Impact of the number of fitted Debye-Waller factors on EXAFS fitting

EXAFS fit applied to asymmetric systems may imply the fit of parameters for many scattering paths. We illustrate on some examples how fitting too many independent DWs may lead to incorrect distances and mask some structural details. We question the physical meaning of the fitted DW values and we propose some ideas to avoid this problem

EXAFS Debye-Waller factors issued from Car-Parrinello molecular dynamics: Application to the fit of oxaliplatin and derivatives

One of the main pitfalls in EXAFS fitting is correlation among parameters, which can lead to unreli- able fits. The use of theoretical Debye-Waller factors (DWs) is a promising way to reduce the number of fitted parameters. When working with molecular dynamics, it is not only possible to evaluate DWs from the statistical distributions issued from the trajectory but also to estimate the distribution an- harmonicity, and to compute simulated average EXAFS spectra that can be fitted as experimental ones, in order to assess the ability of EXAFS fitting to recover information on DWs, as well as other structural and spectroscopical parameters. The case studied is oxaliplatin, a third generation anticancer drug. The structural information and the simulated average spectra were derived from a Car-Parrinello molecular dynamics (CP-MD) trajectory of a compound closely related to oxaliplatin. We present the DWs issued from this simulation and their use, by taking their theoretical absolute values (no DW fitted) or their ratios (one DW fitted). In this second approach, the fit of oxaliplatin experimental spectra leads to DWs values very close to the theoretical ones. This shows that the CP-MD trajectory provides a good representation of the distance distributions for oxaliplatin. Trans- ferability of oxaliplatin DWs, for all relevant single and multiple scattering paths, to closely related compounds is proven for the case of bis(oxalato)platinum(II) and bis(ethylene diamine)platinum(II).Ministerio de Ciencia e Innovación CTQ2011-25932Junta de Andalucía P06-FQM-0148

Heightened immune response to autocitrullinated porphyromonas gingivalis peptidylarginine deiminase: a potential mechanism for breaching immunologic tolerance in rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is characterised by autoimmunity to citrullinated proteins, and there is increasing epidemiologic evidence linking Porphyromonas gingivalis to RA. P gingivalis is apparently unique among periodontal pathogens in possessing a citrullinating enzyme, peptidylarginine deiminase (PPAD) with the potential to generate antigens driving the autoimmune response. Objectives: To examine the immune response to PPAD in patients with RA, individuals with periodontitis (PD) and controls (without arthritis), confirm PPAD autocitrullination and identify the modified arginine residues. Methods: PPAD and an inactivated mutant (C351A) were cloned and expressed and autocitrullination of both examined by immunoblotting and mass spectrometry. ELISAs using PPAD, C351A and another P gingivalis protein arginine gingipain (RgpB) were developed and antibody reactivities examined in patients with RA (n=80), individuals with PD (n=44) and controls (n=82). Results: Recombinant PPAD was a potent citrullinating enzyme. Antibodies to PPAD, but not to Rgp, were elevated in the RA sera (median 122 U/ml) compared with controls (median 70 U/ml; p<0.05) and PD (median 60 U/ml; p<0.01). Specificity of the anti-peptidyl citrullinated PPAD response was confirmed by the reaction of RA sera with multiple epitopes tested with synthetic citrullinated peptides spanning the PPAD molecule. The elevated antibody response to PPAD was abolished in RA sera if the C351A mutant was used on ELISA. Conclusions: The peptidyl citrulline-specific immune response to PPAD supports the hypothesis that, as a bacterial protein, it might break tolerance in RA, and could be a target for therapy

Periodontal disease and some adverse perinatal outcomes in a cohort of low risk pregnant women

Objective: To evaluate the association of periodontal disease (PD) in pregnancy with some adverse perinatal outcomes. Method: This cohort study included 327 pregnant women divided in groups with or without PD. Indexes of plaque and gingival bleeding on probing, probing pocket depth, clinical attachment level and gingival recession were evaluated at one periodontal examination below 32 weeks of gestation. The rates of preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA) neonates and prelabor rupture of membranes (PROM) were evaluated using Risk Ratios (95%CI) and Population Attributable Risk Fractions. Results: PD was associated with a higher risk of PTB (RRadj. 3.47 95% CI 1.62-7.43), LBW (RRadj. 2.93 95% CI 1.36-6.34) and PROM (RRadj. 2.48 95% CI 1.35-4.56), but not with SGA neonates (RR 2.38 95% CI 0.93 - 6.10). Conclusions: PD was a risk factor for PT, LBW and PROM among Brazilian low risk pregnant women

Subacute Sclerosing Panencephalitis in Papua New Guinean Children: The Cost of Continuing Inadequate Measles Vaccine Coverage

Subacute sclerosing panencephalitis (SSPE) is a disabling and usually fatal brain disorder that typically occurs 3–10 years after acute measles infection. Papua New Guinea (PNG) has particularly high rates of SSPE. We report 22 cases of PNG children presenting to the provincial referral hospital in Madang Province who probably contracted acute measles when <12 months of age during a national epidemic in 2002 and who developed SSPE 5–7 years later. Based on these cases, the estimated annual SSPE incidence in Madang province in 2007–2009 was 54/million population aged <20 years. Four sub-districts had an annual incidence >100/million population aged <20 years, the highest rates ever reported. Young PNG children do not respond well to measles vaccine. Because of this, efforts such as supplementary measles immunisation programs should continue in order to reduce the pool of non-immune older people surrounding the youngest and most vulnerable members of PNG communities

Preterm low birthweight and the role of oral bacteria

Preterm and low birthweight (PTLBW) continues to be a major cause of mortality and morbidity across the world. In recent years, maternal periodontal disease has been implicated as a risk factor for adverse pregnancy outcomes. There is conflicting evidence to support such an outcome as illustrated by descriptive, case control and randomised controlled trials involving pregnant women from across the world, using different measurement tools to determine the level of periodontal disease. Whilst considering the literature, there is evidence for both arguments, based on the effect of periodontal inflammatory by products. Bacteria associated with periodontal disease are not dissimilar to those known to be associated with genito-urinary bacterial infections and adverse pregnancy outcomes. Several groups have demonstrated the apparent translocation of Fusobacterium nucleatum, Prevotella nigrescens, Prevotella intermedia, Porphyromonus gingivalis, Treponema denticola to the foetal placental unit whereby a maternal or foetal response has been detected resulting in premature birth or low birthweight. The normal process of parturition involves a cascade of events including a build-up of inflammatory mediators as linked to inflammation, whereby the maternal environment becomes hostile and threatens the well-being of the infant, and the foetus expelled. The question remains therefore, is there a greater risk of delivering a PTLBW infant when the mother has detectable periodontal disease, or is the release of inflammatory mediators and their translocation via the haematogenous route sufficient to induce a poor pregnancy outcome? The data investigated would suggest that there is a positive outcome when certain oral gram-negative bacteria create a cumulative effect sufficient to trigger early delivery, which represents the final straw to result in preterm or low birthweight delivery. There is equally sufficient epidemiological evidence that does not support this outcome, but it is agreed that maintaining oral health during pregnancy is beneficial to the mother and her infant