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Background Phthalates are associated with increased blood pressure in children. Large exposures to di-(2-ethylhexyl) phthalate (DEHP) among premature infants have been a cause for concern. Methods We conducted a prospective observational cohort study to determine if DEHP exposures are related to systolic blood pressure (SBP) in premature infants, and if this exposure is associated with activation of the mineralocorticoid receptor (MR). Infants were monitored longitudinally for 8 months from birth. Those who developed idiopathic hypertension were compared with normotensive infants for DEHP exposures. Appearance of urinary metabolites after exposure was documented. Linear regression evaluated the relationship between DEHP exposures and SBP index and whether urinary cortisol/cortisone ratio (a surrogate marker for 11β-HSD2 activity) mediated those relationships. Urinary exosomes were quantified for sodium transporter/channel expression and interrogated against SBP index. Results Eighteen patients met the study criteria, nine developed transient idiopathic hypertension at a postmenstrual age of 40.6 ± 3.4 weeks. The presence of urinary DEHP metabolites was associated with prior IV and respiratory tubing DEHP exposures ( p < 0.05). Both IV and respiratory DEHP exposures were greater in hypertensive infants ( p < 0.05). SBP index was related to DEHP exposure from IV fluid ( p = 0.018), but not respiratory DEHP. Urinary cortisol/cortisone ratio was related to IV DEHP and SBP index ( p < 0.05). Sodium transporter/channel expression was also related to SBP index ( p < 0.05). Conclusions Increased blood pressure and hypertension in premature infants are associated with postnatal DEHP exposure. The mechanism of action appears to be activation of the MR through inhibition of 11β-HSD2. Electronic supplementary material The online version of this article (10.1007/s00467-019-04244-4) contains supplementary material, which is available to authorized users.

Background: Preeclampsia is a major pregnancy complication that results in significant maternal and infant mortality, most of which occurs in low and middle-income countries. The accurate and timely diagnosis of preeclampsia is critical in management of affected pregnancies to reduce maternal and fetal/neonatal morbidity and mortality, yet difficulties remain in establishing the rigorous diagnosis of preeclampsia based on clinical parameters alone. Biomarkers that detect biochemical disease have been proposed as complements or alternatives to clinical criteria to improve diagnostic accuracy. This cohort study assessed the performance of several biomarkers, including glycosylated fibronectin (GlyFn), to rule-in or rule-out preeclampsia within 4 weeks in a cohort of women at increased risk for preeclampsia. Methods: 151 women with risk factors for or clinical signs and symptoms of preeclampsia were selected from a prospective cohort. Maternal serum samples were collected between 20 and 37 weeks of gestation. Clinical suspicion of preeclampsia was defined as presence of new-onset proteinuria, or clinical symptoms of preeclampsia. Subjects with a clinical diagnosis of preeclampsia at the time of enrollment were excluded. GlyFn, pregnancyassociated plasma protein-A2 (PAPPA2), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured by immunoassay. GlyFn was also determined using a rapid point-of care (POC) test format. Receiver-operating characteristic (ROC) curves derived from logistic regression analysis were used to determine the classification performance for each analyte. Results: 32 of 151 (21%) women developed a clinical diagnosis of preeclampsia within 4 weeks. All biomarkers exhibited good classification performance [GlyFn (area under the curve (AUROC) = 0.

Tick-borne relapsing fever in western North America is a zoonosis caused by the spirochete bacterium, Borrelia hermsii, which is transmitted by the bite of infected Ornithodoros hermsi ticks. The pathogen is maintained in natural cycles involving small rodent hosts such as chipmunks and tree squirrels, as well as the tick vector. In order for these ticks to establish sustained and viable populations, a narrow set of environmental parameters must exist, primarily moderate temperatures and moderate to high amounts of precipitation. Maximum Entropy Species Distribution Modeling (Maxent) was used to predict the species distribution of O. hermsi and B. hermsii through time and space based on current climatic trends and future projected climate changes. From this modeling process, we found that the projected current distributions of both the tick and spirochete align with known endemic foci for the disease. Further, global climate models predict a shift in the distribution of suitable habitat for the tick vector to higher elevations. Our predictions are useful for targeting surveillance efforts in areas of high risk in western North America, increasing the efficiency and accuracy of public health investigations and vector control efforts.

Background: Disabling persistent perceived fatigue occurs in 50% of people with multiple sclerosis (MS), but mechanisms are poorly understood. Low histidine could contribute to fatigue since it is the neurotransmitter histamine precursor and low serum levels are reported in other diseases where fatigue is common (e.g., breast cancer, kidney disease, diabetes). Serum histidine is also inversely correlated with proinflammatory cytokines (e.g., TNF, IFN-y), which have been linked to MS fatigue.Purpose: To determine if serum histidine is low in fatigued women with MS, and if histidine is related to differences in proinflammatory cytokines.Methods: Participants were classified as having elevated (n = 19) or normal (n = 18) perceived fatigue based on a median sample split using Profile of Mood States fatigue scale scores, with the elevated fatigue group having scores >7. Histidine and gene-expression of TNF, IFN-y, and leptin were assayed from a serum sample.Results: After adjustment for depression, serum histidine was significantly lower in women with MS with elevated fatigue, compared to normal fatigue (64.57 vs. 70.48 nmol/ml, p = .048, g = 0.75). There were no differences between groups in cytokine expression (all p > .24). Gene expression of TNF correlated with histidine only in people with normal fatigue (r = .51, p = .034), while no other cytokines related to histidine levels.Conclusions: These results provide evidence that serum histidine is lower in fatigued women with MS, but the study did not find a relationship between histidine and TNF, IFN-y, or leptin gene expression.