliac cases.
The aim of our study was to evaluate our clinical experience of the da Vincitrade mark system for robot-assisted aortoiliac reconstructions to treat occlusive disease and aneurysm. Between November 2005 and January 2008 100 consecutive patients were scheduled to undergo robot-assisted laparoscopic aortoiliac procedures. Patients with serious medical problems and those who had previously undergone major abdominal surgery were excluded from the clinical study. Ninety patients were prospectively evaluated for arterial occlusive disease (AOD), seven patients for abdominal aortic aneurysms (AAA), two for common iliac artery aneurysms (CIAA) and one for a combination of CIAA and AOD. Ninety-seven of 100 procedures (97%) were successfully completed robotically, while conversions were necessary in three patients (3%). The median operating time was 235 minutes (range 150 to 360 minutes), with a median clamp-time of 42 minutes (range 25 to 120 minutes). The median anastomosis time was 29 minutes (range 12 to 60 minutes) and median blood loss was 430mL (range 50 to 1500mL). The median intensive care unit stay was 1.7 days and the median hospital stay was 5.1 days. A regular oral diet was resumed after a mean of 2.4 days. Thirty-day survival was 100% and non-lethal postoperative complications were observed in three patients (3%). Robotic aortoiliac surgery appears to be safe, with a high technical success rate, with operative times and success rates comparable to conventional open surgery. The creation of the aortoiliac anastomosis appears to be quicker, and more accurate than regular laparoscopic techniques.
18,722,141
Inequality in obesigenic environments: fast food density in New York City.
The high prevalence of obesity in African American populations may be due to the food environment in residential communities, and the density of fast food restaurants is an important aspect of the restaurant landscape in US cities. This study investigated racial and socioeconomic correlates of fast food density in New York City. We found that predominantly Black areas had higher densities of fast food than predominantly White areas; high-income Black areas had similar exposure as low-income Black areas; and national chains were most dense in commercial areas. The results highlight the importance of policy level interventions to address disparities in food environments as a key goal in obesity prevention efforts.
18,722,151
Voltammetric and spectroscopic studies on binding of antitumor Morin, Morin-Cu complex and Morin-beta-cyclodextrin with DNA.
A systematic comparative study of the binding of antitumor Morin and its complexes with DNA has been investigated in the Britton-Robison (BR) buffer solutions using voltammetric and spectroscopic methods. The results show that Morin molecule, acting as an intercalator, is inserted into the cavity of the beta-cyclodextrin (beta-CD) as well as into the base stacking domain of the DNA double helix. The interaction of Morin-Cu complex or the inclusion complex of Morin-beta-CD with ds-DNA causes hypochromism in the absorption spectra, along with pronounced changes in the electrochemical behavior of the Morin complexes. An isobestic point and a new spectrum band appeared indicating the formation of the new system of Morin-Cu-DNA at lambda(m)=391 nm and Morin-beta-CD-DNA at lambda(m)=375 nm. The intercalation of Morin-Cu and Morin-beta-CD complexes with DNA produces an electrochemically inactive supramolecular complex. The binding constants were calculated from the increase of the solubility, the strong hypochromism, and the decrease in peak current of Morin and its complexes upon the addition of the host molecules. Calculation of the thermodynamic parameters of the interaction of the inclusion complex of Morin-beta-CD with DNA, including Gibbs free energy change, Helmholz free energy and entropy change shows that the complexation is a spontaneous process of association.
18,722,155
Physical, chemical and in vitro biological profile of chitosan hybrid membrane as a function of organosiloxane concentration.
We attempted to prepare chitosan-silicate hybrid for use in a medical application and evaluated the physico-chemical properties and osteocompatibility of the hybrids as a function of gamma-glycidoxypropyltrimethoxysilane (GPTMS) concentration. Chitosan-silicate hybrids were synthesized using GPTMS as the reagent for cross-linking of the chitosan chains. Fourier transform infrared spectroscopy, (29)Si CP-MAS NMR spectroscopy and the ninhydrin assay were used to analyze the structures of the hybrids, and stress-strain curves were recorded to estimate their Young's modulus. The swelling ability, contact angle and cytocompatibility of the hybrids were investigated as a function of the GPTMS concentration. A certain fraction of GPTMS in each hybrid was linked at the epoxy group to the amino group of chitosan, which was associated with the change in the methoxysilane group of GPTMS due to hybridization. The cross-linking density was around 80% regardless of the volume of GPTMS. As the content of GPTMS increased, the water uptake decreased and the hydrophilicity of the hybrids increased except when the content exceeded amolar ratio of 1.5, when it caused a decrease. The values of the mechanical parameters assessed indicated that significant stiffening of the hybrids was obtained by the addition of GPTMS. The adhesion and proliferation of the MG63 osteoblast cells cultured on the chitosan-GPTMS hybrid surface were improved compared to those on the chitosan membrane, regardless of the GPTMS concentration. Moreover, human bone marrow osteoblast cells proliferated on the chitosan-GPTMS hybrid surface and formed a fibrillar extracellular matrix with numerous calcium phosphate globular structures, both in the presence and in the absence of dexamethasone. Therefore, the chitosan-GPTMS hybrids are promising candidates for basic materials that can promote bone regeneration because of their controllable composition (chitosan/GPTMS ratio).
18,722,166
Assessment and key targets for therapy in the post-myocardial infarction patient with left ventricular dysfunction.
In the post-myocardial infarction (MI) patient with coronary artery disease (CAD) and left ventricular dysfunction (LVD), ischemia and adverse remodeling hinder myocardial performance and increase electrical instability. Collectively, the coronary arteries, myocardium, and conduction system represent the principal pathophysiologic targets in MI complicated by LVD. Consequently, an accurate assessment of disease severity in these targets is essential for the design of an effective therapeutic program. This review describes the current modalities for assessing the key pathophysiologic targets in post-MI patients with LVD and the effects of systemic factors on cardiac disease severity.
18,722,186
Pharmacologic therapies across the continuum of left ventricular dysfunction.
Neurohormonal activation and increased sympathetic stimulation are among the factors that have been linked to the development and progression of left ventricular dysfunction (LVD) and heart failure (HF) in post-myocardial infarction (MI) patients. Various available pharmacologic therapies can target these factors and improve many aspects of the disease, depending on the degree of LVD. The American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and aldosterone antagonists because of their proven favorable effects on symptoms, left ventricular function, cardiac remodeling, hospitalization rates, and survival. However, they are not being used in over two thirds of patients with post-MI LVD. This review illustrates the impact of these therapies on post-MI LVD patients using evidence from multiple clinical trials. In addition, current and emerging treatments for acute decompensated HF will be outlined.
18,722,188
Adherence to radiography guidelines for low back pain: a survey of chiropractic schools worldwide.
This study describes instruction provided at chiropractic schools worldwide on the use of spine radiography and compares instruction with evidence-based guidelines for low back pain. Individuals responsible for radiology instruction at accredited chiropractic schools throughout the world were contacted and invited to participate in a Web-based survey. The survey included questions on the role of conventional radiography in chiropractic practice and instruction given to students for its use in patients with acute low back pain. Of the 33 chiropractic schools identified worldwide, 32 (97%) participated in the survey. Consistent with the guidelines, 25 (78%) respondents disagreed that "routine radiography should be used prior to spinal manipulative therapy," 29 (91%) disagreed that there "was a role for full spine radiography for assessing patients with low back pain," and 29 (91%) disagreed that "oblique views should be part of a standard radiographic series for low back pain." However, only 14 (44%) respondents concurred with the guidelines and disagreed with the statement that there "is a role for radiography in acute low back pain in the absence of 'red flags' for serious disease." This survey suggests that many aspects of radiology instruction provided by accredited chiropractic schools appear to be evidence based. However, there appears to be a disparity between some schools and existing evidence with respect to the role of radiography for patients with acute low back pain without "red flags" for serious disease. This may contribute to chiropractic overutilization of radiography for low back pain.
18,722,195
Nutrition and youth soccer for childhood overweight: a pilot novel chiropractic health education intervention.
The purpose of this pilot novel chiropractic health education intervention was to gather preliminary evidence regarding possible benefits from recreational youth soccer and nutrition education in overweight women. A secondary purpose was to determine whether some nutrition knowledge is an independent predictor of changes in body mass index (BMI). A quiz developed and validated on separate age and sex appropriate blinded cohorts was used on study participants-22 volunteers of 57 eligible fourth-grade, overweight female Mississippi public school students. At the beginning of a 5-month study period, a 15-minute baseline nutrition intervention, grounded in Social Cognitive Theory and based on the United States Department of Agriculture's "My Tips for Families" information, was applied in a chiropractic clinic. Subjects were then randomized to 2 months of recreational soccer (n = 14) or waiting list control (n = 8). No preintervention differences were found in height, weight, BMI, or age. Higher follow-up BMI scores were found in both groups, and no significant differences between groups were found, possibly because of the small sample sizes and the short 8-week soccer intervention period. Gains in nutrition knowledge were sustained (P < .002); however, there was no association between nutrition knowledge and follow-up BMI (r = -.185; P < .462). Minimal nutrition education alone may be an ineffective intervention for overweight children. The study provides an example of how youth soccer may benefit overweight children.
18,722,198
Chiropractic treatment of pregnancy-related low back pain: a systematic review of the evidence.
This study systematically reviewed the published evidence regarding chiropractic care, including spinal manipulation, for pregnancy-related low back pain (LBP). A multimodal search strategy was conducted, including multiple database searches along with reference and journal hand searching. Studies were limited to those published in English and in a peer-reviewed journal or conference proceeding between January 1982 and July 2007. All study designs were considered except single case reports, personal narratives, and qualitative designs. Retrieved articles that met the inclusion criteria were rated for quality by using a validated and reliable checklist. Six studies met the review's inclusion criteria in the form of 1 quasi-experimental single-group pretest-posttest design, 4 case series, and 1 cross-sectional case series study; their quality scores ranged from 5 to 14 of 27. All of the included studies reported positive results for chiropractic care of LBP during pregnancy. Outcome measure use between the studies was inconsistent as were descriptions of patients, treatments, and treatment schedules. Results from the 6 included studies showed that chiropractic care is associated with improved outcomes in pregnancy-related LBP. However, the low-to-moderate quality of evidence of the included studies preclude any definitive statement as to the efficacy of such care because all studies lacked both randomization and control groups. Given the relatively common use of chiropractic care during pregnancy, there is need for higher quality observational studies and controlled trials to determine efficacy.
18,722,200
A systematic review of the use of intranasal steroids in the treatment of chronic rhinosinusitis.
To determine if intranasal steroids (INS) are useful in the management of chronic rhinosinusitis without polyps and chronic rhinosinusitis (CRS) with polyps. Studies for inclusion were searched using Medline, EMBASE, Cochrane databases, and references of included studies. Initial screening of article titles and abstracts obtained from the literature search was performed independently by two reviewers (SAJ and RT) based on the research protocol criteria. These articles then underwent a second-stage review. Each article was read in detail and discussed by the two reviewers before inclusion in the study. The review yielded 13 studies regarding the treatment of sinonasal polyps with intranasal steroids. Six of these could be included in the meta-analysis. The outcome measure used for meta-analysis was change in polyp size from baseline compared between the treatment and control groups. Results from both conservative and optimistic selection of treatment effect are positive, providing significant improvement in polyp size in the treatment group as compared to controls. In the conservative estimate, the mean improvement in polyp size score between the treatment and placebo group is 0.43 with a 95% CI of [0.25, 0.61]. Of those treatment groups with the largest improvement, the mean improvement in polyp size score can go as high as 0.63 with a 95% CI of [0.43, 0.82]. Intranasal steroids are beneficial in the treatment of chronic rhinosinusitis with sinonasal polyps. Further studies looking at the use of INS in the treatment of CRS without polyps are warranted.
18,722,209
Cat-scratch disease of the head and neck in a pediatric population: surgical indications and outcomes.
To identify the presentation of pediatric patients with head and neck manifestations of cat-scratch disease, one of the most common causes of subacute or chronic lymphadenitis in children, and to determine surgical indications and outcomes. Case series. All pediatric patients from infancy to age 19 years who presented with clinical symptoms of cat-scratch disease and had an IgG serological test result of more than 1:128 for Bartonella henselae. Nine patients had cat-scratch disease of the head and neck. Median age at presentation was 4 years; median time from symptom onset to presentation was 20 days. Six (67%) children underwent surgical procedures, and median time from presentation to surgical procedure was 43 days. Despite conservative treatment, a minority of pediatric patients with cat-scratch disease may require surgical drainage of abscess and removal of lymph nodes. Surgical treatment provides tissue for diagnosis, is generally well tolerated, affords improved recovery, and has minimal complications.
18,722,212
Loss of Raf kinase inhibitory protein induces radioresistance in prostate cancer.
External beam radiotherapy (RT) is often used in an attempt to cure localized prostate cancer (PCa), but it is only palliative against disseminated disease. Raf kinase inhibitory protein (RKIP) is a metastasis suppressor whose expression is reduced in approximately 50% of localized PCa tissues and is absent in metastases. Chemotherapeutic agents have been shown to induce tumor apoptosis through induction of RKIP expression. Our goal was to test whether RT similarly induces apoptosis through induction of RKIP expression. The C4-2B PCa cell line was engineered to overexpress or underexpress RKIP. The engineered cells were tested for apoptosis in cell culture and tumor regression in mice after RT. RT induced both RKIP expression and apoptosis of PCa cells. Overexpression of RKIP sensitized PCa cells to radiation-induced apoptosis. In contrast, short-hairpin targeting of RKIP, so that RT could not induce RKIP expression, protected cells from radiation-induced apoptosis. In a murine model, knockdown of RKIP in PCa cells diminished radiation-induced apoptosis. Molecular concept mapping of genes altered on manipulation of RKIP expression revealed an inverse correlation with the concept of genes altered by RT. The data presented in this report indicate that the loss of RKIP, as seen in primary PCa tumors and metastases, confers protection against radiation-induced apoptosis. Therefore, it is conceivable that the loss of RKIP confers a growth advantage on PCa cells at distant sites, because the loss of RKIP would decrease apoptosis, favoring proliferation.
18,722,266
Increased but error-prone nonhomologous end joining in immortalized lymphoblastoid cell extracts from adult cancer patients with late radionecrosis.
To study nonhomologous end joining in extracts of two lymphoblastoid cell lines derived from patients with late radionecrosis after radiotherapy. Both cell lines were previously shown to exhibit impaired rejoining of DNA double-strand breaks in a pulse-field gel electrophoresis assay. We used a cell-free system and quantitative real-time polymerase chain reaction, as well as sequencing analysis of end joining products. Paradoxically, extracts of the two cell lines display increased rates of in vitro end joining of noncohesive termini compared with normal cell extracts. This increase was seen in the absence of added deoxyribonucleoside triphosphates and was sensitive to inhibition by wortmannin. Sequencing of the joined products revealed that, despite increased rates of end joining, the process was error prone with a greater frequency of deletions compared with that observed in normal controls. These findings are consistent with the suggestion that a promiscuous, deletion-prone abnormality of nonhomologous end joining might underpin the predisposition of certain radiotherapy patients to late radionecrosis. We hypothesize that some individuals might harbor subclinical defects in nonhomologous end joining that clinically manifest on challenge with high-dose radiation. Because both quantitative and qualitative aspects of end joining have demonstrably been influenced, we recommend that the study of patient samples should involve a combination of quantitative methods (e.g., quantitative real-time polymerase chain reaction), sequencing analysis, and a comparison of multiple join types.
18,722,268
Engineered modular recombinant transporters: application of new platform for targeted radiotherapeutic agents to alpha-particle emitting 211 At.
To generate and evaluate a modular recombinant transporter (MRT) for targeting 211 At to cancer cells overexpressing the epidermal growth factor receptor (EGFR). The MRT was produced with four functional modules: (1) human epidermal growth factor as the internalizable ligand, (2) the optimized nuclear localization sequence of simian vacuolating virus 40 (SV40) large T-antigen, (3) a translocation domain of diphtheria toxin as an endosomolytic module, and (4) the Escherichia coli hemoglobin-like protein (HMP) as a carrier module. MRT was labeled using N-succinimidyl 3-[211 At]astato-5-guanidinomethylbenzoate (SAGMB), its 125 I analogue SGMIB, or with 131 I using Iodogen. Binding, internalization, and clonogenic assays were performed with EGFR-expressing A431, D247 MG, and U87MG.wtEGFR human cancer cell lines. The affinity of SGMIB-MRT binding to A431 cells, determined by Scatchard analysis, was 22 nM, comparable to that measured before labeling. The binding of SGMIB-MRT and its internalization by A431 cancer cells was 96% and 99% EGFR specific, respectively. Paired label assays demonstrated that compared with Iodogen-labeled MRT, SGMIB-MRT and SAGMB-MRT exhibited more than threefold greater peak levels and durations of intracellular retention of activity. SAGMB-MRT was 10-20 times more cytotoxic than [211 At]astatide for all three cell lines. The results of this study have demonstrated the initial proof of principle for the MRT approach for designing targeted alpha-particle emitting radiotherapeutic agents. The high cytotoxicity of SAGMB-MRT for cancer cells overexpressing EGFR suggests that this 211 At-labeled conjugate has promise for the treatment of malignancies, such as glioma, which overexpress this receptor.
18,722,270
Intrafractional motion of the prostate during hypofractionated radiotherapy.
To report the characteristics of prostate motion as tracked by the stereoscopic X-ray images of the implanted fiducials during hypofractionated radiotherapy with CyberKnife. Twenty-one patients with prostate cancer who were treated with CyberKnife between January 2005 and September 2007 were selected for this retrospective study. The CyberKnife uses a stereoscopic X-ray system to obtain the position of the prostate target through the monitoring of implanted gold fiducial markers. If there is a significant deviation, the treatment is paused while the patient is repositioned by moving the couch. The deviations calculated from X-ray images acquired within the time interval between two consecutive couch motions constitute a data set. Included in the analysis were 427 data sets and 4,439 time stamps of X-ray images. The mean duration for each data set was 697 sec. At 30 sec, a motion >2 mm exists in about 5% of data sets. The percentage is increased to 8%, 11%, and 14% at 60 sec, 90 sec, and 120 sec, respectively. A similar trend exists for other values of prostate motion. With proper monitoring and intervention during treatment, the prostate shifts observed among patients can be kept within the tracking range of the CyberKnife. On average, a sampling rate of approximately 40 sec between consecutive X-rays is acceptable to ensure submillimeter tracking. However, there is significant movement variation among patients, and a higher sampling rate may be necessary in some patients.
18,722,274
Multimodal pain management and arthrofibrosis.
Pain control after arthroplasty has been a key concern for orthopedic surgeons. After total knee arthroplasty (TKA), a small group of patients developed a painful joint with suboptimal range of motion. Manipulation under anesthesia increases flexion and extension while decreasing pain in most cases. The objective of the present investigation is to asses the effect of a multimodal pain management protocol on arthrofibrosis in primary TKAs. A cohort of 1136 patients who underwent primary TKA was selected. Patients were divided into 2 groups: group A had 778 procedures performed using a traditional approach to pain control; group B included 358 procedures that received multimodal pain management. Group A had an incidence of manipulation of 4.75% (37/778). Of 357 patients, 8 required manipulation in group B, which is an incidence of 2.24%. We recommend that orthopedic surgeons consider using a multimodal pain management protocol for TKA.
18,722,306
In hospital complications after total joint arthroplasty.
Total joint arthroplasty is a safe and successful procedure. However, numerous complications may present after elective arthroplasty. This study prospectively collected data on systemic and local in hospital complications after 15383 joint arthroplasties, which included 8230 total hip arthroplasties and 7153 total knee arthroplasties. In general, the incidence of complications was higher after knee arthroplasty, simultaneous bilateral surgery, and revision surgery. There were 22 (0.16%) deaths in this cohort. We identified 486 major systemic complications, the most common was pulmonary embolism (152), followed by tachyarrhythmia (92) and acute myocardial infarction (36). There were 109 major local complications, including 16 vascular injuries, 29 peripheral nerve injuries, 25 periprosthetic fractures, and 18 dislocations. Total joint arthroplasty, despite its success, can be associated with rare serious and life-threatening complications. This study provides a baseline of complications that can occur after elective joint arthroplasty.
18,722,311
Egg yolk enhances early sporulation and toxicity of Bacillus sphaericus H5a5b for small-scale production of a mosquito control agent.
Bacillus sphaericus has been widely used in mosquito control programs, but the production of this bacterium is a little tricky as it does not utilize carbohydrates and requires proteinaceous substrates, which are expensive. In this study, we developed a cost-effective medium that resulted in a lower cost and shorter fermentation time. The locally available raw material, egg yolk was used and the level of sporulation, toxicity and biomass were compared with the conventional medium. Use of the egg yolk culture medium significantly shortened fermentation time to 15 h and yielded high activity, equivalent to that of conventional medium against 3rd instar Culex quinquefasciatus. Conventional NYSM medium required 21 h to attain the maximum activity and biomass. Hence, the egg yolk-based culture medium appears to be suitable and economical for the small-scale production of B. sphaericus.
18,722,337
Mycobacterium tuberculosis UsfX (Rv3287c) exhibits novel nucleotide binding and hydrolysis properties.
The Mycobacterium tuberculosis UsfX protein is an anti-sigma factor which regulates its cognate sigma factor SigF. UsfX shares low sequence homology with other anti-sigma factors making it difficult to identify the nucleotide binding site and characterize its properties. We have identified that the NTP binding site occurs close to Trp106 and the area around the nucleotide binding site is predominantly negatively charged. UsfX binds to a variety of nucleotides unlike other reported anti-sigma factors and exhibits an unusual dual NTPase activity. In silico computational experiments have identified a XGSFS motif close to the nucleotide binding site for metal ion binding. This motif is analogous to the DXSXS motif reported earlier in the human integrin CR3 protein superfamily. Overall, the experiments suggest that the M. tuberculosis UsfX represents a distinct anti-sigma factor family with a novel nucleotide binding motif.
18,722,345
The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist.
Nicotinic acid has been used for several decades to treat dyslipidemia. In mice, the lipid-lowing effect of nicotinic acid is mediated by the Gi coupled receptor PUMA-G. In humans, high (GPR109A) and low (GPR109B) affinity nicotinic acid receptors have been characterized. Here we identify monomethylfumarate as a GPR109A agonist. Monomethylfumarate is the active metabolite of the psoriasis drug Fumaderm. We show that monomethylfumarate activates GPR109A in a calcium based aequorin assay, cAMP assay and demonstrate competitive binding with nicotinic acid. We show that GPR109A is highly expressed in neutrophils and epidermal keratinocytes, and that its expression is increased in human psoriatic lesions. Our findings provide evidence that GPR109A is a target for the drug Fumaderm and suggest that niacin should be investigated to treat psoriasis in addition to its role in treating lipid disorders.
18,722,346
Concatameric cloning of porcine microRNA molecules after assembly PCR.
While the number of human or murine microRNAs (miRNAs) increases continuously, there are limited data available from other species. We report a novel identification method of small RNAs such as miRNAs, which allows simultaneous cloning of five RNA molecules within the same insert. First, RNA molecules <40nt were polyadenylated and five concatamerising 5' DNA adaptors were ligated to the molecules in independent reactions. Reverse transcription was carried out using oligo d(T)(18) primers with concatamerising 5' overhangs. The introduced complementary termini in the different reactions enabled the subsequent coupling of five purified antisense strands to one molecule by means of an assembly PCR. After cloning, small RNAs were identified by DNA sequencing. By means of this cloning approach, we identified 10 novel and one known porcine miRNAs. Furthermore, the endogenous expression of the cloned miRNAs was quantified in various tissues using a qRT-PCR approach.
18,722,348
Inactivation of median preoptic nucleus causes c-Fos expression in hypocretin- and serotonin-containing neurons in anesthetized rat.
The median preoptic nucleus (MnPN) of the hypothalamus contains sleep-active neurons including sleep-active GABAergic neurons and is involved in the regulation of nonREM/REM sleep. The hypocretinergic (HCRT) neurons of the perifornical-lateral hypothalamic area (PF-LHA) and serotonergic (5-HT) neurons of the dorsal raphe nucleus (DRN) are mostly active during waking and have been implicated in the regulation of arousal. MnPN GABAergic neurons project to the PF-LHA and DRN. It is hypothesized that MnPN promotes sleep by inhibiting multiple arousal systems including HCRT and other wake-active neurons within the PF-LHA and 5-HT neurons in the DRN. We examined the effects of inactivation of MnPN neurons by locally microinjecting 0.2 microl of 1 mM or 10 mM solutions of a GABA(A) receptor agonist, muscimol, into the MnPN on Fos expression (Fos-IR) in the PF-LHA neurons including HCRT neurons and 5-HT neurons in the DRN in anesthetized rats. Compared to artificial cerebrospinal fluid control, microinjection of muscimol into the MnPN resulted in significantly higher percentages of HCRT and non-HCRT neurons in the PF-LHA and 5-HT neurons in the DRN that exhibited Fos-IR. The percentage of melanin-concentrating hormone (MCH)+/Fos+ neurons in the PF-LHA did not change after muscimol treatments. These results support a hypothesis that the activation of MnPN neurons contributes to the suppression of wake-promoting systems including HCRT and other unidentified neurons in the PF-LHA and 5-HT neurons in the DRN. These results also suggest that MCH neurons may not be under MnPN inhibitory control. These findings are consistent with a hypothesized role of MnPN in sleep regulation.
18,722,360
Lactobacillus crispatus M247-derived H2O2 acts as a signal transducing molecule activating peroxisome proliferator activated receptor-gamma in the intestinal mucosa.
Accumulating evidence indicates that the peroxisome proliferator activated receptor (PPAR)-gamma is a major player in maintaining intestinal mucosa homeostasis, but whether PPAR-gamma is directly involved in probiotic-mediated effects and the molecular events involved in its activation are not known. We investigated the role of PPAR-gamma in the immunomodulatory effects of Lactobacillus crispatus M247 on intestinal epithelial cells (IEC) and the role of probiotic-derived H(2)O(2) on PPAR-gamma activity. L crispatus M247 supplementation in mice significantly increased PPAR-gamma levels and transcriptional activity in the colonic mucosa. L crispatus M247 induced PPAR-gamma nuclear translocation and enhanced transcriptional activity in epithelial (CMT-93) cells, as demonstrated by the increased luciferase activity of a PPAR-gamma-responsive element, PPAR-gamma-responsive gene up-regulation, and reduced activity of an nuclear factor-kappaB-responsive element. Pharmacologic PPAR-gamma inhibition or silencing by small interfering RNA cancelled the L crispatus M247-mediated effects in CMT-93 cells. Because Lactobacillus strains producing little H(2)O(2) failed to activate PPAR-gamma, we investigated the role of L crispatus M247-derived H(2)O(2) in PPAR-gamma activation. L crispatus M247 induced a transient rise in intracellular H(2)O(2) and PPAR-gamma transcriptional activity was cancelled by antioxidant or H(2)O(2) scavenger. Toll-like receptor (TLR)-2 was not required for PPAR-gamma up-regulation mediated by L crispatus M247 in mice, although the protective effects of L crispatus M247 on dextran sodium sulfate-induced colitis were less pronounced in TLR-2(-/-) mice. L crispatus M247 uses H(2)O(2) as a signal transducing molecule to induce PPAR-gamma activation in IEC, directly modulating epithelial cell responsiveness to inflammatory stimuli.
18,722,375
Electrophysiological correlates of the mesoaccumbens system during male rat sexual behaviour.
It is well known that during the male rat sexual interaction different levels of arousal or sexual motivation are involved and that these motivational changes are associated with variations in the level of dopamine (DA); however, it is not yet known if these changes are associated with a different functionality of the nucleus Accumbens (Acc) and Ventral Tegmental Area (VTA), neural structures that constitute the DA mesoaccumbens system. Thus, in this study was simultaneously recorded the electroencephalogram (EEG) from the VTA and the Acc in order to determine if the EEG correlation (r) between these structures shows characteristic patterns in relation to four different conditions of sexual arousal during the male rat sexual interaction: 1) basal-quiet state (BS); 2) exposure to an inaccessible oestrous female (IF); 3) post-intromission (PI); and, 4) post-ejaculation (PE). Both Acc and VTA showed an increased relative power (RP) in the 8-12 Hz band during the PI condition as compared to the other periods. The correlation patterns between Acc and VTA were sensitive to different arousal levels involved in the male rat sexual interaction: those of the interaccumbens and intertegmental r in the 4-7 and 13-21 Hz bands decreased specifically in the IF condition, when the male rats experienced an aroused state as a result of their exposure to remote stimuli from an inaccessible estrous female; whereas the degree of interaccumbens r in the 8-12 Hz band and those of Acc-VTA in both hemispheres increased specifically in the PI condition, in which the male showed a moderate level of anxiety or alertness provoked by the removal of the female. During the non-sexually aroused states, i.e., basal awake-quiet state and PE condition, no changes were observed. These results suggest the possible participation of the Acc and VTA in both the processing of remote stimuli from an oestrous female and in the aroused state that follows the intromission response, which would indicate that these connections between Acc and VTA are sensitive to the different sexual motivational/arousal states involved in the male rat sexual interaction.
18,722,395
Changes in the functional visual field during search with and without eye movements.
The size of the functional visual field (FVF) is dynamic, changing with the context and attentive demand that each fixation brings as we move our eyes and head to explore the visual scene. Using performance measures of the FVF we show that during search conditions with eye movements, the FVF is small compared to the size of the FVF measured during search without eye movements. In all cases the size of the FVF is constrained by the density of distracting items. During search without eye movements the FVF expands with time; subjects have idiosyncratic spatial biases suggesting covert shifts of attention. For search within the constraints imposed by item density, the rate of item inspection is the same across all search conditions. Array set size effects are not apparent once stimulus density is taken into account, a result that is consistent with a spatial constraint for the FVF based on the cortical separation hypothesis.
18,722,398
Time course of the ethanol-like discriminative stimulus effects of abused inhalants in mice.
Abused solvents have effects similar to those of abused depressant drugs. This experiment evaluated the time course of the discriminative stimulus effects of toluene and 1,1,1-trichloroethane (TRI). Mice were trained to discriminate between i.p. injections of ethanol (EtOH; 1.25 g/kg) and saline in a two-lever operant task in which responding was under the control of a fixed-ratio 20 schedule. After 20-min inhalation exposures to toluene (500-6000 ppm) or TRI (1000-12,000 ppm), stimulus generalization was examined at 0, 5, 10, 20, and 40 min post-exposure. Ethanol doses>or=0.25 g/kg produced increases in EtOH-lever responding with full substitution occurring immediately after testing for doses between 1.25 and 2.5 g/kg. Toluene and TRI produced increased EtOH-lever responding at 0-10 min post-exposure with some EtOH-lever responding occurring up to 20-min post-exposure. Response rates were not decreased for any concentration of toluene or TRI immediately following inhalant exposure but several concentrations elevated rates from 5 to 40 min post-exposure. These results confirm and extend previous studies and show these solvents produce similar effects in EtOH-lever responding but with potency differences. The time-dependent differences in EtOH-lever responding suggest that as solvents are cleared from the body, the EtOH-like subjective effects also fade.
18,722,399
Control of the regioselectivity for new fluorinated amphiphilic cyclodextrins: synthesis of di- and tetra(6-deoxy-6-alkylthio)- and 6-(perfluoroalkypropanethio)-alpha-cyclodextrin derivatives.
Twelve new di- and tetraderivatized alpha-cyclodextrin molecules having either alkylthio and perfluoroalkylpropanethio functions at the primary face have been synthesized by using the procedure of Sinay for di-O-debenzylation of perbenzylated alpha-cyclodextrins. A new strategy of protection/deprotection has been developed for introducing the lipophilic chains. The coupling reaction involves the reaction between the appropriate alpha-cyclodextin derivative, regioselectively modified at C-6 positions by a good leaving group (O-mesityl for disubstituted or iodine for tetrasubstituted derivatives), with the thioalkyl or the thioperfluoroakylpropane chains. These nucleophilic reagents are obtained from the in situ basic hydrolysis of the alkylisothiouronium bromides or perfluoalkylropropane and the isothiouronium iodides. These multistep reactions give the desired amphiphilic alpha-cyclodextrins in good overall yields of 33% to 58%.
18,722,405
Generation of nitrene by the photolysis of N-substituted iminodibenzothiophene.
To evaluate the ability of dibenzothiophene N-substituted sulfilimines as photochemical nitrene sources, their photolyses in the presence of several trapping reagents, such as sulfides, olefins, and phosphorus compounds, were performed. In the reactions, the corresponding imino-transfer compounds, namely sulfilimines, aziridines, and iminophosphoranes, were formed in good yields, indicating dibenzothiophene N-tosyl and N-acylsulfilimines have a potent nature as nitrogen sources.
18,722,411
Large two-photon absorption cross sections of hemiporphyrazines in the excited state: the multiphoton absorption process of hemiporphyrazines with different central metals.
A series of five hemiporphyrazines (Hps) with different coordinating central atoms (H2, GeCl2, InCl, Pt, Pb), and the acyclic derivative 1,3-bis-(6'-amino-4'-butoxy-2'-pyridylimino)-1,3-dihydroisoindoline have been synthesized and their multiphoton absorption properties examined at the second harmonic frequency of the Nd:YAG laser in the nanosecond time regime. Metal-free and platinum Hps display saturation of optical transmittance within incident fluence values of 6 J cm(-2). Comparison with other similar molecular structures like phthalocyanines and related molecules shows that Hps are strong nonlinear absorbers. The experimental curves of nonlinear transmission at 532 nm have been fitted by means of a three-level model with the occurrence of simultaneous two-photon absorption from an excited state. In the sole case of the InCl complex we found that a five-level model is needed because of the participation of triplet states. Contrary to phthalocyanines, naphthalocyanines, and porphyrins, a heavy central atom does not improve the nonlinear absorption properties since a different excited states dynamic is involved. The large nonlinear absorption of Hps combined with the very small absorption in the visible spectral range makes these molecules a very interesting class of molecules for nonlinear optical applications.
18,722,439
Reversible restructuring of aqueous block copolymer assemblies through stimulus-induced changes in amphiphilicity.
ABC triblock copolymers with a hydrophilic-thermomorphic-hydrophobic block sequence can assemble into distinct structures in water above and below the lower critical solution temperature for the thermomorphic block. Characterization of aqueous solutions of a representative poly(ethylene oxide)-block-poly(N-isopropylacrylamide)-block-polyisoprene copolymer by light scattering and transmission electron microscopy shows that small spherical micelles are formed at low temperatures and that large vesicles are favored at higher temperatures. The transformation from micelles to vesicles is reversible but slow, occurring over several weeks.
18,722,446
Structure-property relationships in redox-gated single molecule junctions--a comparison of pyrrolo-tetrathiafulvalene and viologen redox groups.
We demonstrate that the electrical "switching" behavior of single molecules connected between two electrode contacts can be controlled by altering their structure and electrochemical characteristics. The electrical properties of gold|molecule|gold single molecule junctions incorporating HS(CH2)6-X-(CH2)6SH, where X = viologen (4,4'-bipyridinium) or pyrrolotetrathiafulvalene, are determined using a scanning tunneling microscopy based technique. The switching behavior, controlled through a tuneable electrochemical gate, changes from an on-off response (viologen) to an off-on-off response (pyrrolotetrathiafulvalene) on changing the central redox group. In contrast, the electrical properties of junctions incorporating redox-inactive HS(CH2)6-1,4-C6H4-(CH2)6SH do not alter significantly as a function of applied potential.
18,722,447
Optimization of plasmid-only rescue of highly attenuated and temperature-sensitive respiratory syncytial virus (RSV) vaccine candidates for human trials.
Respiratory syncytial virus (RSV) is the most common cause of severe bronchiolitis in infants and young children in the U.S. No licensed RSV vaccines are currently available. Established techniques for recovering RSV from cDNA utilize mammalian cells, such as HEp-2 or BSR T7/5, that are not currently suitable for vaccine manufacture. When using HEp-2 cells, co-infection with an attenuated vaccinia virus that expresses T7 RNA polymerase is also required. For human clinical trials, processes that do not require the use of helper viruses and minimize the use of animal derived materials must be developed to reduce the potential theoretical risk of transmitting adventitious agents such as BSE. RSV was generated by electroporating Vero cells from a well characterized cell bank with 6 plasmids expressing T7 RNA polymerase, the full-length anti-genomic RSV and RSV N, P, M2-1 and L. The process was optimized such that highly attenuated and temperature-sensitive RSV vaccine candidates could be recovered in a system completely free of animal derived components. Efficiencies of virus recovery ranged from 30% to 100%. Human metapneumovirus was also readily recovered, suggesting that this protocol is applicable for the production of clinical trial material of other non-segmented negative sense RNA viruses.
18,722,472
Establishment of retroviral pseudotypes with influenza hemagglutinins from H1, H3, and H5 subtypes for sensitive and specific detection of neutralizing antibodies.
Pseudotype reporter viruses provide a safe, quantitative, and high-throughput tool for assessing antibody neutralization for many viruses, including high pathogenicity H5 and H7 influenza A strains. However, adapting this system to other influenza subtypes has been hampered by variations in the protease cleavage site of hemagglutinin (HA) that make it less susceptible to the cleavage required for infectivity. In this report several proteases, reporter vectors, and cell substrates were evaluated while optimizing pseudovirus production, and robust methods were established for sensitive and specific neutralization of pseudotypes carrying influenza H1, H3, and H5 subtype HA that correlates well with titers obtained in microneutralization assays involving replicating influenza virus These findings should facilitate broad use of HA-pseudotypes that remove the need for infectious virus in a range of applications, including neutralization assays for serological surveys of viral infection and evaluations of vaccine sera.
18,722,473
SRC-dependent signalling regulates actin ruffle formation induced by glycerophosphoinositol 4-phosphate.
The glycerophosphoinositols are diffusible phosphoinositide metabolites reported to modulate actin dynamics and tumour cell spreading. In particular, the membrane permeant glycerophosphoinositol 4-phosphate (GroPIns4P) has been shown to act at the level of the small GTPase Rac1, to induce the rapid formation of membrane ruffles. Here, we have investigated the signalling cascade involved in this process, and show that it is initiated by the activation of Src kinase. In NIH3T3 cells, exogenous addition of GroPIns4P induces activation and translocation of Rac1 and its exchange factor TIAM1 to the plasma membrane; in addition, in in-vitro assays, GroPIns4P favours the formation of a protein complex that includes Rac1 and TIAM1. Neither of these processes involves direct actions of GroPIns4P on these proteins. Thus, through the use of specific inhibitors of tyrosine kinases and phospholipase C (and by direct evaluation of kinase activities and inositol 1,4,5-trisphosphate production), we show that GroPIns4P activates Src, and as a consequence, phospholipase Cgamma and Ca(2+)/calmodulin kinase II, the last of which directly phosphorylates TIAM1 and leads to TIAM1/Rac1-dependent ruffle formation.
18,722,484
The ethics of mandatory vaccination against influenza for health care workers.
Vaccination of health care workers (HCW) in long-term care results in indirect protection of patients who are at high-risk for influenza. The voluntary uptake of influenza vaccination among HCW is generally low. We argue that institutions caring for frail elderly have the responsibility to implement voluntary programmes for vaccination against influenza of HCW. When uptake falls short a mandatory programme may be justified. The main justification stems from the duty of care givers not to harm one's patient when one knows there is a significant risk of harm and the intervention to reduce this chance has a favourable balance of benefit over burdens and risks.
18,722,495
Applying the polyvagal theory to children's emotion regulation: Social context, socialization, and adjustment.
Effective emotion regulation is essential for children's positive development. Polyvagal theory provides a framework for understanding how parasympathetic regulation of cardiac activity contributes to children's adaptive versus maladaptive functioning. Maintenance of cardiac respiratory sinus arrhythmia (RSA) under social challenge should support emotion regulation and behavioral adjustment. Children's effective parasympathetic regulation and behavioral adjustment should be supported by appropriate parental socialization. These proposals were evaluated in a short-term longitudinal study of 94 preschool-aged children. Parenting and basal RSA were measured at home, then 6-10 months later behavioral adjustment and RSA in lab baseline and socially challenging contexts were measured. Children with relatively higher RSA in social challenge than at baseline (DeltaRSA) had fewer internalizing problems (IP) and externalizing problems (EP), and better behavioral self-regulation (SR). Mothers who used more negative control had children with lower DeltaRSA, more IP and EP, and less SR. Structural equation modeling showed that vagal regulation mediated associations between maternal negative control and children's adjustment; maternal negative control did not predict EP or SR after accounting for DeltaRSA. Associations were consistent across boys and girls, with one exception: Higher DeltaRSA was significantly associated with fewer EP in boys only. These findings suggest that the practical significance of physiological regulation might be best revealed in ecologically valid procedures, and that children's physiological mechanisms of emotion regulation are shaped by their experiences of parental socialization.
18,722,499