Dermal exposure to contaminated sites has generally received less attention than oral/inhalation exposure due to limited exposure scenarios and less perceived potential for toxicity, however, the ...risk can be significant for specific contaminants and scenarios. The present study aims to (1) measure Cr, Ni, Pb, and Zn contamination in soil and mine tailings samples (n = 7), (2) determine the dermal bioaccessibility of these metals via in vitro tests using two synthetic sweat formulations (EN 1811; NIHS 96-10), and (3) obtain dermal absorbed doses (DADs) for children's and adults' exposure scenarios and compare them to derived dermal reference values. The NIHS 96-10 formulation yielded higher bioaccessibility values for all metals than EN 1811, possibly due to its lower pH. Zn had the highest bioaccessibility for both formulations whereas Cr had the lowest. There was some evidence of adsorption of initially mobilized Pb and Zn to soil with longer test times, resulting in slightly lower bioaccessibility after 8 h of testing with respect to 2 h. The calculated DADs showed that the risk for exposure was acceptable (DAD < derived dermal reference value) for all metals except for Cr(VI) considering exposure to two of the samples. The risk in the case of children's exposure scenario (play on contaminated medium) was significantly higher than the case for the adults' exposure scenario (exposure in industrial context). Additional bioaccessibility research is recommended on additional samples with differing properties/contamination profiles, on additional contaminants with high dermal affinity (especially As), and on the development/validation of in vitro dermal bioaccessibility tests.
•Metals dermal bioaccessibility was determined via in vitro tests using two fluids.•NIHS 96-10 artificial sweat yielded higher bioaccessibility than EN 1811.•Dermal bioaccessibility of metals: Zn > Ni ≈ Pb > Cr.•The risk from exposure was acceptable for Cr(III), Ni, Pb, and Zn.•Dermal absorbed dose was >; reference value for Cr(VI) suggesting significant risk.
Abstract Background The sweat test is the current gold standard for the diagnosis of cystic fibrosis (CF). CF is unlikely when sweat chloride (Clsw ) is lower than 30 mmol/L, Clsw > 60 is suggestive ...of CF, with intermediate values between 30 and 60 mmol/L. To correctly interpret a sweat chloride value, the biological variability of the sweat chloride has to be known. Methods Sweat tests performed in two centers using the classic Gibson and Cooke method were retrospectively reviewed (n = 5904). Within test variability of Clsw was measured by comparing results from right and left arm collected on the same day. Between test variability was calculated from subjects with sweat tests performed on more than one occasion. Results Within test variability of Clsw calculated in 1022 subjects was low with differences between − 3.2 (p5) and + 3.6 mmol/L (p95). Results from left and right arm were classified differently in only 3 subjects. Between test variability of Clsw in 197 subjects was larger, with differences between − 18.2 mmol/L (p5) and + 14.1 mmol/L (p95) between repeat tests. Changes in diagnostic conclusion were seen in 55/197 subjects, the most frequent being changing from indeterminate to ‘CF unlikely’ range (48/102). Conclusion Variability of sweat chloride is substantial, with frequent changes in diagnostic conclusion, especially in the intermediate range.
We report the case of a 54-year-old woman with antineutrophilic cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis presenting with mononeuritis multiplex, intestinal ...hemorrhage, cardiomyopathy, fever, and worsening asthma symptoms. She was initially treated with steroids and cyclophosphamide but eventually required rituximab to control a vasculitis flare. However, her asthmatic symptoms did not improve, despite attaining vasculitis remission. Symptoms abated only after the treatment transition to mepolizumab. After a 1-year interval, there were no further episodes of asthma exacerbation and no requirement for systemic steroid therapy. This report reinforces the use of rituximab for induction and maintenance of remission in patients with eosinophilic granulomatosis with polyangiitis and predominant vasculitic manifestations, whereas mepolizumab demonstrated better control of the persistent eosinophilic manifestations, ensuing sustained remission and improved quality of life.
Aim
To evaluate the heart rate (HR) and behaviour of children and teenagers with Cerebral Palsy (CP) when having a dental appointment.
Methods
A comparative cross-sectional study was carried out with ...60 participants with CP, between 2 and 14 years old (study group—SG), and 60 normotypical individuals (CG). The sample was paired according to age, gender and socioeconomic status. Behaviour was evaluated during dental prophylaxis using the Frankl Scale, and HR was measured at five moments: before the appointment, when sitting in the dental chair, during the clinical examination, during prophylaxis and immediately after prophylaxis. Mann–Whitney, Friedman and Chi-square tests were applied at a significance level of 5%.
Results
SG presented significantly higher HR (
p
< 0.001) and more participants with uncooperative behaviour (
p
< 0.001) than CG in all observational periods. Furthermore, SG participants with uncooperative behaviour presented higher HR values than those in SG who were cooperative in all observational periods (
p
≤ 0.002).
Conclusions
Individuals with CP have a higher HR before and during the clinical session, and are frequently more uncooperative with the procedure than normotypical individuals.
Checkpoint inhibitor (CPI) therapy revolutionized treatment for advanced non-small-cell lung cancer (NSCLC); however, most patients progress due to primary or acquired resistance. Sitravatinib is a ...receptor tyrosine kinase inhibitor that can shift the immunosuppressive tumor microenvironment toward an immunostimulatory state. Combining sitravatinib with nivolumab (sitra + nivo) may potentially overcome initial CPI resistance.
In the phase III SAPPHIRE study, patients with advanced non-oncogenic driven, nonsquamous NSCLC who initially benefited from (≥4 months on CPI without progression) and subsequently experienced disease progression on or after CPI combined with or following platinum-based chemotherapy were randomized 1 : 1 to sitra (100 mg once daily administered orally) + nivo (240 mg every 2 weeks or 480 mg every 4 weeks administered intravenously) or docetaxel (75 mg/m
every 3 weeks administered intravenously). The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR; all assessed by blinded independent central review), and safety.
A total of 577 patients included randomized: sitra + nivo, n = 284; docetaxel, n = 293 (median follow-up, 17.1 months). Sitra + nivo did not significantly improve OS versus docetaxel median, 12.2 versus 10.6 months; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.70-1.05; P = 0.144. The median PFS was 4.4 versus 5.4 months, respectively (HR 1.08, 95% CI 0.89-1.32; P = 0.452). The ORR was 15.6% for sitra + nivo and 17.2% for docetaxel (P = 0.597); CBR was 75.5% and 64.5%, respectively (P = 0.004); median DOR was 7.4 versus 7.1 months, respectively (P = 0.924). Grade ≥3 treatment-related adverse events were observed in 53.0% versus 66.7% of patients receiving sitra + nivo versus docetaxel, respectively.
Although median OS was numerically longer with sitra + nivo, the primary endpoint was not met in patients with previously treated advanced nonsquamous NSCLC. The safety profiles demonstrated were consistent with previous reports.
Structural adhesives emerge as an alternative technique for joining materials used in tertiary structures in the oil and gas industry instead of welding, for example, in order to mitigate risks ...caused by the use of sparks on offshore platforms. Therefore, the present work aims to evaluate the influence of different surface treatments of the adherent material (carbon fiber/epoxy composite) on the mechanical behavior of the adhesive joints through the lap shear test. Furthermore, the viscoelastic properties of the epoxy-based structural adhesive were analyzed via dynamic-mechanical analysis (DMA). The results indicates that the adhesive exhibits residual curing when cured at room temperature and a post-curing process is required to increase its glass transition temperature (Tg) and its stiffness, Lap Shear tests results shows that the adherent surface treatment that generated the best mechanical response was cleaning with solvent, despite its lower roughness compared to the fuseply treatment, which indicates a strong correlation between roughness and wettability in obtaining resistant adhesive joints.
Background
Despite the global decline in the detection of leprosy cases, its incidence has remained unchanged in certain settings and requires the determination of the factors linked to its ...persistence. We examined the spatial and space–time distribution of leprosy and the influence of social vulnerability on the occurrence of the disease in an endemic area of Northeast Brazil.
Methods
We performed an ecological study of all leprosy cases reported by Sergipe state, Northeast Brazil from 2001 to 2015, to examine the association of the Social Vulnerability Index and the prevalence and persistence of leprosy among the State's municipalities. Socio‐economic and leprosy surveillance information was collected from the Brazilian information systems, and a Bayesian empirical local model was used to identify fluctuations of the indicators. Spatial and space–time clusters were identified using scan spatial statistic tests and to measure the municipalities’ relative risk of leprosy.
Results
Leprosy clusters and burden of disease had a strong statistical association with the municipalities’ Social Vulnerability Index. Municipalities with a high social vulnerability had higher leprosy incidence, multibacillary leprosy and newly diagnosed cases with grade 2 disability than areas with low social vulnerability.
Conclusion
Social vulnerability is strongly associated with leprosy transmission and maintenance of disease incidence. Leprosy control programmes should be targeted to the populations with high social vulnerability.
Linked Commentary: P. Verma et al. J Eur Acad Dermatol Venereol 2019; 33: 1447. https://doi.org/10.1111/jdv.15797.
In patients with cystic fibrosis, cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers, such as sweat chloride concentration and/or nasal potential difference, are used as end-points ...of efficacy in phase-III clinical trials with the disease modifying drugs ivacaftor (VX-770), VX809 and ataluren. The aim of this project was to review the literature on reliability, validity and responsiveness of nasal potential difference, sweat chloride and intestinal current measurement in patients with cystic fibrosis. Data on clinimetric properties were collected for each biomarker and reviewed by an international team of experts. Data on reliability, validity and responsiveness were tabulated. In addition, narrative answers to four key questions were discussed and agreed by the team of experts. The data collected demonstrated the reliability, validity and responsiveness of nasal potential difference. Fewer data were found on reliability of sweat chloride concentration; however, validity and responsiveness were demonstrated. Validity was demonstrated for intestinal current measurement, but further information is required on reliability and responsiveness. For all three end-points, normal values were collected and further research requirements were proposed. This body of work adds useful information to support the promotion of CFTR biomarkers to surrogate end-points and to guide further research in the area.
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