HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

The vast amount of plastic waste emitted into the environment and the increasing concern of potential harm to wildlife has made microplastic and nanoplastic pollution a growing environmental concern. Plastic pollution has the potential to cause both physical and chemical harm to wildlife directly or via sorption, concentration, and transfer of other environmental contaminants to the wildlife that ingest plastic. Small particles of plastic pollution, termed microplastics (>100 nm and <5 mm) or nanoplastics (<100 nm), can form through fragmentation of larger pieces of plastic. These small particles are especially concerning because of their high specific surface area for sorption of contaminants as well as their potential to translocate in the bodies of organisms. These same small particles are challenging to separate and identify in environmental samples because their size makes handling and observation difficult. As a result, our understanding of the environmental prevalence of nanoplastics and microplastics is limited. Generally, the smaller the size of the plastic particle, the more difficult it is to separate from environmental samples. Currently employed passive density and size separation techniques to isolate plastics from environmental samples are not well suited to separate microplastics and nanoplastics. Passive flotation is hindered by the low buoyancy of small particles as well as the difficulty of handling small particles on the surface of flotation media. Here we suggest exploring alternative techniques borrowed from other fields of research to improve separation of the smallest plastic particles. These techniques include adapting active density separation (centrifugation) from cell biology and taking advantage of surface-interaction-based separations from analytical chemistry. Furthermore, plastic pollution is often challenging to quantify in complex matrices such as biological tissues and wastewater. Biological and wastewater samples are important matrices that represent key points in the fate and sources of plastic pollution, respectively. In both kinds of samples, protocols need to be optimized to increase throughput, reduce contamination potential, and avoid destruction of plastics during sample processing. To this end, we recommend adapting digestion protocols to match the expected composition of the nonplastic material as well as taking measures to reduce and account for contamination. Once separated, plastics in an environmental sample should ideally be characterized both visually and chemically. With existing techniques, microplastics and nanoplastics are difficult to characterize or even detect. Their low mass and small size provide limited signal for visual, vibrational spectroscopic, and mass spectrometric analyses. Each of these techniques involves trade-offs in throughput, spatial resolution, and sensitivity. To accurately identify and completely quantify microplastics and nanoplastics in environmental samples, multiple analytical techniques applied in tandem are likely to be required.

Mycobacterium are among the oldest co-evolutionary partners of humans. The attenuated Mycobacterium bovis Bacillus Calmette Guérin (BCG) strain has been administered globally for 100 years as a vaccine against tuberculosis. BCG also shows promise as treatment for numerous inflammatory and autoimmune diseases. Here, we report on a randomized 8-year long prospective examination of type 1 diabetic subjects with long-term disease who received two doses of the BCG vaccine. After year 3, BCG lowered hemoglobin A1c to near normal levels for the next 5 years. The BCG impact on blood sugars appeared to be driven by a novel systemic and blood sugar lowering mechanism in diabetes. We observe a systemic shift in glucose metabolism from oxidative phosphorylation to aerobic glycolysis, a state of high glucose utilization. Confirmation is gained by metabolomics, mRNAseq, and functional assays of cellular glucose uptake after BCG vaccinations. To prove BCG could induce a systemic change to promote accelerated glucose utilization and impact blood sugars, murine data demonstrated reduced blood sugars and aerobic induction in non-autoimmune mice made chemically diabetic. BCG via epigenetics also resets six central T-regulatory genes for genetic re-programming of tolerance. These findings set the stage for further testing of a known safe vaccine therapy for improved blood sugar control through changes in metabolism and durability with epigenetic changes even in advanced Type 1 diabetes.

Separating microplastics (MPs) from environmental samples is challenging, but necessary to determine their environmental prevalence. Current methods are not standardized across environmental sample type, and it is unclear how well they recover smaller sized MPs. In response, we developed a method that extracts plastics magnetically, taking advantage of their hydrophobic surface to magnetize the plastics. We created hydrophobic Fe nanoparticles that bind to plastic, allowing magnetic recovery. With this principle applied to a simple method, we recovered 92% of 10–20 μm polyethylene and polystyrene beads and 93% of >1 mm MPs (polyethylene, polyethylene terephthalate, polystyrene, polyurethane, polyvinyl chloride, and polypropylene) from seawater. We also recovered 84% and 78% of MPs (polyethylene, polystyrene, polyurethane, polyvinyl chloride, and polypropylene) ranging from 200 μm to 1 mm from freshwater and sediments, respectively. Overall, the procedure is efficient for various sizes, polymer types, and sample matrices and can be considered by researchers to be included as a step of the extraction procedure for MPs (i.e., post density separation) or stand-alone for cleaner samples (i.e., drinking water).

BaCKgRoUND aND aIMS:Survival data among patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after achieving sustained virologic response (SVR) with interferon-free direct-acting antivirals (DAAs) in both Asian and western countries are limited. Survival rates were compared between patients with HCV-related HCC who were untreated for HCV and those who achieved SVR. appRoaCH aND ReSUltS: Using data from two U.S. and six Asian centers from 2005 to 2017, we categorized 1,676 patients who were mono-infected with HCV-related HCC into patients untreated for HCV (untreated group) and DAA-treated patients with SVR (SVR group) and matched by propensity score matching (PSM); multivariable Cox regression with HCV treatment status as a time-varying covariate was used to determine mortality risk and landmark analysis to avoid immortal time bias. There were 1,239 untreated patients and 437 patients with SVR. After PSM, background risks of the 321 pairs of matched patients were balanced (all P > 0.05). After time-varying adjustment for HCV treatment initiation compared with untreated patients, patients with SVR had significantly higher 5-year overall survival (87.78% vs. 66.05%, P < 0.001). Multivariable Cox regression showed that SVR was independently associated with a 63% lower risk of 5-year all-cause mortality (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.16-0.83; P = 0.016) and 66% lower risk of 5-year liver-related mortality (HR, 0.34; 95% CI, 0.13-0.88; P = 0.026) with similar trends after removing patients with liver transplants. Landmark analysis at 90, 180, and 360 days showed consistent results (HRs ranged 0.22 to 0.44, all P < 0.05). CoNClUSIoN:In this multinational consortium, patients with HCV-related HCC who obtained SVR achieved a 60%-70% improvement in 5-year survival (both all-cause and liver related) compared with patients untreated for HCV. Patients eligible for HCC therapy should also be considered for DAA therapy.

Observing microplastics in manipulative experiments is of paramount importance for understanding the fate of microplastics in the environment, organisms, and food webs. Labeling microplastics with fluorescent dyes is a useful tool in laboratory experiments for tracking microplastics. However, literature using fluorescence-based detection is heavily biased toward the use of polystyrene and polyethylene microspheres, potentially due to their commercial availability. Consequently, much less is understood about the fate of nonspherical morphologies and other types of plastics common in the environment. Presented here is a heat-mediated microplastic dyeing protocol that facilitates the stable incorporation of inexpensive commercially available fluorescent disperse dyes directly into the polymer structure for use in laboratory-based studies. We demonstrate this microplastic labeling approach is compatible with a wide variety of plastic types [polystyrene (PS), low-density polyethylene (LDPE), high-density polyethylene (HDPE), polyvinyl chloride (PVC), polypropylene (PP), polyethylene terephthalate (PET), and polyacrylonitrile (PAN)] and can be customized with different colors and fluorescent spectra. The stability of the fluorescence intensity of the labeled plastics was measured over 72 h and compared to that of an existing microplastic dying approach using Nile Red. We found the dyeing approach was more fluorescently stable for PS, HDPE, PET, PVC, and PAN than for LDPE and PP. The dyes are also more robust to 4 M KOH digestion and exposure to mineral oil than Nile Red. Finally, the cost of preparing microplastics with the technique shown here is half of the cost of Nile Red. This new plastic dyeing method represents a low-cost, versatile approach enabling laboratory-based experiments with different polymer types and shapes using existing fluorescent microscopy tracking techniques. This will help provide a more representative understanding of the interactions of microplastics with organisms.

People are exposed to phthalates through their wide use as plasticizers and in personal care products. Many phthalates are endocrine disruptors and have been associated with adverse health outcomes. However, knowledge gaps exist in understanding the molecular mechanisms associated with the effects of exposure in early and late pregnancy. In this study, we examined the relationship of eleven urinary phthalate metabolites with isoprostane, an established marker of oxidative stress, among pregnant Mexican-American women from an agricultural cohort. Isoprostane levels were on average 20% higher at 26 weeks than at 13 weeks of pregnancy. Urinary phthalate metabolite concentrations suggested relatively consistent phthalate exposures over pregnancy. The relationship between phthalate metabolite concentrations and isoprostane levels was significant for the sum of di-2-ethylhexyl phthalate and the sum of high molecular weight metabolites with the exception of monobenzyl phthalate, which was not associated with oxidative stress at either time point. In contrast, low molecular weight metabolite concentrations were not associated with isoprostane at 13 weeks, but this relationship became stronger later in pregnancy (p-value = 0.009 for the sum of low molecular weight metabolites). Our findings suggest that prenatal exposure to phthalates may influence oxidative stress, which is consistent with their relationship with obesity and other adverse health outcomes.

OBJECTIVE To determine racial/ethnic differences in perinatal outcomes among women with gestational diabetes mellitus (GDM). STUDY DESIGN Retrospective cohort study of 32,193 singleton births among GDMs in California from 2006, using Vital Statistics Birth and Death Certificate and Patient Discharge Data. Women were divided by race/ethnicity: White, Black, Hispanic, or Asian. Multivariable logistic regression analyzed associations between race/ethnicity and adverse outcomes, controlling for potential confounders. Outcomes included: primary cesarean, preeclampisa, neonatal hypoglycemia, preterm delivery, macrosomia, fetal anomaly, respiratory distress syndrome (RDS). RESULTS Compared to other races, Black women had higher odds of preeclampsia [aOR=1.57, 95%CI(1.47-1.95)], neonatal hypoglycemia [aOR=1.79, 95%CI(1.07-3.00)], and preterm delivery <37 weeks [aOR=1.56, 95%CI(1.33-1.83)]. Asians had the lowest odds of primary cesarean [aOR=0.75, 95%CI(0.69-0.82)], large for gestational age infants [aOR=0.40, 95%CI(0.33-0.48)], and neonatal RDS [aOR=0.54, 95%CI(0.40-0.73)]. CONCLUSION Perinatal outcomes among women with GDM differ by race/ethnicity and may be attributed to inherent sociocultural differences that may impact glycemic control, the development of chronic co-morbidities, genetic variability, and variation in access to as well as quantity and quality of prenatal care.