Objective: To investigate whether an elevated interferon‐α (IFNα) level early in pregnancy is associated with poor pregnancy outcomes and to examine the relationship of an elevated IFNα level to angiogenic imbalance.Methods: Women were enrolled in a longitudinal case–control study of pregnant patients with lupus. Serum samples obtained monthly throughout pregnancy were assayed for IFNα and for the antiangiogenic factor soluble Flt‐1 and the proangiogenic factor placenta growth factor (PlGF). Each of 28 patients with systemic lupus erythematosus (SLE) with a poor pregnancy outcome was matched to an SLE patient with an uncomplicated pregnancy and to a pregnant healthy control. The effects of IFNα and/or soluble Flt‐1 on human endothelial cells and endothelial cell–trophoblast interactions were assessed.Results: Compared to SLE patients with uncomplicated pregnancies, patients with preeclampsia had increased IFNα levels before clinical symptoms. Patients without autoimmune disease who developed preeclampsia did not have increased IFNα levels. In SLE patients with low IFNα levels, marked angiogenic imbalance (higher soluble Flt‐1, lower PlGF, and higher soluble Flt‐1:PlGF ratios) preceded maternal manifestations of preeclampsia, whereas in SLE patients with high IFNα levels, preeclampsia occurred without evidence of systemic angiogenic imbalance. Treatment of human endothelial cells with soluble Flt‐1 induced expression of sFLT1 messenger RNA, and IFNα dramatically amplified responses to soluble Flt‐1. In a model of spiral artery transformation, only the combination of IFNα and soluble Flt‐1 disrupted the ability of trophoblast cells to remodel endothelial tube structures.Conclusion: Our findings identify a new mechanism by which IFNα induces an antiangiogenic milieu and increases the sensitivity of endothelial cells to soluble Flt‐1, and suggest that elevated IFNα levels may contribute to the pathogenesis of preeclampsia in some pregnant patients with SLE.

Malaria transmission in Latin America is typically characterized as hypo-endemic and unstable with ~170 million inhabitants at risk of malaria infection. Although Colombia has witnessed an important decrease in malaria transmission, the disease remains a public health problem with an estimated ~10 million people currently living in areas with malaria risk and ~61,000 cases reported in 2012. This study aimed to establish the malaria prevalence in three endemic regions of Colombia to aid in designing new interventions for malaria elimination. A cross-sectional survey was conducted in three regions of Colombia with different malaria epidemiological profiles: Tierralta (Ta), Tumaco (Tu) and Buenaventura (Bv). The Annual Parasite Index (API) was 10.7, 6.9 and 3.1, respectively. Participants were asked to respond to a sociodemographic questionnaire and then were bled to determine the Duffy genotype and the prevalence of malaria infection by microscopy and quantitative real-time PCR (qPCR). The study was conducted between October 2011 and January 2012. Eight sentinel sites with 1,169 subjects from 267 households were included. The overall prevalence of sub-microscopic infections measured by thick blood smear (TBS) was 0.3% (n = 4) whereas by qPCR it was 9.7% (n = 113), with a greater proportion (13%) in 40-50 years old individuals. Furthermore, different regions displayed different prevalence of sub-microscopic infections: Bv 12%, Ta 15%, and Tu 4%. From these 113 samples (qPCR), 74% were positive for P. vivax and 22% for P. falciparum, and 4% were mixed infections, which correlates to the overall parasite prevalence in Colombia. This study showed that in the southern Pacific coast of Colombia (Bv and Tu), around 56% of the population have a Duffy-negative genotype, compared to the northern region (Ta) where the percentage of Duffy-negative genotype is around 3%. Sub-microscopic infections are prevalent across different regions in Colombia, particularly in areas with relatively low transmission intensity. The poor microscopy results suggest the need for more sensitive diagnostic tools for detection of sub-microscopic infections. This study underscores the importance of conducting active case surveillance to more accurately determine malaria incidence, and highlights the need for updating the malaria guidelines to track and treat sub-microscopic malaria infections.

Food allergies have become a significant heath burden as prevalence continues to rise, affecting 6%‐13% of the global population. In the absence of drugs approved by regulatory agencies, the current standard of care remains avoidance of allergenic foods and management of acute allergic reactions with antihistamines and epinephrine autoinjectors. Allergen immunotherapy has been shown to increase the threshold of reactivity in the majority of food‐allergic individuals. However, challenges include long treatment periods, high rates of adverse reactions, and lack of permanence of desensitization and established protocols. To address these limitations, adjunctive allergen‐specific immunotherapy, vaccines, and non–allergen‐specific therapies (eg, monoclonal antibodies) are being explored. The future of food allergy treatment is promising with a number of clinical trials in progress. Currently, although desensitization can be achieved for the majority of individuals with food allergy through immunotherapy, continued ingestion of allergen is needed for most individuals to maintain desensitization. Further understanding of the mechanisms of food allergy and identification of biomarkers to distinguish between temporary and permanent resolution of allergies is needed before a cure, where reactivity to the allergen is permanently lost enabling the individual to consume the allergen in any amount at any time, can be envisioned.

Background: Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study is performed.Objectives: The objectives of this paper were to evaluate the impact of applying a common study protocol to study benzodiazepines (BZDs) (anxiolytics, hypnotics, and related drugs) and the risk of hip/femur fracture (HFF) across three European primary care DBs and to investigate any resulting discrepancies.Methods: To measure the risk of HFF among adult users of BZDs during 2001–2009, three cohort and nested case control (NCC) studies were performed in Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) (Spain), Clinical Practice Research Datalink (CPRD) (UK), and Mondriaan (The Netherlands). Four different models (A–D) with increasing levels of adjustment were analyzed. The risk according to duration and type of BZD was also explored. Adjusted hazard ratios (cohort), odds ratios (NCC), and their 95% confidence intervals were estimated.Results: Adjusted hazard ratios (Model C) were 1.34 (1.23–1.47) in BIFAP, 1.66 (1.54–1.78) in CPRD, and 2.22 (1.55–3.29) in Mondriaan in cohort studies. Adjusted odds ratios (Model C) were 1.28 (1.16–1.42) in BIFAP, 1.60 (1.49–1.72) in CPRD, and 1.48 (0.89–2.48) in Mondriaan in NCC studies. A short‐term effect was suggested in Mondriaan, but not in CPRD or BIFAP. All DBs showed an increased risk with the concomitant use of anxiolytic and hypnotic drugs.Conclusions: Applying similar study methods to different populations and DBs showed an increased risk of HFF in BZDs users but differed in the magnitude of the risk, which may be because of inherent differences between DBs.