Racial/Ethnic Differences in Hormonally-Active Hair Product Use: A Plausible Risk Factor for Health Disparities

Estrogen and endocrine-disrupting chemicals (EDCs) that are associated with several health outcomes have been found in hair products. We evaluated the proportion, frequency, duration, and content of hair products in a racially/ethnically diverse population. We recruited n?=?301 African-American, African-Caribbean, Hispanic, and white women from the New York metropolitan area. We collected data on hair oil, lotion, leave-in conditioner, root stimulator, perm, and other product use. Estrogen and EDC information was collected from commonly used hair products?? labels (used by?>3% of population). African-American and African-Caribbean women were more likely to use all types of hair products compared to white women (P?相似文献   

The association of circulating angiogenic factors and HbA1c with the risk of preeclampsia in women with preexisting diabetes

Objective: To assess whether glycemic control, soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) were associated with the development of preeclampsia (PE) or gestational hypertension (GHTN) in women with preexisting diabetes. Methods: Maternal circulating angiogenic factors (sFlt1 and PlGF) measured on automated platform were studied at four time points during pregnancy in women with diabetes (N?=?159) and reported as multiples of the median (MOM) of sFlt1/PlGF ratio (median, 25th–75th percentile) noted in non-diabetic non-hypertensive control pregnant population (N?=?139). Diagnosis of PE or GHTN was determined by review of de-identified clinical data. Results: PE developed in 12% (N?=?19) and GHTN developed in 23% (N?=?37) of the women with diabetes. Among diabetic women without PE or GHTN, median sFlt1/PlGF levels at 35–40 weeks was threefold higher than in non-diabetic controls [MOM 3.21(1.19–7.24), p?=?0.0001]. Diabetic women who subsequently developed PE had even greater alterations in sFlt1/PlGF ratio during the third trimester [MOM for PE at 27–34 weeks 15.18 (2.37–26.86), at 35–40 weeks 8.61(1.20–18.27), p?≤?0.01 for both windows compared to non-diabetic controls]. Women with diabetes who subsequently developed GHTN also had significant alterations in angiogenic factors during third trimester; however, these findings were less striking. Among women with diabetes, glycosylated hemoglobin (HbA1c) during the first trimester was higher in subjects who subsequently developed PE (7.7 vs 6.7%, p?=?0.0001 for diabetic PE vs diabetic non-PE). Conclusions: Women with diabetes had a markedly altered anti-angiogenic state late in pregnancy that was further exacerbated in subjects who developed PE. Altered angiogenic factors may be one mechanism for the increased risk of PE in this population. Increased HbA1c in the first trimester of pregnancies in women with diabetes was strongly associated with subsequent PE.     

The Initial 96 Hours of Invasive Pulmonary Aspergillosis: Histopathology,Comparative Kinetics of Galactomannan and (1→3)-β-d-Glucan,and Consequences of Delayed Antifungal Therapy

Acute invasive pulmonary aspergillosis is a rapidly progressive and frequently lethal infection. Relatively little is known about early events in the pathogenesis and relationship between the cell wall biomarkers galactomannan and (1→3)-β-d-glucan. The consequences of delayed antifungal therapy are also poorly defined. A persistently neutropenic rabbit model of invasive pulmonary aspergillosis was used to describe the histopathology of early invasive pulmonary aspergillosis and the kinetics of galactomannan and (1→3)-β-d-glucan. The time course of both molecules was mathematically modeled by using a population methodology, and Monte Carlo simulations were performed. The effect of progressive delay in the administration of amphotericin B deoxycholate 1 mg/kg at 24, 48, 72, and 96 h postinoculation on fungal burden, lung weight, pulmonary infarct score, and survival was determined. Histopathology showed phagocytosis of conidia by pulmonary alveolar macrophages at 4 h postinoculation. At 12 to 24 h, there was a progressive focal inflammatory response with conidial germination and hyphal extension. Subsequently, hyphae invaded into the contiguous lung. Galactomannan and (1→3)-β-d-glucan had similar trajectories, and both exhibited considerable interindividual variability, which was reflected in Monte Carlo simulations. Concentrations of both molecules began to rise <24 h postinoculation before pulmonary hemorrhagic infarction was present. Delays of 72 and 96 h in the administration of amphotericin B resulted in fungal burdens and lung weights that were indistinguishable from those of controls, respectively. Galactomannan and (1→3)-β-d-glucan have similar kinetics and are comparable biomarkers of early invasive pulmonary aspergillosis. Antifungal treatment at ≥48 h postinoculation is associated with suboptimal therapeutic outcomes.Acute invasive pulmonary aspergillosis is a leading cause of morbidity and mortality in immunocompromised patients. There have been considerable efforts to improve the diagnostic accuracy and therapeutic outcomes associated with this frequently lethal infection. A better understanding of the relationship of clinically relevant biomarkers and the pathogenesis of invasive pulmonary aspergillosis would facilitate further development of strategies to identify and treat patients at the earliest possible time.Galactomannan and (1→3)-β-d-glucan are complex carbohydrate cell wall molecules produced by Aspergillus spp. The diagnostic and prognostic value of these biomarkers in experimental models and humans is relatively well characterized (7, 12, 17, 18, 23). Despite this, there is little understanding of the relationship of the time course of galactomannan and (1→3)-β-d-glucan to early events in the pathogenesis of invasive pulmonary aspergillosis, and no studies that have rigorously compared their kinetics in laboratory animals or humans.Recently, we described the kinetics of galactomannan in persistently neutropenic rabbits with early invasive pulmonary aspergillosis (12). In the present study, we extend our previous findings by defining the critical histopathological events in early invasive pulmonary aspergillosis and further characterize and compare the kinetics of the circulating fungal antigens galactomannan and (1→3)-β-d-glucan. We further explore the consequences of delayed antifungal therapy with amphotericin B deoxycholate to provide insight into the period after inoculation in which favorable therapeutic outcomes can be secured in profoundly immunocompromised hosts.     

Assessing Indoor Dust Interference with Human Nuclear Hormone Receptors in Cell-Based Luciferase Reporter Assays

Background: Per- and polyfluoroalkyl substances (PFAS), organophosphate esters (OPEs), and polybrominated diphenyl ethers (PBDEs) are hormone-disrupting chemicals that migrate from building materials into air and dust.Objectives: We aimed to quantify the hormonal activities of 46 dust samples and identify chemicals driving the observed activities.Methods: We evaluated associations between hormonal activities of extracted dust in five cell-based luciferase reporter assays and dust concentrations of 42 measured PFAS, OPEs, and PBDEs, transformed as either raw or potency-weighted concentrations based on Tox21 high-throughput screening data.Results: All dust samples were hormonally active, showing antagonistic activity toward peroxisome proliferator-activated receptor (PPARγ2) (100%; 46 of 46 samples), thyroid hormone receptor (TRβ) (89%; 41 samples), and androgen receptor (AR) (87%; 40 samples); agonist activity on estrogen receptor (ERα) (96%; 44 samples); and binding competition with thyroxine (T4) on serum transporter transthyretin (TTR) (98%; 45 samples). Effects were observed with as little as 4μg of extracted dust. In regression models for each chemical class, interquartile range increases in potency-weighted or unknown-potency chemical concentrations were associated with higher hormonal activities of dust extracts (potency-weighted: ΣPFAS–TRβ, ↑28%, p<0.05; ΣOPEs–TRβ, ↑27%, p=0.08; ΣPBDEs–TRβ, ↑20%, p<0.05; ΣPBDEs–ERα, ↑7.7%, p=0.08; unknown-potency: ΣOPEs–TTR, ↑34%, p<0.05; ΣOPEs–AR, ↑13%, p=0.06), adjusted for chemicals with active, inactive, and unknown Tox21 designations.Discussion: All indoor dust samples exhibited hormonal activities, which were associated with PFAS, PBDE, and OPE levels. Reporter gene cell-based assays are relatively inexpensive, health-relevant evaluations of toxic loads of chemical mixtures that building occupants are exposed to. https://doi.org/10.1289/EHP8054     

Time-specific placental growth factor (PlGF) across pregnancy and infant birth weight in women with preexisting diabetes

Objective: Determine the independent association between time-specific placental growth factor (PIGF)—a marker of placental vasculature—and infant birth weight in offspring of mothers with preexisting type 1 and 2 diabetes. Methods: A total of 150 women were recruited from Joslin Diabetes Center’s/Beth Israel Deaconess Medical Center’s Diabetes in Pregnancy Program. PlGF was measured up to four times during pregnancy. Infant birth weight and covariate data were collected from medical records. Hemoglobin A1c was assessed from drawn blood samples. We used generalized linear and log-binomial models to calculate the change in continuous birth weight, as well as macrosomia for every unit change in time-specific ln-transformed PlGF, respectively. Models were adjusted for potential confounders. Results: Approximately 75% of women had type 1 diabetes. Third trimester PlGF levels were significantly associated with infant birth weight (r = 0.24, p = 0.02 at 27–34 weeks; r = 0.26, p < 0.009 for 36–40 weeks). After full adjustment, there was a 6.1% and 6.6% increase in birth weight for gestational age percentile for each unit increase in ln-transformed PlGF level at 27–34 weeks and 35–40 weeks, respectively (95% CI for 27–34 weeks gestation: 1.1, 11.0, and 95% CI for 35–40 weeks gestation: 0.7%, 12.5%). We found a statistically significant increased risk of macrosomia among women with higher ln-transformed PlGF levels (RR: 1.72; 95% CI: 1.09, 2.70). Associations were not mediated by hemoglobin A1c. Conclusions: Third trimester PlGF levels were associated with higher birth weight in women with preexisting diabetes. These findings may provide insight to the pathophysiology of fetal overgrowth in women with diabetes.     

Short-Term Insulin Requirements Following Gastric Bypass Surgery in Severely Obese Women with Type 1 Diabetes

Background

In severely obese type 2 diabetes patients, gastric bypass surgery (GB) reduces body mass index (BMI) and hemoglobin A1c (HbA1c) and allows reduced doses of insulin and other medications. Data regarding the effects of GB on severely obese patients with type 1 diabetes are limited.

Methods

Severely obese women with type 1 diabetes (n?=?9) were studied immediately before and after GB (7.7?±?5.8 weeks, mean ± SD).

Results

On average, GB reduced mean BMI by 11 % and mean HbA1c by 0.9 % (from 8.0 to 7.1 %), with a parallel 38 % decrease in basal insulin requirements (expressed per kilogram of body weight).

Conclusion

GB rapidly decreased BMI, HbA1c, and insulin requirements in severely obese women with type 1 diabetes. However, physiologic insulin replacement remains necessary in patients with type 1 diabetes.     

The Stoichiometric Production of IL-2 and IFN-γ mRNA Defines Memory T Cells That Can Self-Renew After Adoptive Transfer in Humans

Adoptive immunotherapy using ex vivo-expanded tumor-reactive lymphocytes can mediate durable cancer regression in selected melanoma patients. Analyses of these trials have associated the in vivo engraftment ability of the transferred cells with their antitumor efficacy. Thus, there is intensive clinical interest in the prospective isolation of tumor-specific T cells that can reliably persist after transfer. Animal studies have suggested that central memory CD8(+) T cells (T(CM)) have divergent capabilities including effector differentiation to target antigen and stem cell-like self-renewal that enable long-term survival after adoptive transfer. We sought to isolate human melanoma-specific T(CM) to define their in vivo fate and function after autologous therapeutic transfer to metastatic patients. To facilitate the high-throughput identification of these rare cells from patients, we report that T(CM) have a defined stoichiometric production of interleukin-2 (IL-2) and interferon-γ (IFN-γ) mRNA after antigen stimulation. Melanoma-specific T cells screened for high relative IL-2 production had a T(CM) phenotype and superior in vitro proliferative capacity compared to cells with low IL-2 production. To investigate in vivo effector function and self-renewal capability, we allowed melanoma-specific T(CM) to undergo in vitro expansion and differentiation into lytic effector clones and then adoptively transferred them back into their hosts. These clones targeted skin melanocytes in all five patients and persisted long term and reacquired parental T(CM) attributes in four patients after transfer. These findings demonstrate the favorable engraftment fitness for human T(CM)-derived clones, but further efforts to improve their antitumor efficacy are still necessary.