Evolutionary dynamics of Newcastle disease virus

A comprehensive dataset of NDV genome sequences was evaluated using bioinformatics to characterize the evolutionary forces affecting NDV genomes. Despite evidence of recombination in most genes, only one event in the fusion gene of genotype V viruses produced evolutionarily viable progenies. The codon-associated rate of change for the six NDV proteins revealed that the highest rate of change occurred at the fusion protein. All proteins were under strong purifying (negative) selection; the fusion protein displayed the highest number of amino acids under positive selection. Regardless of the phylogenetic grouping or the level of virulence, the cleavage site motif was highly conserved implying that mutations at this site that result in changes of virulence may not be favored. The coding sequence of the fusion gene and the genomes of viruses from wild birds displayed higher yearly rates of change in virulent viruses than in viruses of low virulence, suggesting that an increase in virulence may accelerate the rate of NDV evolution.     

Gastroesophageal Reflux Disease and Obesity. Pathophysiology and Implications for Treatment

Although the etiology of gastroesophageal reflux disease (GERD) is multifactorial, the pathophysiology of the disease in morbidly obese patients remains incompletely understood. The aims of this study were to compare in morbidly obese (body mass index (BMI) ≥35) and nonmorbidly patients (BMI <35) with GERD: (a) lower esophageal sphincter (LES) profile; (b) esophageal body function; and (c) esophageal acid exposure. We reviewed esophageal manometry and ambulatory 24-hour pH monitoring studies of 599 consecutive patients with GERD (DeMeester score >14.7). Patients were divided into two groups according to the BMI: (1) 520 patients (86.8%) with BMI <35 and (2) 79 patients (13.2%) with BMI ≥35. While the DeMeester score was not different between the two groups, morbidly obese patients had higher LES pressure and higher amplitude of peristalsis in the distal esophagus (DEA). Among these patients, LES and DEA pressures were often hypertensive. A linear regression model showed that BMI, LES pressure, LES abdominal length, and DEA were independently associated with the DeMeester score. These data showed that: (a) BMI was independently associated to the severity of GERD; and (b) in most morbidly obese patients with GERD, reflux occurred despite normal or hypertensive esophageal motility. These findings show that the pathophysiology of GERD in morbidly obese patients might differ from that of nonobese patients, suggesting the need for a different therapeutic approach. Presented at the 47th Annual Meeting of the Society for Surgery of the Alimentary Tract, Los Angeles, CA, May 22–24, 2006.     

Human papillomavirus type distribution in cervical cancer in Delhi, India.

This hospital-based study in New Delhi, North India was performed to evaluate the prevalence of human papillomavirus (HPV) in cases of invasive cervical carcinoma (ICC). A total of 10 cases presenting with an obvious cervical growth were included in this study. 108 cases that was shown to be ICC on histology (101 squamous cell carcinomas, 4 adenocarcinomas, and one neuroendocrine carcinoma) were included in the analysis. DNA was extracted from tumor tissue and HPV genotype was determined by a consensus PCR assay using a reverse line blot hybridization assay. Of 106 evaluable cases, 104 (98.1%) were positive for HPV infection. Twelve different high-risk HPV types were found. There were 125 infections, 119 of which were high risk. Six cases had associated low risk infections. HPV 16 was the commonest type, seen in 73.6% cases followed by HPV 18 (14.2%) and 45 (11.3%). A vaccine with 100% efficacy in prevention of HPV 16 and 18 infections would theoretically reduce the total cancer burden in New Delhi by more than 75% (assuming 100% coverage). Increasing the genotype spectrum (e.g. valency) if the existing vaccines would be expected to have only a modest impact on the potential for cervical protection.     

超负荷剂量氯吡格雷减少PCI术患者围操作期心肌梗死：ARMYDA-2的研究结果（抗血小板治疗降低血管成形术中心肌损害）

积极抗血小板治疗对减少经皮冠脉介入（PCI）后的心肌损伤和早期心脏事件甚为重要。虽然观察性研究资料提示，超负荷剂量氯吡格雷可能比常用剂量更有效，但尚无随机性临床试验验证过此假说。此项研究采用前瞻性、随机对照的方法，来对比分析600mg超负荷剂量与300mg常规负荷剂量氯吡格雷提高PCI后改善心肌缺血的安全性、有效性。255例计划行PCI的患者在术前4～8h服用氯吡格雷，随机分入氯吡格雷600mg（n=126）和300mg（n=129）组。两组均检测术前及介入后8h、24h肌酸激酶MB（CK—MB）、肌钙蛋白Ⅰ（TnⅠ）及肌红蛋白的水平。一级终点为30d时死亡、MI或TLR的发生。结果显示，超负荷剂量组一级终点发生率为4％，     

Early interleukin-1 receptor antagonist elevation in patients with acute myocardial infarction

OBJECTIVES: We sought to evaluate interleukin-1 receptor antagonist (IL-1Ra) levels in patients with ST-segment elevation acute myocardial infarction (AMI) upon emergency department (ED) admission in order to assess the sensitivity of such a determination by comparison with common markers of myocardial necrosis. BACKGROUND: Inflammatory markers are elevated in patients with unstable coronary syndromes, but IL-1Ra levels during the early phases of AMI have not been previously investigated. METHODS: Levels of IL-1Ra were measured in 44 consecutive patients with AMI and compared with creatine kinase (CK), CK-MB, troponin I, myoglobin, and C-reactive protein (CRP). RESULTS: Upon admission, 82% of patients had elevated (>230 pg/ml) IL-1Ra levels, compared with 41% of patients with raised CK (p = 0.001), CK-MB (45%, p = 0.002), troponin I (57%, p = 0.027), myoglobin (48%, p = 0.004), and CRP (57%, p = 0.019) levels. The IL-1Ra values were significantly higher in patients with heralded AMI than in those without pre-infarction angina (671 vs. 320 pg/ml, p = 0.013). The sensitivity of IL-1Ra determination increased to 86% when chest pain duration was < or =3 h and to 91% if heralded infarction occurred. CONCLUSIONS: Our study indicates that, unlike markers of necrosis, an increase of IL-1Ra levels occurs early in patients with AMI, is more significant in those with heralded infarction and symptom onset < or =3 h, and precedes the release of markers of necrosis. Thus, IL-1Ra determination may be an important early adjuvant toward the diagnosis of AMI in the ED.     

The clinical reality of guidelines for primary prevention of cardiovascular disease in type 2 diabetes in Italy

Background

Health aspects of seafood have primarily been linked to n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Although animal studies have suggested beneficial contributions from taurine, highly abundant in seafood, its effect in humans is obscure. This study evaluates the combined effects of n-3 PUFA and taurine.

Methods

Healthy volunteers (n = 80) were recruited to a 7-week double-blind and parallel intervention trial. One group (n = 39) received fish pâté (36 g/day) enriched in n-3 (1.1 g EPA + DHA/day) and the second (n = 41) an identical pâté enriched both in n-3 and taurine (425 mg/day).

Results

Total cholesterol (TC) (−5%, P < 0.001), low-density lipoprotein (LDL)-cholesterol (−8%, P < 0.001) and Apo B (−4%, P < 0.001) decreased more in the n-3 + taurine compared to the n-3 group. A significant within-group enhancement of high-density lipoprotein (HDL)-cholesterol was demonstrated in the n-3 + taurine group (6%, P < 0.0001). Reductions in triacylglycerol (TG) (−16%, P < 0.05 in n-3; −14%, P < 0.05 in n-3 + taurine), thromboxane B₂ (TxB₂) (−21%, P < 0.001 in n-3; −15%, P < 0.05 in n-3 + taurine), tumor necrosis factor (TNFα) (−24%, P < 0.001 in n-3; −12%, P < 0.05 in n-3 + taurine) and monocyte chemotactic protein (MCP-1) (−12%, P < 0.05 in n-3; −6%, P < 0.0001 in n-3 + taurine) were evident in both groups. Reductions in interleukin (IL)-6 (−16%, P < 0.05) and LTB₄ (−18%, P < 0.05) were only significant in the n-3 group.

Conclusions

The effects, particularly on blood lipids, of combining n-3 PUFA's and taurine proved superior to those of n-3 alone.