Perfluorooctanesulfonylfluoride (POSF)-based compounds have been manufactured and used in a variety of industrial applications. These compounds degrade to perfluorooctanesulfonate (PFOS) which is ...regarded as a persistent end-stage metabolite and is found to accumulate in tissues of humans and wildlife. PFOS, perfluorohexanesulfonate (PFHxS), perfluorooctanoate (PFOA), and perfluorooctanesulfonamide (PFOSA) have been found in human sera from the United States. In this study, concentrations of PFHxS, perfluorobutanesulfonate (PFBS), PFOS, perfluorohexanoic acid (PFHxA), PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), and PFOSA were measured in 85 samples of whole human blood collected from nine cities (eight provinces) in China, including Shenyang (Liaoning), Beijing (Hebei), Zhengzhou (Henan), Jintan (Jiangsu), Wuhan (Hubei), Zhoushan (Zhejiang), Guiyang (Guizhou), Xiamen (Fujian), and Fuzhou (Fujian). Among the 10 perfluorinated compounds (PFCs) measured, PFOS was the predominant compound. The mean concentration of PFOS was greatest in samples collected from Shenyang (79.2 ng/mL) and least in samples from Jintan (3.72 ng/mL). PFHxS was the next most abundant perfluorochemical in the samples. No age-related differences in the concentrations of PFOA, PFOS, PFOSA, and PFHxS were observed. Gender-related differences were found, with males higher for PFOS and PFHxS, and females higher in PFUnDA. Concentrations of PFHxS were positively correlated with those of PFOS, while concentrations of PFNA, PFDA, and PFUnDA were positively correlated with those of PFOA. There were differences in the concentration profiles (percentage composition) of various PFCs in the samples among the nine cities.
Recent reports of increased tolerance to artemisinin derivatives--the most recently adopted class of antimalarials--have prompted a need for new treatments. The spirotetrahydro-β-carbolines, or ...spiroindolones, are potent drugs that kill the blood stages of Plasmodium falciparum and Plasmodium vivax clinical isolates at low nanomolar concentration. Spiroindolones rapidly inhibit protein synthesis in P. falciparum, an effect that is ablated in parasites bearing nonsynonymous mutations in the gene encoding the P-type cation-transporter ATPase4 (PfATP4). The optimized spiroindolone NITD609 shows pharmacokinetic properties compatible with once-daily oral dosing and has single-dose efficacy in a rodent malaria model.
Fibrolamellar carcinoma (FLC) is a rare liver tumor driven by the DNAJ-PKAc fusion protein that affects healthy young patients. Little is known about the immune response to FLC, limiting rational ...design of immunotherapy. Multiplex immunohistochemistry and gene expression profiling were performed to characterize the FLC tumor immune microenvironment and adjacent non-tumor liver (NTL). Flow cytometry and T cell receptor (TCR) sequencing were performed to determine the phenotype of tumor-infiltrating immune cells and the extent of T cell clonal expansion. Fresh human FLC tumor slice cultures (TSCs) were treated with antibodies blocking programmed cell death protein-1 (PD-1) and interleukin-10 (IL-10), with results measured by cleaved caspase-3 immunohistochemistry. Immune cells were concentrated in fibrous stromal bands, rather than in the carcinoma cell compartment. In FLC, T cells demonstrated decreased activation and regulatory T cells in FLC had more frequent expression of PD-1 and CTLA-4 than in NTL. Furthermore, T cells had relatively low levels of clonal expansion despite high TCR conservation across individuals. Combination PD-1 and IL-10 blockade signficantly increased cell death in human FLC TSCs. Immunosuppresion in the FLC tumor microenvironment is characterized by T cell exclusion and exhaustion, which may be reversible with combination immunotherapy.
This study examined the environmental behaviour and fate of polyfluoroalkyl compounds (PFCs) found in water, suspended particulate matter (SPM) and sediment. The sampling of the sediment was ...performed at two stations from Tokyo Bay, Japan, in 2008. In addition, a depth profile of seawater was collected at three water layers from both sampling stations. The ∑PFC concentrations ranged from 16.7 to 42.3
ng
L
−1 in the water column, from 6.4 to 15.1
ng
g
−1 dry weight (dw) in the SPM fraction and from 0.29 to 0.36
dw in surface sediment. The distribution of PFCs was found to depend on their physicochemical characteristics. While short-chain perfluoroalkyl carboxylic acids (PFCAs) (C
<
7) were exclusively detected in the dissolved phase, longer-chain PFCAs (C
⩾
7), perfluoroalkyl sulfonates (PFSAs), ethylperfluorooctane sulfonamidoacetic acid (EtFOSAA), and perfluorooctane sulfonamide (PFOSA) appeared to bind more strongly to particles. Results showed that the sorption of PFCs on SPM increases by 0.52–0.75 log units for each additional CF
2 moiety and that the sorption of PFSAs was 0.71–0.76 log units higher compared to the PFCA analogs. In addition, the sorption of PFCs was influenced by the organic carbon content. These data are essential for modelling the transport and environmental fate of PFCs.
► The partitioning of PFOA, PFOS and PFOSA between water and sediment was evaluated. ► The log
K
OC was 4.1
cm
3
g
−1 for PFOSA, 3.7
cm
3
g
−1 for PFOS and 2.4
cm
3
g
−1 for PFOA. ► PFOA, PFOS and ...PFOSA were present in the dissolved phase at low SPM concentration. ► The organic content and density of the sediment influencing the partitioning.
Laboratory partitioning experiments were conducted to elucidate the sorption behaviour and partitioning of perfluoroalkyl compounds (PFCs). Three different sediment types were used and separately spiked with perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS) and perfluorooctane sulfonamide (PFOSA) at low environmentally realistic concentrations. PFOA, PFOS and PFOSA were mainly distributed in the dissolved phase at low suspended solid concentrations, indicating their long-range transport potential in the marine environment. In all cases, the equilibrium isotherms were linear and the organic carbon normalised partition coefficients (
K
OC) decreased in the following order: PFOSA (log
K
OC
=
4.1
±
0.35
cm
3
g
−1)
>
PFOS (3.7
±
0.56
cm
3
g
−1)
>
PFOA (2.4
±
0.12
cm
3
g
−1). The level of organic content had a significant influence on the partitioning. For the sediment with negligible organic content the density of the sediment became the most important factor influencing the partitioning. Ultimately, data on the partitioning of PFCs between aqueous media and suspended solids are essential for modelling their transport and environmental fate.
Perfluorinated compounds (PFCs) are known to biomagnify in temperate and Arctic food webs, but little is known about their behavior in subtropical systems. The environmental distribution and ...biomagnification of PFCs, extractable organic fluorine (EOF), and total fluorine were investigated in a subtropical food web. Surface water, sediment, phytoplankton, zooplankton, gastropods, worms, shrimps, fishes, and waterbirds collected in the Mai Po Marshes Nature Reserve in Hong Kong were analyzed. Trophic magnification was observed for perfluorooctanesulfonate (PFOS), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnDA), and perfluorododecanoate (PFDoDA) in this food web. Risk assessment results for PFOS, PFDA, and perfluorooctanoate (PFOA) suggest that current PFC concentrations in waterbird livers are unlikely to pose adverse biological effects to waterbirds. All hazard ratio (HR) values reported for PFOS and PFOA are less than one, which suggests that the detected levels will not cause any immediate health effects to the Hong Kong population through the consumption of shrimps and fishes. However, only 10–12% of the EOF in the shrimp samples was comprised of known PFCs, indicating the need for further investigation to identify unknown fluorinated compounds in wildlife.
Concentrations of nine antibiotics erythromycin-H
2O (ERY-H
2O); trimethoprim (TMP); tetracycline (TET); norfloxacin (NOR); penicillin G (PEN G); penicillin V (PEN V); cefalexin (CLX); cefotaxim ...(CTX); and cefazolin (CFZ) were measured in influent and effluent samples from four sewage treatment plants (STPs) in Hong Kong as well as in influent samples from one STP in Shenzhen. Levels of PEN V and CFZ were below method detection limits in all of the samples analyzed. CLX concentrations were the highest in most of the Hong Kong samples, ranging from 670 to 2900
ng/L and 240 to 1800
ng/L in influent and effluent samples, respectively, but CLX was not detected in the samples from Shenzhen. Comparatively lower concentrations were observed for ERY-H
2O (470–810
ng/L) and TET (96–1300
ng/L) in the influent samples from all STPs in Hong Kong. CTX was found to be the dominant antibiotic in the Shenzhen STP influents with a mean concentration of 1100
ng/L, but occurred at lower concentrations in Hong Kong sewage. These results likely reflect regional variations in the prescription and use patterns of antibiotics between Hong Kong and Shenzhen. Antibiotic removal efficiencies depended on their chemical properties and the wastewater treatment processes used. In general, relatively higher removal efficiencies were observed for NOR (5–78%) and TET (7–73%), which are readily adsorbed to particulate matter, while lower removal efficiencies were observed for ERY-H
2O (9–19%), which is relatively persistent in the environment. Antibiotics were removed more efficiently at Hong Kong STPs employing secondary treatment processes compared with those using primary treatment only. Concentrations of NOR measured in effluents from STPs in Hong Kong were lower than the predicted no-effect concentration of 8000
ng/L determined in a previous study. Therefore, concentrations of antibiotics measured in this preliminary study would be unlikely to cause adverse effects on microorganisms used in wastewater treatment processes at the sampled STPs.
The reliability of N95 filtering facepiece respirators (FFRs) depends on correct fitting. The perceived usability of FFRs is equally important because discomfort during usage may affect compliance. ...Body movements during nursing procedures may also increase the risk of face seal leakage.
To evaluate the mask fit and usability of the best-fitting 3M N95 FFR and the nanofibre N95 FFR before and after nursing procedures. The physical properties of these FFRs were also examined.
This experimental study had a one-group multiple comparison design. In total, 104 nursing students participated, and performed nursing procedures for 10 min when wearing the best-fitting 3M FFR and the nanofibre FFR. Mask fit and perceived usability of the FFRs were evaluated.
More participants failed to obtain a fit factor ≥100 when using the best-fitting 3M FFR than when wearing the nanofibre FFR (33.7% vs 21.2%) after the procedures (P=0.417). The nanofibre FFR also demonstrated higher usability than the 3M FFRs in terms of facial heat, breathability, facial pressure, speech intelligibility, itchiness, difficulty of maintaining the mask in place, and comfort level (P<0.001). The nanofibre FFR was also lighter, thinner and had slightly higher bacterial filtration efficiency than the 3M FFRs.
The nanofibre FFR demonstrated significantly better usability than the 3M FFRs. None of the respirators were able to provide consistent protection for the wearer, as detected by face seal leakage after performing nursing procedures. Further improvement in the prototype design is needed to increase compliance and ensure the respiratory protection of users.
The recent development of a sensitive and accurate analytical method for the analysis of 20 perfluorinated compounds (PFCs), including several short-chain PFCs, has enabled their quantification in ...tap water collected in China, Japan, India, the United States, and Canada between 2006 and 2008. Of the PFCs measured, PFOS, PFHxS, PFBS, PFPrS, PFEtS, PFOSA, N-EtFOSAA, PFDoDA, PFUnDA, PFDA, PFNA, PFHpA, PFHxA, PFPeA, PFBA, and PFPrA were found at detectable concentrations in the tap water samples. The water samples from Shanghai (China) contained the greatest concentrations of total PFCs (arithmetic mean = 130 ng/L), whereas those from Toyama (Japan) contained only 0.62 ng/L. In addition to PFOS and PFOA, short-chain PFCs such as PFHxS, PFBS, PFHxA, and PFBA were found to be prevalent in drinking water. According to the health-based values (HBVs) and advisory guidelines derived for PFOS, PFOA, PFBA, PFHxS, PFBS, PFHxA, and PFPeA by the U.S.EPA and the Minnesota Department of Health, tap water may not pose an immediate health risk to consumers.