Infections due to Actinobacillus actinomycetemcomitans

Three cases are described which show the typical range of infections which may be caused by Actinobacillus actinomycetemcomitans. namely an actinomycosis-like infection. a prosthetic cardiac valve endocarditrs and a post-traumatic soft-tissue infection. Cultural studies are detailed. and a short review of the disease-producing potential of this organism and its treatment is presented

Parent satisfaction with the Loire Infant Follow-up Team (LIFT) premature and at-risk infant network in the Pays-de-la-Loire area (France)

BACKGROUND: The Loire Infant Follow-up Team (LIFT) is a network for caring for premature infants whose gestational age is 34 WA or less and at-risk neonates in the Pays-de-la-Loire area in France. The network aims to screen for clinical anomalies early and to propose adapted care. Trained physicians follow the included children in a standardized manner at 3, 6, 9, 12, and 18 months and 2 years, with a specific examination by psychologists at 2 years. The aim of the study was to assess the satisfaction of the parents of the children followed.METHODS: To evaluate parent satisfaction, a questionnaire from the Consumer Satisfaction Survey (CSS) in its French version was sent to parents whose infants were 2 years old, stratifying on the presence of an anomaly. The questioner had 39 items, with 8 specific items on the network and 31 from the CSS. The questionnaire was mailed twice in September 2006. RESULTS: Out of 300 questionnaires mailed, 269 were returned (rate 89.7 %). The questionnaire was assessed using principal component analysis with 2 dimensions for the 30 items common to all children, one of which covered empathy with physicians and the other with the consulting psychologists at 2 years. The validity was good (Cronbach coefficient, 0.91). The answers to overall questions such as "We are satisfied with the care in the network" scored 16.1±0.7/20, with 90 % "totally agree" or "moderately agree" responses. The "The care is perfect" scored 14.6±0.7/20 with 78 % agreeing with the statement. The total score for 30 general questions was 14.6±3.1 (median, 14.9). The total score was lower for infants with anomalies: 13.7±3.3 versus 14.9±2.9 (P<0.01). The answers with a low score (<10) were given by 22 parents (8.2 %). There was no significant relation between the total score or the satisfaction score and neonatal events. CONCLUSION: A postal survey is helpful to know the views of parents on the follow-up of their infants. This good level of satisfaction seems to stem from the parents feeling they belong to the network, the quality of the relationships with personnel, and the doctors\u27 empathy, as well as the number of contacts between parents and the network coordinator

Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation

The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Deletion of a gene encoding a putative deacetylase, Agd3, leads to defects in GAG deacetylation, biofilm formation, and virulence. Here, we show that Agd3 deacetylates GAG in a metal-dependent manner, and is the founding member of carbohydrate esterase family CE18. The active site is formed by four catalytic motifs that are essential for activity. The structure of Agd3 includes an elongated substrate-binding cleft formed by a carbohydrate binding module (CBM) that is the founding member of CBM family 87. Agd3 homologues are encoded in previously unidentified putative bacterial exopolysaccharide biosynthetic operons and in other fungal genomes. The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Here, the authors study an A. fumigatus enzyme that deacetylates GAG in a metal-dependent manner and constitutes a founding member of a new carbohydrate esterase family.Bio-organic Synthesi

The interaction between artemether-lumefantrine and lopinavir/ritonavir-based antiretroviral therapy in HIV-1 infected patients

Background: Artemether-lumefantrine is currently the most widely recommended treatment of uncomplicated malaria. Lopinavir–based antiretroviral therapy is the commonly recommended second-line HIV treatment. Artemether and lumefantrine are metabolised by cytochrome P450 isoenzyme CYP3A4, which lopinavir/ritonavir inhibits, potentially causing clinically important drug-drug interactions. Methods: An adaptive, parallel-design safety and pharmacokinetic study was conducted in HIV-infected (malaria-negative) patients: antiretroviral-naïve and those stable on lopinavir/ritonavir-based antiretrovirals. Both groups received the recommended six-dose artemether-lumefantrine treatment. The primary outcome was day-7 lumefantrine concentrations, as these correlate with antimalarial efficacy. Adverse events were solicited throughout the study, recording the onset, duration, severity, and relationship to artemether-lumefantrine. Results: We enrolled 34 patients. Median day-7 lumefantrine concentrations were almost 10-fold higher in the lopinavir than the antiretroviral-naïve group [3170 versus 336 ng/mL; p = 0.0001], with AUC(0-inf) and Cmaxincreased five-fold [2478 versus 445 μg.h/mL; p = 0.0001], and three-fold [28.2 versus 8.8 μg/mL; p < 0.0001], respectively. Lumefantrine Cmax, and AUC(0-inf) increased significantly with mg/kg dose in the lopinavir, but not the antiretroviral-naïve group. While artemether exposure was similar between groups, Cmax and AUC(0-8h) of its active metabolite dihydroartemisinin were initially two-fold higher in the lopinavir group [p = 0.004 and p = 0.0013, respectively]. However, this difference was no longer apparent after the last artemether-lumefantrine dose. Within 21 days of starting artemether-lumefantrine there were similar numbers of treatment emergent adverse events (42 vs. 35) and adverse reactions (12 vs. 15, p = 0.21) in the lopinavir and antiretroviral-naïve groups, respectively. There were no serious adverse events and no difference in electrocardiographic QTcF- and PR-intervals, at the predicted lumefantrine Tmax. Conclusion: Despite substantially higher lumefantrine exposure, intensive monitoring in our relatively small study raised no safety concerns in HIV-infected patients stable on lopinavir-based antiretroviral therapy given the recommended artemether-lumefantrine dosage. Increased day-7 lumefantrine concentrations have been shown previously to reduce the risk of malaria treatment failure, but further evidence in adult patients co-infected with malaria and HIV is needed to assess the artemether-lumefantrine risk : benefit profile in this vulnerable population fully. Our antiretroviral-naïve patients confirmed previous findings that lumefantrine absorption is almost saturated at currently recommended doses, but this dose-limited absorption was overcome in the lopinavir group

Clinical Outcomes in 3343 Children and Adults with Rheumatic Heart Disease from 14 Low and Middle Income Countries: 2-Year Follow-up of the Global Rheumatic Heart Disease Registry (the REMEDY study)

Background: There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease or information on their predictors. We report the 2-year follow-up of individuals with rheumatic heart disease from 14 low- and middle-income countries in Africa and Asia. Methods: Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for 2 years to assess mortality, congestive heart failure, stroke or transient ischemic attack, recurrent acute rheumatic fever, and infective endocarditis. Results: Vital status at 24 months was known for 2960 (88.5%) patients. Two-thirds were female. Although patients were young (median age, 28 years; interquartile range, 18–40), the 2-year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.80–3.11), congestive heart failure (HR, 2.16; 95% CI, 1.70–2.72), New York Heart Association functional class III/IV (HR, 1.67; 95% CI, 1.32–2.10), atrial fibrillation (HR, 1.40; 95% CI, 1.10–1.78), and older age (HR, 1.02; 95% CI, 1.01–1.02 per year increase) at enrollment. Postprimary education (HR, 0.67; 95% CI, 0.54–0.85) and female sex (HR, 0.65; 95% CI, 0.52–0.80) were associated with lower risk of death. Two hundred and four (6.9%) patients had new congestive heart failure (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or transient ischemic attack (8.45/1000 patient-years), 19 (0.6%) had recurrent acute rheumatic fever (3.49/1000 patient-years), and 20 (0.7%) had infective endocarditis (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/transient ischemic attack or systemic embolism. Patients from low- and lower-middle–income countries had significantly higher age- and sex-adjusted mortality than patients from upper-middle–income countries. Valve surgery was significantly more common in upper-middle–income than in lower-middle– or low-income countries. Conclusions: Patients with clinical rheumatic heart disease have high mortality and morbidity despite being young; those from low- and lower-middle–income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and the treatment of clinical rheumatic heart disease are required to improve outcomes. </jats:sec

Reliability analysis of a 65nm Rad-Hard SRAM-Based FPGA for CERN applications

In search of alternative solutions for Field Programmable Gate Arrays (FPGA) that can withstand the higher dose levels foreseen in the upcoming upgrades of the Large Hadron Collider (LHC), a new Radiation Hardened FPGA is targeted. More specifically, in this work, the effects of proton induced radiation on a 65nm Rad Hard SRAM-Based FPGA are investigated, while applying tailored tests for each resource of the FPGA. The results of the study are then used to perform a Reliability analysis of this device, adapted to the CERN radiation environment while using standard models