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Plastic pollution is now so widespread that microplastics are regularly detected in biological samples surveyed for their presence. Despite their pervasiveness, very little is known about the effects of microplastics on the health of terrestrial vertebrates. While emerging studies are showing that microplastics represent a potentially serious threat to animal health, data have been limited to in vivo studies on laboratory rodents that were force fed plastics. The extent to which these studies are representative of the conditions that animals and humans might actually experience in the real world is largely unknown. Here, we review 114 papers from the peer-reviewed literature in order to understand how the concentrations and types of microplastics being administered to rodents in lab studies compare to those found in terrestrial soils. From 73 in vivo lab studies, and 41 soil studies, we found that lab studies have heretofore fed rodents microplastics at concentrations that were hundreds of thousands of times greater than they would be exposed to in nature. Furthermore, health effects have been studied for only 20% of the microplastic polymers that are known to occur in soils. Plastic pollution is arguably one of the most pressing ecological and public health issues of our time, yet existing lab-based research on the health effects of terrestrial microplastics does not reflect the conditions that free-ranging vertebrates are actually experiencing. Going forward, performing more true-to-life research will be of the utmost importance to fully understand the impacts of microplastics and maintain the public’s faith in the scientific process. Graphical Abstract

Right ventricular failure (RVF) is a leading cause of morbidity and mortality in multiple cardiovascular diseases, but there are no approved treatments for RVF as therapeutic targets are not clearly defined. Contemporary transcriptomic/proteomic evaluations of RVF are predominately conducted in small animal studies, and data from large animal models are sparse. Moreover, a comparison of the molecular mediators of RVF across species is lacking. Here, we used transcriptomics and proteomics analyses to define the molecular pathways associated with cardiac MRI-derived values of RV hypertrophy, dilation, and dysfunction in pulmonary artery banded (PAB) piglets. Publicly available data from rat monocrotaline-induced RVF and pulmonary arterial hypertension patients with preserved or impaired RV function were used to compare the three species.Transcriptomic and proteomic analyses identified multiple pathways that were associated with RV dysfunction and remodeling in PAB pigs. Surprisingly, disruptions in fatty acid oxidation (FAO) and electron transport chain (ETC) proteins were different across the three species. FAO and ETC proteins and transcripts were mostly downregulated in rats, but were predominately upregulated in PAB pigs, which more closely matched the human data. Thus, the pig PAB metabolic molecular signature was more similar to human RVF than rodents. These data suggest there may be divergent molecular responses of RVF across species, and that pigs more accurately recapitulate the metabolic aspects of human RVF.

Recent years have seen considerable scientific attention devoted towards documenting the presence of microplastics (MPs) in environmental samples. Due to omnipresence of environmental microplastics, however, disentangling environmental MPs from sample contamination is a challenge. Hence, the environmental (collection site and laboratory) microplastics contamination of samples during processing is a reality that we must address, in order to generate reproducible and reliable data. Here we investigated published literature and have found that around 1/5 of studies failed to use blank controls in their experiments. Additionally, only 34% of the studies used a controlled air environment for their samples processing (laminar flow, fume hood, closed laboratory, clean room, etc.). In that regard, we have also shown that preparing samples in the fume hood, leads to more microplastics contamination than preparing it in the laboratory bench and the laminar flow. Although it did not completely prevent microplastics contamination, the processing of sample inside the laminar flow is the best option to reduce sample contamination during processing. Overall, we showed that blank controls are a must in microplastics sample preparation, but it is often overlooked by researchers.HighlightsMost of the contaminant microplastics in blank controls were particles < 20 μm.Fume hoods result in more contamination than processing the samples on the bench.Laminar flow was the best option for reducing MPs contamination of samples.1/5 of studies failed to use blank controls, and 1/3 did not correct their data.Improving the use and description of blanks is imperative for ensuring data quality.Mandatory graphical abstract

Plastic pollution is now so widespread that microplastics are consistently detected in every biological sample surveyed for their presence. Despite their pervasiveness, very little is known about the effects of microplastics on the health of terrestrial species. While emerging studies are showing that microplastics represent a potentially serious threat to animal health, data have been limited toin vivostudies on laboratory rodents that were force fed plastics. The extent to which these studies are representative of the conditions that animals and humans might actually experience in the real world is largely unknown. Here, we review the peer-reviewed literature in order to understand how the concentrations and types of microplastics being administered in lab studies compare to those found in terrestrial soils. We found that lab studies have heretofore fed rodents microplastics at concentrations that were hundreds of thousands of times greater than they would be exposed to in nature. Furthermore, health effects have been studied for only 10% of the microplastic polymers that are known to occur in soils. The plastic pollution crisis is arguably one of the most pressing ecological and public health issues of our time, yet existing lab-based research on the health effects of terrestrial microplastics does not reflect the conditions that free-ranging animals are actually experiencing. Going forward, performing more true-to-life research will be of the utmost importance to understand the impacts of microplastics and maintain the public’s faith in the scientific process.

Charting the evolutionary history of rampant somatic copy number alterations (SCNA) is an indispensable step toward a deeper understanding of their roles in tumor development. However, the existing SCNA timing analysis is limited to low copy number states and initiating gains, which are not necessarily close to the onset of the malignant proliferation. Moreover, it remains a critical question if the timing of an SCNA reveals the corresponding variant’s fitness effect. Here we propose a framework to estimate the arrival time of a clonal SCNA, i.e., the time delay from its last alteration to the start of population expansion, in addition to its initiation time when the first alteration occurs. Our method leverages the bias that a genomic segment, when resting on a copy number (CN) state, accumulates somatic single nucleotide variants (SSNV) at a rate proportional to its CN. From the whole genome sequencing data of 184 samples from 75 patients across five tumor types, we commonly observed late clonal CN gains following early initiating events, which appear right before the expansion leading to the observed tumor sample(s). Genome doubling (GD) can be late, but post-GD CN evolution is prevalent in the genealogy of the most recent common ancestor of patient tumors. Notably, mathematical modeling suggests that late evolving events could contain rate-limiting drivers. The advantage of evolving gains could arise from the dosage increase of cancer genes in proliferative signaling and amplification of early functional variants. In addition, evolving SCNAs bolster the diversification of SSNVs between sub-populations, exacerbating the vicious circle between malignant growth and accumulation of genomic heterogeneity. Our findings have broad implications for resolving the trajectory of SCNAs, discerning the CN markers of malignant growth in vivo, and properly quantifying tumor heterogeneity in aneuploid tumors.

Disseminated coccidioidomycosis is a disease caused by Coccidioides species, fungi endemic to the southwestern United States. We present here an uncommon case of a young child with erythema nodosum and fever of unknown origin, found to have the infection. While more common in adults, coccidioidomycosis should be considered in all patients with erythema nodosum.

Behavioral intervention is the only treatment for pediatric feeding problems with well documented empirical support. However, parents may be hesitant to pursue behavioral intervention because of concerns about possible negative side effects on child behavioral health and the parent-child relationship. This study investigated associations between behavioral feeding treatment and parenting stress, internalizing and externalizing behavior problems in young children, and parent-child attachment quality.Participants included 16 mother-child dyads seeking treatment from a behavioral feeding clinic at a large Midwestern university medical center. Children were between the ages of 30 and 45 months (adjusted) at baseline. Caregivers completed the Child Behavior Checklist for ages 1.5 to 5 (CBCL/1.5-5), the Parenting Stress Index, 3rd Edition Short Form (PSI/SF), and mother-child dyads participated in the Strange Situation procedure at baseline and again after 6 months. The treatment group (n = 12) began outpatient behavioral feeding intervention following the baseline evaluation, whereas the control group (n = 12) remained on the clinic waitlist until after the 6-month follow-up.The treatment group demonstrated decreases in internalizing and externalizing child behavior problems and parenting stress compared with the control group. No significant differences were demonstrated in parent-child attachment quality within or between groups.Behavioral feeding intervention had positive effects on perceptions of child emotional and behavioral functioning and maternal parenting stress. Intervention also did not impact the quality of the mother-child attachment relationship. Further research with a larger sample size and additional observational measures of behavior is needed to support the replicability and generalizability of these results.

A 15-year-old high school football player sustained direct impact to his anteromedial left knee by a teammate's helmet during practice. The physician referred the athlete immediately to an after-hours clinic for imaging to rule out a fracture. Radiographs of the knee showed a nondisplaced Salter-Harris type II fracture. The treating physician also ordered magnetic resonance imaging, the results of which allowed for a more specific diagnosis of the fracture as a Salter-Harris type III fracture of the left femur.J Orthop Sports Phys Ther 2019;49(3):209. doi:10.2519/jospt.2019.7984.

Aims and objectives To develop and test strategies to reduce interruptions to enteral feeding to improve practice and promote attainment of nutritional goals. Background Enteral nutrition is preferred for feeding patients in the intensive care unit who are unable to have oral nutrition. Interruption to feeding is likely to be a major contributor to patients not receiving their prescribed nutrition goals. Design Prospective before (May–November 2009) and after (March–September 2010) study. Method Patients admitted to the intensive care unit (except cardiac surgery) and who were eligible to receive enteral nutrition were enrolled. After gaining Ethics Committee approval, baseline data were collected to identify interruptions to enteral nutrition. Nurse-led multidisciplinary teams developed interventions to target specific reasons for interruption. Change champions implemented the improvements after staff were provided with an education package. Postintervention data were then collected. Results Six hundred and fifty-three patients received enteral nutrition with the majority (88%) fed within 48 hours. Considering the first 28 days of feeding for patients fed longer than 24 hours (505 patients), the number of interruptions for patients who had an interruption decreased from 907–662. Interruptions due to gastrointestinal issues decreased (14 vs 10%), while those due to airway issues, enteral nutrition delivery system problems and other interruptions were similar before-and-after the practice change. Time lost to feeding because of interruptions was similar between groups. Conclusion Targeted strategies to enteral feeding practice resulted in a reduction to the number of interruptions but not the duration of enteral nutrition lost to interruption. Reducing unnecessary interruption of feeding circuits is likely to minimise the risk for splash injury and contamination of feeding sets through less manipulation and interruption to enteral nutrition flow. Relevance to clinical practice Review of practice may reveal opportunities for improvement. Nurse champions can facilitate change processes to improve care.

Anomalous DNA methylation contributes to carcinogenesis by regulating gene expression and may be important in germ cell tumor (GCT) development as germ cells undergo tremendous epigenetic reprogramming during embryogenesis. Histologic subtypes of GCTs show differences in global methylation patterns with less differentiated tumors (e.g. embryonal carcinoma) experiencing lower levels of global methylation relative to more differentiated tumors (e.g. teratoma). Differences in promoter methylation have also been reported in GCTs. In particular, developmental signaling pathways and the BMP/TGF beta pathway have been consistently found to be differentially methylated. In this analysis, we conducted an epigenome wide association study to identify gene-specific methylation differences by GCT histology. Using the Illumina HumanMethylation450K array we determined methylation profiles for 154 pediatric GCTs (21 germinomas, 54 mixed, 9 teratomas, 70 yolk sac tumors [YST]) from fresh frozen and formalin fixed paraffin embedded tumor tissue samples. Fisher's exact tests were used to assess differences in the distributions of age group, sex, and tumor location by histologic subtype (alpha=0.05 for a two-sided test of significance [SAS v9.4]). Bioconductor package minfi was used to identify differential methylation between GCT histologic subtypes by comparing the methylation beta values. To identify differential methylation of genes predictive of tumor histology, a generalized linear model (glm) with LASSO was fit (R v3.4.1) to the quantile normalized beta values for all probes from all samples. There were significant differences in age, sex, and tumor location by histologic subtype (all p Citation Format: Lindsay A. Williams, Lauren Mills, Anthony J. Hooten, Erica Langer, Michelle Roesler, A Lindsay Frazier, James Amatruda, Jenny N. Poynter, Jenny N. Poynter. Differences in methylation patterns by pediatric germ cell tumor histologic subtype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2064.

Enteral nutrition (EN) tolerance is often monitored by aspirating stomach contents by syringe at prescribed intervals. No studies have been conducted to assess the most appropriate time interval for aspirating gastric tubes. We compared gastric tube aspirations every 4 hours (usual care) with a variable regimen (up to every 8 hours aspirations).This randomized controlled trial (RCT) enrolled patients who stayed in the intensive care unit (ICU) for48 hours, had a gastric tube, and were likely to receive EN for 3 or more days. Patients were randomized (computer-generated randomization) to either the control (every 4 hours) or intervention group (variable regimen). The primary outcome was number of gastric tube aspirations per day from randomization until EN was ceased or up to 2 weeks postrandomization.Following Institutional Ethics Committee approval, 357 patients were recruited (control group, n = 179; intervention group, n = 178). No differences were found in age, sex, worst APACHE II score, or time to start of EN. In the intention-to-treat analysis, the intervention group had fewer tube aspirations per day (3.4 versus 5.4 in the control group, P.001). Vomiting/regurgitation was increased in the intervention group (2.1% versus 3.6%, P = .02). There were no other differences in complications.This is the first RCT to examine the frequency of gastric tube aspirations. The frequency of gastric tube aspirations was reduced in the variable-regimen group with no increase in risk to the patient. Reducing the frequency of aspirations saves nursing time, decreases risk of contamination of feeding circuit, and minimizes risk of body fluid exposure.

Chemiluminescence assays are used widely for the detection of nitric oxide (NO)-derived species in biological fluids and tissues. Here, we demonstrate that these assays can be interfaced with mass-sensitive detectors for parallel determination of isotopic abundance. Results obtained with tri-iodide and ascorbic acid-based reductive assays indicate that mass spectrometric detection enables NO isotope-tracing experiments to be carried out to a limit of detectability of a few picomoles, a sensitivity similar to that of standard gas phase chemiluminescence methods. The advantage afforded by mass spectrometric detection is demonstrated using the murine macrophage cell line J774, which is shown here to reduce 15NO3 - to 15NO2 - under anoxic conditions. The particular combination of an analytical and cellular system described here may hold promise for future characterization of the enzymatic pathways contributing to mammalian nitrate reductase activity, without background interference from 14NO2 - derived from other sources.

Enteral nutrition (EN) is preferred method for feeding patients unable to eat in the intensive care unit (ICU). Interruption to feeding is likely to be a major contributor to patients not receiving their prescribed nutrition goals. We aimed to develop and test strategies to reduce interruptions to EN. A prospective before (May–November 2009) and after (March–September 2010) study was conducted. Patients admitted to the 22-bed ICU of a tertiary-referral teaching hospital and who were eligible to receive EN (except cardiac surgery) were recruited. Ethics Committee approval was obtained. Baseline data were collected to identify interruptions to EN. Multidisciplinary teams led by ICU EN champions, skilled nurses who became expert in the evidence-based guidelines and practice changes, developed interventions to improve practice. These included a revised feeding guidance and changes to the management of patients weaning from mechanical ventilation and having procedures. Staff were provided with an education package and data were collected prospectively for 6 months after the practice changes. Of 652 eligible patients, the majority (79%) were fed within 24 hours. Patients fed for more than 24 h had more interruptions (median 3 [IQR 2–5] pre-intervention compared to 2 [IQR 1–4] post-intervention, p = 0.04) during the first 28 days of feeding. Reasons for interruption included weaning or removal from mechanical ventilation (29%), procedures (36%) and gastrointestinal issues (12%). A targeted strategy to improve EN practice resulted in a reduction in the number of interruptions to feeding.