BackgroundMaternal and paternal high-fat (HF) diet intake before and/or during pregnancy increases mammary cancer risk in several preclinical models. We studied if maternal consumption of a HF diet that began at a time when the fetal primordial germ cells travel to the genital ridge and start differentiating into germ cells would result in a transgenerational inheritance of increased mammary cancer risk.MethodsPregnant C57BL/6NTac mouse dams were fed either a control AIN93G or isocaloric HF diet composed of corn oil high in n-6 polyunsaturated fatty acids between gestational days 10 and 20. Offspring in subsequent F1–F3 generations were fed only the control diet.ResultsMammary tumor incidence induced by 7,12-dimethylbenz[a]anthracene was significantly higher in F1 (p < 0.016) and F3 generation offspring of HF diet-fed dams (p < 0.040) than in the control offspring. Further, tumor latency was significantly shorter (p < 0.028) and burden higher (p < 0.027) in F1 generation HF offspring, and similar trends were seen in F3 generation HF offspring. RNA sequencing was done on normal mammary glands to identify signaling differences that may predispose to increased breast cancer risk by maternal HF intake. Analysis revealed 1587 and 4423 differentially expressed genes between HF and control offspring in F1 and F3 generations, respectively, of which 48 genes were similarly altered in both generations. Quantitative real-time polymerase chain reaction analysis validated 13 chosen up- and downregulated genes in F3 HF offspring, but only downregulated genes in F1 HF offspring. Ingenuity Pathway Analysis identified upregulation of Notch signaling as a key alteration in HF offspring. Further, knowledge-fused differential dependency network analysis identified ten node genes that in the HF offspring were uniquely connected to genes linked to increased cancer risk (ANKEF1, IGFBP6, SEMA5B), increased resistance to cancer treatments (SLC26A3), poor prognosis (ID4, JAM3, TBX2), and impaired anticancer immunity (EGR3, ZBP1).ConclusionsWe conclude that maternal HF diet intake during pregnancy induces a transgenerational increase in offspring mammary cancer risk in mice. The mechanisms of inheritance in the F3 generation may be different from the F1 generation because significantly more changes were seen in the transcriptome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0866-x) contains supplementary material, which is available to authorized users.

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Under longstanding federal law, pregnancy-related Medicaid coverage is only guaranteed through 60-days postpartum, at which point many women become uninsured. Barriers to care, including lack of insurance, contribute to maternal mortality and morbidity. Leveraging the Families First Coronavirus Response Act, a federal law requiring that states provide continuous coverage to Medicaid enrollees during the COVID-19 pandemic as a condition of receiving enhanced federal financial support, we examine whether postpartum women seek additional care, and what types of care they use, with extended coverage. We analyze claims from the Parkland Community Health Plan (a Texas Medicaid Health Maintenance Organization) before and after implementation of the pandemic-related Medicaid extension. We find that after implementation of the coverage extension, women used twice as many postpartum services, 2 × to 10 × as many preventive, contraceptive, and mental/behavioral health services, and 37% fewer services related to short interval pregnancies within the first-year postpartum. Our findings provide timely insights for state legislators, Medicaid agencies, and members of Congress working to improve maternal health outcomes. We add empirical evidence to support broad extension of Medicaid coverage throughout the first-year postpartum.

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Background Diffusion‐weighted imaging (DWI) is a useful technique to detect pancreatic lesion. In DWIs, field‐of‐view optimized and constrained undistorted single‐shot (FOCUS) can improve the spatial resolution and multiplexed sensitivity‐encoding (MUSE) can gain a high signal‐to‐noise ratio (SNR). Based on the advantage of FOCUS and MUSE, a new DWI sequence—named FOCUS‐MUSE DWI (FOCUS combined with MUSE)—was developed to delineate the pancreas. Purpose To investigate the reliability of FOCUS‐MUSE DWI compared to FOCUS, MUSE and single‐shot (SS) DWI via the systematical evaluation of the apparent diffusion coefficient (ADC) measurements, SNR and image quality. Study Type Prospective. Subjects A total of 33 healthy volunteers and 9 patients with pancreatic lesion. Field Strength/Sequence A 3.0 T scanner. FOCUS‐MUSE DWI, FOCUS DWI, MUSE DWI, SS DWI. Assessment For volunteers, ADC and SNR were measured by two readers in the pancreatic head, body, and tail. For all subjects, the diagnostic image quality score was assessed by three other readers on above four DWIs. Statistical Tests Paired‐sample T‐test, intraclass correlation (ICC), Bland–Altman method, Friedman test, Dunn‐Bonferroni post hoc test and kappa coefficient. A significance level of 0.05 was used. Results FOCUS‐MUSE DWI had the best intersession repeatability of ADC measurements (head: 59.53, body: 101.64, tail: 42.30) among the four DWIs, and also maintained the significantly highest SNR (reader 1 [head: 19.68 ± 3.23, body: 23.42 ± 5.00, tail: 28.85 ± 4.96], reader 2 [head: 19.93 ± 3.52, body: 23.02 ± 5.69, tail: 29.77 ± 6.33]) except for MUSE DWI. Furthermore, it significantly achieved better image quality in volunteers (median value: 4 score) and 9 patients (most in 4 score). Data Conclusion FOCUS‐MUSE DWI improved the reliability of pancreatic images with the most stable ADC measurement, best image quality score and sufficient SNR among four DWIs. Evidence Level 2 Technical Efficacy Stage 2

Bone marrow mesenchymal stem cells (BMMSCs) can differentiate into cardiomyocytes and be used in cardiac tissue engineering for heart regeneration. However, the effective clinical application of cardiomyocytes derived from BMMSCs is limited because of their immature phenotype. The aim of this study was to investigate the potential of triiodo-L-thyronine (T3) to drive cardiomyocytes derived from BMMSCs to a more mature state. BMMSCs were divided into 3 groups: untreated controls, differentiated, and T3 treated. The differentiation potential was evaluated by immunofluorescence microscopy and flow cytometry. Data were represented as the numbers of cells positive for the troponin I (cTnI), α-actinin, GATA4, and the connexin-43 (Cx-43). The mRNA levels of these specific markers of cardiomyocytes were determined by quantitative real-time polymerase chain reaction. The levels of cardiomyocytes markers protein and octamer-binding transcription factor 4 (Oct-4) were determined by Western blot analyses. Our data demonstrate that T3 treatment leads to a significant increase in cells positive for cTnI, GATA4, Cx-43, and α-actinin. The mRNA and protein expression levels of these specific markers of cardiomyocytes were also increased after T3 treatment. At the same time, the protein expression level of Oct-4 was substantially downregulated in T3-treated cells. These results demonstrate that T3 treatment increases the differentiation of BMMSCs induced to cardiomyocytes and promotes their maturation.