Spatial and Temporal Dynamics of Hepatitis B Virus D Genotype in Europe and the Mediterranean Basin

Hepatitis B virus genotype D can be found in many parts of the world and is the most prevalent strain in south-eastern Europe, the Mediterranean Basin, the Middle East, and the Indian sub-continent. The epidemiological history of the D genotype and its subgenotypes is still obscure because of the scarcity of appropriate studies. We retrieved from public databases a total of 312 gene P sequences of HBV genotype D isolated in various countries throughout the world, and reconstructed the spatio-temporal evolutionary dynamics of the HBV-D epidemic using a Bayesian framework

E-NTPDases in human airways: Regulation and relevance for chronic lung diseases

Chronic obstructive lung diseases are characterized by the inability to prevent bacterial infection and a gradual loss of lung function caused by recurrent inflammatory responses. In the past decade, numerous studies have demonstrated the importance of nucleotide-mediated bacterial clearance. Their interaction with P2 receptors on airway epithelia provides a rapid ‘on-and-off’ signal stimulating mucus secretion, cilia beating activity and surface hydration. On the other hand, abnormally high ATP levels resulting from damaged epithelia and bacterial lysis may cause lung edema and exacerbate inflammatory responses. Airway ATP concentrations are regulated by ecto nucleoside triphosphate diphosphohydrolases (E-NTPDases) which are expressed on the mucosal surface and catalyze the sequential dephosphorylation of nucleoside triphosphates to nucleoside monophosphates (ATP → ADP → AMP). The common bacterial product, Pseudomonas aeruginosa lipopolysaccharide (LPS), induces an acute reduction in azide-sensitive E-NTPDase activities, followed by a sustained increase in activity as well as NTPDase 1 and NTPDase 3 expression. Accordingly, chronic lung diseases, including cystic fibrosis (CF) and primary ciliary dyskinesia, are characterized by higher rates of nucleotide elimination, azide-sensitive E-NTPDase activities and expression. This review integrates the biphasic regulation of airway E-NTPDases with the function of purine signaling in lung diseases. During acute insults, a transient reduction in E-NTPDase activities may be beneficial to stimulate ATP-mediated bacterial clearance. In chronic lung diseases, elevating E-NTPDase activities may represent an attempt to prevent P2 receptor desensitization and nucleotide-mediated lung damage

Oxidative protein labeling in mass-spectrometry-based proteomics

Oxidation of proteins and peptides is a common phenomenon, and can be employed as a labeling technique for mass-spectrometry-based proteomics. Nonspecific oxidative labeling methods can modify almost any amino acid residue in a protein or only surface-exposed regions. Specific agents may label reactive functional groups in amino acids, primarily cysteine, methionine, tyrosine, and tryptophan. Nonspecific radical intermediates (reactive oxygen, nitrogen, or halogen species) can be produced by chemical, photochemical, electrochemical, or enzymatic methods. More targeted oxidation can be achieved by chemical reagents but also by direct electrochemical oxidation, which opens the way to instrumental labeling methods. Oxidative labeling of amino acids in the context of liquid chromatography(LC)–mass spectrometry (MS) based proteomics allows for differential LC separation, improved MS ionization, and label-specific fragmentation and detection. Oxidation of proteins can create new reactive groups which are useful for secondary, more conventional derivatization reactions with, e.g., fluorescent labels. This review summarizes reactions of oxidizing agents with peptides and proteins, the corresponding methodologies and instrumentation, and the major, innovative applications of oxidative protein labeling described in selected literature from the last decade

Economic implications of neonatal intensive care unit collaborative quality improvement

Objective. To make measurable improvements in the quality and cost of neonatal intensive care using a multidisciplinary collaborative quality improvement model. Design. Interventional study. Data on treatment costs were collected for infants with birth weight 501 to 1500 g for the period of January 1, 1994 to December 31, 1997. Data on resources expended by hospitals to conduct this project were collected in a survey for the period January 1, 1995 to December 31, 1996. Setting. Ten self-selected neonatal intensive care units (NICUs) received the intervention. They formed 2 subgroups (6 NICUs working on infection, 4 NICUs working on chronic lung disease). Nine other NICUs served as a contemporaneous comparison group. Patients. Infants with birth weight 501 to 1500 g born at or admitted within 28 days of birth between 1994 and 1997 to the 6 study NICUs in the infection group (N = 2993) and the 9 comparison NICUs (N = 2203); infants with birth weight 501 to 1000 g at the 4 study NICUs in the chronic lung disease group (N = 663) and the 9 comparison NICUs (N = 1007). Interventions. NICUs formed multidisciplinary teams which worked together to undertake a collaborative quality improvement effort between January 1995 and December 1996. They received instruction in quality improvement, reviewed performance data, identified common improvement goals, and implemented "potentially better practices" developed through analysis of the processes of care, literature review, and site visits. Main Outcome Measures. Treatment cost per infant is the primary economic outcome measure. In addition, the resources spent by hospitals in undertaking the collaborative quality improvement effort were determined. Results. Between 1994 and 1996, the median treatment cost per infant with birth weight 501 to 1500 g at the 6 project NICUs in the infection group decreased from $57 606 to$46 674 (a statistical decline); at the 4 chronic lung disease hospitals, for infants with birth weights 501 to 1000 g, it decreased from $85 959 to$77 250. Treatment costs at hospitals in the control group rose over the same period. There was heterogeneity in the effects among the NICUs in both project groups. Cost savings were maintained in the year following the intervention. On average, hospitals spent $68 206 in resources to undertake the collaborative quality improvement effort between 1995 and 1996. Two thirds of these costs were incurred in the first year, with the remaining third in the second year. The average savings per hospital in patient care costs for very low birth weight infants in the infection group was$2.3 million in the post-intervention year (1996). There was considerable heterogeneity in the cost savings across hospitals associated with participation in the collaborative quality improvement project. Conclusion. Cost savings may be achieved as a result of collaborative quality improvement efforts and when they occur, they appear to be sustainable, at least in the short run. In high-cost patient populations, such as infants with very low birth weights, cost savings can quickly offset institutional expenditures for quality improvement efforts