New global indicator for workers' health: mortality rate from diseases attributable to selected occupational risk factors.

Through sustainable development goals 3 and 8 and other policies, countries have committed to protect and promote workers' health by reducing the work-related burden of disease. To monitor progress on these commitments, indicators that capture the work-related burden of disease should be available for monitoring workers' health and sustainable development. The World Health Organization and the International Labour Organization estimate that only 363 283 (19%) of 1 879 890 work-related deaths globally in 2016 were due to injuries, whereas 1 516 607 (81%) deaths were due to diseases. Most monitoring systems focusing on workers' health or sustainable development, such as the global indicator framework for the sustainable development goals, include an indicator on the burden of occupational injuries. Few such systems, however, have an indicator on the burden of work-related diseases. To address this gap, we present a new global indicator: mortality rate from diseases attributable to selected occupational risk factors, by disease, risk factor, sex and age group. We outline the policy rationale of the indicator, describe its data sources and methods of calculation, and report and analyse the official indicator for 183 countries. We also provide examples of the use of the indicator in national workers' health monitoring systems and highlight the indicator's strengths and limitations. We conclude that integrating the new indicator into monitoring systems will provide more comprehensive and accurate surveillance of workers' health, and allow harmonization across global, regional and national monitoring systems. Inequalities in workers' health can be analysed and the evidence base can be improved towards more effective policy and systems on workers' health.

Par le biais des objectifs de développement durable 3 et 8 ainsi que d'autres mesures, plusieurs pays se sont engagés à protéger et promouvoir la santé des travailleurs en réduisant l'impact des maladies liées au travail. Mais pour évaluer leurs progrès en la matière, il convient de mettre en place des indicateurs estimant l'impact des maladies liées au travail afin de placer le développement durable et la santé des travailleurs sous surveillance. D'après l'Organisation mondiale de la Santé et l'Organisation internationale du Travail, seulement 363 283 (19%) des 1 879 890 décès liés au travail dans le monde en 2016 découlaient de blessures, tandis que 1 516 607 (81%) d'entre eux étaient causés par des maladies. La plupart des systèmes de surveillance qui s'intéressent à la santé des travailleurs ou au développement durable, comme le cadre mondial d'indicateurs pour les objectifs de développement durable, comportent un indicateur relatif à l'impact des accidents de travail. Cependant, rares sont ceux qui possèdent un indicateur concernant l'impact des maladies professionnelles. Pour combler cette lacune, nous dévoilons un nouvel indicateur mondial: le taux de mortalité dû aux maladies attribuables à certains facteurs de risque professionnels classé par maladie, facteur de risque, sexe et catégorie d'âge. Nous exposons le motif politique de l'indicateur, décrivons l'origine des données et les méthodes de calcul, et communiquons et analysons l'indicateur officiel pour 183 pays. Nous fournissons également des exemples de la façon dont l'indicateur peut être utilisé dans des systèmes nationaux de surveillance de la santé des travailleurs et soulignons ses forces et faiblesses. Nous concluons en affirmant que l'intégration de ce nouvel indicateur dans les systèmes de surveillance offrira un suivi plus complet et précis de la santé des travailleurs et ouvrira la voie à une harmonisation des systèmes mondiaux, nationaux et régionaux. Il est possible d'analyser les inégalités en matière de santé des travailleurs et d'en améliorer les bases factuelles afin d'établir des politiques et systèmes plus efficaces dans ce domaine.

A través de los objetivos de desarrollo sostenible 3 y 8 y de otras políticas, los países se han comprometido a proteger y promover la salud de los trabajadores reduciendo la carga de morbilidad relacionada con el trabajo. Para supervisar los avances en el cumplimiento de estos compromisos, debería disponerse de indicadores que reflejen la carga de morbilidad relacionada con el trabajo, a fin de controlar la salud de los trabajadores y el desarrollo sostenible. La Organización Mundial de la Salud y la Organización Internacional del Trabajo estiman que solo 363 283 (19%) de las 1 879 890 muertes relacionadas con el trabajo a nivel mundial en 2016 se debieron a lesiones, mientras que 1 516 607 (81%) muertes se debieron a enfermedades. La mayoría de los sistemas de vigilancia centrados en la salud de los trabajadores o el desarrollo sostenible, como el marco de indicadores mundiales para los objetivos de desarrollo sostenible, incluyen un indicador sobre la carga de las lesiones laborales. No obstante, pocos de estos sistemas cuentan con un indicador sobre la carga de las enfermedades relacionadas con el trabajo. Para subsanar esta carencia, presentamos un nuevo indicador mundial: la tasa de mortalidad por enfermedades atribuibles a factores de riesgo laborales seleccionados, por enfermedad, factor de riesgo, sexo y grupo de edad. Describimos la justificación política del indicador, describimos sus fuentes de datos y métodos de cálculo, e informamos y analizamos el indicador oficial para 183 países. También proporcionamos ejemplos del uso del indicador en los sistemas nacionales de vigilancia de la salud de los trabajadores y destacamos las ventajas y las limitaciones del indicador. Concluimos que la integración del nuevo indicador en los sistemas de vigilancia proporcionará una vigilancia más exhaustiva y precisa de la salud de los trabajadores, y permitirá la armonización entre los sistemas de vigilancia mundiales, regionales y nacionales. Se podrán analizar las desigualdades en la salud de los trabajadores y se podrá mejorar la base de evidencias para lograr políticas y sistemas más eficaces en materia de salud de los trabajadores.

The use of HRM shifts in qPCR to investigate a much neglected aspect of interference by intracellular nanoparticles.

Genetic molecular studies used to understand potential risks of engineered nanomaterials (ENMs) are incomplete. Intracellular residual ENMs present in biological samples may cause assay interference. This report applies the high-resolution melt (HRM) feature of RT-qPCR to detect shifts caused by the presence of gold nanoparticles (AuNPs). A universal RNA standard (untreated control) sample was spiked with known amounts of AuNPs and reverse transcribed, where 10 reference genes were amplified. The amplification plots, dissociation assay (melt) profiles, electrophoretic profiles and HRM difference curves were analysed and detected interference caused by AuNPs, which differed according to the amount of AuNP present (i.e. semi-quantitative). Whether or not the assay interference was specific to the reverse transcription or the PCR amplification step was tested. The study was extended to a target gene-of-interest (GOI), Caspase 7. Also, the effect on in vitro cellular samples was assessed (for reference genes and Caspase 7). This method can screen for the presence of AuNPs in RNA samples, which were isolated from biological material in contact with the nanomaterials, i.e., during exposure and risk assessment studies. This is an important quality control procedure to be implemented when quantifying the expression of a GOI from samples that have been in contact with various ENMs. It is recommended to further examine 18S, PPIA and TBP since these were the most reliable for detecting shifts in the difference curves, irrespective of the source of the RNA, or, the point at which the different AuNPs interacted with the assay.

The presence of residual gold nanoparticles in samples interferes with the RT-qPCR assay used for gene expression profiling.

BACKGROUND: RT-qPCR is routinely used in expression profiling of toxicity pathway genes. However, genetic and molecular level studies used to determine, understand and clarify potential risks of engineered nanomaterials (ENMs) are still incomplete. Concerns regarding possible interference caused by intracellular ENMs during analyses have been raised. The aim of this study was to verify a qPCR procedure for gene expression assays, which can be used in toxicity and exposure assessments. RESULTS: Amplification of ten reference genes was performed to test the expression stability. A preliminary study was performed on RNA from BEAS-2B cells that had been treated with AuNPs. Also, a reference total RNA standard from ten cell lines was spiked with various amounts of the same AuNP. This treatment mimics exposure assessment studies, where assay-interference may be caused by intracellular residual ENMs still being present in the biological samples (during and after isolation/purification procedures). Both types of RNA samples were reverse transcribed and then amplified by qPCR. The qPCR-related software and statistical programs used included BestKeeper, NormFinder, REST and qBase+. These results proved that using standard qPCR analysis and statistical programs should not be the only procedure applied to verify the assay for gene expression assessment related to ENMs. A comparison of SYBR Green to EVA Green was discussed, in addition to a comparison to the latest reports regarding the influence of ENM thermal conductivity, surface interactions with ENMs, effects of ENM size and charge, as well as, the limit of detection in a qPCR assay. CONCLUSIONS: AuNPs have the potential to interfere with the assay mechanism of RT-qPCR, thus, assay verification is required for AuNP-related gene expression studies used to evaluate toxicity. It is recommended to use HSP90 and YWHAZ as reference genes, i.e. these were the most stable in our study, irrespective of the source of the RNA, or, the point at which the AuNPs interacted with the assay. This report describes steps that can be utilised to generate a suitable method for gene expression studies associated with toxicity testing of various ENMs. For example, RNA standards that have been spiked with known amounts of ENMs should be run in conjunction with the unknown samples, in order to verify any RT-qPCR assay and determine the degree of error.

Alternative splicing of the receptor-like kinase Nt-Sd-RLK in tobacco cells responding to lipopolysaccharides: suggestive of a role in pathogen surveillance and perception?

Nt-Sd-RLK encodes an S-domain lectin receptor-like kinase that is induced in response to microbe-associated molecular pattern molecules (MAMPs) such as lipopolysaccharide (LPS). In this study, we investigated the alternative splicing of Nt-Sd-RLK in response to LPS stimulation. Our data indicate that in nonstimulated cells, a shorter transcript of Nt-Sd-RLK is generated and that in response to LPS, alternative splicing produces the full-length transcript. We propose that the extracellular domain of Nt-Sd-RLK encoded by the shorter transcript functions in pathogen surveillance. Once this domain binds LPS, alternative splicing generates the kinase domain-containing Nt-Sd-RLK that activates downstream signalling leading to a defence response. Thus, our findings suggest that plant defence signalling may be regulated through the alternative splicing of receptor-like kinases involved in pathogen recognition.

The induction of cell death by phosphine silver(I) thiocyanate complexes in SNO-esophageal cancer cells.

Esophageal cancer is one of the least studied cancers and is found to be prominent in black South African males. It is mainly diagnosed in the late stages, and patients tend to have a low 5-year survival rate of only 10%. Silver is generally used as an antimicrobial agent, with limited reports on anticancer studies. In this study, dimeric silver(I) thiocyanate complexes were used containing a variation of 4-substitued triphenylphosphines, including [AgSCN(PPh(3))(2)](2) (1), [AgSCN{P(4-MeC(6)H(4))(3)}(2)](2) (2), [AgSCN{P(4-FC(6)H(4))(3)}(2)](2) (3) and [AgSCN{P(4-ClC(6)H(4))(3)}(2)](2) (4). All four complexes, with their respective phosphine ligands, PPh(3) (L1), P(4-MeC(6)H(4))(3) (L2), P(4-FC(6)H(4))(3) (L3) and P(4-ClC(6)H(4))(3) (L4), were subjected to in vitro toxicity studies in SNO-esophageal cancer cells, using an alamarBlue(®) assay. Morphological changes, including blebbing and apoptotic body formation, were observed. Phosphatidylserine externalization, a marker of apoptosis, was quantified by flow cytometry. The phosphine ligands L1-L4, on their own, had minimal effect on the malignant while complexes 1-4 resulted in significant cell death. A 10x decreased concentration of these complexes had similar effects than cisplatin, used as the positive control. These complexes show promise as anticancer agents.

Gold nanoparticle interference study during the isolation, quantification, purity and integrity analysis of RNA.

Investigations have been conducted regarding the interference of nanoparticles (NPs) with different toxicological assay systems, but there is a lack of validation when conducting routine tests for nucleic acid isolation, quantification, integrity, and purity analyses. The interference of citrate-capped gold nanoparticles (AuNPs) was investigated herein. The AuNPs were added to either BEAS-2B bronchial human cells for 24 h, the isolated pure RNA, or added during the isolation procedure, and the resultant interaction was assessed. Total RNA that was isolated from untreated BEAS-2B cells was spiked with various concentrations (v/v%) of AuNPs and quantified. A decrease in the absorbance spectrum (220-340 nm) was observed in a concentration-dependent manner. The 260 and 280 nm absorbance ratios that traditionally infer RNA purity were also altered. Electrophoresis was performed to determine RNA integrity, but could not differentiate between AuNP-exposed samples. However, the spiked post-isolation samples did produce differences in spectra (190-220 nm), where shifts were observed at a shorter wavelength. These shifts could be due to alterations to chromophores found in nucleic acids. The co-isolation samples, spiked with 100 µL AuNP during the isolation procedure, displayed a peak shift to a longer wavelength and were similar to the results obtained from a 24 h AuNP treatment, under non-cytotoxic test conditions. Moreover, hyperspectral imaging using CytoViva dark field microscopy did not detect AuNP spectral signatures in the RNA isolated from treated cells. However, despite the lack of AuNPs in the final RNA product, structural changes in RNA could still be observed between 190-220 nm. Consequently, full spectral analyses should replace the traditional ratios based on readings at 230, 260, and 280 nm. These are critical points of analyses, validation, and optimization for RNA-based techniques used to assess AuNPs effects.

Molecular characterisation and regulation of a Nicotiana tabacum S-domain receptor-like kinase gene induced during an early rapid response to lipopolysaccharides.

The isolation, characterization and regulation of the first lipopolysaccharide (LPS)-responsive S-domain receptor-like kinase (RLK) in Nicotiana tabacum are reported. The gene, corresponding to a differentially expressed LPS-responsive EST, was fully characterised to investigate its involvement in LPS-induced responses. The full genomic sequence, designated Nt-Sd-RLK, encodes for a S-domain RLK protein containing conserved modules (B-lectin-, S- and PAN-domains) reported to function in mediating protein-protein and protein-carbohydrate interactions in its extracellular domain, as well as the molecular architecture to transduce signals intracellularly through a Ser/Thr kinase domain. Phylogenetic analysis clustered Nt-Sd-RLK with S-domain RLKs induced by bacteria, wounding and salicylic acid. Perception of LPS induced a rapid, bi-phasic response in Nt-Sd-RLK expression with a 17-fold up-regulation at 3 and 9h. A defence-related W-box cis element was found in the promoter region of Nt-Sd-RLK and the transient induction of Nt-Sd-RLK in cultured cells by LPS exhibited a pattern typical of early response defence genes. Nt-Sd-RLK was also responsive to salicylic acid induction and was expressed in differentiated leaf tissue, where LPS elicited local as well as systemic up-regulation. The results contribute new knowledge about the potential role that S-domain RLKs may play within interactive signal transduction pathways associated with immunity and defence.

Nonself perception in plant innate immunity.

The ability to distinguish' self' from 'nonself' is the most fundamental aspect of any immune system. The evolutionary solution in plants to the problems of perceiving and responding to pathogens involves surveillance of nonself, damaged-self and altered-self as danger signals. This is reflected in basal resistance or nonhost resistance, which is the innate immune response that protects plants against the majority of pathogens. In the case of surveillance of nonself, plants utilize receptor-like proteins or -kinases (RLP/Ks) as pattern recognition receptors (PRRs), which can detect conserved pathogen/microbe-associated molecular pattern (P/MAMP) molecules. P/MAMP detection serves as an early warning system for the presence of a wide range of potential pathogens and the timely activation of plant defense mechanisms. However, adapted microbes express a suite of effector proteins that often interfere or act as suppressors of these defenses. In response, plants have evolved a second line of defense that includes intracellular nucleotide binding leucine-rich repeat (NB-LR)-containing resistance proteins, which recognize isolate-specific pathogen effectors once the cell wall has been compromised. This host-immunity acts within the species level and is controlled by polymorphic host genes, where resistance protein-mediated activation of defense is based on an 'altered-self' recognition mechanism.

Self/nonself perception in plants in innate immunity and defense.

The ability to distinguish 'self' from 'nonself' is the most fundamental aspect of any immune system. The evolutionary solution in plants to the problems of perceiving and responding to pathogens involves surveillance of nonself, damaged-self and altered-self as danger signals. This is reflected in basal resistance or non-host resistance, which is the innate immune response that protects plants against the majority of pathogens. In the case of surveillance of nonself, plants utilize receptor-like proteins or -kinases (RLP/Ks) as pattern recognition receptors (PRRs), which can detect conserved pathogen/microbe-associated molecular pattern (P/MAMP) molecules. P/MAMP detection serves as an early warning system for the presence of a wide range of potential pathogens and the timely activation of plant defense mechanisms. However, adapted microbes express a suite of effector proteins that often interfere or act as suppressors of these defenses. In response, plants have evolved a second line of defense that includes intracellular nucleotide binding leucine-rich repeat (NB-LRR)-containing resistance proteins, which recognize isolate-specific pathogen effectors once the cell wall has been compromised. This host-immunity acts within the species level and is controlled by polymorphic host genes, where resistance protein-mediated activation of defense is based on an 'altered-self' recognition mechanism.

Differential display profiling of the Nicotiana response to LPS reveals elements of plant basal resistance.

The identification of cDNAs, representing up-regulated genes induced by lipopolysaccharides from Burkholderia cepacia, was achieved by differential display of mRNAs isolated from tobacco cells. In addition to up-regulation of superoxide dismutase, involved in the production of the signalling and defense molecule, hydrogen peroxide; differentially expressed cDNAs, indicative of the operation of an innate immune recognition system and expression of basal resistance, were identified. These include homologs to a receptor-like protein kinase; a binding protein for the type III secreted effector protein, harpin; a virus resistance N gene; an endogenous pararetrovirus and the Pto kinase. The altered gene expression may be responsible for activation of surveillance mechanisms and enhancement of the non-self recognition capacity. The putative roles of these transcripts in LPS-induced responses are discussed in relation to emerging concepts of innate immunity.