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Nucleic acid testing (NAT), as a molecular diagnostic technique, including nucleic acid extraction, amplification and detection, plays a fundamental role in medical diagnosis for timely medical treatment. However, current NAT technologies require relatively high-end instrumentation, skilled personnel, and are time-consuming. These drawbacks mean conventional NAT becomes impractical in many resource-limited disease-endemic settings, leading to an urgent need to develop a fast and portable NAT diagnostic tool. Paper-based devices are typically robust, cost-effective and user-friendly, holding a great potential for NAT at the point of care. In view of the escalating demand for the low cost diagnostic devices, we highlight the beneficial use of paper as a platform for NAT, the current state of its development, and the existing challenges preventing its widespread use. We suggest a strategy involving integrating all three steps of NAT into one single paper-based sample-to-answer diagnostic device for rapid medical diagnostics in the near future.

Bisphenol A (BPA) is widely used in industrial products. Due to the toxicity of this compound, and to comply with restrictions and regulations, manufacturers have progressively replaced it by substitutes. One of the main substitutes used is bisphenol S (BPS). Despite increasing use in many products, the effects of BPS on human health have been little investigated, and studies on percutaneous BPS absorption and particularly toxicokinetic data are lacking. However, the endocrine-disrupting activity of BPA and BPS appears comparable. Dermal contact is a significant source of occupational exposure and is the main route during handling of bisphenol-containing receipts by cashiers. Here, percutaneous BPS absorption was investigated and compared to that of BPA. Experiments were performed according to OECD guidelines. Test compounds dissolved in a vehicle - acetone, artificial sebum or water – were applied in vitro to fresh human skin samples in static Franz diffusion cells. Flux, cumulative absorbed dose and distribution of dose recovered were measured. BPA absorption was vehicle-dependent ranging from 3% with sebum to 41% with water. BPS absorption was much lower than BPA absorption whatever the vehicle tested (less than 1% of applied dose). However, depending on the vehicle 20% to 47% of the applied BPS dose remained in the skin, and was consequently potentially absorbable. Both BPA and BPS were mainly absorbed without biotransformation. Taken together, these results indicate that workers may be exposed to BPS through skin when handling products containing it. This exposure is of concern as its toxicity is currently incompletely understood.

Pulp and paper mill effluents (PPMEs) have been shown to increase gonad size, cause early maturation, and disrupt hormone functions in native and non-native Chilean fish. In this study, we assessed reproductive (plasma vitellogenin; VTG, gonad development) and metabolic (ethoxyresorufin-. O-deethylase activity; EROD) end points, relative liver size (LSI) and condition factor (K) of juvenile female and male rainbow trout exposed to effluents. Unlike previous studies, which have focus either on the specific effects of effluent on fish in laboratory exposures or biotic population statuses downstream of discharge sites, we simultaneously assessed the impacts of PPMES on trout using two approaches: (1) laboratory exposures of tertiary treated PPME produced from processing Eucalyptus globulus or Pinus radiata; and (2) in situ bioassay downstream of the combined discharge of the same pulp mill. Despite an increase in the average gonadosomatic index (GSI) in exposed fish, no statistical differences in gonad size between exposed and unexposed individuals was detected. However, both female and male fish exposed to effluents showed significantly higher concentrations of plasma VTG, so more in fish exposed to Eucalyptus-based effluent when compared to Pinus PPME. In addition, male fish showed intersex characteristics in all exposure assays (Eucaliptus and Pinus) and, despite the low concentration of effluent in the river (

Alternatives to bisphenol A (BPA) are more and more used in thermal paper receipts. To get an overview of the situation in Switzerland, 124 thermal paper receipts were collected and analyzed. Whereas BPA was detected in most samples (n=100), some alternatives, namely bisphenol S (BPS), Pergafast® 201 and D-8 have been found in 4, 11 and 9 samples respectively. As no or few data on their endocrine activity are available, these chemicals and bisphenol F (BPF) were tested in vitro using the H295R steroidogenesis assay. 17β-Estradiol production was induced by BPA and BPF, whereas free testosterone production was inhibited by BPA and BPS. Both non-bisphenol substances did not show significant effects. The binding affinity to 16 proteins and the toxicological potential (TP) were further calculated in silico using VirtualToxLab™. TP values lay between 0.269 and 0.476 and the main target was the estrogen receptor β (84.4 nM to 1.33 μM). A substitution of BPA by BPF and BPS should be thus considered with caution, since they exhibit almost a similar endocrine activity as BPA. D-8 and Pergafast® 201 could be alternatives to replace BPA, however further analyses are needed to better characterize their effects on the hormonal system.

In this paper, Graphene oxide@SiO2@CeO2 hybrid nanosheets (GSCs) have been successfully synthesized by the wet-chemical strategy. TEM, FITR and XPS were applied to characterize the morphology and composition of the nanosheets. The colorimetric assay of these nanosheets indicated that they possessed high intrinsic peroxidase activity, which should be ascribed to the combination of graphene oxide and CeO2. A fully integrated reagentless bioactive paper based on GSCs was fabricated, which were able to simultaneously detect glucose, lactate, uric acid and cholesterol. The results demonstrated that GSCs have great potential as an alternative to the commonly employed peroxidase in daily nursing and general physical examination.

A number of high molecular weight (HMW) lignin derivatives possessing varied chemical properties were screened for their biological effects in order to obtain more information on the possible structural features of HMW lignin-related effects. The studied compounds were both commercial and in-house extracted lignin derivatives. Bioassays used include reverse electron transport (RET), Vibrio fischeri, Daphnia magna , and juvenile rainbow trout ( Oncorhynchus mykiss) hepatocytes. The studied lignin derivatives inhibited the in vitro systems and luminescence of V. fischeri bacteria to some extent–daphnids were not affected. It seems that, at least in the RET assay, certain pH-dependent functional groups in lignin may be of importance regarding the biological effects.

Introduction: The preparation of bloodspot calibrators and quality control samples for neonatal thyrotropin (TSH), as part of the national quality assessment scheme in The Netherlands, is sometimes problematic. Often, the recovery of the added TSH is well above 100% when measured in plasma. Results from other External Quality Assessment Schemes for neonatal TSH show similar problems. Methods and Results: A questionnaire was sent to 17 kit manufacturers and organizers of EQAS concerning the preparation of bloodspot calibrators for TSH; 13 completed questionnaires were returned. There are large differences with respect to type of filterpaper, matrix, assessment of TSH-concentrations to the calibrators, size of the bloodspots, shelf life, etc. Discussion: Attention is focused on several items to be considered when attempting standardization of the preparation of TSH bloodspot calibrators.

Terminal differentiation of the keratinocytes (cornification) has been linked to a restricted supply of retinol. Retinol is distributed to target cells by the retinol-binding protein (RBP), which circulates in the plasma in complex with transthyretin (TTR). In this study we have addressed the question of retinol delivery to the epidermis via RBP. Retinol radiobinding assays, affinity chromatography with TTR coupled to Sepharose beads, polyacrylamide gel electrophoresis, and immunoblotting techniques were used to show that epidermal extracts contain retinol binding sites with no affinity for TTR. Immunoreactive RBP was detected in the epidermal extracts. The RBP in the epidermis was in the apoform (without retinol) in contrast to serum where the majority of RBP is in the holoform (with retinol). Epidermal RBP was converted in vitro into the holoform only after addition of 20 times more retinol, which was needed to reconstitute holoforms of RBP in dermal extracts, human buccal mucosal extracts, and delipidized normal serum or purified delipidized RBP. Moreover, several immunoreactive RBP bands (possibly degradation products) were identified in the epidermal but not in dermal extracts. Retinol-binding protein from nonkeratinizing human oral mucosa showed different immunoblotting patterns when compared to epidermal RBP. These results suggest that degradation of RBP within the epidermis may result in a decreased retinol supply to the keratinocytes, and may lead to the cornification of the epidermis.

An immunoradiometric two-site assay for thyrotrophin (TSH) in dried blood filter paper spots is described. The assay is automated by means of the Kemtek 3000 automated immunoassay system. The technique uses a 6.0 mm disc punched from the dried blood samples collected as part of the screening programme for phenylketonuria. The method is sensitive and precise, and results correlate well with those obtained in TSH assays of serum samples. The procedure is rapid, results being available within 24 h of receipt of samples. Of 25204 specimens so far screened by this assay, 99.9% have TSH levels less than 15 mU/1. One false positive result has been obtained and six confirmed cases of neonatal hypothyroidism detected, giving a prevalence of 1 in 4200.

Autoimmune thyroid disease in man is commonly associated with autoantibodies against thyroglobulin, microsomes, and the TSH receptor, and the character and specificity of these antithyroid antibodies have been extensively utilized in investigating these conditions. In the present study we have asked whether other thyroid-related antigens exist, against which autoantibodies may be directed. A crude thyroid extract was separated by polyacrylamide gel electrophoresis followed by immunoblotting with serum obtained from patients with Graves' disease or Hashimoto's thyroiditis. Antibodies in sera from patients with Graves' disease and Hashimoto's thyroiditis reacted with many antigenic determinants in immunoblots of the thyroid membrane preparation (2000g supernatant). These determinants were disease specific in that sera from normals and patients with Addison's disease and rheumatoid arthritis did not react, but there was no difference between the patterns of reactivity with Graves' disease or Hashimoto's thyroiditis sera. Thyroglobulin produced two predominant bands of reactivity at 320 and 200 kDa, whereas purified microsomal antigen produced a triplet of bands around 105 kDa, when these preparations were reacted with appropriate autoimmune sera. Nonetheless, some sera produced additional bands with the microsomal antigen blots, indicating that some of the antigens which were detected using crude thyroid membrane remained in the microsome preparation to produce multiple antibody binding reactivities. We were unable to inhibit any of the antibody binding with TSH. Purification of individual thyroid antigens on the basis of their molecular weights should standardize current antibody assays and permit more detailed evaluation of the cellular immune responses in Graves' disease and Hashimoto's thyroiditis.