Platypnea-Orthodeoxia Syndrome in Two Previously Healthy Adults: A Case-based Review

We describe here the clinical manifestations of platypnea-orthodeoxia in two patients with interatrial shunting. In both cases, the patients were asymptomatic prior to developing additional cardiopulmonary issues that apparently enhanced right-to-left intracardiac shunting. The patients were both treated with percutaneously deployed occlusion devices, with excellent results. Symptoms and positional oxygen desaturation resolved after device placement in both cases. In addition, these patients remain symptom-free 30 months after device implantation

Gelatin Methacryloyl Bioadhesive Improves Survival and Reduces Scar Burden in a Mouse Model of Myocardial Infarction.

Background Delivery of hydrogels to the heart is a promising strategy for mitigating the detrimental impact of myocardial infarction (MI). Challenges associated with the in vivo delivery of currently available hydrogels have limited clinical translation of this technology. Gelatin methacryloyl (GelMA) bioadhesive hydrogel could address many of the limitations of available hydrogels. The goal of this proof-of-concept study was to evaluate the cardioprotective potential of GelMA in a mouse model of MI. Methods and Results The physical properties of GelMA bioadhesive hydrogel were optimized in vitro. Impact of GelMA bioadhesive hydrogel on post-MI recovery was then assessed in vivo. In 20 mice, GelMA bioadhesive hydrogel was applied to the epicardial surface of the heart at the time of experimental MI. An additional 20 mice underwent MI but received no GelMA bioadhesive hydrogel. Survival rates were compared for GelMA-treated and untreated mice. Left ventricular function was assessed 3 weeks after experimental MI with transthoracic echocardiography. Left ventricular scar burden was measured with postmortem morphometric analysis. Survival rates at 3 weeks post-MI were 89% for GelMA-treated mice and 50% for untreated mice (P=0.011). Left ventricular contractile function was better in GelMA-treated than untreated mice (fractional shortening 37% versus 26%, P<0.001). Average scar burden in GelMA-treated mice was lower than in untreated mice (6% versus 22%, P=0.017). Conclusions Epicardial GelMA bioadhesive application at the time of experimental MI was performed safely and was associated with significantly improved post-MI survival compared with control animals. In addition, GelMA treatment was associated with significantly better preservation of left ventricular function and reduced scar burden

Outcomes of Patients With Takotsubo Syndrome Compared With Type 1 and Type 2 Myocardial Infarction

Background Takotsubo syndrome (TS) and myocardial infarction (MI) share similar clinical and laboratory characteristics but have important differences in causes, demographics, management, and outcomes. Methods and Results In this observational study, the National Inpatient Sample and National Readmission Database were used to identify patients admitted with TS, type 1 MI, or type 2 MI in the United States between October 1, 2017, and December 31, 2019. We compared patients hospitalized with TS, type 1 MI, and type 2 MI with respect to key features and outcomes. Over the 27‐month study period, 2 035 055 patients with type 1 MI, 639 075 patients with type 2 MI, and 43 335 patients with TS were identified. Cardiac arrest, ventricular fibrillation, and ventricular tachycardia were more prevalent in type 1 MI (4.02%, 3.2%, and 7.2%, respectively) compared with both type 2 MI (2.8%, 0.8%, and 5.4% respectively) and TS (2.7%, 1.8%, and 5.3%, respectively). Risk of mortality was lower in TS compared with both type 1 MI (3.3% versus 7.9%; adjusted odds ratio [OR], 0.3; P<0.001) and type 2 MI (3.3% versus 8.2%; adjusted OR, 0.3; P<0.001). Mortality rate (OR, 1.2; P<0.001) and cardiac‐cause 30‐day readmission rate (adjusted OR, 1.7; P<0.001) were higher in type 1 MI than in type 2 MI. Conclusions Patients with type 1 MI had the highest rates of in‐hospital mortality and cardiac‐cause 30‐day readmission. Risk of all‐cause 30‐day readmission was highest in patients with type 2 MI. The risk of ventricular arrhythmias in patients with TS is lower than in patients with type 1 MI but higher than in patients with type 2 MI

Rewirable gene regulatory networks in the preimplantation embryonic development of three mammalian species

Mammalian preimplantation embryonic development (PED) is thought to be governed by highly conserved processes. While it had been suggested that some plasticity of conserved signaling networks exists among different mammalian species, it was not known to what extent modulation of the genomes and the regulatory proteins could “rewire” the gene regulatory networks (GRN) that control PED. We therefore generated global transcriptional profiles from three mammalian species (human, mouse, and bovine) at representative stages of PED, including: zygote, two-cell, four-cell, eight-cell, 16-cell, morula and blastocyst. Coexpression network analysis suggested that 40.2% orthologous gene triplets exhibited different expression patterns among these species. Combining the expression data with genomic sequences and the ChIP-seq data of 16 transcription regulators, we observed two classes of genomic changes that contributed to interspecies expression difference, including single nucleotide mutations leading to turnover of transcription factor binding sites, and insertion of cis-regulatory modules (CRMs) by transposons. About 10% of transposons are estimated to carry CRMs, which may drive species-specific gene expression. The two classes of genomic changes act in concert to drive mouse-specific expression of MTF2, which links POU5F1/NANOG to NOTCH signaling. We reconstructed the transition of the GRN structures as a function of time during PED. A comparison of the GRN transition processes among the three species suggested that in the bovine system, POU5F1's interacting partner SOX2 may be replaced by HMGB1 (a TF sharing the same DNA binding domain with SOX2), resulting in rewiring of GRN by a trans change.Stem Cell and Regenerative Biolog

Rewirable gene regulatory networks in the preimplantation embryonic development of three mammalian species

Mammalian preimplantation embryonic development (PED) is thought to be governed by highly conserved processes. While it had been suggested that some plasticity of conserved signaling networks exists among different mammalian species, it was not known to what extent modulation of the genomes and the regulatory proteins could “rewire” the gene regulatory networks (GRN) that control PED. We therefore generated global transcriptional profiles from three mammalian species (human, mouse, and bovine) at representative stages of PED, including: zygote, two-cell, four-cell, eight-cell, 16-cell, morula and blastocyst. Coexpression network analysis suggested that 40.2% orthologous gene triplets exhibited different expression patterns among these species. Combining the expression data with genomic sequences and the ChIP-seq data of 16 transcription regulators, we observed two classes of genomic changes that contributed to interspecies expression difference, including single nucleotide mutations leading to turnover of transcription factor binding sites, and insertion of cis-regulatory modules (CRMs) by transposons. About 10% of transposons are estimated to carry CRMs, which may drive species-specific gene expression. The two classes of genomic changes act in concert to drive mouse-specific expression of MTF2, which links POU5F1/NANOG to NOTCH signaling. We reconstructed the transition of the GRN structures as a function of time during PED. A comparison of the GRN transition processes among the three species suggested that in the bovine system, POU5F1's interacting partner SOX2 may be replaced by HMGB1 (a TF sharing the same DNA binding domain with SOX2), resulting in rewiring of GRN by a trans change