The Risk of Obstetric Complications and the Effects of Treatment in Women with Low Titer and Medium-High Titer Anti-Phospholipid Antibodies

Background/Purpose: The association of low titer anti-phospholipid antibodies (aPL) with obstetric anti-phospholipid syndrome (APS) is increasingly acknowledged, even though some studies have showed conflicting results. To raise further evidence on the relevance of low titer aPL in pregnancy morbidity (PM), we retrospectively reviewed the clinical records of pregnant women attending a joint obstetric/rheumatology clinic over the years 2009-2016. Methods: Patients were included when positive in at least one criteria aPL assay, at any titer, in two occasions minimum 12 weeks apart. Statistical analysis was performed using R package. Results: 111 women (338 pregnancies) were identified. 51 women displayed low-titer aPL, with 160 pregnancies. 60 patients carried aPL at medium-high titers, with 178 pregnancies. 4 patients (4%) had thrombotic APS, 27 (24%) obstetric APS, 7 (6%) thrombotic and obstetric APS, 15 (14%) medium-high titer aPL and non criteria PM, 7 (6%) medium-high titer aPL and no PM, 18 (16%) low titer aPL and non criteria PM and 15 (14%) low titer aPL and no PM. Low-titer aPL were significantly associated with pregnancy complications (c2=8.82, p=0.003). Considering 245 untreated pregnancies, a significant difference in PM distribution was noted for low titer and medium-high titer aPL (p=0.003, Table 1). Among patients with low titer aPL, treatment with low molecular weight heparin [LMWH] + low-dose aspirin [LDASA] significantly improved pregnancy outcomes (p<<0.001, odds ratio [OR]=0.07, 95% CI=0.007\u20130.300), leading to a 14.3-fold reduction of obstetric complications. Hydroxychloroquine [HCQ] was not associated with a significant improvement in live birth rate (p=0.079). Among women with medium-high titer aPL, the standard therapeutic approach with LMWH+LDASA resulted in a significant improvement of obstetric outcome (p<<0.001, OR=0.20, 95% CI=0.100\u20130.400). HCQ treatment significantly improved obstetric outcome, carrying a 3-fold increase in the live birth rate (p=0.025, OR=0.34, 95% CI=0.117\u20130.894). Conclusion: According to our data, low titer aPL are significantly associated with aPL-associated obstetric complications, with a lower prevalence of premature birth compared to medium-high titer aPL. Treatment with LDASA+LMWH led to a higher increase of live birth rate in women with low titer aPL compared to those with medium-high titer aPL. Additional treatment such as HCQ were effective in women with medium-high titer aPL but not those with low titer aPL. Table 1. Obstetric outcomes (defined according to Miyakis et al, 2006) in 245 untreated pregnancies in women with low titer and medium-high titer anti-phospholipid antibodies

Antibodies Against Domain 1 and Domain 4/5 of &#946;2 Glycoprotein I : Clinical Relevance in Obstetric Anti-Phospholipid Syndrome

Background/Purpose: The domain reactivity of antibodies against b2 glycoprotein I (anti-b2GPI) has been investigated in patients with thrombotic anti-phospholipid syndrome (APS), leading to the identification of antibodies targeting domain 1 of the molecule (anti-D1) as the most relevant autoantibody subpopulation. Scarce attention has been paid to the domain profiling of patients with pregnancy morbidity (PM). The aim of this study was to characterize the relevance of the fine epitope reactivity of anti-b2GPI antibodies in anti-phospholipid antibody (aPL)-associated PM. Methods: Women with persistent positivity for anti-b2GPI IgG antibodies at medium-high titers, with at least one pregnancy and without systemic autoimmune disease were included. Anti-D1 and anti-D4/5 antibodies were tested using a chemiluminescent immunoassay and a research ELISA assay, respectively (QUANTA Flash b2GPI IgG and QUANTA Lite, Inova Diagnostics). Statistical analysis was performed using R package. Results: 138 women fulfilling the inclusion criteria were retrospectively recruited at 3 referral centres. 49 patients (35%) had obstetric APS, 18 (13%) thrombotic APS, 37 (27%) thrombotic and obstetric APS while 34 women (25%) were asymptomatic aPL carriers. 81 women (60%) displayed triple aPL positivity, 32 (23%) had two positive aPL test and 23 (17%) carried a single aPL positivity. 110 patients had at least one untreated pregnancy, culminating in a live birth in 31 cases (28%). 89 women underwent a pregnancy course while receiving treatment, with 71 women (80%) having a live birth. A significant difference in the distribution of positive anti-D1 antibodies emerged between women with or without PM and with or without thrombosis (p=0.05, c2=2.710 and p<0.001, c2=12.174, respectively); no significant difference was observed for anti-D4/5 antibodies (Table 1). In a multivariate logistic regression model also encompassing treatment, positive anti-D1 antibodies, but not anti-D4/5, were significantly associated with obstetric complications, conferring an odds ratio (OR) of 2.32 (p=0.040 and p=0.724, respectively). Triple aPL positivity corrected by treatment significantly predicted PM (p=0.015, OR=2.78). Conclusion: Our data suggest that anti-D1 antibodies are significantly associated not only with thrombosis but also with obstetric morbidity while positive anti-D4/5 antibodies are not predictive of PM

A tetracationic porphyrin with dual anti-prion activity

Prions are deadly infectious agents made of PrPSc, a misfolded variant of the cellular prion protein (PrPC) which self-propagates by inducing misfolding of native PrPC. PrPSc can adopt different pathogenic conformations (prion strains), which can be resistant to potential drugs, or acquire drug resistance, hampering the development of effective therapies. We identified Zn(II)-BnPyP, a tetracationic porphyrin that binds to distinct domains of native PrPC, eliciting a dual anti-prion effect. Zn(II)-BnPyP binding to a C-terminal pocket destabilizes the native PrPC fold, hindering conversion to PrPSc; Zn(II)-BnPyP binding to the flexible N-terminal tail disrupts N- to C-terminal interactions, triggering PrPC endocytosis and lysosomal degradation, thus reducing the substrate for PrPSc generation. Zn(II)-BnPyP inhibits propagation of different prion strains in&nbsp;vitro,&nbsp;in neuronal cells and organotypic brain cultures. These results identify a PrPC-targeting compound with an unprecedented dual mechanism of action which might be exploited to achieve anti-prion effects without engendering drug resistance

Visual Languages and Quality Evaluation in Multichannel Adaptive Information Systems

Multichannel Adaptive Information Systems (ISs) are becoming the new paradigm for building complex interorganization ISs based on the use of different devices, Web services, and XML specifications. Modeling Multichannel Adaptive ISs requires complex interactions between the users and the system front-end due to the different capabilities of existing devices. Unfortunately, the expressive power and effectiveness of visual languages have not been fully exploited in this new area. In this paper we address two related issues. First we propose a visual language that allows for adapting the presentation layer to different physical devices; then we describe a technique to evaluate possible tradeoffs between usability and other qualities of service in Web services design

Housing Recovery Lessons From Chile

Problem, research strategy and findings: The 8.8 magnitude earthquake and subsequent tsunami that struck south-central Chile on February 27, 2010, affected 75% of the country's population and damaged or destroyed 370,000 housing units (about 10% of the housing in six regions). Within six months, the Ministry of Housing and Urban Development published a plan to repair or rebuild 220,000 units of low- and middle-income housing with government assistance within four years. By February 2014, 94% of the housing was complete. The successful rebuilding effort had strong leadership at the national and local levels and used existing programs and institutions. The management staff adapted programs over time to meet the needs of local conditions. When compared with housing recovery programs in other countries, Chile's program stands out, combining national government management with local citizen input. The reconstruction plan also included updated zoning plans, road and infrastructure improvements, heritage recovery, and new master plans for affected cities. Going forward, the earthquake created an opportunity for Chile to use the recovery planning to expand national urban policy and to develop a framework for citizen participation at the local level.Takeaway for practice: Successful planning in disaster recovery involves strong government leadership and coordination together with the engagement of local government and the participation of citizens