Over the last three decades, there have been significant advancements in knee and hip replacement technology. The implants and the surgical technology we now have to aid in their implantation are advancing and improving functional outcomes and survivorship. Despite these advancements, there are still issues with patient satisfaction, functional limitations, and early revisions due to instability and aseptic loosening. This article reviews the state of current technology in hip and knee replacement implant design and surgical technique, and reviews some of the current implant designs and surgical technologies that may be able to solve some of the most common issues in the knee and hip replacement surgery.Statement of Clinical Significance There remains the need to develop materials and surfaces that can increase the rate of implant osseointegration. Though osteoanabolic agents, like bone morphogenetic protein (BMP), can provide signaling for osteogenesis, the appropriate design of implants can also produce an innate cellular response that may reduce or eliminate the need to use additional agents to stimulate bone formation. Studies show that titanium implant surfaces that mimic the physical properties of osteoclast resorption pits regulate cellular responses of bone marrow stromal cells (MSCs) by altering cell morphology, transcriptomes, and local factor production to increase their differentiation into osteoblasts without osteogenic media supplements required for differentiation of MSCs on tissue culture polystyrene (TCPS). The goal of this study was to determine how cells in contact with biomimetic implant surfaces regulate the microenvironment around these surfaces in vitro. Two different approaches were used. First, unidirectional signaling was assessed by treating human MSCs grown on TCPS with conditioned media from MSC cultures grown on Ti6Al4V biomimetic surfaces. In the second set of studies, bidirectional signaling was assessed by coculturing MSCs grown on mesh inserts that were placed into culture wells in which MSCs were grown on the biomimetic Ti6Al4V substrates. The results show that biomimetic Ti6Al4V surface properties induce MSCs to produce factors within 7 days of culture that stimulate MSCs not in contact with the surface to exhibit an osteoblast phenotype via endogenous BMP2 acting in a paracrine signaling manner.Intermittent fasting has grown in popularity as a weight loss strategy in recent years. In particular, time restricted eating (TRE) has been popularized in the diet industry with dozens of books touting its ability to promote weight loss and improve glucose regulation. TRE involves confining the eating window to a specified number of hours per day (usually 4-10 h), and fasting (with zero-calorie beverages) for the remaining hours of the day. While several studies of TRE have been performed in rodent models, human studies are only now emerging. The goal of this review is to summarize the effects of TRE on body weight and cardiometabolic disease risk factors in human subjects. Accumulating evidence shows that TRE may spontaneously decrease energy intake by 20-30% under ad libitum conditions, producing small but statistically significant weight loss of 1-4%. In addition, TRE may significantly decrease systolic and diastolic blood pressure independent of weight loss. Further, improvements in fasting insulin and insulin resistance have also been reported. Taken together, these preliminary data suggest that TRE produces mild weight loss, and also may improve some aspects of cardiometabolic health by lowering blood pressure and insulin resistance.There is emerging concern about the potential health and environmental impacts of nanoplastics in the environment. Information on exposure has been lacking, but a growing amount of ecotoxicological hazard data is now available, allowing a hazard assessment to be conducted for nanoplastics in freshwater and marine systems. Based on a critical evaluation of published studies and the construction of probabilistic species sensitivity distributions (PSSDs), we present a comprehensive, state-of-the-art understanding of nanoplastic ecotoxicity. Different freshwater and marine datasets were constructed based on different data quality levels, and for each of the datasets, PSSDs were built for both mass- and particle number-based concentrations. Predicted no-effect concentrations (PNECs) were then extracted from the PSSDs. learn more We report PNECs at 99 and 72 μg L-1 , respectively, for the freshwater and marine dataset after the removal of data measured in the presence of sodium azide (NaN3 ), which is considered to be a major interfering factor in the ecotoxicity testing of nanoplastics. By comparing the PNECs, we found that nanoplastics are less toxic than microplastics and many engineered nanomaterials. In addition, the effects of size and polymer type on toxicity were also statistically tested. We observed no significant difference in ecotoxicity for nanoplastics of different sizes, whereas polystyrene nanoplastics were significantly more toxic than all other tested nanoplastics. In conclusion, the results we present provide a comprehensive description of nanoplastic ecotoxicity based on current knowledge. The results constitute a fundamental step toward an environmental risk assessment for nanoplastics in freshwater and marine systems. Environ Toxicol Chem 2020;392588-2598. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

We explored the potential of genome-wide epigenomic liquid biopsy for the comprehensive analysis of cell-free DNA (cfDNA) methylation signatures in maternal plasma in early gestation.

We used solution phase hybridization for targeted region capture of bisulfite-converted DNA obtained from plasma of pregnant women in early gestation and nonpregnant female controls.

Targeted sequencing of ~80.5 Mb of the plasma methylome generated an average read depth across all 17 plasma samples of ~42x. We used these data to explore the pregnancy-specific characteristics of cfDNA methylation in plasma and found that pregnancy resulted in clearly detectable global alterations in DNA methylation patterns that were influenced by genomic location. We analyzed similar, previously published, data from first-trimester maternal leukocyte populations and gestational age-matched chorionic villus (CV) and confirmed that tissue-specific DNA methylation signatures in these samples had a significant influence on global and gene-specific methylation in the plasma of pregnant women.