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Background: Annual mammography is recommended for breast cancer survivors; however, population-level temporal trends in surveillance mammography participation have not been described. Our objective was to characterize trends in annual surveillance mammography participation among women with a personal history of breast cancer over a 13-year period., Methods: We examined annual surveillance mammography participation from 2004 to 2016 in a nationwide sample of commercially insured women with prior breast cancer. Rates were stratified by age group (40-49 vs 50-64 years), visit with a surgical/oncology specialist or primary care provider within the prior year, and sociodemographic characteristics. Joinpoint models were used to estimate annual percentage changes (APCs) in participation during the study period., Results: Among 141,672 women, mammography rates declined from 74.1% in 2004 to 67.1% in 2016. Rates were stable from 2004 to 2009 (APC, 0.1%; 95% CI, -0.5% to 0.8%) but declined 1.5% annually from 2009 to 2016 (95% CI, -1.9% to -1.1%). For women aged 40 to 49 years, rates declined 2.8% annually (95% CI, -3.4% to -2.1%) after 2009 versus 1.4% annually in women aged 50 to 64 years (95% CI, -1.9% to -1.0%). Similar trends were observed in women who had seen a surgeon/oncologist (APC, -1.7%; 95% CI, -2.1% to -1.4%) or a primary care provider (APC, -1.6%; 95% CI, -2.1% to -1.2%) in the prior year., Conclusions: Surveillance mammography participation among breast cancer survivors declined from 2009 to 2016, most notably among women aged 40 to 49 years. These findings highlight a need for focused efforts to improve adherence to surveillance and prevent delays in detection of breast cancer recurrence and second cancers.

Background: Supplemental breast cancer screening with breast magnetic resonance imaging (MRI) is recommended for women at high risk of breast cancer. To the authors' knowledge, recent national trends in breast MRI use are unknown., Methods: The authors used claims data from a large national insurer to calculate screening breast MRI rates from 2006 to 2016 in a US cohort of 10 million women aged 20 to 64 years. Use was stratified by subgroups of women with a BRCA mutation, family history of breast cancer, and prior breast cancer history and stratified by age. Joinpoint regression evaluated annual changes in trends., Results: The total sample included 37,447 screening breast MRI examinations in 25,617 women. Overall screening breast MRI rates were low and increased from 2.9 to 12.1 examinations per 10,000 women from 2006 to 2016. MRI use in women with a BRCA mutation increased by 21% on average annually from 210.8 per 10,000 women to 1562.0 per 10,000 women from 2006 to 2016. By 2016, women aged 50 to 64 years who had a BRCA mutation had the highest use of breast MRI (1669.6 MRI examinations per 10,000 women) compared with younger women (1198.4 MRI examinations per 10,000 women, 1519.1 MRI examinations per 10,000 women, and 1567.2 MRI examinations per 10,000 women, respectively, among women aged 20-29 years, 30-39 years, and 40-49 years). Women with a BRCA mutation comprised <1% of the current study population but received approximately 9% of screening breast MRI examinations. Breast MRI rates among women with a family history of breast cancer or prior breast cancer history initially increased from 2006 to 2008, but then stabilized or decreased., Conclusions: The increases in breast MRI use observed in the current study have indicated improvements in concordance with breast imaging guidelines. However, women with BRCA mutations remain underscreened, particularly younger women, thereby identifying a clear gap with which to enhance access., (© 2020 American Cancer Society.)

As the average life expectancy continues to increase, so does the need for resorbable materials designed to treat, augment, or replace components and functions of the body. Naturally occurring biopolymers such as silks are already attractive candidates due to natural abundance and high biocompatibility accompanied by physical properties which are easily modulated through blending with another polymer. In this paper, the authors report on the fabrication of biocomposite materials made from binary blends of Bombyx mori silk fibroin (SF) protein and renewably sourced low molecular weight nylon 610 and high molecular weight nylon 1010. Films were characterized using scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Results of this study demonstrated that enhanced structural and thermal properties were achievable in composite films SF-N610/N1010 due to their chemical similarity and the possible formation of hydrogen bonds between nylon and silk molecular chains. This study provides useful insight into the sustainable design of functional composite materials for biomedical and green technologies.

HLA-DM catalyzes peptide dissociation and exchange in class II MHC molecules through a mechanism that has been proposed to involve the disruption of specific components of the conserved hydrogen bond network in MHC-peptide complexes. HLA-DR1 molecules with alanine substitutions at each of the six conserved H- bonding positions were expressed in cells, and susceptibility to DM catalytic activity was evaluated by measuring the release of CLIP. The mutants alphaN62A, alphaN69A, alphaR76A, and betaH81A DR1 were fully susceptible to DM-mediated CLIP release, and betaN82A resulted in spontaneous release of CLIP. Using recombinant soluble DR1 molecules, the amino acid betaN82 was observed to contribute disproportionately in stabilizing peptide complexes. Remarkably, the catalytic potency of DM with each beta-chain mutant was equal to or greater than that observed with wild-type DR1. Our results support the conclusion that no individual component of the conserved hydrogen bond network plays an essential role in the DM catalytic mechanism.

ERK2 is a proline-directed protein kinase that displays a high specificity for a single threonine (Thr-38) on the substrate Ets-1, which lies within the consensus sequence 36phi-chi-Thr-Pro39 (where phi is typically a small hydrophobic residue and chi appears to be unrestricted). Thr-38 lies in a long flexible N-terminal tail (residues 1-52), which also contains a second potential phosphorylation site, Ser-26. How Ets-1 binds ERK2 to promote the phosphorylation of Thr-38 while simultaneously discriminating against the phosphorylation of Ser-26 is unclear. To delineate the details of the molecular recognition of Ets-1 by ERK2, the binding of various mutants and truncations of Ets-1 were analyzed by fluorescence anisotropy. The data that were obtained support the notion that the N-terminal tail contains a previously unrecognized docking site that promotes the phosphorylation of Thr-38. This new docking site helps assemble the complex of Ets-1 and ERK2 and makes a similar contribution to the stabilization of the complex as does the pointed domain of Ets-1. The in vitro activation of ERK2 by MKK1 induces a large conformational transition of the activation segment (DFG-APE), but neither induces self-association of ERK2 nor destabilizes the stability of the ERK2.Ets-1 complex. This latter observation suggests that interactions intrinsic to the active site are not important for complex assembly, a notion further supported by the observation that the substitution of a number of different amino acids for Pro-39 does not destabilize the complex. Mutagenesis of ERK2 within loop 13 suggests that Ets-1 binds the substrate-binding groove. These data suggest that ERK2 uses two weak docking interactions to specifically assemble the complex, perhaps in doing so denying Ser-26 access to the active site. Displacement of residues 1-138 of Ets-1 (EtsDelta138) from ERK2 by the peptide N-QKGKPRDLELPLSPSL-C, derived from Elk-1, suggests that Ets-1 engages the D-recruitment site (beta7-beta8 reverse turn and the alphaD-alphaE helix) of ERK2. Displacement of EtsDelta138 from ERK2 by the peptide N-AKLSFQFPS-C derived from Elk-1 shows that EtsDelta138 communicates with the F-recruitment site of ERK2 also.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase was purified to homogeneity from rat liver cytoplasm. The active enzyme is a dimer composed of identical subunits of Mr = 53,000. The amino acid composition and the NH2-terminal sequence are presented. Partial cDNA clones for the enzyme were isolated by screening of a rat liver lambda gt11 expression library with antibodies raised against the purified protein. The identity of the clones was confirmed by hybrid selection and translation. When rats were fed diets supplemented with cholesterol, cholestyramine, or cholestyramine plus mevinolin, the hepatic protein mass of cytoplasmic synthase, as determined by immunoblotting, was 25, 160, and 1100%, respectively, of the mass observed in rats fed normal chow. Comparable changes in enzyme activity were observed. Approximately 9-fold increases in both HMG-CoA synthase mRNA mass and synthase mRNA activity were observed when control diets were supplemented with cholestyramine and mevinolin. When rats were fed these two drugs and then given mevalonolactone by stomach intubation, there was a 5-fold decrease of synthase mRNA within 3 h. These results indicate that cytoplasmic synthase regulation occurs primarily at the level of mRNA. This regulation is rapid and coordinate with that observed for HMG-CoA reductase. The chromosomal localization of human HMG-CoA synthase was determined by examining a panel of human-mouse somatic cell hybrids with the rat cDNA probe. Interestingly, the synthase gene resides on human chromosome 5, which has previously been shown to contain the gene for HMG-CoA reductase. Regional mapping, performed by examination of a series of chromosome 5 deletion mutants and by in situ hybridization to human chromosomes indicates that the two genes are not tightly clustered.