Baileydickey8750

opulation, E/e' is a stronger predictor of cardiovascular mortality and morbidity than in individuals without diabetes and contributes with incremental prognostic value in addition to established cardiovascular risk factors.Perinatal smoke/nicotine exposure alters lung development and causes asthma in exposed offspring, transmitted transgenerationally. The mechanism underlying the transgenerational inheritance of perinatal smoke/nicotine-induced asthma remains unknown, but germline epigenetic modulations may play a role. Using a well-established rat model of perinatal nicotine-induced asthma, we determined the DNA methylation pattern of spermatozoa of F1 rats exposed perinatally to nicotine in F0 gestation. To identify differentially methylated regions (DMRs), reduced representation bisulfite sequencing was performed on spermatozoa of F1 litters. The top regulated gene body and promoter DMRs were tested for lung gene expression levels, and key proteins involved in lung development and repair were determined. The overall CpG methylation in F1 sperms across gene bodies, promoters, 5'-UTRs, exons, introns, and 3'-UTRs was not affected by nicotine exposure. However, the methylation levels were different between the different genomic regions. Eighty one CpG sites, 16 gene bodies, and 3 promoter regions were differentially methylated. Gene enrichment analysis of DMRs revealed pathways involved in oxidative stress, nicotine response, alveolar and brain development, and cellular signaling. Among the DMRs, Dio1 and Nmu were the most hypermethylated and hypomethylated genes, respectively. Gene expression analysis showed that the mRNA expression and DNA methylation were incongruous. Key proteins involved in lung development and repair were significantly different (FDR less then 0.05) between the nicotine and placebo-treated groups. Our data show that DNA methylation is remodeled in offspring spermatozoa upon perinatal nicotine exposure. These epigenetic alterations may play a role in transgenerational inheritance of perinatal smoke/nicotine induced asthma.Local adaptation in coastal areas is driven chiefly by tolerance to salinity stress. To survive high salinity, plants have evolved mechanisms to specifically tolerate sodium. ODQ nmr However, the pathways that mediate adaptive changes in these conditions reach well beyond Na+ . Here we perform a high-resolution genetic, ionomic, and functional study of the natural variation in Molybdenum transporter 1 (MOT1) associated with coastal Arabidopsis thaliana accessions. We quantify the fitness benefits of a specific deletion-harbouring allele (MOT1DEL ) present in coastal habitats that is associated with lower transcript expression and molybdenum accumulation. Analysis of the leaf ionome revealed that MOT1DEL  plants accumulate more copper (Cu) and less sodium (Na+ ) than plants with the noncoastal MOT1 allele, revealing a complex interdependence in homeostasis of these three elements. Our results indicate that under salinity stress, reduced MOT1 function limits leaf Na+  accumulation through abscisic acid (ABA) signalling. Enhanced ABA biosynthesis requires Cu. This demand is met in Cu deficient coastal soils through MOT1DEL  increasing the expression of SPL7 and the copper transport protein COPT6. MOT1DEL  is able to deliver a pleiotropic suite of phenotypes that enhance salinity tolerance in coastal soils deficient in Cu. This is achieved by inducing ABA biosynthesis and promoting reduced uptake or better compartmentalization of Na+ , leading to coastal adaptation.

The clinical utility of cardiopulmonary exercise testing (CPET) has not been extensively studied yet in heart transplantation (HTX) patients.

To analyze the predictive value of the CPET on hospitalizations and mortality in HTX recipients.

A retrospective cohort was performed from a secondary database. Patients>18years with HTX who underwent a CPET between 3 and 12months after transplantation were included. Time to the first primary endpoint (HTX-related hospitalization) was analyzed and adjusted using Cox proportional hazards regression model.

A total of 122 patients (mean age 50.1years, 77.0% men) were included. Fifty-seven patients (46.7%) had the primary endpoint. Peak VO

(HR .95; CI 95% .90-.99, P=.03), oxygen pulse (HR .57; CI 95% .34-.96, P=.03) and predicted VO

(HR .97; CI 95% .96-.99, P=.002) were associated with the endpoint. We did not find a significant association between the other variables and the outcome.

In HTX recipients, peak VO

, oxygen pulse, and predicted VO

were independently associated with hospitalizations at follow up.

In HTX recipients, peak VO2 , oxygen pulse, and predicted VO2 were independently associated with hospitalizations at follow up.

Tissue-engineered tracheal grafts (TETGs) offer a potential solution for repair of long-segment airway defects. However, preclinical and clinical TETGs have been associated with chronic inflammation and macrophage infiltration. Macrophages express great phenotypic heterogeneity (generally characterized as classically activated [M1] vs. alternatively activated [M2]) and can influence tracheal repair and regeneration. We quantified and characterized infiltrating host macrophages using mouse microsurgical tracheal replacement models.

Translational research, animal model.

We assessed macrophage infiltration and phenotype in animals implanted with syngeneic tracheal grafts, synthetic TETGs, or partially decellularized tracheal scaffolds (DTSs).

Macrophage infiltration was observed following tracheal replacement with syngeneic trachea. Both M1 and M2 macrophages were present in native trachea and increased during early tracheal repair (P= .014), with an M1/M2 ratio of 0.48 ± 0.15. In contrast, orthotopic implantation of synthetic TETGs resulted in a shift to M1 predominant macrophage phenotype with an increased M1/M2 ratio of 1.35 ± 0.41 by 6 weeks following implant (P= .035). Modulation of the synthetic scaffold with the addition of polyglycolic acid (PGA) resulted in a reduction of M1/M2 ratio due to an increase in M2 macrophages (P= .006). Using systemic macrophage depletion, the M1/M2 ratio reverted to native values in synthetic TETG recipients and was associated with an increase in graft epithelialization. Macrophage ratios seen in DTSs were similar to native values.

M1 and M2 macrophages are present during tracheal repair. Poor epithelialization with synthetic TETG is associated with an elevation of the M1/M2 ratio. Macrophage phenotype can be altered with scaffold composition and host-directed systemic therapies. DTSs exhibit M1/M2 ratios similar to those seen in native trachea and syngeneic tracheal replacement.

NA Laryngoscope, 2021.

NA Laryngoscope, 2021.