Transdermal Uptake of Diethyl Phthalate and Di(n-butyl) Phthalate Directly from Air: Experimental Verification

Background

Fundamental considerations indicate that, for certain phthalate esters, dermal absorption from air is an uptake pathway that is comparable to or greater than inhalation. Yet this pathway has not been experimentally evaluated and has been largely overlooked when assessing uptake of phthalate esters.

Objectives

This study investigated transdermal uptake, directly from air, of diethyl phthalate (DEP) and di(n-butyl) phthalate (DnBP) in humans.

Methods

In a series of experiments, six human participants were exposed for 6 hr in a chamber containing deliberately elevated air concentrations of DEP and DnBP. The participants either wore a hood and breathed air with phthalate concentrations substantially below those in the chamber or did not wear a hood and breathed chamber air. All urinations were collected from initiation of exposure until 54 hr later. Metabolites of DEP and DnBP were measured in these samples and extrapolated to parent phthalate intakes, corrected for background and hood air exposures.

Results

For DEP, the median dermal uptake directly from air was 4.0 μg/(μg/m³ in air) compared with an inhalation intake of 3.8 μg/(μg/m³ in air). For DnBP, the median dermal uptake from air was 3.1 μg/(μg/m³ in air) compared with an inhalation intake of 3.9 μg/(μg/m³ in air).

Conclusions

This study shows that dermal uptake directly from air can be a meaningful exposure pathway for DEP and DnBP. For other semivolatile organic compounds (SVOCs) whose molecular weight and lipid/air partition coefficient are in the appropriate range, direct absorption from air is also anticipated to be significant.

Citation

Weschler CJ, Bekö G, Koch HM, Salthammer T, Schripp T, Toftum J, Clausen G. 2015. Transdermal uptake of diethyl phthalate and di(n-butyl) phthalate directly from air: experimental verification. Environ Health Perspect 123:928–934; http://dx.doi.org/10.1289/ehp.1409151     

Left-Atrial Appendage Thrombosis in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation

BackgroundData about the impact of left-atrial appendage thrombosis (LAAT) on early safety and mortality in patients undergoing transfemoral transcatheter aortic valve implantation (TF-TAVI) are scarce. We aimed to investigate the prevalence and predictors of LAAT and the outcome associated with this condition in patients treated by TF-TAVI.MethodsRetrospective data analysis was derived from a prospective single-centre registry comparing patients with and without LAAT regarding early safety at 30 days, according to Valve Academic Research Consortium-2 (VARC-2) and 2-year mortality.ResultsLAAT was found in 7.6% of the whole cohort (n = 2527) and in 16.6% in those patients with known pre-existing atrial fibrillation (AF cohort, n = 1099). Compared with controls, patients with LAAT were sicker, indicated by a higher Society of Thoracic Surgeons (STS) score and burden of comorbidities. Neither VARC-2–defined early safety at 30 days nor the rate of stroke was different between LAAT and controls in both the whole (early safety: 29.2% vs 24.2%, P = 0.123; stroke: 5.9% vs 4.7%, P = 0.495) and AF cohort (early safety: 29.1% vs 22.9%, P = 0.072; stroke: 5.6% vs 3.3%, P = 0.142). Evaluating the whole cohort in a univariate analysis, the 2-year mortality was significantly higher in LAAT compared with controls (hazard ratio, 1.41; 95% confidence interval, 1.07-1.86; P = 0.014). However, multivariate analysis of the whole cohort and the AF cohort revealed no association between LAAT and 2-year mortality.ConclusionsLAAT was frequent in patients undergoing TF-TAVI— in particular, in patients with histories of AF—but it was not associated with an increase in periprocedural complications and did not predict 2-year mortality.     

Determinants of ST-segment elevation myocardial infarction as clinical presentation of acute coronary syndrome

Journal of Thrombosis and Thrombolysis - Antiplatelet agents and statin therapies are widely used in patients with known cardiovascular disease. Plaque rupture (PR) and plaque erosion (PE) are the...     

Adjuvant treatment of pancreatic carcinoma in a clinically adapted mouse resection model.

BACKGROUND: The high rate of local recurrence after radical resection of pancreatic adenocarcinoma fosters intensive efforts to develop new approaches for adjuvant treatment. The established animal models show significant limitations in simulating an adjuvant therapeutic setting. For optimal approximation to the clinical situation we therefore improved a murine orthotopic human xenotransplantation model. METHODS: Subtotal pancreatectomy in mice was performed after orthotopic inoculation of human pancreatic cancer cells and manifestation of solid tumours. The natural course of disease, tumour growth and metastases were analysed. Gemcitabine as a cytotoxic drug was tested in vitro on the cell line used in this model and the effect of adjuvant treatment with gemcitabine in vivo was investigated. RESULTS: All tumour-resected animals showed local recurrence. Organ metastases occurred in 67% in resected compared to 25% of non-resected animals. Gemcitabine in vitro was ineffective, but as adjuvant monotherapy resulted in a highly significant reduction of tumour weight and metastatic events. CONCLUSION: Subtotal pancreatectomy for xenotransplanted pancreatic cancer in SCID beige mice is feasible. Due to high rates of local recurrence and increased organ metastases, this model offers a relevant option for preclinical adjuvant testing, especially as in vitro and in vivo effects of cytotoxic drugs differ enormously.     

How experience shapes memory for faces: An event-related potential study on the own-age bias

Young adults more accurately remember own-age than older faces. We tested whether this own-age bias (OAB) is reduced by increased experience. Young experts (geriatric nurses) and controls performed a recognition experiment with young and old faces. Critically, while control participants demonstrated better memory for young faces, no OAB was observed in the experts. Event-related potentials revealed larger N170 and P2 amplitudes for young than old faces in both groups, suggesting no group differences during early perceptual processing. At test, N250 repetition effects were more anteriorily distributed for own- than other-age faces in control participants, whereas experts showed no corresponding effects. A larger late positive component (LPC) for old than young faces was observed in controls, but not in experts. Larger LPCs may reflect prolonged stimulus processing compromising memory retrieval. In sum, experience with other-age faces does not affect early perceptual processing, but modulates later stages related to memory retrieval.     

Successful treatment of COVID-19 infection with convalescent plasma in B-cell-depleted patients may promote cellular immunity

Treatment with convalescent plasma has been shown to be safe in coronavirus disease in 2019 (COVID-19) infection, although efficacy reported in immunocompetent patients varies. Nevertheless, neutralizing antibodies are a key requisite in the fight against viral infections. Patients depleted of antibody-producing B cells, such as those treated with rituximab (anti-CD20) for hematological malignancies, lack a fundamental part of their adaptive immunity. Treatment with convalescent plasma appears to be of general benefit in this particularly vulnerable cohort. We analyzed clinical course and inflammation markers of three B-cell-depleted patients suffering from COVID-19 who were treated with convalescent plasma. In addition, we measured serum antibody levels as well as peripheral blood CD38/HLA-DR-positive T-cells ex vivo and CD137-positive T-cells after in vitro stimulation with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides in these patients. We observed that therapy with convalescent plasma was effective in all three patients and analysis of CD137-positive T-cells after stimulation with SARS-CoV-2 peptides showed an increase in peptide-specific T-cells after application of convalescent plasma. In conclusion, we here demonstrate efficacy of convalescent plasma therapy in three B-cell-depleted patients and present data that suggest that while application of convalescent plasma elevates systemic antibody levels only transiently, it may also boost specific T-cell responses.     

Artificial Intelligence for Fast and Accurate 3-Dimensional Tooth Segmentation on Cone-beam Computed Tomography

IntroductionTooth segmentation on cone-beam computed tomographic (CBCT) imaging is a labor-intensive task considering the limited contrast resolution and potential disturbance by various artifacts. Fully automated tooth segmentation cannot be achieved by merely relying on CBCT intensity variations. This study aimed to develop and validate an artificial intelligence (AI)-driven tool for automated tooth segmentation on CBCT imaging.MethodsA total of 433 Digital Imaging and Communications in Medicine images of single- and double-rooted teeth randomly selected from 314 anonymized CBCT scans were imported and manually segmented. An AI-driven tooth segmentation algorithm based on a feature pyramid network was developed to automatically detect and segment teeth, replacing manual user contour placement. The AI-driven tool was evaluated based on volume comparison, intersection over union, the Dice score coefficient, morphologic surface deviation, and total segmentation time.ResultsOverall, AI-driven and clinical reference segmentations resulted in very similar segmentation volumes. The mean intersection over union for full-tooth segmentation was 0.87 (±0.03) and 0.88 (±0.03) for semiautomated (SA) (clinical reference) versus fully automated AI-driven (F-AI) and refined AI-driven (R-AI) tooth segmentation, respectively. R-AI and F-AI segmentation showed an average median surface deviation from SA segmentation of 9.96 μm (±59.33 μm) and 7.85 μm (±69.55 μm), respectively. SA segmentations of single- and double-rooted teeth had a mean total time of 6.6 minutes (±76.15 seconds), F-AI segmentation of 0.5 minutes (±8.64 seconds, 12 times faster), and R-AI segmentation of 1.2 minutes (±33.02 seconds, 6 times faster).ConclusionsThis study showed a unique fast and accurate approach for AI-driven automated tooth segmentation on CBCT imaging. These results may open doors for AI-driven applications in surgical and treatment planning in oral health care.