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Common polymorphisms in the vascular endothelial growth factor gene and colorectal cancer development, prognosis, and survival.
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Angiogenesis plays an important role in growth, progression, and metastasis of tumors. The most important regulator of angiogenesis is vascular endothelial growth factor (VEGF). VEGF expression has been associated with advance stage and poor survival of several cancers. In the present study we evaluated the association of functional polymorphisms in the VEGF gene with colorectal cancer development, prognosis, and survival. Three hundred twelve consecutive patients with surgically treated colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and five VEGF (-2578C>A, -1154G>A, -634G>C, -460T>C, and +936C>T) gene polymorphisms were determined using a polymerase chain reaction-restriction fragment length polymorphism assay. VEGF -2578C>A, -1154G>A, -634G>C, -460T>C, and +936C>T genotype and allele frequencies were similar among patients and controls. There was a trend showing carriers of the -2578A and +936T alleles more frequent among patients with CRC, but these differences did not reach statistical significance. Furthermore, no correlation was found between all these variants and tumor characteristics like size, histological grading, positive regional lymph node metastases or tumor stage. However, the -2578AA, -634CC, and +936TT genotypes found to be related with a significantly lower overall survival in our study. In conclusion, VEGF gene polymorphisms were found to be an independent prognostic marker for Greek CRC patients.
| 19,009,560
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Diffusion-weighted imaging of the prostate and rectal wall: comparison of biexponential and monoexponential modelled diffusion and associated perfusion coefficients.
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This study compares parameters from monoexponential and biexponential modelling of diffusion-weighted imaging of normal and malignant prostate tissue and normal rectal wall tissues. Fifty men with Stage Ic prostate cancer were studied using endorectal T(2)-weighted imaging and diffusion-weighted imaging with 11 diffusion-sensitive values (b-values = 0, 1, 2, 4, 10, 20, 50, 100, 200, 400, 800 s/mm(2)). Regions of interest were drawn within non-malignant central gland and peripheral zone, malignant prostate tissue and normal rectal wall tissue. Both a monoexponential and biexponential model was fitted over various b-value ranges, giving an apparent diffusion coefficient (ADC) from the monoexponential model and a diffusion coefficient, perfusion coefficient and perfusion fraction from the biexponential model. In all tissues, over the full range of b-values, the ADC from the monoexponential model was significantly higher than the corresponding diffusion coefficient from the biexponential model. As the minimum b-value increased, the ADC decreased and was equal to the diffusion coefficient for some b-value ranges. The biexponential model best described the data when low b-values were included, suggesting that there is a fast perfusion component. Neither model could distinguish between benign prostate tissues on the basis of diffusion coefficients, but the rectal wall tissue and malignant prostate tissue had significantly lower diffusion coefficients than normal prostate tissues. Perfusion coefficients and fractions were highly variable within the population, so their clinical utility may be limited, but removal of this variable perfusion component from reported diffusion coefficients is important when attributing clinical differences to diffusion within tissues.
| 19,009,566
|
"Half-bonds" in an unusual coordinated S(4) (2-) rectangle.
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Don't be square! A rare S(4) (2-) rectangle bridging two M(2)Cp(2)(mu(2)-CH(2))(2) (M=Rh, Ir) fragments is found to contain two "half-bonds" with S-S distances of 2.70 or 2.90 A. Computational studies explore the connection between these "half-bonds" and a Jahn-Teller distortion, as well as possible intermediates that form M(4)S(4) (2+) clusters having the S(4) (2-) rectangle rotated by 90 degrees. The bonding of a rare S(4) (2-) rectangle coordinated to four transition metals (synthesized by Isobe, Nishioka, and co-workers), [{M(2)(eta(5)-C(5)Me(5))(2)(mu-CH(2))(2)}(2)(mu-S(4))](2+) (M=Rh, Ir) is analyzed. DFT calculations indicate that, while experiment gives the rectangle coordinated with its long edge parallel to Rh-Rh bonds and perpendicular to the Ir-Ir bonds, either orientation is feasible for both metals. Although rotation of the S(4) rectangle is likely a multi-step process, a calculated barrier of 46 kcal mol(-1) for a simple interconversion pathway goes through a trapezoidal, not a square, transition state. An argument is presented, based on molecular orbital (MO) calculations, that the long S-S contacts (2.70 and 2.90 A) in the rectangle are in fact two-center, three-electron bonds (or "half-bonds"). Moreover, the 2- charge on the S(4) rectangle is related to a Jahn-Teller distortion from a square to a rectangle. Finally, DFT is used to explore possible stable intermediates in the oxidative process giving these M(4)S(4) (2+) compounds: for Ir, the coupling of two Ir(2)S(2) (+) molecules appears feasible, as opposed to a possible two-electron oxidation of a neutral Rh(4)S(4) molecule.
| 19,009,582
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Inflammation and sleep disordered breathing in children: a state-of-the-art review.
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Sleep disordered breathing (SDB) represents a spectrum of breathing disorders, ranging from snoring to obstructive sleep apnea syndrome (OSAS), that disrupt nocturnal respiration and sleep architecture. OSAS is a common disorder in children, with a prevalence of 2-3%. It is associated with neurobehavioral, cognitive, and cardiovascular morbidities. In children, adenotonsillectomy is the first choice for treatment and is reserved for moderate to severe OSAS, as defined by an overnight polysomnography. In adults, OSAS is the result of mechanical dysfunction of the upper airway, manifesting as severity-dependent nasal, oropharyngeal, and systemic inflammation that decrease after continuous positive airway pressure therapy. Inflammatory changes have been reported in upper airway samples from children with OSAS, and systemic inflammation, as indicated by high-sensitivity C-reactive protein (hsCRP) levels, has been shown to decrease in children with OSAS after adenotonsillectomy. Anti-inflammatory treatments for children with mild OSAS are associated with major improvements in symptoms, polysomnographic respiratory values, and radiologic measures of adenoid size. Inflammation is correlated to some extent with OSAS-related neurocognitive morbidity, but the role of inflammatory markers in the diagnosis and management of OSAS, and the role of anti-inflammatory treatments, remains to be clarified. This review examines the role of inflammation in the pathophysiology of sleep-disordered breathing in pediatric patients and the potential therapeutic implications.
| 19,009,600
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Understanding patellofemoral pain with maltracking in the presence of joint laxity: complete 3D in vivo patellofemoral and tibiofemoral kinematics.
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Patellofemoral pain is widely accepted as one of the most common pathologies involving the knee, yet the etiology of this pain is still an open debate. Generalized joint laxity has been associated with patellofemoral pain, but is not often discussed as a potential source of patellar maltracking. Thus, the objective of this study was to compare the complete 6 degree of freedom patellofemoral and tibiofemoral kinematics from a group of patients diagnosed with patellofemoral pain syndrome and maltracking to those from an asymptomatic population. The following null hypotheses were tested: kinematic alterations in patellofemoral maltracking are limited to the axial plane; knee joint kinematics are the same in maltrackers with and without generalized joint laxity (defined by a clinical diagnosis of Ehlers Danlos Syndrome); and no correlations exist between tibiofemoral and patellofemoral kinematics or within patellofemoral kinematics. This study demonstrated that alterations in patellofemoral kinematics, associated with patellofemoral pain, are not limited to the axial plane, minimal correlations exist between patellofemoral and tibiofemoral kinematics, and distinct subgroups likely exist within the general population of maltrackers. Being able to identify subgroups correctly within the omnibus diagnosis of patellar maltracking is a crucial step in correctly defining the pathophysiology and the eventual treatment of these patients.
| 19,009,601
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Predictive value of serologic markers in a population-based Norwegian cohort with inflammatory bowel disease.
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Perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) are proposed to be specific markers for ulcerative colitis (UC) and Crohn's disease (CD). Their prevalence and relationship to disease phenotype and outcome in unselected cohorts of patients with inflammatory bowel disease (IBD), however, is largely unclear. We studied the prevalence of these serologic markers in a population-based IBD cohort 10 years after diagnosis, and examined whether their presence could be related to distinct subgroups and outcome of disease. Of 685 living IBD patients, 620 met for a 10-year follow-up, of whom 526 (UC, n = 357 and CD, n = 169) participated in this study. Twenty-seven percent (n = 46) of CD patients were ASCA-positive and 31% (n = 109) of UC patients were pANCA-positive. Positive ASCA was more frequent in CD patients with stricturing (P = 0.003) or penetrating (P = 0.012) complications than in those with inflammatory behavior at diagnosis. Moreover, the presence of ASCA was associated with an at least twice higher risk of evolving more severe disease behavior during follow-up (P < 0.001). In UC, pANCA expression was related to female gender (P = 0.005) and the use of azathioprine (P < 0.001), and in CD, to colon-limited disease and age >/=40 years at diagnosis (P = 0.009 and P = 0.001, respectively). The prevalence of ASCA in CD and pANCA in UC appears markedly lower than in referral-based populations. Even with the low prevalence, our study gives further support to the role of ASCA and pANCA as markers for distinct phenotype and outcome of disease.
| 19,009,607
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Feeding behavior and gene expression of appetite-related neuropeptides in mice lacking for neuropeptide Y Y5 receptor subclass.
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Neuropeptide Y (NPY) is a potent neurotransmitter for feeding. Besides NPY, orexigenic neuropeptides such as agouti-related protein (AgRP), and anorexigenic neuropeptides such as alpha-melatonin stimulating hormone (MSH) and cocaine-amphetamine-regulated transcript (CART) are also involved in central feeding regulation. During fasting, NPY and AgRP gene expressions are up-regulated and POMC and CART gene expressions are down-regulated in hypothalamus. Based on the network of peptidergic neurons, the former are involved in positive feeding regulation, and the latter are involved in negative feeding, which exert these feeding-regulated peptides especially in paraventricular nucleus (PVN). To clarify the compensatory mechanism of knock-out of NPY system on feeding, change in gene expressions of appetite-related neuropeptides and the feeding behavior was studied in NPY Y5-KO mice. Food intake was increased in Y5-KO mice. Fasting increased the amounts of food and water intake in the KO mice more profoundly. These data indicated the compensatory phenomenon of feeding behavior in Y5-KO mice. RT-PCR and ISH suggested that the compensation of feeding is due to change in gene expressions of AgRP, CART and POMC in hypothalamus. Thus, these findings indicated that the compensatory mechanism involves change in POMC/CART gene expression in arcuate nucleus (ARC). The POMC/CART gene expression is important for central compensatory regulation in feeding behavior.
| 19,009,645
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Ghrelin and Helicobacter pylori infection.
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Ghrelin is primarily secreted from the stomach and has been implicated in the coordination of eating behavior and weight regulation. Ghrelin also plays an essential role in the mechanism of gastric mucosal defense. Thus, it is important to clarify which diseases primarily influence changes in plasma ghrelin concentrations. Helicobacter pylori (H pylori) infection is involved in the pathogenesis of gastritis, gastric and duodenal ulcer, gastric carcinoma, and mucosa-associated lymphoid tissue lymphoma. H pylori eradication is related to body weight change. Compared, H pylori infected and negative subjects with normal body mass index, plasma ghrelin concentration, gastric ghrelin mRNA, and the number of ghrelin producing cells in gastric mucosa are significantly lower in H pylori infected subjects than in H pylori-negative controls. Plasma ghrelin concentration decreases with the progression of gastric atrophy. Impaired gastric ghrelin production in association with atrophic gastritis induced by H pylori infection accounts for the decrease in plasma ghrelin concentration. However, the ratio of plasma acylated ghrelin to total ghrelin levels is higher in patients with chronic atrophic gastritis than in healthy subjects. This may result from the compensatory increase in plasma active ghrelin concentration in response to gastric atrophy. After H pylori eradication, gastric preproghrelin mRNA expression is increased nearly 4-fold in most cases. However, changes in plasma ghrelin concentrations before and after H pylori cure are not associated with the gastric ghrelin production. Plasma ghrelin changes are inversely correlated with both body weight change and initial plasma ghrelin levels.
| 19,009,647
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Effects of n-3 polyunsaturated fatty acids from seal oils on nonalcoholic fatty liver disease associated with hyperlipidemia.
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To investigate the efficacy and safety of n-3 polyunsaturated fatty acids (PUFA) from seal oils for patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. One hundred and forty-four patients with NAFLD associated with hyperlipidemia were included in the 24-wk, randomized, controlled trial. The patients were randomized into two groups. Group A (n=72) received recommended diet and 2 g n-3 PUFA from seal oils, three times a day. Group B (n=72) received recommended diet and 2 g placebo, three times a day. Primary endpoints were fatty liver assessed by symptom scores, liver alanine aminotransferase (ALT) and serum lipid levels after 8, 12, 16, and 24 wk. Hepatic fat infiltration was detected by ultrasonography at weeks 12 and 24 after treatment. A total of 134 patients (66 in group A, 68 in group B) were included in the study except for 10 patients who were excluded from the study. After 24 wk of treatment, no change was observed in body weight, fasting blood glucose (FBG), renal function and blood cells of these patients. Total symptom scores, ALT and triglyceride (TG) levels decreased more significantly in group A than in group B (P<0.05). As expected, there was a tendency toward improvement in aspartate aminotransferase (AST), gamma-glutamyltranspeptidase (GGT), and total cholesterol (TCHO) and high-density lipoprotein (HDL) cholesterol levels (P<0.05) after administration in the two groups. However, no significant differences were found between the two groups. The values of low-density lipoprotein (LDL) were significantly improved in group A (P<0.05), but no significant change was found in group B at different time points and after a 24-wk treatment. After treatment, complete fatty liver regression was observed in 19.70% (13/66) of the patients, and an overall reduction was found in 53.03% (35/66) of the patients in group A. In contrast, in group B, only five patients (7.35%, 5/68) achieved complete fatty liver regression (P=0.04), whereas 24 patients (35.29%, 24/68) had a certain improvement in fatty liver (P=0.04). No serious adverse events occurred in all the patients who completed the treatment. Our results indicate that n-3 PUFA from seal oils is safe and efficacious for patients with NAFLD associated with hyperlipidemia and can improve their total symptom scores, ALT, serum lipid levels and normalization of ultrasonographic evidence. Further study is needed to confirm these results.
| 19,009,658
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Regional anesthesia techniques for ambulatory orthopedic surgery.
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The purpose of this review is to present advances in the use of regional anesthetic techniques in ambulatory orthopedic surgery. New findings regarding the use of both neuraxial anesthesia and peripheral nerve block are discussed. Neuraxial anesthesia: The use of short-acting local anesthetic agents such as mepivacaine, 2-chloroprocaine, and articaine permits rapid onset intrathecal anesthesia with early recovery profiles. Advantages and limitations of these agents are discussed.Peripheral nerve block: Peripheral nerve blocks in limb surgery have the potential to transform this patient cohort into a truly ambulatory, self-caring group. Recent trends and evidence regarding the benefits of regional anesthesia techniques are presented.Continuous perineural catheters permit extension of improved perioperative analgesia into the ambulatory home setting. The role and reported safety of continuous catheters are discussed. In summary, shorter acting, neuraxial, local anesthetic agents, specific to the expected duration of surgery, may provide superior recovery profiles in the ambulatory setting. A trend towards more peripheral and selective nerve blocks exists. The infrapatellar block is a promising technique to provide analgesia following knee arthroscopy. Improved analgesia seen in the perioperative period can be safely and effectively extended to the postoperative period with the use of perineural catheters.
| 19,009,687
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Web-based education in anesthesiology: a critical overview.
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The purpose of this review is to discuss the rise of web-based educational resources available to the anesthesiology community. Recent developments of particular importance include the growth of 'Web 2.0' resources, the development of the concepts of 'open access' and 'information philanthropy', and the expansion of web-based medical simulation software products.In addition, peer review of online educational resources has now come of age. The worldwide web has made available a large variety of valuable medical information and education resources only dreamed of two decades ago. To a large extent,these developments represent a shift in the focus of medical education resources to emphasize free access to materials and to encourage collaborative development efforts.
| 19,009,692
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Impact of the model for end-stage liver disease allocation policy on the use of high-risk organs for liver transplantation.
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Although priority for liver transplantation is determined by the model for end-stage liver disease (MELD) score, the quality of organs used is subject to physician discretion. We aimed to determine whether implementation of MELD affected the quality of organs transplanted, the type of patients who receive the higher-risk organs, and the impact of these changes on their posttransplant survival. Data were analyzed from the United Network for Organ Sharing of adults who underwent deceased-donor liver transplantation between January 1, 2007, and August 1, 2007 (n = 47,985). Dependent variables included the donor risk index (a continuous variable that measures the risk of graft failure associated with a particular organ) and patient survival after transplantation. The overall organ quality of transplanted livers has worsened since MELD implementation, with an increase in the donor risk index equivalent to a 4% increased risk of graft failure after adjusting for temporal trends (P < .001). This was accompanied by a shift from using the higher-risk organs in the more urgent patients (in the pre-MELD era) to using the higher-risk organs in the less urgent patients (in the post-MELD era). Posttransplant survival has worsened over time (hazard ratio, 1.017/y; P = .005) among the less urgent patients (MELD scores, <20); mediation analysis suggests this change in survival was caused primarily by changes in organ quality. As an unintended consequence of the MELD allocation policy, patients that are least in need of a liver transplant now receive the highest-risk organs. This has reduced posttransplant survival in recent years among patients with low MELD scores.
| 19,009,713
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Faculty awards at US colleges and schools of pharmacy.
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To determine recognition given for outstanding teaching, service, and scholarship at US colleges and schools of pharmacy, the types of awards given, and the process used to select the recipients. A self-administered questionnaire was made available online in 2006 to deans at 89 colleges and schools of pharmacy. Sixty-four usable responses (72%) were obtained. An award to acknowledge teaching excellence was most commonly reported (92%), followed by an award for adjunct/volunteer faculty/preceptors (79%). The majority of the institutions (31 out of 58) reported offering 1 teaching award annually. The 2 most common methods for selecting the recipient of the teaching award were by student vote and by college/school committee vote following nominations. Twenty-four of the 63 respondents indicated that their institution provided an award for research/scholarship and 18 offered an award for outstanding service. Teaching excellence was recognized and rewarded at most US colleges and schools of pharmacy; however, research/scholarship and service were formally recognized less frequently.
| 19,009,732
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Role of some biomarkers of atherogenic risk in the screening for molecular defects in the low density lipoprotein receptor in severe hypercholesterolemia.
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Familial hypercholesterolemia is difficult to diagnose because of different expressions of the defective gene in low density lipoprotein (LDL) receptor mutation carriers and the presence of elevated LDL levels in noncarriers. To study specific biomarkers of atherogenic risk in carriers and noncarriers of low density lipoprotein receptor (LDLR) defective gene and utilize them to screen in molecular biological analysis for defects in the LDL receptor (spot mutation and polymorphism) in severe hypercholesterolemia. We investigated 120 patients after screening using the Simon-Broome criteria. According to whether there were molecular defects or not, the patients were assigned to two groups--carriers (22 patients, 18.33%) and non-carriers (98 patients, 81.67%). Total cholesterol, triglycerides, HDL cholesterol, apolipoproteins Apo-B and Al were determined using routine methods. LDL-cholesterol was determined by direct methods. ELISA was used in determining the soluble cell adhesion molecules (sICAM-1, sVCAM-1), P-selectine and E-selectine, and high-performance liquid chromatography--total homocysteine. There were no significant differences in gender and anthropometric parameters (P > 0.05) between carriers and non-carriers, but the groups differed significantly in age (P < 0.001). No significant differences were found between the groups in the routine lip profile, the atherogenic lipid index, apolipoproteins B and A1, ADMA, total homocysteine, and the soluble cell adhesion molecules (P > 0.05). We found a statistically significant difference only for the Apo-B/Apo-A1 index in values non standardized by age, which was confirmed after standardization. Examining all 18 exons of LDLR gene in patients with severe HC we found that 18.33% of them were carriers of mutations and polymorphisms. There was no correlation between the presence of a molecular defect and the routine lipid profile, ADMA, total homocysteine and the soluble cell adhesion molecules; the presence of a molecular defect however, correlated with the Apo-B/Apo-A1 index.
| 19,009,746
|
[Immediate and long-term results of conventionally performed radiofrequency catheter ablations of paroxysmal atrial fibrillation].
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Atrial fibrillation is the most frequent cardiac arrhythmia. Epidemiological studies show sharp increase of incidence and prevalence of atrial fibrillation all over the world. Atrial fibrillation is becoming to be a serious problem, not only clinical, but even social and economical. Aim of the paper was to evaluate immediate and long-term results of radiofrequency catheter ablation of paroxysmal atrial fibrillation at Dpt. of Internal Medicine-Cardiology, University Hospital Brno. The patients were indicated for ablation, when the anti-arrhythmic therapy was ineffective. End-point of the ablation was disconnection of myocardial sleeves between left atrium and pulmonary veins and complete electrical isolation of pulmonary veins. GROUP OF THE PATIENTS, RESULTS: There were 67 catheter ablations of paroxysmal atrial fibrillation performed within the years 9/2004 to 12/2006 at our department, out of the whole amount of 1,285 ablations of supraventricular tachyarrhythmias from 1995 to 2006. There were 27 women (40%) and 40 men (60%) in our group of patients, with the mean age 56.9 +/- 9.5 years. The average ejection fraction of left ventricle was 62 +/- 5%, left atrial dimension 42.8 +/- 6 mm. The mean follow-up period was 16.9 +/- 10.9 months. The patients were treated before and after the ablation by 1 anti-arrhythmic drug in 44.8 vs 50%, by 2 drugs in 40.3 vs 14.9% and by 3 drugs in 10.4 vs 9%, respectively. The percentage of patients without any anti-arrhythmic drug increased after successful ablation from 2.9 to 25.4%, the percentage of patients using amiodarone decreased from 29.8 to 16.4%, propafenon from 29.8 to 16.4% and sotalol from 26.8 to 10.4% respectively. The median of RF application duration was 43.8 min, fluoroscopy time 43.8 min and procedure duration 240 min. The success rates were 87.5% in year 2004, 77.4% in 2005 and 79.2% in 2006. Catheter ablation of paroxysmal atrial fibrillation has become a routine curative method in symptomatic patients without major structural heart disease, with ineffective anti-arrhythmic treatment. Ablation was associated with significant reduction of anti-arrhythmic and anticoagulation therapy.
| 19,009,761
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In vivo assessment of Mg2+ in human brain and skeletal muscle by 31P-MRS.
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Phosphorus magnetic resonance spectroscopy offers a unique opportunity to measure in vivo the free cytosolic magnesium [Mg2+] of different tissues. In particular, this technique has been employed in human brain and in skeletal muscle providing new hints on Mg2+ homeostasis and on its involvement in cellular bioenergetics. In skeletal muscle it has been shown that the changes of free Mg2+ concentration occurring during contraction and in post-exercise recovery are mainly due to the cytosolic pH influence. The possibility of assessing the free cytosolic [Mg2+] in the human brain offered the chance of studying the involvement of Mg2+ in different neurological pathologies, and particularly in those where defective mitochondrial energy production represents the primary causative factor in the pathogenesis. The results obtained, studying patients affected by different types of mitochondrial cytopathies, helped to clarify the functional relationship between energy metabolism and free [Mg2+], providing evidence that cytosolic [Mg2+] is regulated in brain cells to equilibrate any changes in rapidly available free energy. Moreover, it has also been shown that the measurement of brain Mg2+ can help in the differential diagnosis of neurodegenerative diseases sharing common clinical features, such as Multiple System Atrophy and Parkinson's disease.
| 19,009,818
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[Chronic obstructive pulmonary disease and infection].
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Patients with COPD are exposed to many infections of the lower respiratory tract. The evolution of their disease is characterized by an increasing number of episodes of exacerbation associated with a worsening dyspnea and an increase of the sputum volume and purulence. Fifty to 80% of these episodes are due to bacterial or viral agents which have an impact on the frequency of exacerbations, and on the pulmonary functions. In addition to smoking cessation, preventive measures to consider according to the clinical situation include vaccinations against influenza and invasive pneumococcal infections, and the use of corticosteroids combined with bronchodilatators. Beta-lactams constitute the antibiotics of choice for the treatment of exacerbations due to infections.
| 19,009,845
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Is intraocular pressure in myotonic dystrophy patients spuriously low?
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Ocular hypotony is a common unexplained feature of myotonic dystrophy type 1. Spuriously low applanation tonometric readings can be caused by thin corneas, flat corneal curvature and corneal edema. To determine whether structure abnormalities of the cornea cause spuriously low readings in applanation tonometry. We utilized a TMS-2N corneal topographer, a NonconRobo SP-6000 Specular microscope and a Corneo-Gage Plus 1A Pachymeter to examine seven patients with DM1 and eight healthy controls. Intraocular pressure, central corneal thickness, and endothelial cell density were measured, and simulated keratometry readings were made. Cornea guttata and irregularity of corneal topography patterns were also sought. The mean intraocular pressure was 9.86 +/- 1.29 mmHg for all patients (intraocular operated and non-operated eyes) and 12.88 +/- 1.89 mmHg for the controls (P=0.000021, two-tailed t-test). Central corneal thickness was 530.57 +/- 35.30 micron for all patients and 535.00 +/- 39.62 micron for the controls (P=0.75, two-tailed t-test). Endothelial cell density was 3164 +/- 761 cells/ mm2 for all patients and 3148 +/- 395 cells/mm2 for the controls (P=0.94, two-tailed t-test). Simulated keratometry readings were similar in both groups when the operated eyes were excluded. Cornea guttata and irregularity of corneal topography patterns were also noted in the study group. Corneal thickness, corneal curvature and corneal hydration were within normal limits and thus were not the cause for the low applanation tonometry reading in DM1. The presence of cornea guttata and irregularity of corneal topography patterns in DM1 warrants further investigation.
| 19,009,949
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Neuropathic pain in people treated for multibacillary leprosy more than ten years previously.
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To identify patients with typical symptoms of neuropathic pain in a well-defined cohort of multibacillary patients being followed up as part of a relapse study in Ethiopia; to identify risk factors for the development of neuropathic pain. 96 patients who had completed MDT more than 10 years previously participated in the study, through a questionnaire. 28 (29%) had symptoms of neuropathic pain and it was reported as severe in 12. Because the past history of these subjects is well documented, a risk factor analysis was carried out. The presence of leprosy-related impairment was the only significant risk factor for neuropathic pain that was identified. Neuropathic pain is an important problem in a proportion of people previously treated for leprosy. Further research into the management of the condition is required.
| 19,009,976
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Emissions of total volatile organic compounds and indoor environment assessment in dental clinics in Athens, Greece.
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To quantify the amount of Total Volatile Organic Compounds (TVOCs) emitted from five dental substances commonly used in a dental clinic. An assessment of the indoor air quality in two clinics of the Athens University Dentistry Faculty was conducted. It was found that TVOC emissions from Kalocryl and Bacillol reached extremely high values affecting the air in the dental clinics at short and long distances from the source. Six pollutants TVOCs, CO2, PM10, PM2.5, SO2 and NO(x) were measured and indoor sources associated with dental activities were identified. Very high concentrations of TVOCs were found which exceeded the acceptable levels by a factor of 20, associated with the nature of the dental activities and the ventilation conditions. The CO2 concentration levels were high and the indoor conditions were considered unsatisfactory, associated with the number of occupants and the ventilation conditions. PM concentrations were high due to the nature of the dental activities and they exceeded the outdoor levels by a factor of 5 to 6. The concentrations of the gaseous pollutants NO(x) were low while the SO2 concentrations were hardly detectable.
| 19,009,994
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The criminalisation of professional misconduct under the Health Professions Registration Act 2005 (VIC): how is a fine of $50,000 not punitive?
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The purpose of medical boards is to protect patients and guide doctors. Courts and tribunals have constantly emphasised that their role is entirely protective and not punitive. By a huge increase in the fine that can be imposed on health professionals in Victoria to a level more commensurate with serious criminal activity, the regulatory environment has shifted from a simple and straightforward indication of disapproval to one where a medical practitioner can be sanctioned as a criminal without the protections afforded by the criminal jurisdiction. A standard of proof beyond reasonable doubt, double jeopardy and pleading remorse and contrition in mitigation are not available. No good reasons have been advanced for this change. One can only hope that when a national Health Registration Board National Registration and Accreditation Scheme for the Health Professions, due for implementation in 2010, is completed, it will include a recognition of the true purpose of medical regulation and correct this anomaly, encouraging compliance by professionals rather than persisting with a command-and-control punitive regime. Punishment should be left to the courts.
| 19,009,997
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Apologies, medicine and the law.
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This column considers some of the imperatives and barriers which may impact on a medical practitioner who apologises to a patient following an adverse event in New South Wales. It also considers the inclusion of the apology provisions in ss 67-69 of the Civil Liability Act 2002 (NSW) and the extent to which those provisions may protect apologising practitioners from liability.
| 19,009,998
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Preimplantation genetic diagnosis for susceptibility conditions: a new frontier or a logical extension?
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A susceptibility or "lower penetrance" condition is a condition to which a person may be predisposed by virtue of a particular gene mutation they carry within their genetic code. Genetic testing for susceptibility to late-onset conditions, an increasingly available phenomenon, has recently been associated with preimplantation genetic diagnosis (PGD). Performing PGD for conditions that occur later in life and that may be preventable or, if not, may be treatable, or that may never even develop, is highly contentious. It constitutes a significant departure from traditional PGD, going beyond testing for serious heritable disorders that are apparent at birth or in very early childhood or late-onset diseases that are certain to manifest themselves. It is likely that, as technology advances, there will be a growing demand for PGD to detect these types of conditions. This article considers the issues raised by susceptibility testing. It questions whether embryonic testing for late-onset susceptibility conditions is more appropriately a matter for regulatory restraint or reproductive liberty.
| 19,010,004
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The non-compliance of clinical guidelines for organ donation with Australian statute law.
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Organ procurement is possible under statutes defining death as either irreversible cessation of all functions of the brain or irreversible cessation of the circulation, thus fulfilling the "dead donor rule". However, present practice does not conform strictly to these conditions. Clinical guidelines for the diagnosis of whole-brain death are equated, with coma, to absence of brain-stem reflexes which essentially means the absence of spontaneous respiration which is clinically interpreted as "dead enough" or "as good as dead" for the purpose. Moreover, Krommydas v Sydney West Area Health Service [2006] NSWSC 901 suggests public distrust of brain-stem reflexes as tests to diagnose whole-brain death. Mandatory adoption of a test of brain blood circulation, at present optional, would strengthen reliability of the diagnosis. Organ procurement is performed after cessation of the circulation following orchestrated withdrawal of futile life-support and is commenced when the heart fails to "auto-resuscitate" two minutes after it stops, rather than proven irreversible cessation. Ante-mortem procedures are performed on the donor to increase organ availability and viability but may contribute to or cause death. State and national ethical guidelines on this practice conflict and it appears proscribed under State guardianship legislation which requires actions in the best interests of the donor, not the recipient. Considerations should be given to organ procurement in situations where the donor is dying or in which survival is impossible. Simple abandonment of the "dead donor rule", however, is not feasible since organ procurement would be the direct cause of death.
| 19,010,008
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Development of human patient simulation programs: achieving big results with a small budget.
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The benefits of simulation in nursing education are well documented. Nursing students learn in a safe environment that enhances critical thinking and collaboration. Barriers to simulation include cost, resources, and fear of technology. This article describes how to design and implement a quality simulation program for less than $20,000.
| 19,010,052
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Tracking the prevalence of rollover protective structures on U.S. farm tractors: 1993, 2001, and 2004.
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Between 1992 and 2005, 1412 workers on farms died from tractor overturns. A Rollover Protective Structure (ROPS) is a proven intervention to reduce overturn deaths. However, farm characteristics that are associated with the adoption of ROPS are not well understood. ROPS prevalence statistics were derived from National Institute for Occupational Safety and Health (NIOSH) surveys that tracked ROPS use on farms. Data were from the years 1993, 2001, and 2004. In 1993, 38% of tractors were equipped with ROPS. This increased to 51% by 2004. ROPS prevalence rates were higher on farms in the Southern region of the United States, on farms where the operator was 25-34 years old, and on farms with $100,000 or more of farm sales. Low ROPS prevalence rates were associated with farm operators 65 years old or older and with farms with less than $10,000 of farm product sales. The increase in ROPS prevalence between 1993 and 2004 has not been sufficient to decrease the rate of tractor overturn deaths on farms. Incentive programs targeting older farm operators and low-income farm operations are suggested to increase ROPS use on tractors. The study provides farm characteristics associated with low ROPS prevalence rates. The results can be used to target farms for future ROPS promotion activities.
| 19,010,124
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Increased organ donations from people born outside Spain.
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Organs donated from persons born outside Spain are becoming increasingly numerous. These persons now account for 26.1% of all donors in the "Malaga sector," an area of tourism with a high percentage of immigrants. Acceptance to donation among persons from Europe and South America is similar to that of Spanish persons but lower among those born in Africa. We must recognize the great help that cultural mediators provided not only by assistance with the language barrier but also by generating confidence among families and understanding their emotions, feelings, and traditions, mainly during interviews with families from different social and cultural miliere. To be efficient, the interpreters or cultural mediators need to have received specific training in the organ donation process and to be involved and convinced that organ donation and transplantation is the best solution for severe health problems.
| 19,010,131
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Induction treatment with low-dose thymoglobulin or basiliximab in renal transplants from older donors.
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Transplantation of kidneys from older donors is followed by an increase in delayed graft function (DGF) and acute rejection episodes (ARE). In these circumstances, induction treatment, whether with antithymocyte globulin or with interleukin-2 receptor blockers, may delay the introduction of calcineurin inhibitors (CNI) with effective prevention of ARE. We examined the efficacy and safety of induction treatment with 2 low doses of thymoglobulin compared with 2 doses of basiliximab. A group of 27 patients were treated with thymoglobulin and another 36 with basiliximab. CNI introduction was delayed until day 3 posttransplantation. The thymoglobulin group received 2 doses of 1.25 mg/kg on alternate days and the basiliximab group 2 doses of 20 mg. A trend to a lower incidence of DGF was observed in the thymoglobulin group (33% vs 55.6%; P = .08), with lower levels of serum creatinine on days 7 (P = .02) and 14 (P = .02) posttransplantation. No patient in the thymoglobulin group experienced ARE, but 11 patients (30.6%) in the basiliximab group did (P < .001), and 5 needed rescue treatment with thymoglobulin. We found no differences in the incidence of cytomegalovirus (CMV) disease (P = .945), admission due to infections (P = .274), or neoplasia (P = .340), or differences in graft (P = .69) and patient (P = .21) survivals at 1 and 3 years. Low-dose thymoglobulin was more effective at preventing DGF and ARE in renal transplant recipients of organs from older donors, with no differences in infectious complications or graft and patient survivals.
| 19,010,141
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Left ventricular structure and function in long-term kidney transplantation: the influence of glucose metabolism and oxidative stress.
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Impaired cardiac structure and function are fundamental components of cardiovascular disease, leading to morbidity, mortality, and graft loss after renal transplantation. The aim of this study was to describe and determine the factors involved in these cardiac abnormalities, paying special attention to the role of glucose metabolism and oxidative stress. We studied 54 long-term, nondiabetic recipients with no valvulopathy who underwent an echocardiographic examination and simultaneous biochemical determinations of lipid profile, hemoglobin A1c (HbA1c), and various oxidative stress parameters: malondialdehyde, superoxide dismutase, total glutathione, and isoprostanes. We calculated the left ventricular mass index (LVMI) and ejection fraction and the peak velocity of early rapid filling to peak velocity of atrial filling (E/A) ratio. Left ventricular hypertrophy (LVH), systolic dysfunction, and diastolic dysfunction (LVDD) were present in 25.9%, 5.6%, and 59.25% of the patients, respectively. The mean blood pressure (MBP) was higher and the hemoglobin lower among patients with LVH, which was related to the age of the patients. We observed a significant negative association of the E/A ratio-used as an index of LVDD-with HbA1c (r = -.448, P = .002) and age (r = -.57, P = .000) and a positive association with the level of total glutathione (r = .322, P = .029). Multiple regression analysis of the E/A ratio showed significance only for HbA1c but not for MBP or LVMI. These results suggested a possible causal influence of subclinical glucose metabolism impairment as detected by HbA1c on the presentation of LVDD via the impaired oxidative stress status, independent of blood pressure control or LVH grade.
| 19,010,145
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Hepatitis C virus infection after renal transplantation.
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Hepatitis C virus (HCV) infection is the main cause of liver disease after renal transplantation. Most patients have seroconverted on dialysis to positive RNA. The viral load increases during immunosuppressive therapy. The risk of developing chronic liver disease is related to the histopathologic findings, duration and severity of the disease, immunosuppression, and transplantation time. Hepatitis C virus infection can predict onset, of proteinuria and diabetes. We studied 868 patients who received renal transplants between (1987 and 2006), of whom 18.7% were seropositive for HCV. We observed a higher rate of HCV-seropositive patients related to the duration of hemodialysis therapy. Of the HCV seropositive patients, 77% had received renal allografts before 1998. There was no difference between the sexes; however, the HCV positive patients were younger. Polymerase chain reaction tests results were positive in 91.6% of the patients with HCV antibodies. The prevalence of diabetes was greater among HCV positive patients, as was as the persistence of proteinuria. Cryoglobulins were positive in 30.8%. The incidence of acute rejection episodes in the first year was similar between groups. Of the HCV-positive patients, 80.2% were treated with cyclosporine, most patients continued this therapy throughout the study. We observed no significant difference in mortality end graft survival rate between the two groups. However, renal function differed significantly at some points during the evolution of the clinical course. Renal transplantation is still the best treatment option in patients with chronic renal disease.
| 19,010,152
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Cancer incidence and survival in kidney transplant patients.
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Immunosuppression after organ transplantation is associated with a markedly increased risk of nonmelanoma skin cancer (NMSC) and malignancies, including posttransplant lymphoproliferative disorder (PTLD) and solid organ cancer. This study sought to investigate the incidence of malignancies and the clinical characteristics and risk factors of the renal transplant patients with solid organ tumors and NMSC. We included 1017 patients who received a kidney transplant in our hospital from 1979 to 2007. Results were contrasted with a cohort of patients from the same center without malignancies. The mean follow-up of patients in our series was 10 years. The mean age at presentation of the malignancy was 61 +/- 5 years. The malignancy and NMSC incidences were 6% and 5%, respectively. Patients with malignancy had a longer posttransplant time and greater recipient and donor age. In the multivariate analysis, independent risk factors for developing NMSC were: male sex (hazard ratio [HR] 3.1, P = .004); greater patient age (HR 1.09, P < .001), longer posttransplant time (HR 1.2, P = .004) and tacrolimus treatment (HR 4.4, P = .001). Risk factors associated with developing any malignancy were: patient age (HR 1.06, P < .001), number of grafts (HR 3.2, P = .019), tacrolimus treatment (HR 2.5, P = .035), and time posttransplantation (HR 1.2, P = .011). The mean times to development of an NMSC, solid organ malignancy, on PTLD were 7.5, 6.1, or 3.9 years, respectively. The mean survival time from the diagnosis of any malignancy was 9.6 months (95% confidence interval, 0.12-30) for solid organ malignancies and 1 month (95% confidence interval, 0.24-1.87) for PTLD.
| 19,010,153
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Response to a vaccination schedule with 4 doses of 40 microg against hepatitis B virus in cirrhotic patients evaluated for liver transplantation.
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We conducted a retrospective study to evaluate the response to recombinant hepatitis B vaccine after 4 intramuscular doses (40 microg) administered at 0, 1, 2, and 6 months in 157 cirrhotic patients who were liver transplant candidates. Seventeen nonresponders were revaccinated with the same schedule. We studied the association between the following variables and the vaccine response: age, gender, etiology of cirrhosis, diabetes, severity of liver disease (Child-Pugh class and Model for End-Stage Liver Disease [MELD] score), and the number of administered doses. The response rates were: 1 dose, 40% (2/5); 2 doses, 0% (0/7); 3 doses, 32.7% (16/49); and 4 doses, 31.3% (30/96) of patients. The median hepatitis B surface antibody (anti-HBs) titer was 45 mU/mL (range, 11-620 mU/mL). The response rate to revaccination was 41.2% (median anti-HBs titer, 88 mU/mL; range, 18-190 mU/mL). Diabetics showed a lower response rate than nondiabetic patients (17.2% vs 35.3%; P = .046). No association was observed between the response rate to vaccine and the other variables. In conclusion, the response rate to hepatitis B vaccine reached a little more than 30% in cirrhotic patients who received 3 or 4 doses. No higher response rate was observed among patients who received 4 doses. Diabetes was associated with a lower response rate. Anti-HBs seroconversion rates were not associated with the other variables. Revaccination may significantly increase the response rate to hepatitis B vaccine in cirrhotic patients, and may be considered in nonresponders after the third dose. Early vaccination against HBV should be considered in such patients.
| 19,010,154
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Hypertension after heart transplantation: predictive factors and number and classes of drugs for its management.
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This study was performed to determine the factors that cause arterial hypertension after heart transplantation (HT) and the drugs used in its management. We studied 247 consecutive patients who had undergone HT between 2000 and 2006 and who survived for at least 6 months. We excluded patients who received combination transplants, those who underwent repeat transplantation, and pediatric patients who had received transplants. Hypertension was defined as the need to use drugs for its control. Renal dysfunction was defined as serum creatinine concentration greater than 1.4 mg/dL, and diabetes as the need for an antidiabetes drug for its control. Statistical analyses were performed using the t test, the chi(2) test, and Cox regression. Mean (SD) patient age was 52 (10) years, and 87.4% of the patients were men. Follow-up was 72 (42) months. Hypertension was present in 33.3% of patients before HT and in 71.1% at some time after HT. The number of drugs used to control hypertension was 1.3 (0.5); one drug was used in 72.9% of patients. The most often used single class of drugs were calcium channel blockers (63.2%), followed by angiotensin-converting enzyme inhibitors (20%), and angiotensin receptor blockers (15.8%). Only pre-HT hypertension was significantly associated with greater use of antihypertensive drugs post-HT (mean [SD], 1.48 [0.65] vs 1.22 [0.41]; P = .005). At univariate analysis, only pre-HT hypertension was associated with the presence of post-HT hypertension (80.5% vs 65.5%; P = .02). At Cox regression analysis, recipient age (P = .02) and pre-HT hypertension (P = .004) were associated with post-HT hypertension. Hypertension is common after HT; however, in most patients, it can be controlled with a single antihypertensive agent. The most important factors in the development of hypertension are the presence of pre-HT hypertension and advanced age.
| 19,010,190
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Prognostic factors influencing survival rates in children following lung transplantation.
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To assess the results of lung transplantation (LT) in children under 17 years of age and identify factors affecting long-term survival. A retrospective review was performed of 37 patients (<17 years) who had received a lung transplant between 1996 and 2007. Morbidity, mortality, and survival were analyzed by the Kaplan-Meier method and the log-rank test. There were 37 LTs: 30 bilateral, four lobar, two liver-lung, one unilateral. Indications for transplantation were: cystic fibrosis (n = 30), pulmonary fibrosis (n = 1), bronchiectasis (n = 1), Kartagener's syndrome (n = 1), bronchiolitis obliterans (n = 3), and pulmonary fibrosis due to radiotherapy-chemotherapy (n = 1). The intubation time and oxygenation index of donors were 49 +/- 36 hours and 455 +/- 83.5 mm Hg, respectively. Seventeen patients needed extracorporeal circulation (ECC) and 13 were coded as priorities. High blood pressure and renal failure were the most frequent complications. Overall survival rates were 65.7%, 59.4%, 56.1%, 44.5%, and 39.6% at 1, 2, 3, 5, and 10 years, respectively. Need for ECC (P = .001), surgical complications (P = .037), oxygenation index <450 mm Hg (P = .005), OLT in priority code (P = .04), and age of donor >16 years (P = .005) were associated with poor survival. LT is an appropriate procedure for certain types of end-stage pediatric pulmonary pathologies, achieving acceptable long-term survival rates. When the procedure is carried out under a surgical priority code, it is associated with a high rate of perioperative morbidity and mortality and poorer long-term survival. Other factors that have a negative influence on survival include the need for ECC, surgical complications, an oxygenation index <450 mm Hg, and donor age >16 years.
| 19,010,197
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Results of lung transplantation in patients with chronic obstructive pulmonary disease.
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The objective of this study was to evaluate the results and survival rates of patients who underwent lung transplantation (LT) to treat chronic obstructive pulmonary disease (COPD). We performed a retrospective analysis of 63 patients with COPD who underwent LT between 1996 and 2007. Our statistical analysis was based on descriptive statistics and survival analysis (Kaplan-Meier and log-rank test). Sixty-three LTs were performed in 53 male and 10 female patients with COPD. Twenty-eight LTs were unipulmonary and 35 were bipulmonary. Four cases required extracorporeal circulation. Surgical complications arose in 18 cases. There were 3 cases of intraoperative death as a result of cardiac failure. The most frequent long-term complications were hypertension (39.7%), renal failure (42.9%), and neoplasms (20.6%). Overall survival times (mean, 2553 days) were 75.9%, 74.15%, 65.67%, 55.87%, and 42.05% at 1, 2, 3, 5, and 10 years, respectively. No differences were observed in survival according to the following: donor age >30 years (P = 8), type of transplantation (unilateral vs bilateral; P = .57), donor intubation time >48 hours (P = .2), or donor oxygenation index <450 mm Hg (P = .3). No differences were observed in survival according to the type of transplantation (unilateral vs bilateral), which suggests that unipulmonary transplantation is a reasonable option, given that this procedure reduces both the ischemia time compared with bilateral transplantation and the surgery time, as well as offering more efficient use of donor organs.
| 19,010,198
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Experience of the Reina Sofia Hospital in lung transplantation from donors older than forty years.
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The shortage of suitable donors for lung transplantation (LT) has led to liberalization of criteria for donor selection. This study evaluated the outcomes of LT among a subset of patients receiving organs from standard donors older than 40 years of age. We distributed patients who underwent LTs performed between 1993 and 2007 into 2 groups: Group A, donors younger than 40 years; and Group B, donors 40 years of age or older. We compared donor and recipient preoperative, operative, and recipient postoperative factors by univariate analyses. We reviewed 255 consecutive LT patients: Group A, 198 patients (78%); and Group B, 57 patients (22%). Donors from Group A showed longer intubation times (43 hours vs 34 hours; P = .026) and a better PaO2/FiO2 ratio (477 vs 454 mm Hg; P = .020), with no differences in other donor variables. Among patients dying of primary graft failure, 20% were from Group B versus 5.6% from Group A (P = .04). There were no differences in mortality or other postoperative variables. Survival rates did not differ between groups (70%, 62%, 52%, and 45% in Group A vs 60%, 45%, 45%, and 20% in Group B at 1, 3, 5, and 10 years, respectively; P = .13). The use of ideal donors older than 40 years of age might be related to a higher incidence of primary graft failure. However, long-term survival is similar to that of recipients from younger donors.
| 19,010,200
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Selective transarterial chemoembolization of advanced hepatocellular carcinomas: a reasonable palliative option.
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The purpose of this study was to provide information concerning the performance of selective transarterial chemoembolization (TACE) as a palliative treatment in patients with hepatocellular carcinoma (HCC), also in the case of multifocal lesions. We reviewed prospectively collected data on 43 patients with cirrhosis and HCC who underwent selective TACE as a palliative treatment. Patients were assigned to one of two groups: (1) those with one to three HCC lesions, and (2) those with four or more HCC lesions. One hundred and two TACE sessions were applied in 43 patients. There were 39 men and 4 women with a mean age of 65.5 +/- 8.273 years. Alpha fetoprotein levels were elevated to a median value of 73.8 U/mL prior to first TACE (range, 1.5-25615 U/mL). Fourteen patients underwent one session, and 29 patients from two to eight TACE sessions. Bilobar HCC distribution prior to initial TACE was evident in 40% of the patients. Solitary HCC was radiologically diagnosed in 14 patients. Twenty-seven patients were assigned to group 1 and 16 patients to group 2. No significant differences were found between the two groups concerning the number of TACE sessions and the severity of liver cirrhosis. Currently 12 patients are alive after a median follow-up of 25 months (range, 3-84 months). Three- and 5-year survival rates according to patient groups were 45% and 19%, and 42% and 11% for the patients' groups 1 and 2, respectively (P = .87). HCC patients without a curative therapy option may benefit from palliative TACE, also in the case of multifocal lesions.
| 19,010,226
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The evolution of the role of liver transplantation in treating alcoholic cirrhosis in Greece.
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Liver transplantation represents the main treatment for alcoholic cirrhosis. The goal of this article is to review the results of liver transplantation for alcoholic cirrhosis in Greece over the last 2 decades. Among 247 patients who underwent liver transplantation between 1991 and 2007, 34 (13.7%) experienced alcoholic cirrhosis as the primary diagnosis. We reviewed their demographic data, stage of liver disease, and outcomes regarding survival via a Kaplan-Meier curve. Also we analyzed the causes of death and the postoperative complications. Mean Model for End-Stage Liver Disease (MELD) score was 18.4. Other diagnoses included hepatitis C virus (HCV; 23.5%), hepatitis B virus (HBV; 14.7%), and hepatocellular carcinoma (8.8%). Eleven patients died the most frequent causes being primary graft nonfunction (n = 3), hepatic artery thrombosis (n = 2), sepsis (n = 2), and portal vein thrombosis (n = 2). Complications included rejection (32.4%), infection (26.5%), hepatic graft dysfunction (11.8%), and recurrent HCV, recurrent HBV, and renal failure (8.8% each). Recurrence of alcoholism was observed in 3 patients (8.8%) with mild effects on liver function tests. There has been a significant increase in the number of liver transplantations for alcoholic cirrhosis in the last 6 years, namely 25 patients versus 9 in the previous 10 years. We observed a significant increase in the frequency of alcoholic cirrhosis leading to liver transplantation in the last several years in Greece.
| 19,010,229
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NMD: multitasking between mRNA surveillance and modulation of gene expression.
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Gene expression is a highly specific and regulated multilayer process with a plethora of interconnections as well as safeguard and feedback mechanisms. Messenger RNA, long neglected as a mere subcarrier of genetic information, is more recently recognized as a linchpin of regulation and control of gene expression. Moreover, the awareness of not only proteins but also mRNA as a modulator of genetic disorders has vastly increased in recent years. Nonsense-mediated mRNA decay (NMD) is a posttranscriptional surveillance mechanism that uses an intricate network of nuclear and cytoplasmic processes to eliminate mRNAs, containing premature termination codons. It thus helps limit the synthesis of potentially harmful truncated proteins. However, recent results suggest functions of NMD that go far beyond this role and affect the expression of wild-type genes and the modulation of whole pathways. In both respects--the elimination of faulty transcripts and the regulation of error-free mRNAs--NMD has many medical implications. Therefore, it has earned increasing interest from researchers of all fields of the life sciences. In the following text, we (1) present current knowledge about the NMD mechanism and its targets, (2) define its relevance in the regulation of important biochemical pathways, (3) explore its medical significance and the prospects of therapeutic interventions, and (4) discuss additional functions of NMD effectors, some of which may be networked to NMD. The main focus of this chapter lies on mammalian NMD and resorts to the features and factors of NMD in other organisms if these help to complete or illuminate the picture.
| 19,010,255
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Human papillomavirus in HNSCC: a European epidemiologic perspective.
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The aim of this study was to assess incidence and survival of human papillomavirus-related and unrelated head and neck squamous cell carcinoma sites from 15 European population-based cancer registries. This analysis was performed on 29,265 adult (aged approximately 15 years) cancer patients diagnosed in the period from 1988 to 2002. The human papillomavirus-unrelated cancer sites had an age-standardized incidence higher than the human papillomavirus-related cancer cases (3.8 versus 2.5/100,000 year). Incidence rates of head and neck squamous cell carcinomas increased more for human papillomavirus-related than unrelated cancer sites. Three-year survival rates improved more in human papillomavirus-related than unrelated cancer sites, and women had better rates of survival than men.
| 19,010,264
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Induction chemotherapy in locally advanced head and neck cancer: a new standard of care?
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Locally advanced squamous cell cancer of the head and neck is a major contributor to morbidity and mortality worldwide. Despite progress through the use of multimodality treatment involving surgery, radiotherapy, and chemotherapy in recent years, the survival remains poor, and treatment-related morbidity-mainly caused by radiation-induced effects such as soft tissue scarring, esophageal stenosis, xerostomia, dental decay, and osteoradionecrosis-is a major problem in long-term survivors. Data from early trials and encouraging results from meta-analyses have revived interest in the use of neoadjuvant or induction chemotherapy before definitive local treatment. Recent randomized trials have demonstrated marked improvements in survival with the addition of the taxane docetaxel (Taxotere) to the traditional induction regimen consisting of cisplatin and 5FU (TPF) compared with cisplatin and 5FU (PF) alone and have established a new standard of care. The newer TPF induction chemotherapy regimens also appear to be tolerated better than PF when accompanied by adequate supportive measures. Studies to enhance the efficacy of TPF induction chemotherapy by adding new targeted agents, such as the EGF-R inhibitors cetuximab and panitumumab, are underway.
| 19,010,265
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Molecularly targeted agents in the treatment of recurrent or metastatic squamous cell carcinomas of the head and neck.
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Proof of principle that molecularly targeted therapy is a valid therapeutic approach for squamous cell carcinoma of the head and neck (SCCHN) has emerged with epidermal growth factor receptor targeting agents. Other interesting targets, such as Src, insulin-like growth factor 1 receptor, and the proteasome, have been shown in vitro to play key roles in SCCHN, and their inhibition is currently being studied in phase II trials. Identification of predictive biomarkers of resistance or sensitivity to these therapies remains one of the main challenges in the optimal selection of patients most likely to benefit from them. However, clinical trials with these novel agents need to be designed rationally to improve the overall outcome of patients. Given the emerging evidence that human papilloma virus-related SCCHN is a distinct disease, it should be studied in specific trials.
| 19,010,269
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Sinonasal malignancies of neuroendocrine origin.
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The sinonasal malignancies of putative neuroendocrine origin-esthesioneuroblastoma, sinonasal neuroendocrine carcinoma, sinonasal undifferentiated carcinoma, and sinonasal small cell carcinoma-are uncommon malignancies that frequently present with locally advanced disease. Pathologic distinction between these entities can be difficult, but is important to guide management. These malignancies require complex multimodality treatment and are best managed by multidisciplinary teams in major centers that have expertise in sinonasal malignancies.
| 19,010,275
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Pancoast tumors.
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Pancoast tumors (superior sulcus tumors or apical lung tumors) typically invade structures at the thoracic outlet, including the inferior elements of the brachial plexus (C8, T1 nerve roots and lower trunk). Historically, these tumors are rapidly fatal, but newer treatment with induction chemotherapy and radiotherapy, followed by surgical resection of the tumor has resulted in improved patient survival. To accomplish oncologic excision, resection of the involved brachial plexus elements is still standard practice in most centers, resulting in loss of hand function and/or development of neuropathic pain. We present a modification of this protocol that incorporates induction chemoradiation, surgical resection of the lung tumor by a thoracic surgeon, and neurolysis and preservation of the brachial plexus by a neurosurgeon. Improved survival outcome, especially in patients demonstrating a pathologic complete response, with preservation of hand function, supports our hypothesis that involved brachial plexus does not need resection in these patients.
| 19,010,280
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What's new in common upper extremity entrapment neuropathies.
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Upper extremity entrapment neuropathies are common and disabling, and correct diagnosis is essential for proper management. This article is a review of the recent developments related to diagnosis and treatment of common upper extremity nerve entrapments, including novel treatment strategies for suprascapular, median, ulnar, and radial nerve entrapments. When combined with classic peripheral nerve examination techniques, innovations in imaging modalities have led to more reliable diagnoses. Innovations in surgical techniques, such as endoscopic approaches, have been controversial as to their effects on patient outcome, but recent randomized controlled trials have provided important information regarding common operative techniques, particularly with regard to carpal tunnel surgery and ulnar nerve transpositions.
| 19,010,282
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A readapted Malone schistosome transmission index model.
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Schistosome transmission index can be directly used to give an overall evaluation and prediction of schistosomiasis transmission through a mathematical model. In the light of the mechanism of schistosomiasis transmission process, an improved Malone schistosome transmission index model was established based on the previous study of survivor rate of the snail under extreme temperatures by Hong Qingbiao. Meteorological data from FAO and Institute of Geographic Sciences and Resources Research, CAS was used to calculate the schistosome transmission index by the new model in the schistosomiasis epidemic region of China, and the result was re-classified into transmission index classes. The new model changed the class of "epidemic area" into that of "non-epidemic area" in the regions of the southern Henan province, the northern Anhui province and the middle Jiangsu province by transmission index threshold of 900. The geographic boundary between the epidemic and the non-epidemic regions was found fitly to coincide with the -2 degrees C isotherm of January in China, whereas the underpinning cause needs to be further explored in the future. Finally discussed was the calculation result of this meteorological model having some difference from actual epidemiology as more factors of relevance could be considered to be incorporated into the model, also discussed were a few questions concerning the model itself and the possible future improvement directions.
| 19,010,297
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A rapid gas chromatography-mass spectrometry method for quantification of alkylresorcinols in human plasma.
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Alkylresorcinols (ARs) are phenolic lipids that among foods are found almost exclusively in whole grain and bran products based on wheat and rye. They have been suggested to be used as selective biomarkers of whole grain wheat and rye intake and, thus, may serve as an alternative/complement to commonly used dietary assessment methods in epidemiological studies. For such investigations where analysis of large numbers of valuable samples is required, rapid, sensitive, and repeatable methods are essential. In this article, we describe a rapid and sensitive gas chromatography-mass spectrometry (GC-MS) method for quantification of AR homologues C17:0, C19:0, C21:0, C23:0, and C25:0 in human plasma. The method uses Oasis MAX solid phase extraction cartridges for sample cleanup. A plasma sample of 0.2 ml could be used without preincubation with water. Samples in the range of 7 to 8750 nmol total AR/L were successfully analyzed with the method described, and the average total AR recovery within the reported range was 92+/-12%. The within- and between-day precision values of total AR concentration in a quality control sample, determined as the coefficients of variation, were on average 7 and 10%, respectively. Approximately 30 to 50 samples could be analyzed within 1 day. The improved GC-MS method presented can be used for rapid analysis of ARs in relatively small sample volumes.
| 19,010,298
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Structure, membrane orientation, mechanism, and function of pexiganan--a highly potent antimicrobial peptide designed from magainin.
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The growing problem of bacterial resistance to conventional antibiotic compounds and the need for new antibiotics have stimulated interest in the development of antimicrobial peptides (AMPs) as human therapeutics. Development of topically applied agents, such as pexiganan (also known as MSI-78, an analog of the naturally occurring magainin2, extracted from the skin of the African frog Xenopus laevis) has been the focus of pharmaceutical development largely because of the relative safety of topical therapy and the uncertainty surrounding the long-term toxicology of any new class of drug administered systemically. The main hurdle that has hindered the development of antimicrobial peptides is that many of the naturally occurring peptides (such as magainin), although active in vitro, are effective in animal models of infection only at very high doses, often close to the toxic doses of the peptide, reflecting an unacceptable margin of safety. Though MSI-78 did not pass the FDA approval, it is still the best-studied AMP to date for therapeutic purposes. Biophysical studies have shown that this peptide is unstructured in solution, forms an antiparallel dimer of amphipathic helices upon binding to the membrane, and disrupts membrane via toroidal-type pore formation. This article covers functional, biophysical, biochemical and structural studies on pexiganan.
| 19,010,301
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Effects of different corticosteroids on the brain weight and hippocampal neuronal loss in rats.
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Equivalent antiinflammatory doses of steroids including betamethasone, methylprednisolone and dexamethasone were administered in the neonatal period in a rat model. In situ cell death in hippocampus quantified by Terminal Deoxynucleated Transferase Nick-End Labeling and on ratio of brain to body weight was investigated. Apoptotic index (AI) was significantly higher in methylprednisolone, and high dose dexamethasone groups than the other groups. AI in "Cornu ammonis 1" (CA1) and "Cornu ammonis 3" (CA3) subregions of high dose dexamethasone group was the highest among the five groups tested. AI in CA3 subregions of methylprednisolone group was also significantly higher than the control, betamethasone and low dose dexamethasone groups. AI in CA1 subregion were not different among control, betamethasone, methylprednisolone and low dose dexamethasone groups. In addition, high dose dexamethasone resulted significant decrease in the ratio of brain weight to body weight in comparison to all other groups tested. In conclusion, betamethasone and low dose dexamethasone may be better alternative treatments among agents tested in this study for chronic lung disease (CLD).
| 19,010,310
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Type 5 17beta-hydroxysteroid dehydrogenase/prostaglandin F synthase (AKR1C3): role in breast cancer and inhibition by non-steroidal anti-inflammatory drug analogs.
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Aldo-keto reductase (AKR) 1C3 catalyzes the NADPH-dependent reduction of Delta(4)-androstene-3,17-dione to yield testosterone, reduction of estrone to yield 17beta-estradiol and reduction of progesterone to yield 20alpha-hydroxyprogesterone. In addition, it functions as a prostaglandin (PG) F synthase and reduces PGH(2) to PGF(2)alpha and PGD(2) to 11beta-PGF(2). Immunohistochemistry showed that AKR1C3 is over-expressed in invasive ductal carcinoma of the breast. Retroviral expression of AKR1C3 in MCF-7 breast carcinoma cells shows that each of the assigned reactions occur in a breast cell microenvironment. Steroid and prostaglandin conversions were monitored by radiochromatography. Prostaglandin conversion was validated by a second method using HPLC coupled to APCI-MRM/MS. The combined effect of the AKR1C3 catalyzed 17- and 20-ketosteroid reductions will be to increase the 17beta-estradiol:progesterone ratio in the breast. In addition, formation of PGF(2) epimers would activate F prostanoid receptors and deprive PPARgamma of its putative anti-proliferative PGJ(2) ligands. Thus, AKR1C3 is a source of proliferative signals and a potential therapeutic target for hormone-dependent and -independent breast cancer. Two strategies for AKR1C3 inhibition based on non-steroidal anti-inflammatory drugs were developed. The first strategy uses the Ullmann coupling reaction to generate N-phenylanthranilate derivatives that inhibit AKR1C enzymes without affecting PGH(2) synthase (PGHS) 1 or PGHS-2. The second strategy exploits the selective inhibition of AKR1C3 by indomethacin, which did not inhibit highly related AKR1C1 or AKR1C2. Using known structure-activity relationships for the inhibition of PGHS-1 and PGHS-2 by indole acetic acids we obtained N-(4-chlorobenzoyl)-melatonin as a specific AKR1C3 inhibitor (K(I)=6.0muM) that does not inhibit PGHS-1, PGHS-2, AKR1C1, or AKR1C2. Both strategies are informed by crystal structures of ternary AKR1C3.NADP(+).NSAID complexes. The identification of NSAID analogs as specific inhibitors of AKR1C3 will help validate its role in the proliferation of breast cancer cells.
| 19,010,312
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Differential action of methylselenocysteine in control and alloxan-diabetic rabbits.
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Antidiabetic action of inorganic selenium compounds is commonly accepted. Since in diet selenium mainly exists as selenoamino acids, potential hypoglycemic properties of methylselenocysteine (MSC) were investigated in four groups of rabbits: untreated and MSC-treated control animals as well as alloxan-diabetic and MSC-treated diabetic rabbits. MSC (at a dose of 1mg/kg body weight) was administered daily for 3 weeks via intraperitoneal injection. The data show, that in MSC-treated control animals plasma glucose concentration was diminished, while plasma urea and creatinine levels as well as urine albumin content were elevated and necrotic changes occurred in kidney-cortex. Decreased GSH/GSSG ratios in blood, liver and kidney-cortex were accompanied by increased glutathione peroxidase and glutathione reductase activities and a diminished renal gamma-glutamylcysteine synthetase activity. Death of 50% of control animals was preceded by a dramatic decline in blood glucose concentration. Surprisingly, in MSC-treated diabetic rabbits, plasma glucose levels were either normalized or significantly decreased. Blood and liver GSH/GSSG ratios were increased and renal functions were markedly improved, as indicated by a diminished albuminuria and attenuated histological changes characteristic of diabetes. However, after administration of MSC to diabetic rabbits plasma urea and creatinine levels as well as renal GSH/GSSG ratios were not altered. In view of MSC-induced marked accumulation of selenium in kidneys and liver of control rabbits, accompanied by a decline in blood glucose level, disturbance of glutathione homeostasis and kidney-injury, application of MSC in chemotherapy needs a careful evaluation. On the contrary, MSC supplementation might be beneficial for diabetes therapy due to an improvement of both glycemia and renal function.
| 19,010,315
|
Mass spectrometry based metabolomic approaches in urinary biomarker study of women's cancers.
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The metabolomic approaches for mining biomarkers of women's cancers based on gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry combined with partial least squares-discriminant analysis are described. To identify urinary potential biomarkers, the qualitative and quantitative analyses were introduced with 10 breast, 9 ovarian and 12 cervical cancer patients as well as 22 normal controls, which were considered with their ages and menopausal state. For comprehensive metabolomic approaches, the non-targeted qualitative profiling was first achieved to get metabolic patterns of collected samples and the targeted quantitative analysis focused on hormonal metabolism was also conducted. Two known biomarkers, i.e., 5-hydroxymethyl-2-deoxyuridine and 8-hydroxy-2-deoxyguanosine, in breast cancer were also confirmed using the present methods. In addition, 3 potential biomarkers for ovarian cancer i.e. 1-methyladenosine, 3-methyluridine, and 4-androstene-3,17-dione, which were categorized in significantly increased level using one way of variance analysis (p<0.05), were identified as quantitatively targeted metabolites with pattern analysis. The cancer markers identified in this study are highly related to metabolites which are responsible for oxidative DNA damage and DNA methylation process. The present metabolomic approaches are not only useful for diagnostic tools and patient stratification, but may be mapped on metabolic network to reflect disease states.
| 19,010,317
|
Characteristics of a novel Pseudomonas aeruginosa bacteriophage, PAJU2, which is genetically related to bacteriophage D3.
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Pseudomonas aeruginosa bacteriophage (phage) is one of the most taxonomically and genetically diverse phages. Although phage D3 is one of well-studied P. aeruginosa phages, no D3-related P. aeruginosa phage has been reported. We report a novel P. aeruginosa siphovirus, PAJU2, which is genetically related to but morphology distinct (highly elongated head) from phage D3. A PAJU2 capsid protein, Orf3, is thought to be synthesized as a protein fused to a prohead protease and is autocatalytically cleaved, which may form the head chain mail. Despite such morphological differences, PAJU2 is expected to be a useful genetic reference for phage D3.
| 19,010,363
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Characterization of a concealed antigen Hq05 from the hard tick Haemaphysalis qinghaiensis and its effect as a vaccine against tick infestation in sheep.
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Positive clone Hq05 of Haemaphysalis qinghaiensis (named following those cDNA clones cloned from the tick before) was obtained by differentially screening of a cDNA library of the tick with rabbit anti-tick salivary gland serum and rabbit anti-tick saliva serum. Hq05 contains an open reading frame (ORF) of 540bp that codes for 179amino acid residues with a coding capacity of 20kDa. Sequence similarity and phylogenetic analyses indicated that Hq05 was a novel gene. Expression analysis by reverse transcription-polymerase chain reaction indicated that the gene was expressed in nymphal and adult stage of H. qinghaiensis tick and its salivary glands, but not in midguts. The cDNA was expressed as glutathione S-transferase (GST)-fused protein in a procariotic system. Western blot showed that only rabbit anti-H. qinghaiensis salivary gland serum could recognize the expressed GST-Hq05 (46kDa) protein, while both rabbit negative serum and rabbit anti-H. qinghaiensis saliva serum could not react with the expressed protein. This proved the recombinant protein was a "concealed" antigen of H. qinghaiensis. Vaccination of sheep with rHq05 conferred a significant protective immunity in sheep, resulting in a 40% reduction of the amount of eggs laid by each tick and the hatching capability of eggs decreased by 37% compared to the controls. These results showed that rHq05 could be a candidate tick vaccine molecule for the control of H. qinghaiensis.
| 19,010,370
|
A four-stage strategy to reduce childhood pneumonia-related mortality by 2015 and beyond.
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The global community has considered several vaccines to reduce pneumonia morbidity and mortality among children <5 years. Recent burden estimates support pneumococcal vaccine introduction, however, influenza vaccine has received only recent attention. The effect of influenza vaccine on early childhood pneumonia has not been adequately explored. As part of an integrated four-stage strategy, both pneumococcal and influenza vaccine impact on pneumonia burden reduction should be evaluated in controlled trials in tropical and sub-tropical Asian and African countries, along with evaluation of new aetiology diagnostics, research into common pneumonia mortality pathways and interventions targeting those pathways.
| 19,010,371
|
Quantum-like model of cognitive decision making and information processing.
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In this paper we offer the quantum-like (QL) representation of the Shafir-Tversky statistical effect which is well known in cognitive psychology. We apply the so-called contextual approach. We consider the Shafir-Tversky effect to result from mixing statistical data obtained in incompatible contexts which are involved, e.g. in Prisoner's Dilemma or in more general games in which the disjunction effect can be found. As a consequence, the law of total probability is violated for the experimental data obtained in experiments on cognitive psychology by Shafir and Tversky [Shafir, E., Tversky, A., 1992. Thinking through uncertainty: nonconsequential reasoning and choice. Cogn. Psychol. 24, 449-474] as well as Tversky and Shafir [Tversky, A., Shafir, E., 1992. The disjunction effect in choice under uncertainty. Psychol. Sci. 3, 305-309]. Moreover, we can find a numerical measure of contextual incompatibility (the so-called coefficient of interference) as well as represent contexts which are involved in Prisoner's Dilemma (PD) by probability amplitudes-normalized vectors ("mental wave functions"). We remark that statistical data from Shafir and Tversky [Shafir, E., Tversky, A., 1992. Thinking through uncertainty: nonconsequential reasoning and choice. Cogn. Psychol. 24, 449-474] and Tversky and Shafir [Tversky, A., Shafir, E., 1992. The disjunction effect in choice under uncertainty. Psychol. Sci. 3, 305-309] experiments differ crucially from the point of view of mental interference. The second one exhibits the conventional trigonometric (cos-type) interference while the first one exhibits even the so-called hyperbolic (cosh-type) interference. We discuss the QL processing of information by cognitive systems, especially, the QL decision making and both classical and QL rationality and ethics.
| 19,010,383
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Sex differences in the neuroanatomy of human mirror-neuron system: a voxel-based morphometric investigation.
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Females frequently perform better in empathy, interpersonal sensitivity, and emotional recognition than do males. The mirror-neuron system has been proposed to play an important role in social cognition. It remains to be clarified, however, whether the neuroanatomy underlying the human mirror neuron system exhibits sex differences. With the use of voxel-based morphometry analysis, a whole-brain unbiased technique to characterize regional cerebral volume differences in structural magnetic resonance images, concurrent with the dispositional empathy measures, we demonstrate that young adult females (n=25) had significantly larger gray matter volume in the pars opercularis and inferior parietal lobule than matched males (n=25) participants. Moreover, higher self-report scores in the emotional empathic disposition was tightly coupled with larger gray matter volume of the pars opercularis across all female and male participants (P=0.002). These results indicate that the existence of neuroanatomical sex differences in the human mirror-neuron system. They also suggest that the network of the human mirror-neuron system is strongly linked to empathy competence.
| 19,010,397
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Preparation of ultrafine fenofibrate powder by solidification process from emulsion.
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The solidification process from emulsion, which consisted of emulsifier, water and molten drug as oil phase without use of any organic solvent, was firstly employed to prepare ultrafine fenofibrate (FF) powder. The effects of stirring speed and volume ratios of hot emulsion to cold water on the particle size and morphology were discussed as well as the impacts of different emulsifiers on emulsion. The produced ultrafine powder was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, specific surface area analysis and a dissolution test. XRD patterns and FT-IR spectra showed that the ultrafine FF was crystalline powder with the structure and the components similar to those of bulk drug. The product had a mean particle size of about 3 microm with a narrow distribution from 1 microm to 5 microm. The specific surface area reached up to 6.23 m(2)/g, which was about 25 folds as large as that of bulk FF. In the dissolution tests, about 96.1% of ultrafine FF was dissolved after 120 min, while there was only 38.1% of bulk drug dissolved, proving that the dissolution property of ultrafine FF was significantly improved when compared to commercial drug.
| 19,010,406
|
Oligonucleotide-based assays for integrase activity.
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Oligonucleotide assays have been invaluable for elucidation of the molecular mechanisms of retroviral integrases. A suite of rapid and sensitive fluorescence assays to measure the DNA binding, processing, and joining activities of integrase (IN) is described here. The assays are especially useful for characterizing the major activities of the enzyme, and for handling large numbers of samples efficiently. They can greatly facilitate further biochemical and structural analyses for HIV-1 and other IN proteins. The assays can also be adapted for moderate-high throughput testing of various inhibitory compounds.
| 19,010,419
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The alpha-1-antitrypsin gene promoter in human A549 lung derived cells, and a novel transcription initiation site.
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Alpha-1-antitrypsin (AAT), also called serine proteinase inhibitor A1 (Serpin A1), is the most abundant serpin in human plasma. A major physiological role of AAT is to protect the lung from the destructive effects of excess uninhibited neutrophil elastase. During inflammation, circulating levels of AAT may increase twofold-to-threefold as part of the acute-phase response. The liver is the main contributor to this increase. However, local synthesis may provide an important mechanism for controlling neutrophil elastase activity at sites of inflammation, and previous studies have shown a marked increase in production after cytokine stimulation. In the current study we report a distinct transcription initiation site for AAT expression in the lung alveolar epithelial cell line A549, which is located nine bases upstream of the previously mapped full-length monocyte transcription start-site, and show using site-directed mutagenesis that two Sp1 sites and a putative TATA box are functional. EMSA experiments provide evidence for Sp1 and Sp3 binding to these two Sp1 sites. We have also mapped the minimal promoter region and a cell-specific element essential for expression in A549 cells, both of which reside in an 865bp fragment upstream of the transcription start-site. Understanding the mechanisms of AAT gene regulation in a lung-derived cell line has important implications for understanding the control of localised lung tissue damage which occurs as a result of excess proteolytic activity.
| 19,010,440
|
Phylogeography and evolutionary history of dengue virus type 3.
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In this study, we revisited the phylogeography of the three of major DENV-3 genotypes and estimated its rate of evolution, based on the analysis of the envelope (E) gene of 200 strains isolated from 31 different countries around the world over a time period of 50 years (1956-2006). Our phylogenetic analysis revealed a geographical subdivision of DENV-3 population in several country-specific clades. Migration patterns of the main DENV-3 genotypes showed that genotype I was mainly circumspect to the maritime portion of Southeast-Asia and South Pacific, genotype II stayed within continental areas in South-East Asia, while genotype III spread across Asia, East Africa and into the Americas. No evidence for rampant co-circulation of distinct genotypes in a single locality was found, suggesting that some factors, other than geographic proximity, may limit the continual dispersion and reintroduction of new DENV-3 variants. Estimates of the evolutionary rate revealed no significant differences among major DENV-3 genotypes. The mean evolutionary rate of DENV-3 in areas with long-term endemic transmissions (i.e., Indonesia and Thailand) was similar to that observed in the Americas, which have been experiencing a more recent dengue spread. We estimated the origin of DENV-3 virus around 1890, and the emergence of current diversity of main DENV-3 genotypes between the middle 1960s and the middle 1970s, coinciding with human population growth, urbanization, and massive human movement, and with the description of the first cases of DENV-3 hemorrhagic fever in Asia.
| 19,010,450
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Deletion of bradykinin B1 receptor reduces renal fibrosis.
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The Kallikrein-kinin system works through activation of two receptors. One constitutive, named B2 receptor (B2R) and another inducible, denominated B1 receptor (B1R). In renal fibrosis, B2R receptor activation appears to be protective, however B1R participation is unveiled. The aim of this study was to analyze how the deletion of the B1R would modify tissue responses after unilateral ureteral obstruction (UUO). For that, B1R knockout (B1KO) and wild-type mice (B1B2WT) were subjected to UUO and sacrificed at days 1, 5 and 14. Renal dysfunction was assayed by urine proteinuria/creatinine ratio and percentage of tubulointerstitial fibrosis. Kidneys were harvested at day 5 to analyze anti and pro-inflammatory molecules expression by real-time PCR. We demonstrated that at all time points, B1KO mice presented lower proteinuria/creatinine ratio from bladder urine. B1KO protection was reinforced by its lower tubular interstitial fibrosis percentage at day 14 (B1B2WT: 12.16+/-1.53% vs. B1KO: 6.73+/-1.07%, p<0.02). UUO was able to induce B1R expression and its highest transcription was achieved at day 5. At this day, B1KO had significant lower expression of pro-inflammatory molecules such as TGF-beta, MCP-1, OPN and IL-6 and higher anti-inflammatory components, as IL-10 and HO-1. Herein, we observed that B1R deletion may be an important component in renal fibrosis prevention.
| 19,010,452
|
Neuropeptide Y (NPY) and NPY Y1 receptor in periodontal health and disease.
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Neuropeptide Y (NPY) coordinates inflammation and bone metabolism which are central to the pathogenesis of periodontitis. The present study was designed to determine whether NPY was quantifiable in human gingival crevicular fluid (GCF) and to test the null hypothesis that GCF levels of NPY were the same in periodontal health and disease. A subsidiary aim was to determine the potential functionality of released NPY by detecting the presence of NPY Y1 receptors in gingival tissue. The periodontitis group consisted of 20 subjects (10 females and 10 males) mean age 41.4 (S.D. 9.6 years). The control group comprised 20 subjects (10 females and 10 males) mean age 37.4 (S.D. 11.7 years). NPY levels in GCF were measured in periodontal health and disease by radioimmunoassay. NPY Y1 receptor expression in gingival tissue was determined by Western blotting of membrane protein extracts from healthy and inflamed gum. Healthy sites from control subjects had significantly higher levels of NPY than diseased sites from periodontitis subjects. NPY Y1 receptor protein was detected in both healthy and inflamed gingival tissue by Western blotting. The significantly elevated levels of NPY in GCF from healthy compared with periodontitis sites suggests a tonic role for NPY, the functionality of which is indicated by the presence of NPY Y1 receptors in local gingival tissue.
| 19,010,457
|
Diabetes causes the accelerated loss of cartilage during fracture repair which is reversed by insulin treatment.
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Fracture healing in diabetic individuals and in animal models of diabetes is impaired. To investigate mechanisms by which diabetes may affect fracture healing we focused on the transition from cartilage to bone, a midpoint in the fracture healing process. Femoral fractures were induced in mice rendered diabetic by multiple low dose streptozotocin treatment and compared to matching normoglycemic mice. One group of diabetic animals was treated with slow release insulin to maintain normal serum glucose levels. The results indicate that there was relatively little difference in the initial formation of the fracture callus on day 10. However, on day 16 the diabetic group had significantly smaller callus, greater loss of cartilage and enhanced osteoclastogenesis that was normalized by treatment with insulin when assessed by histomorphometric analysis. Chondrocyte apoptosis was significantly higher in diabetic mice and this increase was blocked by insulin. These changes were accompanied by diabetes-increased mRNA levels of RANKL, TNF-alpha, and ADAMTS-4 and -5 measured by real-time PCR, which was reversed by insulin treatment. On days 16 and 22 bone formation within the callus of diabetic mice was significantly less than the normoglycemic and brought to normal levels by insulin treatment. These results suggest that a significant effect of diabetes on fracture healing is increased chondrocyte apoptosis and osteoclastogenesis that accelerates the loss of cartilage and reduces the anlage for endochondral bone formation during fracture repair. That insulin reverses these effects demonstrates that they are directly related to the diabetic condition.
| 19,010,456
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A probabilistic corpus-based model of syntactic parallelism.
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Work in experimental psycholinguistics has shown that the processing of coordinate structures is facilitated when the two conjuncts share the same syntactic structure [Frazier, L., Munn, A., & Clifton, C. (2000). Processing coordinate structures. Journal of Psycholinguistic Research, 29(4) 343-370]. In the present paper, we argue that this parallelism effect is a specific case of the more general phenomenon of syntactic priming-the tendency to repeat recently used syntactic structures. We show that there is a significant tendency for structural repetition in corpora, and that this tendency is not limited to syntactic environments involving coordination, though it is greater in these environments. We present two different implementations of a syntactic priming mechanism in a probabilistic parsing model and test their predictions against experimental data on NP parallelism in English. Based on these results, we argue that a general purpose priming mechanism is preferred over a special mechanism limited to coordination. Finally, we show how notions of activation and decay from ACT-R can be incorporated in the model, enabling it to account for a set of experimental data on sentential parallelism in German.
| 19,010,463
|
The effects of the extraocular muscles on eye impact force-deflection and globe rupture response.
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There are over 1.9 million eye injuries per year in the United States, with blunt impacts the cause of approximately one-half of all civilian eye injuries. No previous experimental studies have investigated the effects of the extraocular muscles on the impact response of the eye. A spring-powered blunt impactor was used to determine the effects that the extraocular muscles have on the force-deflection and injury response of the eye to blunt trauma. A total of 10 dynamic impact tests were performed at 8.2+/-0.1m/s on five human cadaver heads. With the extraocular muscles left intact, the average peak force was found to be 271+/-51N at 7.5+/-0.9mm posterior translation; with the muscles transected, the average peak force was 268+/-26N at 7.6+/-1.3mm of posterior translation. From the data available from this study, the peak impact force and overall amount of translation during the impact are not affected by the extraocular muscles. Additionally, from the data presented in this study, the eyes with the extraocular muscles left intact do not rupture with a different injury pattern or display an increased risk for rupture than the eyes with the extraocular muscles transected. Therefore, it is believed that the effect of the extraocular muscles is not sufficient to drastically alter the response of the eye under dynamic impact. This information is useful to characterize the boundary conditions that dictate the eye response from blunt impact and can be used to define the biofidelity requirements for the impact response of synthetic eyes.
| 19,010,469
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Depletion of high-abundance proteins from human plasma using a combination of an affinity and pseudo-affinity column.
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Human serum albumin (HSA) and immunoglobulin G (IgG) represent over 75% of all proteins present in human plasma. These high-abundance proteins prevent the detection of low-abundance proteins which are potential markers for various diseases. The depletion of HSA and IgG is therefore essential for further proteome analysis. In this paper we describe the optimization of conditions for selective depletion of HSA and IgG using affinity and pseudo-affinity chromatography. A BIA Separations CIM (convective interaction media) Protein G disk was applied for the removal of IgG and the Mimetic Blue SA A6XL stationary phase for the removal of HSA. The binding and the elution buffer for CIM Protein G disk were chosen on the basis of the peak shape. The dynamic binding capacity was determined. It was shown to be dependent on the buffer system used and independent of the flow rate and of the concentration of IgG. Beside the binding capacity for the IgG standard, the binding capacity was also determined for IgG in human plasma. The Mimetic Blue SA A6XL column was characterized using human plasma. The selectivity of the depletion was dependent on the amount of human plasma that was loaded on the column. After the conditions on both supports had been optimized, the Mimetic Blue SA A6XL stationary phase was combined with the CIM Protein G disk in order to simultaneously deplete samples of human plasma. A centrifuge spin column that enables the removal of IgG and HSA from 20 microL of human plasma was designed. The results of the depletion were examined using sodium dodecyl sulfate polyacrylamide gel electrophoresis and two-dimensional gel electrophoresis.
| 19,010,473
|
Quantification of the interactions between a cationic dye and humic substances in aqueous solutions.
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Humic substances (HS) are ubiquitous in natural waters. Due to their plentiful binding sites, HS play an important role in the mobilization and transport of pollutants in natural environments. However, the presence state of HS causes difficulty in exploring the interactions between HS and pollutants in aqueous solutions. In this study, an effective and rapid method was proposed to quantify the interaction between a cationic dye and HS in aqueous solutions. Humic acids (HA) and Toluidine Blue (TB) were respectively used as the model HS and model cationic dye. This characterization method was based on the binding of TB to HA molecule to form a TB-HA complex. From the difference between the visible spectra of the dye and the TB-HA complex, the adsorption capability of HA could be evaluated. Results demonstrate that the Langmuir adsorption isotherm theory was appropriate to describe the interaction between TB and HA. Both pH and ionic strength had significant effects on the adsorption of TB onto HA. These results suggest that the binding reaction was a physical adsorption driven by the electrostatic interaction.
| 19,010,483
|
Wettability of model fountain solutions: the influence on topo-chemical and -physical properties of offset paper.
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The surface chemical and physical character of offset paper was studied before and after application of model fountain solutions based on isopropyl alcohol and an alcohol-free surfactant solution. The paper surface features were characterised with atomic force microscopy and the surface energies were determined by contact angle measurements. Changes in the surface chemical properties induced by the fountain solutions were investigated with X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectroscopy. Coated papers wetted with the surfactant solution revealed a slight increase in the root mean square roughness, but the isopropyl alcohol solution led to no observable changes. The change in sub-micro roughness is ascribed not only to substrate swelling or migration of coating constituents but also to the presence of surfactant on the surface. A change in the surface energy and particularly the polar contribution was observed after application of the surfactant solution. The X-ray photoelectron spectroscopy showed an increase in the oxygen-to-carbon ratio, which confirms the presence of surfactant on the surface. Time-of-flight secondary ion mass spectroscopy showed that the isopropyl alcohol solution did not change the elemental composition of the surface whereas the surfactant solution clearly did so. The distribution of surfactant on the surface was confirmed by mapping the characteristic fragments of the molecule.
| 19,010,484
|
Prediction of Salmonella in seawater by total and faecal coliforms and Enterococci.
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The power of total coliforms (TC), faecal coliforms (FC) and Enterococci to predict the presence of Salmonella in seawater was investigated. Indicator cut-off values with the most satisfactory combination of sensitivity and specificity in predicting Salmonella presence were 1,000 CFU 100ml(-1)TC, 200 CFU 100ml(-1)FC, 500 CFU 100ml(-1) Enterococci. When TC or FC were used for Salmonella prediction in logistic regression, then the addition of another indicator did not have a statistically significant effect. When Enterococci were used for prediction, then the addition of either of the two other indicators led to a statistically significant improvement (P=0.001 for TC, P=0.003 for FC). These results suggest that using either TC or FC alone provided an adequate indicator of Salmonella presence, but a statistically significant improvement is possible over using Enterococci alone. Concerning Enterococci, European Union limits for excellent coastal water quality (100 CFU 100 ml(-1)) and United States Environmental Protection Agency criteria for marine bathing waters (35 CFU 100 ml(-1)) have the same value in predicting Salmonella absence (92.5%).
| 19,010,501
|
Developmental levels of phospholipase D isozymes in the brain of developing rats.
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The developmental levels of phospholipase D (PLD) isozymes was examined in the cerebrum and hindbrain of the developing rat to better understand the involvement of PLD in brain development. Western blot analysis of PLD in the cerebrum showed that PLD1, a major PLD isoform in the brain, was detected weakly in the cerebrum at day 17 embryonic stage and its levels gradually increased until postnatal day 35 and remained unaltered thereafter. In the hindbrain, comprising the cerebellum and pons, the peak level of PLD1 was detected at 21 days postnatally and declined progressively thereafter. The level of PLD2 in both the cerebrum and hindbrain was minimal compared to that of PLD1. Based on immunohistochemistry, PLD was detected in some neurons and glial cells in the cerebrum. In the hindbrain, PLD was found in some Purkinje cells and some cells of the molecular layer, as well as glial cells, consistent with the results obtained from Western blot analysis. These findings suggest that PLD may differentially play a role in the course of early development of the brain, with special reference to the cerebrum and hindbrain, in rats.
| 19,010,519
|
The clinical significance of hepatic parenchymal metastasis in patients with primary epithelial ovarian cancer.
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The objective of this study was to determine the clinical significance of hepatic parenchymal metastasis on survival in patients with advanced epithelial ovarian cancer. We conducted a retrospective review of ovarian cancer patients with stages IIIc and IV hepatic parenchymal metastasis who were treated at the National Cancer Center in Korea between January 2001 and January 2008. Hepatic metastases were divided into unresectable, hematogenous parenchymal metastasis and resectable, parenchymal metastasis from peritoneal seeding. One hundred twenty patients were identified, 113 of whom were included in the study. The stage IIIc group included 97 patients, and the group with stage IV disease and hepatic parenchymal metastasis included 16 patients. Of the 16 patients with hepatic parenchymal metastasis, 2 patients had unresectable, hematogenous parenchymal metastasis with a poor prognosis compared to the patients with resectable, hepatic parenchymal metastasis from peritoneal seeding. Fourteen patients with hepatic parenchymal metastases from peritoneal seeding underwent complete resection without complications as follows: wedge resection (n=7), segmentectomy (n=5), and hemi-hepatectomy (n=2). Age, tumor grade, histology, serum CA-125 level, and the rate of optimal debulking were similar in patients with stage IIIc disease and patients with stage IV disease who had resectable, hepatic parenchymal metastasis from peritoneal seeding. The 5-year progression free survival rate and the 5-year overall survival rate for patients with stage IIIc disease and patients with stage IV disease and hepatic parenchymal metastasis from peritoneal seeding were 25 and 23% (p=0.8063), and 55 and 51% (p=0.5671), respectively. Our findings suggest that complete hepatic resection should be attempted for patients with hepatic parenchymal metastasis from peritoneal seeding.
| 19,010,521
|
The effect of RGD density on osteoblast and endothelial cell behavior on RGD-grafted polyethylene terephthalate surfaces.
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Hybrid materials combining polyethylene terephthalate and different types of cells (endothelial and osteoblastic cells) have been developed thanks to the covalent grafting of different densities of RGD containing peptides onto the polymer surface. Biomimetic modifications were performed by means of a three-step reaction procedure: creation of COOH functions, coupling agent grafting and the immobilization of the RGDC peptides. High resolution mu-imager was used to evaluate RGD densities (varying between 0.6 and 2.4 pmol/mm(2)) and has exhibited the stability of the surface grafted peptides when treated in harsh conditions. The efficiency of this route for biomimetic modification of a PET surface was demonstrated by measuring the adhesion of MC3T3 and HSVEC cells and by focal adhesion observation. Results obtained prove that a minimal RGDC density of 1 pmol/mm(2) is required to improve MC3T3 and HSVEC cells responses. Indeed, cells seeded onto a RGDC-modified PET with a density higher than 1 pmol/mm(2) were able to establish focal adhesion as visualized by fluorescence microscope compared to cells immobilized onto unmodified PET and RGDC-modified PET with densities lower than 1 pmol/mm(2). Moreover, the number of focal contacts was enhanced by the increase of RGDC peptide densities grafted onto the material surface. With this study we proved that the density of peptides immobilized on the surface is a very important parameter influencing osteoblast or endothelial cell adhesion and focal contact formation.
| 19,010,529
|
The geometric control of E14 and R1 mouse embryonic stem cell pluripotency by plasma polymer surface chemical gradients.
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Plasma polymer surfaces were fabricated such that the cell response to a range of carboxylic acid concentrations on a single sample could be investigated. Surface chemical gradients from hydrophobic plasma polymerised octadiene (OD) to a more hydrophilic plasma polymerised acrylic acid (AA) were formed on glass coverslips. Surface characterisation of the chemical gradients was performed using X-ray photoelectron spectroscopy to determine elemental composition. Following culture of E14 and R1 mouse embryonic stem cells (mES) in differing culture media, cell pluripotency was determined by alkaline phosphatase staining. The results demonstrate that for these cell lines the capacity for self-renewal is maintained if the cells are restricted in their spreading to <120 microm2.
| 19,010,532
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Induction of apoptosis in leukemic cell lines treated with captopril, trandolapril and losartan: a new role in the treatment of leukaemia for these agents.
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Renin-angiotensin system (RAS) in the bone marrow is related to proliferation and cellular differentiation. We investigated the effect of ACE inhibitors (ACEI) captopril (>1mM) and trandolapril (>0.05 mM) and losartan (0.2 mM) on K562 cell line and K562 transfected with c-myc, bcl-x and bcl-2 (KmycB, Kbclx and Kbcl2 respectively). RAS components, proliferation, apoptosis and c-myc expression were analyzed. ACEI and losartan inhibited cell growth, decreased c-myc expression and increased apoptosis. These effects seem to be associated to angiotensin II-induced Smad activation. This work offers a new possible line of treatment for some acute myeloid leukemias and a new area of clinical research.
| 19,010,543
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Influenza vaccination coverages among children, adults, health care workers and immigrants in Spain: related factors and trends, 2003-2006.
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This study sought to: describe influenza vaccination coverage among Spanish children, adults, health care workers (HCWs), and immigrants according to the 2006 Spanish National Health Survey (NHS); and analyze the time trend for the period 2003-2006. We analyzed 38,329 questionnaires drawn from the 2006 NHS, covering subjects aged 6 months and over. As the dependent variable, we took the answer to the question, "Did you (or your child) have a 'flu shot in the last campaign?". Independent variables were age group, gender, nationality, occupation (HCWs), and coexistence of chronic conditions. In 2006, vaccination coverage for the Spanish population was: 22.2% overall; 6.8% for all children; and 19.1% for children with a chronic medical condition. Coverages were: 66.8% among subjects aged >/=65 years; 26.6% among high-risk subjects aged <65 years; and 24.2% among HCWs. A significantly lower proportion of immigrants reported vaccination than did indigenous subjects. After controlling for possible confounders, the likelihood of having been vaccinated in 2006 was lower than in 2003 for the entire population (adjusted OR 92, 95%CI 0.86-0.97). In specific target groups, however, coverage underwent a significant reduction from 2003 to 2006 among high-risk subjects aged 16-64 years, and immigrants. Significant improvements were found among subjects aged over 64 years, and children. Available data show unacceptably low levels of influenza vaccination coverage among high-risk subjects aged under 65 years, children with chronic medical conditions, and HCWs. A special effort is thus called for to implement strategies that have demonstrated their effectiveness in enhancing vaccination coverages.
| 19,010,553
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Acute effects of three high-fat meals with different fat saturations on energy expenditure, substrate oxidation and satiety.
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To compare the acute effects of three fatty meals with different fat quality on postprandial thermogenesis, substrate oxidation and satiety. Twenty-nine healthy men aged between 18 and 30 years participated in a randomised crossover trial comparing the thermogenic effects of three isocaloric meals: high in polyunsaturated fatty acids from walnuts, high in monounsaturated fatty acids from olive oil, and high in saturated fatty acids from fat-rich dairy products. Indirect calorimetry was used to determine resting metabolic rate, respiratory quotient, 5-h postprandial energy expenditure and substrate oxidation. Satiety was estimated by using visual analogue scales and measuring caloric intake in a subsequent ad libitum meal. Five-h postprandial thermogenesis was higher by 28% after the high-polyunsaturated meal (p=0.039) and by 23% higher after the high-monounsaturated meal (p=0.035) compared with the high-saturated meal. Fat oxidation rates increased nonsignificantly after the two meals rich in unsaturated fatty acids and decreased nonsignificantly after the high-saturated fatty acid meal. Postprandial respiratory quotient, protein and carbohydrate oxidation, and satiety measures were similar among meals. Fat quality determined the thermogenic response to a fatty meal but had no clear effects on substrate oxidation or satiety.
| 19,010,571
|
Sampling atmospheric pesticides with SPME: Laboratory developments and field study.
|
To estimate the atmospheric exposure of the greenhouse workers to pesticides, solid phase microextraction (SPME) was used under non-equilibrium conditions. Using Fick's law of diffusion, the concentrations of pesticides in the greenhouse can be calculated using pre-determined sampling rates (SRs). Thus the sampling rates (SRs) of two modes of SPME in the lab and in the field were determined and compared. The SRs for six pesticides in the lab were 20.4-48.3 mL min(-1) for the exposed fiber and 0.166-0.929 mL min(-1) for the retracted fiber. In field sampling, two pesticides, dichlorvos and cyprodinil were detected with exposed SPME. SR with exposed SPME for dichlorvos in the field (32.4 mL min(-1)) was consistent with that in the lab (34.5 mL min(-1)). SR for dichlorvos in the field (32.4 mL min(-1)) was consistent with that in the lab (34.5 mL min(-1)). The trends of temporal concentration and the inhalation exposure were also obtained.
| 19,010,574
|
A geospatial analysis of persons opting out of an exception from informed consent out-of-hospital clinical trial.
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For trials involving exception from informed consent, some IRBs require that community members be allowed to "opt out" prior to enrollment. We tested for geospatial clustering of opt-out requests and the associated census tract characteristics in one study region. This was a retrospective study at a single site of a multicenter exception from informed consent resuscitation trial. We collected and geocoded mailing addresses for persons requesting opt-out bracelets over 16 months, then tested for geospatial clustering using geographic information systems (GIS) analysis. Characteristics for tracts with and without bracelet clustering were compared using univariate tests, multivariable regression, and classification and regression tree (CART) analysis. We received 395 phone calls requesting 718 bracelets, of which 673 were analyzable. Of 397 census tracts in the region, 208 (52%) had at least one request and 38 (10%) demonstrated clustering. In multivariable models, an increasing proportion of family households (OR .90, 95%CI .85-.93), veterans (OR .91, 95%CI .81-1.02), and renters (OR .96, 95%CI .92-.99) were associated with lower odds of requesting an opt-out bracelet, while census tracts with higher income had higher odds of opting-out (OR 1.07, 95%CI 1.02-1.11). Using CART, the proportion of family households and graduate education identified the majority of opt-out requests by census tracts (cross-validation sensitivity 92%, specificity 56%). Opt-out requests for an exception from informed consent trial at one study site were geographically clustered and associated with certain population demographics. These findings may help identify key target groups for community consultation in future trials.
| 19,010,580
|
The use of the laryngeal tube disposable (LT-D) by paramedics during out-of-hospital resuscitation-an observational study concerning ERC guidelines 2005.
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In the current guidelines of the European Resuscitation Council (ERC), tracheal intubation, as an instrument for securing the airway during resuscitation, has become less important for persons not trained in this method. For those persons, different supraglottic airway devices are recommended by the ERC. The present investigation deals with the application of the laryngeal tube disposable (LT-D) during pre-hospital resuscitation by paramedics. During a period of 2 years (2006-2008), we registered all cardiac arrest situations in which the LT-D had been applied according to the ERC guidelines 2005. Therefore, we investigated one emergency medical system in Germany. During the defined period, 92 resuscitation attempts, recorded on standardised data sheets, were included. The LT-D was used in 46% of all cardiac arrest situations. Overall, the LT-D was successfully inserted in more than 90% of all cases on first attempt. In 95% of all cases, no problems concerning ventilation of the patient were described. As an alternative airway device recommended by the ERC in 2005, the LT-D may enable airway control rapidly and effectively. Additionally, by using the LT-D, a reduced "no-flow-time" and a better outcome may be possible.
| 19,010,582
|
The cutoff values of intrathecal interleukin 8 and 6 for predicting the neurological outcome in cardiac arrest victims.
|
To evaluate the changes in inflammatory cytokines, such as interleukin (IL)-8 and IL-6, in the cerebrospinal fluid (CSF) and serum, and to identify any correlations with the neurological outcomes in patients resuscitated from cardiopulmonary arrest (CPA). This study was designed as a prospective clinical trial. Thirteen patients, who were resuscitated from out-of-hospital CPA and survived for more than 48 h, were enrolled in this study. Arterial blood was taken from the patients at 48 h after the return of spontaneous circulation (ROSC) and CSF was taken by lumbar puncture at the same time. In the CSF, the median levels of IL-8 and IL-6 in the patients resuscitated from CPA were significantly higher than those in the control subjects (1311 pg/ml vs 82 pg/ml, P<0.001; 2040 pg/ml vs 1 pg/ml, P<0.001, respectively). The Glasgow Outcome Scale (GOS) score evaluated at 6 months after the ROSC correlated significantly with the levels of IL-8 and IL-6. The cutoff values and sensitivity values with 100% specificity for the prediction of an unfavorable neurological outcome were 1423 pg/ml and 86% for IL-8, and 2708 pg/ml and 86% for IL-6, respectively. We demonstrated the cutoff values of IL-8 and IL-6 in the CSF to predict the neurological outcome in the patients resuscitated from CPA. The excessive inflammatory cytokine reactions in the brain might therefore be related to the poor neurological outcome in patients with post-resuscitation encephalopathy.
| 19,010,583
|
Dibucaine effects on structural and elastic properties of lipid bilayers.
|
In this work we report the interaction effects of the local anesthetic dibucaine (DBC) with lipid patches in model membranes by Atomic Force Microscopy (AFM). Supported lipid bilayers (egg phosphatidylcholine, EPC and dimyristoylphosphatidylcholine, DMPC) were prepared by fusion of unilamellar vesicles on mica and imaged in aqueous media. The AFM images show irregularly distributed and sized EPC patches on mica. On the other hand DMPC formation presents extensive bilayer regions on top of which multibilayer patches are formed. In the presence of DBC we observed a progressive disruption of these patches, but for DMPC bilayers this process occurred more slowly than for EPC. In both cases, phase images show the formation of small structures on the bilayer surface suggesting an effect on the elastic properties of the bilayers when DBC is present. Dynamic surface tension and dilatational surface elasticity measurements of EPC and DMPC monolayers in the presence of DBC by the pendant drop technique were also performed, in order to elucidate these results. The curve of lipid monolayer elasticity versus DBC concentration, for both EPC and DMPC cases, shows a maximum for the surface elasticity modulus at the same concentration where we observed the disruption of the bilayer by AFM. Our results suggest that changes in the local curvature of the bilayer induced by DBC could explain the anesthetic action in membranes.
| 19,010,585
|
Isolation of Ochrobactrum sp.QZ2 from sulfide and nitrite treatment system.
|
A bacterial strain QZ2 was isolated from sludge of anoxic sulfide-oxidizing (ASO) reactor. Based on 16S rDNA sequence analysis and morphology, the isolate was identified as Ochrobactrum sp. QZ2. The strain was facultative chemolithotroph, able of using sulfide to reduce nitrite anaerobically. It produced either elemental sulfur or sulfate as the product of sulfide oxidation, depending on the initial sulfide and nitrite concentrations. The optimum growth pH and temperature for Ochrobactrum sp. QZ2 were found as 6.5-7.0 and 30 degrees C, respectively. The specific growth rate (micro) was found as 0.06 h(-1) with a doubling time of 19.75h; the growth seemed more sensitive to highly alkaline pH. Ochrobactrum sp. QZ2 catalyzed sulfide oxidation to sulfate was more sensitive to sulfide compared with nitrite as indicated by IC(50) values for sulfide and nitrite utilization implying that isolate was relatively more tolerant to nitrite. The comparison of physiology of Ochrobactrum sp. QZ2 with those of other known sulfide-oxidizing bacteria suggested that the present isolate resembled to Ochrobactrum anthropi in its denitrification ability.
| 19,010,594
|
Liquid phase microextraction and ultratrace determination of cadmium by modified graphite furnace atomic absorption spectrometry.
|
A powerful microextraction technique was used for determination of cadmium in water samples using liquid phase microextraction (LPME) followed by graphite furnace atomic absorption spectrometry (GF-AAS). In a preconcentration step, cadmium was extracted from a 2 ml of its aqueous sample in the pH 7 as 5,7-dibromoquinoline-8-ol (DBQ) complex into a 4 microl drop of benzyl alcohol. After extraction, the micro drop was retracted and directly transferred into a graphite tube modified by [W.Rh.Pd](c). Some effective parameters on extraction and complex formation, such as type and volume of organic solvent, pH, concentration of chelating agent, extraction time and stirring rate were optimized. Under the optimum conditions, the enrichment factor and recovery were 450% and 90%, respectively. The calibration graph was linear in the range of 0.008-1 microg L(-1) with correlation coefficient of 0.9961 under the optimum conditions of the recommended procedure. The detection limit based on the 3Sb criterion was 0.0035 microg L(-1) and relative standard deviation (RSD) for eight replicate measurement of 0.1 microg L(-1) and 0.4 microg L(-1) cadmium was 5.2% and 4.5%, respectively. The characteristic concentration was 0.0032 microg L(-1) equivalent to a characteristic mass of 12.8 fg. In order to evaluate the accuracy and recovery of the presented method the procedure was applied to the analysis of reference materials and seawater.
| 19,010,596
|
Self-initiated tobacco cessation and substance use outcomes among adolescents entering substance use treatment in a managed care organization.
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Adolescents with substance use (SU) problems have high rates of tobacco use, yet SU treatment has historically ignored treatment for tobacco use. Barriers to such efforts include the belief that tobacco cessation could compromise other SU abstinence. This study examines self-initiated tobacco cessation and 12-month alcohol and drug abstinence in adolescents entering SU treatment in a private, managed care organization. Self-initiated tobacco cessation at 6 months, and at both 6 and 12 months, were related to higher odds of drug abstinence but not alcohol abstinence. Self-initiated tobacco cessation was not related to poor SU outcomes, and may be important to maintaining drug abstinence. Implementing tobacco cessation efforts in SU treatment can be challenging, but comprised SU outcomes may not be a barrier. The positive associations for drug abstinence and lack of associations for alcohol abstinence could be due to differences in motivation, medical conditions, or to the illicit nature of drug use. Tobacco use has serious long-term health consequences, and tobacco cessation efforts in adolescent SU treatment programs need further research.
| 19,010,600
|
Epidemiology of risk factors and symptoms associated with menopause in Spanish women.
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(1) To assess the prevalence of risk factors for osteoporosis and cardiovascular disease and the prevalence and severity of the appearance of menopausal symptoms among Spanish menopausal women. (2) To identify the main factors responsible for this severity. (3) To detect symptom differences between perimenopausal and postmenopausal women. Cross-sectional descriptive study encompassing women aged 45-65 years in the whole Spanish territory. The study population sample was collected through random sampling. A total of 10,514 women were included. The sociodemographic, medical history and lifestyle data were assessed by means of a survey. The Kupperman scale was used to assess the severity of menopausal symptoms. The prevalence of risk factors for osteoporosis and cardiovascular disease were 67.6% and 74.8%, respectively. The most common risk factors were physical inactivity (53.6%), obesity (44.3%), arterial hypertension (36.6%), hypercholesterolemia (31.4%), low calcium intake (30.1%) and smoking (28.7%). The predominant symptoms experienced by menopausal women were hot flushes (51.4%), insomnia (45.7%) and irritability (42.2%). These were severe in 3.3% of the sample, moderate in 27.3%, mild in 24.6% while 44.8% had no symptoms. The prevalence of joint pain (40.1%) and depressive mood (40%) was higher in perimenopausal than in postmenopausal women. Logistic regression analysis showed that there were differences for age, BMI, smoking, social class and poor consumption of dairy products in the severity of menopausal symptoms. A high prevalence of risk factors for osteoporosis and cardiovascular disease was observed in our study. The main factors contributing to more severe menopausal symptoms were age, BMI, smoking social class and poor consumption of dairy products. In general, postmenopausal women presented significantly higher rates of menopausal symptoms when compared to perimenopausal women.
| 19,010,615
|
2-Methoxyestradiol attenuates hypertension and coronary vascular remodeling in spontaneously hypertensive rats.
|
Accumulating data provide evidence that some metabolites of 17beta-estradiol are biologically active and mediate multiple effects on the cardiovascular and renal systems. We investigated the effect of 2-methoxyestradiol (an active metabolite of estradiol with non-feminizing activity) on the development of hypertension and myocardial vascular remodeling in male and female ovarectomized SHR. Rats were divided into five groups: intact females, ovarectomized (OVX), OVX+ 2-methoxyestradiol (2ME), control males, and male+2ME. Systolic blood pressure was determined from 10 to 18 weeks. Structural changes in coronary vessels were quantified by an image analyzer. Immunoblotting of phosphorylated ERK1/2 and NADPH oxidase activity were performed on mesenteric arteries. Treatment with 2ME reduced the increase in systolic blood pressure in male and ovarectomized rats to values not different from those obtained in intact females. Myocardial arterioles and small arteries showed significant increases in wall-to-lumen ratio and perivascular fibrosis in male and ovarectomized rats when compared with intact females. NADPH oxidase activity was increased in mesenteric arteries from males and ovarectomized females as compared with intact females. Finally, the expression of phosphorilated ERK1/2 were significantly higher in mesenteric arteries from male and ovariectomized animals than in those from intact females. Those effects of ovarectomy and gender differences were totally or partially prevented by treatment with 2-methoxyestradiol. These data demonstrate that 2-methoxyestradiol protects the vasculature from hypertension-induced myocardial arterial remodeling in male and ovarectomized SHR, and that might be in part related to decreased superoxide generation and ERK1/2 activation.
| 19,010,616
|
Role of an anti-acetonemic diet in reducing the need for tonsillectomy in children with recurrent tonsillitis.
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The aim of this study was to investigate the effectiveness of an anti-acetonemic diet in reducing the need for tonsillectomy especially in the first years of life in children with recurrent tonsillitis. From 2002 to 2005 we carried out a prospective randomized study enrolling 1200 children aged 2-10 who were referred to our outpatient services complaining of recurrent tonsillitis. Children were randomly assigned to the case group or to the control group. In case children, clinical signs of persistent ketosis were investigated and a hypolipidic anti-acetonemic diet was prescribed. We compared the mean age of children who underwent tonsillectomy and evaluated the association between an anti-acetonemic diet and avoidance of tonsillectomy. The association between an anti-acetonemic diet and avoidance of tonsillectomy was statistically significant; the mean age of case children who underwent tonsillectomy resulted significantly higher than that of control children. By prescribing an appropriate dietetic regimen we obtained a significant decrease in the number of tonsillectomies for recurrent tonsillitis and an increase in the mean age of the children treated surgically.
| 19,010,622
|
C-kit protein expression in Wilms' tumour: an immunohistochemical study.
|
The use of a non-toxic tyrosine kinase receptor inhibitor, Imatinib Mesylate (IM), has become an ever-more common therapeutic alternative in some Kit (CD117) over-expressing neoplasms. As the treatment eligibility for these drugs hinges on CD117 expression, Kit immunostaining has recently been widely examined in various tumours. There are only limited data in the literature on the expression of c-kit expression in Wilms' Tumour. We examined CD117 expression in Wilms' tumour in order to correlate this marker with clinico-pathological data and to clarify its prognostic impact. This study included 40 cases of Wilms' tumour. Sections from paraffin-embedded tumour samples were immunostained by standard ABC technique using c-kit polyclonal antibody with antigen retrieval. In the case of C-kit positive examples, the staining was focal, with patch distribution. On univariate analysis, significantly higher c-kit expression was observed in neoplasms in a more advanced stage of development than those in a less advanced stage (p=0.0055). In addition, over-expression of this marker was significantly correlated with the death of patients (p=0.0294) and recurrences of disease (p=0.0118). Moreover, all our Wilms' tumour anaplastic subtypes showed over-expression of c-kit and this was significantly higher than in favourable histology examples (p=0.0182). The results of multivariate analysis, instead, did not reveal any correlation of c-kit expression and prognosis. In our opinion these results could be due to the number of cases considered which is not particularly high. However, it seems likely that c-kit expression could be a secondary event related to tumour progression and could be influenced by chemotherapy and unfavourable histology.
| 19,010,635
|
[Inflammation and acute brain injuries in intensive care].
|
Patients with acute brain injuries or susceptibility to post-surgery stroke are a major therapeutic challenge for intensive care and anaesthesiology medicine. The control of systemic stress involved in brain damage is necessary to reduce the frequency and severity of secondary brain lesions. Inflammation is known to be directly involved in acute brain lesions. The brain is a major participant in inflammation control through activation or inhibition effects. The exact mechanisms involved in deleterious effects following acute brain injuries due to inflammation are still unknown. This non-exhaustive study will expose the principal processes involved in inflammatory brain disease and explain the consequences of peripheral inflammation for the brain. Neuroprotection strategies in acute neuroinflammation will be reported with a focus on anaesthetic agents and the inflammation cascade.
| 19,010,639
|
A pharmaceutical preparation of Salvia miltiorrhiza protects cardiac myocytes from tumor necrosis factor-induced apoptosis and reduces angiotensin II-stimulated collagen synthesis in fibroblasts.
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Salvia miltiorrhiza is a medicinal herb commonly used in traditional Chinese medicine for the prevention and treatment of cardiovascular disease. This study investigated the effects of Cardiotonic Pill (CP), a pharmaceutical preparation of Salvia miltiorrhiza, on cardiac myocytes and fibroblasts with respect to the viability, proliferation, and collagen synthesis in these cells under various conditions. A cardiac myocyte line, H9c2, and primarily cultured fibroblasts from rat hearts were incubated with CP over a broad concentration range (50-800 microg/ml) under normal cultures, conditions of ischemia (serum-free culture), and stimulation by angiotensin II (AII, 100 nM), hydrogen peroxide (H(2)O(2), 50-200 microM), or tumor necrosis factor alpha (TNFalpha, 40 ng/ml) for 24-48 h. Cell growth, apoptosis, DNA and collagen synthesis, and expression of relevant genes were assessed via cell number study, morphological examination, Annexin-V staining, flow-cytometry, [(3)H]-thymidine or [(3)H]-proline incorporation assay, and Western blotting analysis. It was found that (1) at therapeutic (50 microg/ml) and double therapeutic (100 microg/ml) concentrations, CP did not significantly affect normal DNA synthesis and cell growth in these cardiac cells, while at higher (over 4-fold therapeutic) concentrations (200-800 microg/ml), CP decreased DNA synthesis and cell growth and increased cell death; (2) CP treatment (50 microg/ml) significantly inhibited TNFalpha-induced apoptosis in myocytes, with 12.3+/-1.46% cells being apoptosis in CP treatment group and 37.0+/-7.34% in the control (p<0.01), and simultaneously, expression of activated (phosphorylated) Akt protein was increased by about 2 folds in the CP-treated cells; and (3) in cultured fibroblasts, CP significantly reduced AII-induced collagen synthesis in a concentration-dependent manner (by approximately 50% and approximately 90% reduction of AII-induced collagen synthesis at 50 and 100 microg/ml, respectively). Thus, Salvia miltiorrhiza preparation CP is physiologically active on cardiac cells. The actions by CP to reduce apoptotic damage in myocytes and collagen synthesis in fibroblasts may help to preserve the heart function and reduce heart failure risk. The actions by CP to inhibit DNA synthesis and cell growth, which occurred at over therapeutic doses, may weaken the ability of heart repair. Further studies are needed to identify the chemical compounds in this herbal product that are responsible for these observed physiological effects.
| 19,010,649
|
Social injecting and other correlates of high-risk sexual activity among injecting drug users in northern Vietnam.
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Sexual risk and STDs are relatively high among injecting drug users (IDUs) in Vietnam. We sought to determine characteristics of sexually active IDUs and correlates of high-risk sexual practices among IDUs in Bac Ninh province in northern Vietnam. We used data collected for a community-based cross-sectional pilot study to identify correlates of recent high-risk sex (>1 sex partner and inconsistent/no condom use in the past year). Factors associated with high-risk sex were identified using logistic regression. Among 216 sexually active male IDUs, one third (n=72) had engaged in high-risk sex within the last year. IDUs who reported injecting with others more frequently, having someone else inject their drugs at last injection, sharing needles or sharing any injection equipment were more likely to have reported recent high-risk sex. Factors independently associated with high-risk sexual activity were not injecting oneself [AOR: 2.22; 95% CI (1.09-4.51)], and sharing needles in the past 12 months [AOR: 2.57; 95% CI (1.10-5.99)]. IDUs who inject socially and IDUs who share needles are likely to engage in high-risk sexual behaviours and may serve as an important bridge group for epidemic HIV transmission in Vietnam. In addition to messages regarding the dangers of sharing needles and other injection equipment, preventive interventions among newly initiated IDUs should also focus on reducing sexual risk.
| 19,010,656
|
A glucose biosensor based on Prussian blue/chitosan hybrid film.
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Based on electrodeposition of Prussian blue (PB) and chitosan (CS) directly on gold electrode, a hybrid film of PB/CS has been prepared. PB in this film shows a good stability compared with pure PB film when it worked in neutral and weak alkalescent solution and can act as redox mediator. It provides the potential application of such film in biosensor fabrication. A glucose biosensor was fabricated by electrodepositing glucose oxidase (GOD)/CS film on this PB/CS modified electrode. The optimum experimental conditions of biosensor for the detection of glucose have been studied in detail. Under the optimal conditions, a linear dependence of the catalytic current upon glucose concentration was obtained in the range of 2x10(-6) to 4x10(-4)M with a detection limit of 3.97x10(-7)M. The resulting biosensor could be applied to detect the blood sugar in real samples without any pretreatment.
| 19,010,659
|
Treatment and phosphorus removal from high-concentration organic wastewater by the yeast Hansenula anomala J224 PAWA.
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A flocculent yeast, Hansenula anomala J224 PAWA, bred in this study, accumulated twice as much phosphorus as the wild type. Over a 30-d period, PAWA removed 70-80% of dissolved total phosphorus from sweet-potato and barley shochu wastewaters (alcoholic distillery wastewaters) while the wild type removed only 30%. Waste sludge was easily separated from effluent wastewater because PAWA cells made large flocks that rapidly settled. Component analysis suggested that PAWA sludge could be used as a protein source for feedstuff and as a phosphorus source for fertilizer. Under anaerobic conditions, denitrification was rapid, resulting in the removal of large amounts of nitrogen from barley shochu wastewater. These results suggest that small shochu manufacturers could benefit from using PAWA to remove phosphorus and organic compounds and then by using a combination of the upflow anaerobic sludge blanket and the downflow hanging sponge method (UASB-DHS method) for nitrification/denitrification.
| 19,010,663
|
Synthesis and antiinflammatory activity of some new 1,3,5-trisubstituted pyrazolines bearing benzene sulfonamide.
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Nineteen new 2-pyrazoline bearing benzenesulfonamide derivatives were synthesized by condensing chalcones with 4-hydrazinonbenzenesulfonamide hydrochloride. Their chemical structures were proved by means of IR, (1)H NMR, (13)C NMR, mass spectroscopic and elemental analyses data. These compounds were tested at dose of 20mg/kg for their anti-inflammatory activity in carrageenan-induced rat paw edema model and volume of paw edema was measured at 0, 3 and 5h. Two compounds 3k and 3l were found to be more active than celecoxib throughout the study (at 3 and 5h). While two other compounds 3m and 3n showed more potent activity than celecoxib at 5h. They are devoid of ulcerogenic potential when administered orally at a dose of 60 mg/kg. Compounds (3k-m) showed COX-1 and COX-2 inhibitory activity at 0.05 microM.
| 19,010,670
|
N,N-Dichloroaminosulfonic acids as novel topical antimicrobial agents.
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2-Dichloroamino-2-methyl-propane-1-sulfonic acid sodium salt (2a), a stable derivative of endogenous N,N-dichlorotaurine (1), has been identified and is under development as a topical antimicrobial agent. Structure-activity relationships of analogs were explored to achieve optimal antimicrobial activity with minimal mammalian toxicity while maintaining the desired stability. All the analogs synthesized showed antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans in the range of 1-128 microg/mL and cytotoxicity against mammalian L929 cells in the range 80-1900 microg/mL.
| 19,010,674
|
Engineered production of iso-migrastatin in heterologous Streptomyces hosts.
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Glutarimide-containing polyketides such as migrastatin (MGS) are well known for their ability to inhibit tumor cell migration. We have previously shown that MGS is derived from iso-migrastatin (iso-MGS) via a H(2)O-mediated ring-expansion rearrangement. A bacterial artificial chromosome (BAC) library of Streptomyces platensis NRRL18993, an iso-MGS producer, was constructed. From this library, pBS11001, a BAC clone harboring the intact iso-MGS biosynthetic gene cluster, was identified. Mobilization of pBS11001 into five heterologous Streptomyces hosts afforded recombinant strains, SB11001, SB11002, SB11003, SB11004, and SB11005, respectively. Under a standard set of media and fermentation conditions, the recombinant strains all produced the same profile of iso-MGS as that of S. platensis NRRL18993. These findings highlight the strength and flexibility of the BAC-based technology for natural product production and engineering in heterologous Streptomyces model hosts.
| 19,010,685
|
[Two observations of evisceration after caesarean section performed according the so-called Stark procedure].
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Two cases of evisceration after caesarean sections performed according the Misgav Ladach General Hospital procedure (Stark's procedure) are reported. In these cases, omentum was sutured between the edges of fascia recti, creating a weakness of the abdominal sheath. These cases claim about a strict procedure for fascia suture. Also, these cases question about the parietal peritoneal closure and the drawing of rectus muscles, which are vertical breaks; so, these sutures close transversal incision of the abdominal wall with cross sutures, which are very secure.
| 19,010,708
|
Optical test strip for trace Hg(II) based on doped sol-gel film.
|
Optical test strip based on the use of Br-PADAP as a sensitive reagent immobilised into sol-gel thin film for detection of Hg(II) in aqueous solution had been thoroughly carried out. It has a square-sensing zone (1.0 cm x 1.0 cm) containing the sensitive reagent necessary to produce response to trace level of mercury. This method offer sensitivity and simplicity in detecting Hg(II) as no prior treatment or extraction is required. A linear response was attained in the Hg(II) concentration in the range of 0.5-2.5 ppm with calculated limit of detection of 6.63 ppb. This method also showed a reproducible result with relative standard deviation (R.S.D.) of 2.15% and response time of approximately 5 min. Interference studies showed that Al(III), Co(II) and Ni(II) significantly interfered during the determination. The developed sensor has been validated against Atomic Absorption Spectroscopy method and proven comparable.
| 19,010,723
|
The spectroscopic detection of drugs of abuse in fingerprints after development with powders and recovery with adhesive lifters.
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The application of powders to fingerprints has long been established as an effective and reliable method for developing latent fingerprints. Fingerprints developed in situ at a crime scene routinely undergo lifting with specialist tapes and are then stored in evidence bags to allow secure transit and also to preserve the chain of evidence. In a previous study we have shown that exogenous material within a fingerprint can be detected using Raman spectroscopy following development with powders and lifting with adhesive tapes. Other reports have detailed the use of Raman spectroscopy to the detection of drugs of abuse in latent fingerprints including cyanoacrylate-fumed fingerprints. This study involves the application of Raman spectroscopy for the analysis of drugs of abuse in latent fingerprints for fingerprints that had been treated with powders and also subsequently lifted with adhesive tapes. Samples of seized ecstasy, cocaine, ketamine and amphetamine were supplied by East Sussex Police and by the TICTAC unit at St. Georges Hospital Tooting. Contaminated fingerprints were deposited on clean glass slides. The application of aluminium or iron based powders to contaminated fingerprints did not interfere with the Raman spectra obtained for the contaminants. Contaminated fingerprints developed with powders and then lifted with lifting tapes were also examined. The combination of these two techniques did not interfere with the successful analysis. The lifting process was repeated using hinge lifters. As the hinge lifters exhibited strong Raman bands the spectroscopic analysis was more complex and an increase in the number of exposures to the detector allowed for improved clarification. Spectral subtraction was performed to remove peaks due to the hinge lifters using OMNIC software. Raman spectra of developed and lifted fingerprints recorded through evidence bags were obtained and it was found that the detection process was not compromised. Although the application of powders did not interfere with the detection process the time taken to locate the contaminant was increased due to the physical presence of more material within the fingerprint.
| 19,010,725
|
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