Associations of Pre- and Postnatal Air Pollution Exposures with Child Blood Pressure and Modification by Maternal Nutrition: A Prospective Study in the CANDLE Cohort

Background: Limited data suggest air pollution exposures may contribute to pediatric high blood pressure (HBP), a known predictor of adult cardiovascular diseases.Methods: We investigated this association in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study, a sociodemographically diverse pregnancy cohort in the southern United States with participants enrolled from 2006 to 2011. We included 822 mother–child dyads with available address histories and a valid child blood pressure measurement at 4–6 y. Systolic (SBP) and diastolic blood pressures (DBP) were converted to age-, sex-, and height-specific percentiles for normal-weight U.S. children. HBP was classified based on SBP or DBP ≥90th percentile. Nitrogen dioxide (NO2) and particulate matter ≤2.5μm in aerodynamic diameter (PM2.5) estimates in both pre- and postnatal windows were obtained from annual national models and spatiotemporal models, respectively. We fit multivariate Linear and Poisson regressions and explored multiplicative joint effects with maternal nutrition, child sex, and maternal race using interaction terms.Results: Mean PM2.5 and NO2 in the prenatal period were 10.8 [standard deviation (SD): 0.9] μg/m3 and 10.0 (SD: 2.4) ppb, respectively, and 9.9 (SD: 0.6) μg/m3 and 8.8 (SD: 1.9) ppb from birth to the 4-y-old birthday. On average, SBP percentile increased by 14.6 (95% CI: 4.6, 24.6), and DBP percentile increased by 8.7 (95% CI: 1.4, 15.9) with each 2-μg/m3 increase in second-trimester PM2.5. PM2.5 averaged over the prenatal period was only significantly associated with higher DBP percentiles [β= 11.6 (95% CI: 2.9, 20.2)]. Positive associations of second-trimester PM2.5 with SBP and DBP percentiles were stronger in children with maternal folate concentrations in the lowest quartile (pinteraction= 0.05 and 0.07, respectively) and associations with DBP percentiles were stronger in female children (pinteraction= 0.05). We did not detect significant association of NO2, road proximity, and postnatal PM2.5 with any outcomes.Conclusions: The findings suggest that higher prenatal PM2.5 exposure, particularly in the second trimester, is associated with elevated early childhood blood pressure. This adverse association could be modified by pregnancy folate concentrations. https://doi.org/10.1289/EHP7486     

Identification of Inflamed Atherosclerotic Lesions In Vivo Using PET-CT

Inflammation plays a major pathogenetic role in the development of atherosclerotic plaques and related thromboembolic events. The identification of vulnerable plaques is of the utmost importance, as this may allow the implementation of more effective preventive and therapeutic interventions. Fluorodeoxyglucose positron emission tomography (FDG-PET) has been shown to be useful for tracing inflammation within plaques. However, its relationship to immunohistochemical findings in different territories of the peripheral circulation was not completely elucidated. We aimed to determine whether plaque inflammation could be measured by PET in combination with computer tomography (CT) using FDG and what is the relationship between FDG uptake and immunohistochemical findings in the removed atherosclerotic lesions of the femoral and carotid arteries. The study included 31 patients, 21 patients with high-grade stenosis of the internal carotid artery (ICA) and 10 patients with occlusion of the common femoral artery (CFA), all of whom underwent endarterectomy. Before endarterectomy in all patients, FDG-PET/CT imaging was performed. FDG uptake was measured as the maximum blood—normalized standardized uptake value, known as the target to background ratio (TBR max). TBR max amounted to 1.72?±?0.8, and in patients with ICA, stenosis was not significantly different from patients with CFA occlusion. Immunohistochemical and morphometric analyses of the plaques obtained at endarterectomy showed that the density of T lymphocytes and macrophages (number of cells per square millimeter) was significantly higher in subjects with stenosis of the ICA than in subjects with occlusion of the femoral arteries: lymphocytes, 1.26?±?0.21 vs. 0.77?±?0.29; p?=?0.02 and macrophages, 1.01?±?0.18 vs. 0.69?±?0.23; p?=?0.003. In the whole group of patients, the density of inflammatory cells significantly correlated with FDG uptake represented by PET-TBR max: T lymphocytes, r?=?0.60; p?<?0.01 and macrophages, r?=?0.65; p?<?0.01. The results of our study show that FDG uptake is related to the accumulation of inflammatory cells in atherosclerotic lesions. This finding suggests that FDG uptake reflects the severity of atherosclerotic vessel wall inflammation, and in stenotic lesions, it could be an indicator of their vulnerability. However, data from large outcome studies is needed to estimate the usefulness of this technique in identifying the most dangerous atherosclerotic lesions and vulnerable patients.     

The quality of mother–child shared reading: its relations to child’s storytelling and home literacy environment

In the present study, we analysed the relations among the quality of mother–child shared reading, child’s storytelling and family literacy environment. The sample included 20 mother–child dyads, with 5-year-old children, who were recorded during shared reading. The quality of shared reading was assessed with the Scale for Observing Shared Reading while children’s storytelling was assessed with the textless book Frog Goes to Dinner. We found that the quality of mother–child shared reading was related to the coherence of children’s stories and to the factors of home literacy environment. Child’s age when parents started reading to him, the number of all books and children’s books in child’s home together explained 43.1% of the variance in the quality of shared reading. The findings give an insight into the process of the quality of the interactive reading between a child and an adult and emphasize the importance of shared reading for child’s storytelling.     

Orexins Protect Neuronal Cell Cultures Against Hypoxic Stress: an Involvement of Akt Signaling

Orexins A and B are peptides produced mainly by hypothalamic neurons that project to numerous brain structures. We have previously demonstrated that rat cortical neurons express both types of orexin receptors, and their activation by orexins initiates different intracellular signals. The present study aimed to determine the effect of orexins on the Akt kinase activation in the rat neuronal cultures and the significance of that response in neurons subjected to hypoxic stress. We report the first evidence that orexins A and B stimulated Akt in cortical neurons in a concentration- and time-dependent manner. Orexin B more potently than orexin A increased Akt phosphorylation, but the maximal effect of both peptides on the kinase activation was very similar. Next, cultured cortical neurons were challenged with cobalt chloride, an inducer of reactive oxygen species and hypoxia-mediated signaling pathways. Under conditions of chemical hypoxia, orexins potently increased neuronal viability and protected cortical neurons against oxidative stress. Our results also indicate that Akt kinase plays an important role in the pro-survival effects of orexins in neurons, which implies a possible mechanism of the orexin-induced neuroprotection.     

Compliance with treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, progressive, debilitating disease that demands continuous therapy with multiple medications. Noncompliance with disease-modifying drugs may cause disease flares, preventable functional impairment, unnecessary treatment changes, and loss of health care resources. The aim of the current study was to explore self-reported compliance with treatment and the factors contributing to this compliance using a representative sample of an RA patient population in Estonia. Two thousand patients diagnosed with RA were randomly selected from the Estonian Health Insurance Fund database. The eligible response rate of the study was 60%. Using prestructured questionnaires, the following information about the disease and treatment was evaluated: self-reported compliance with treatment, reasons for noncompliance, disease history, sociodemographic variables, health care utilization, and satisfaction with health care providers. The self-reported compliance rate was 80.3%, reflecting the percentage of patients who reported that they always took their medications exactly as described. The most often reported reasons for noncompliance were side effects and fear of side effects. Compliance was found to be the lowest in a group of younger and active patients with higher income. Higher frequency of visits to the rheumatologist, satisfaction with health care providers, and sufficient information about RA treatment correlated with better compliance.     

Cognitive and Psychosocial Predictors of Subjective Well-Being in Urban Older Adults

Prior research indicates that physical health and social support have substantial influences on subjective well-being among older adults. However, little research has examined the influences of coping style and cognitive functioning on subjective well-being among older adults. This study investigated cognitive and psychosocial predictors of subjective well-being among 129 adults, ages 65-89 years. Canonical correlation indicated that subjective well-being was characterized by two dimensions: life satisfaction and affective balance (happiness). The use of emotion-focused coping strategies and poor perceived health were associated with diminished perceptions of life satisfaction, whereas task-oriented and avoidance-oriented coping were positively related to happiness. Cognitive functioning was positively related to life satisfaction and pleasant emotions independent of education and income.     

Sequential mTOR inhibitor treatment with temsirolimus in metastatic renal cell carcinoma following failure of VEGF receptor tyrosine kinase inhibitors

Purpose

Agents targeting the mammalian target of rapamycin (mTOR) pathway, e. g. everolimus, can provide clinical benefit in pretreated patients with metastatic renal cell carcinoma (mRCC), but data from randomized trials on the sequential use of temsirolimus are lacking. We retrospectively studied the efficacy and safety of temsirolimus therapy following failure of rTKI therapy.

Methods

Twenty-nine patients treated with temsirolimus (25 mg/week) following progression on rTKI therapy were studied at four institutions. All patients had failed at least one prior rTKI therapy (sunitinib, n = 6; sorafenib, n = 1; both, n = 22). Over 80% had two or more prior therapies. Data on efficacy (response assessment, progression-free survival [PFS], overall survival [OS]) and safety (NCI-CTC) were analyzed.

Results

Adverse events occurred in 90% of patients with the majority being grade 1 (n = 4, 14%) or grade 2 (n = 12, 41%). Most grade 3/4 toxicities (n = 10, 34%) were manageable and included anemia (n = 4, 14%), leukopenia/neutropenia (n = 2, 7%), hyperglycemia (n = 1, 3%), acidosis/alkalosis (n = 2, 7%), and infection (n = 1, 3%). One patient discontinued temsirolimus for grade 3 pneumonitis. Median (range) PFS and OS were 5.1 months (1–10.4) and 18.0 months (12.6–23.3), respectively. Best response included partial response (n = 1) and stable disease (n = 15) for a disease control rate of 55%, and disease progression of 45% (n = 13).

Conclusions

Temsirolimus after rTKI failure appears to provide promising safety and efficacy comparable to other treatment options in pretreated patients with mRCC.