Systematic Review of Screening and Surveillance Programs to Protect Workers from Nanomaterials

BackgroundScreening and surveillance approaches for workers exposed to nanomaterials could aid in early detection of health effects, provide data for epidemiological studies and inform action to decrease exposure. The aim of this review is to identify such screening and surveillance approaches, in order to extract available data regarding (i) the studies that have successfully been implemented in present day, (ii) identification of the most common and/or toxic nano-related health hazards for workers and (iii) possible exposure surveillance markers. This review contributes to the current understanding of the risk associated with nanomaterials by determining the knowledge gap and making recommendations based on current findings.MethodsA systematic review was conducted. PubMed and Embase were searched to identify articles reporting on any surveillance-related study that described both exposure to nanomaterials and the health indicators that were measured. Four reviewers worked in pairs to independently assess the eligibility of studies and risk of bias before extraction of data. Studies were categorised according to the type of study and the medical surveillance performed, which included the type of nanomaterial, any exposure details provided, as well as health indicators and biomarkers tested.ResultsInitially 92 studies were identified, from which 84 full texts were assessed for eligibility. Seven studies met all the inclusion criteria, i.e. those performed in Taiwan, Korea, Czech Republic and the US. Of these, six compared health indicators between exposed and unexposed workers and one study described a surveillance program. All studies were at a high risk of bias. Workers were exposed to a mix of nanomaterials in three studies, carbon-based nanomaterials in two studies, nano-silver in one study and nano-titanium oxide in the other study. Two studies did not find a difference in biomarkers between exposed and unexposed workers. In addition, differences in early effects on pulmonary function or neurobehavioral tests were not observed. One study found an increased prevalence of allergic dermatitis and “sneezing” in the exposed group.ConclusionsThis review of recently published data on surveillance studies proves that there is a gap in the current knowledge, where most of the surveillance-related studies reported do not follow a set format that provides the required information on ENM characterisation, the type of exposure and the measured indicators/biomarkers. Hence, there is very low quality evidence that screening and surveillance might detect adverse health effects associated with workplace exposure. This systematic review is relevant because it proves that, although surveillance programs have been initiated and preliminary results are being published, the current studies are actually not answering the important questions or solving the overall problem regarding what the potential health hazards are among workers either handling or potentially exposed to ENMs. The recommendations, thus proposed, are based on an obvious need for (i) exposure registries, where longitudinal follow-up studies should inform surveillance, (ii) known exposure measurements or summary indices for ENMs as a reference (iii) validation of candidate biomarkers and (iv) studies that compare the effects of these surveillance approaches to usual care, e.g. those commonly followed for bulk-size hazardous materials.     

A structural and in vitro characterization of asoprisnil: a selective progesterone receptor modulator

Selective progesterone receptor modulators (SPRMs) have been suggested as therapeutic agents for treatment of gynecological disorders. One such SPRM, asoprisnil, was recently in clinical trials for treatment of uterine fibroids and endometriosis. We present the crystal structures of progesterone receptor (PR) ligand binding domain complexed with asoprisnil and the corepressors nuclear receptor corepressor (NCoR) and SMRT. This is the first report of steroid nuclear receptor crystal structures with ligand and corepressors. These structures show PR in a different conformation than PR complexed with progesterone (P4). We profiled asoprisnil in PR-dependent assays to understand further the PR-mediated mechanism of action. We confirmed previous findings that asoprisnil demonstrated antagonism, but not agonism, in a PR-B transfection assay and the T47D breast cancer cell alkaline phosphatase activity assay. Asoprisnil, but not RU486, weakly recruited the coactivators SRC-1 and AIB1. However, asoprisnil strongly recruited the corepressor NCoR in a manner similar to RU486. Unlike RU486, NCoR binding to asoprisnil-bound PR could be displaced with equal affinity by NCoR or TIF2 peptides. We further showed that it weakly activated T47D cell gene expression of Sgk-1 and PPL and antagonized P4-induced expression of both genes. In rat leiomyoma ELT3 cells, asoprisnil demonstrated partial P4-like inhibition of cyclooxygenase (COX) enzymatic activity and COX-2 gene expression. In the rat uterotrophic assay, asoprisnil demonstrated no P4-like ability to oppose estrogen. Our data suggest that asoprisnil differentially recruits coactivators and corepressors compared to RU486 or P4, and this specific cofactor interaction profile is apparently insufficient to oppose estrogenic activity in rat uterus.     

Phenotypic plasticity mediates climate change responses among invasive and indigenous arthropods

Synergies between global change and biological invasion have been identified as a major potential threat to global biodiversity and human welfare. The global change-type drought characteristic of many temperate terrestrial ecosystems is especially significant because it will apparently favour invasive over indigenous species, adding to the burden of conservation and compromising ecosystem service delivery. However, the nature of and mechanisms underlying this synergy remain poorly explored. Here we show that in a temperate terrestrial ecosystem, invasive and indigenous springtail species differ in the form of their phenotypic plasticity such that warmer conditions promote survival of desiccation in the invasive species and reduce it in the indigenous ones. These differences are consistent with significant declines in the densities of indigenous species and little change in those of invasive species in a manipulative field experiment that mimicked climate change trends. We suggest that it is not so much the extent of phenotypic plasticity that distinguishes climate change responses among these invasive and indigenous species, as the form that this plasticity takes. Nonetheless, this differential physiological response provides support for the idea that in temperate terrestrial systems experiencing global change-type drought, invasive species may well be at an advantage relative to their indigenous counterparts.     

Landscape use and fruit cultivation in Petra (Jordan) from Early Nabataean to Byzantine times (2nd century <Emphasis Type="SmallCaps">bc</Emphasis>–5th century <Emphasis Type="SmallCaps">ad</Emphasis>)

Archaeobotanical analyses of charred seeds, fruit and wood charcoal from the residential part of the ez-Zantur area at Petra, Jordan, provide new data on the agricultural economy and use of the landscape in this famous merchant Nabataean city from the middle of the 2nd century bc to the beginning of the 5th century ad. The study is based on analyses of 7,640 whole and fragmented seeds, pips and fruit stones and 624 charcoal fragments sampled from household deposits. The results show that the food supply was based on common Mediterranean cultivated taxa such as cereals (Hordeum vulgare, Triticum aestivum/durum), pulses (Lens culinaris) and fruit (Olea europaea, Ficus carica, Vitis vinifera), which were probably cultivated both in the city and its hinterland. The by-products from the processing of cereals and fruit trees played a significant role in fuel supply, supplementing woody wild plants obtained from rocky slopes and the desert valley. The variety of fuel resources shows a major capacity to manage complex supply networks and perhaps the rarity of natural woodland cover. The existence of orchards within the city centre and notably olive groves is indicated in the Early Nabataean period (mid 2nd century to mid 1st century bc) but they expanded during the Classical Nabataean period (mid 1st century bc to 1st century ad), probably reflecting specialised fruit growing. Unusual plant remains such as Prunus armeniaca (apricot), P. persica (peach) and Juglans regia (walnut) are considered to be social indicators of prosperity. These archaeobotanical results fit with others from this region and match with the urbanization and social dynamics of the city of Petra.     

Discovery of a novel and potent class of anti-HIV-1 maturation inhibitors with improved virology profile against gag polymorphisms

A new class of betulin-derived α-keto amides was identified as HIV-1 maturation inhibitors. Through lead optimization, GSK8999 was identified with IC₅₀ values of 17 nM, 23 nM, 25 nM, and 8 nM for wild type, Q369H, V370A, and T371A respectively. When tested in a panel of 62 HIV-1 isolates covering a diversity of CA-SP1 genotypes including A, AE, B, C, and G using a PBMC based assay, GSK8999 was potent against 57 of 62 isolates demonstrating an improvement over the first generation maturation inhibitor BVM. The data disclosed here also demonstrated that the new α-keto amide GSK8999 has a mechanism of action consistent with inhibition of the proteolytic cleavage of CA-SP1.     

World without borders—genetic population structure of a highly migratory marine predator,the blue shark (Prionace glauca)

Highly migratory, cosmopolitan oceanic sharks often exhibit complex movement patterns influenced by ontogeny, reproduction, and feeding. These elusive species are particularly challenging to population genetic studies, as representative samples suitable for inferring genetic structure are difficult to obtain. Our study provides insights into the genetic population structure one of the most abundant and wide‐ranging oceanic shark species, the blue shark Prionace glauca, by sampling the least mobile component of the populations, i.e., young‐of‐year and small juveniles (<2 year; N = 348 individuals), at three reported nursery areas, namely, western Iberia, Azores, and South Africa. Samples were collected in two different time periods (2002–2008 and 2012–2015) and were screened at 12 nuclear microsatellites and at a 899‐bp fragment of the mitochondrial control region. Our results show temporally stable genetic homogeneity among the three Atlantic nurseries at both nuclear and mitochondrial markers, suggesting basin‐wide panmixia. In addition, comparison of mtDNA CR sequences from Atlantic and Indo‐Pacific locations also indicated genetic homogeneity and unrestricted female‐mediated gene flow between ocean basins. These results are discussed in light of the species' life history and ecology, but suggest that blue shark populations may be connected by gene flow at the global scale. The implications of the present findings to the management of this important fisheries resource are also discussed.     

The lived experience of psychosis: a bottom‐up review co‐written by experts by experience and academics

Psychosis is the most ineffable experience of mental disorder. We provide here the first co‐written bottom‐up review of the lived experience of psychosis, whereby experts by experience primarily selected the subjective themes, that were subsequently enriched by phenomenologically‐informed perspectives. First‐person accounts within and outside the medical field were screened and discussed in collaborative workshops involving numerous individuals with lived experience of psychosis as well as family members and carers, representing a global network of organizations. The material was complemented by semantic analyses and shared across all collaborators in a cloud‐based system. The early phases of psychosis (i.e., premorbid and prodromal stages) were found to be characterized by core existential themes including loss of common sense, perplexity and lack of immersion in the world with compromised vital contact with reality, heightened salience and a feeling that something important is about to happen, perturbation of the sense of self, and need to hide the tumultuous inner experiences. The first episode stage was found to be denoted by some transitory relief associated with the onset of delusions, intense self‐referentiality and permeated self‐world boundaries, tumultuous internal noise, and dissolution of the sense of self with social withdrawal. Core lived experiences of the later stages (i.e., relapsing and chronic) involved grieving personal losses, feeling split, and struggling to accept the constant inner chaos, the new self, the diagnosis and an uncertain future. The experience of receiving psychiatric treatments, such as inpatient and outpatient care, social interventions, psychological treatments and medications, included both positive and negative aspects, and was determined by the hope of achieving recovery, understood as an enduring journey of reconstructing the sense of personhood and re‐establishing the lost bonds with others towards meaningful goals. These findings can inform clinical practice, research and education. Psychosis is one of the most painful and upsetting existential experiences, so dizzyingly alien to our usual patterns of life and so unspeakably enigmatic and human.