Giant Left Atrial Myxoma Presenting with Severe Pulmonary Hypertension.

The etiology of cardiac tumors has a broad differential diagnosis. The use of a multidisciplinary team along with appropriate workup with multimodality imaging is critical for patient management. A 41-year-old man with a history of heavy tobacco use presented with abdominal distension, edema, and dyspnea for the past month.

How do we justify research into enhanced warfighters?

State militaries have strong interests in developing enhanced warfighters: taking otherwise healthy service personnel (soldiers, marines, pilots, etc.) and pushing their biological, physiological, and cognitive capacities beyond their individual statistical or baseline norm. However, the ethical and regulatory challenges of justifying research into these kinds of interventions to demonstrate the efficacy and safety of enhancements in the military has not been well explored.

Design, Synthesis, and Evaluation of Oleyl-WRH Peptides for siRNA Delivery.

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH), would enhance STAT3 silencing efficiency in breast and ovarian cancer cells.

Governing with public engagement: an anticipatory approach to human genome editing.

In response to calls for public engagement on human genome editing (HGE), which intensified after the 2018 He Jiankui scandal that resulted in the implantation of genetically modified embryos, we detail an anticipatory approach to the governance of HGE. By soliciting multidisciplinary experts' input on the drivers and uncertainties of HGE development, we developed a set of plausible future scenarios to ascertain publics values-specifically, their hopes and concerns regarding the novel technology and its applications. In turn, we gathered a subset of multidisciplinary experts to propose governance recommendations for HGE that incorporate identified publics' values.

A Reinterpretation of the Relationship between Persistent and Resurgent Sodium Currents.

The resurgent sodium current (I) activates on membrane repolarization, such as during the downstroke of neuronal action potentials. Due to its unique activation properties, I is thought to drive high rates of repetitive neuronal firing. However, I is often studied in combination with the persistent or noninactivating portion of sodium currents (I).

Substrate mechanics unveil early structural and functional pathology in iPSC micro-tissue models of hypertrophic cardiomyopathy.

Hypertension is a major cause of morbidity and mortality in patients with hypertrophic cardiomyopathy (HCM), suggesting a potential role for mechanics in HCM pathogenesis. Here, we developed an physiological model to investigate how mechanics acts together with HCM-linked myosin binding protein C (MYBPC3) mutations to trigger disease. Micro-heart muscles (μHM) were engineered from induced pluripotent stem cell (iPSC)-derived cardiomyocytes bearing MYBPC3 mutations and challenged to contract against substrates of different elasticity.

Giant Left Ventricular Aneurysm With Dynamic Right Ventricular Compression and Subsequent End-Stage Heart Failure.

We report a case of a patient with a missed anterior myocardial infarction and associated ischemic cardiomyopathy. The patient had a massive true left ventricular aneurysm causing dynamic right ventricular compression, with associated cardiogenic shock, for which a heart transplantation was ultimately performed.

The importance of professional responsibility and fetal viability in the management of abortion.

In June 2022, the Dobbs v. Jackson Women's Health Organization Supreme Court decision ended the constitutional right to the professional practice of abortion throughout the United States. The removal of the constitutional right to abortion has significantly altered the practice of obstetricians and gynecologists across the US.

A Reinterpretation of the Relationship Between Persistent and Resurgent Sodium Currents.

The resurgent sodium current (I) activates on membrane repolarization, such as during the downstroke of neuronal action potentials. Due to its unique activation properties, I is thought to drive high rates of repetitive neuronal firing. However, I is often studied in combination with the persistent or non-inactivating portion of sodium currents (I).

Mechanical Resistance to Micro-Heart Tissue Contractility unveils early Structural and Functional Pathology in iPSC Models of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy is the most common cause of sudden death in the young. Because the disease exhibits variable penetrance, there are likely nongenetic factors that contribute to the manifestation of the disease phenotype. Clinically, hypertension is a major cause of morbidity and mortality in patients with HCM, suggesting a potential synergistic role for the sarcomeric mutations associated with HCM and mechanical stress on the heart.

Addressing challenges related to the professional practice of abortion post-Roe.

The landmark Roe vs Wade Supreme Court decision in 1973 established a constitutional right to abortion. In June 2022, the Dobbs vs Jackson Women's Health Organization Supreme Court decision brought an end to the established professional practice of abortion throughout the United States. Rights-based reductionism and zealotry threaten the professional practice of abortion.

Counseling for the option of termination of pregnancy for severe fetal anomalies in light of the recent Supreme Court ruling to remove the constitutional right to an abortion.

A birth defect is a structural or chromosomal change present at birth that can affect almost any part or parts of the body. Birth defects can vary from mild to severe. On June 24, 2022, with its Dobbs v Jackson Women's Health Organization decision the Supreme Court of the United States overturned Roe v.

Emerging methods to model cardiac ion channel and myocyte electrophysiology.

In the field of cardiac electrophysiology, modeling has played a central role for many decades. However, even though the effort is well-established, it has recently seen a rapid and sustained evolution in the complexity and predictive power of the models being created. In particular, new approaches to modeling have allowed the tracking of parallel and interconnected processes that span from the nanometers and femtoseconds that determine ion channel gating to the centimeters and minutes needed to describe an arrhythmia.

Amphiphilic Cell-Penetrating Peptides Containing Arginine and Hydrophobic Residues as Protein Delivery Agents.

The entry of proteins through the cell membrane is challenging, thus limiting their use as potential therapeutics. Seven cell-penetrating peptides, designed in our laboratory, were evaluated for the delivery of proteins. Fmoc solid-phase peptide synthesis was utilized for the synthesis of seven cyclic or hybrid cyclic-linear amphiphilic peptides composed of hydrophobic (tryptophan (W) or 3,3-diphenylalanine (Dip) and positively-charged arginine (R) residues, such as [WR], [WR], [WWRR], [WWRR], [(RW)K](RW), [RK]W, and [DipR].

Transcriptome Sequencing Reveals the Mechanism behind Chemically Induced Oral Mucositis in a 3D Cell Culture Model.

Oral mucositis is a common side effect of cancer treatment, and in particular of treatment with the mTORC1 inhibitor everolimus. Current treatment methods are not efficient enough and a better understanding of the causes and mechanisms behind oral mucositis is necessary to find potential therapeutic targets. Here, we treated an organotypic 3D oral mucosal tissue model consisting of human keratinocytes grown on top of human fibroblasts with a high or low dose of everolimus for 40 or 60 h and investigated (1) the effect of everolimus on microscopic sections of the 3D cell culture for evidence of morphologic changes and (2) changes in the transcriptome by high throughput RNA-Seq analysis.

Cyclic and Linear Peptides Containing Alternate WW and RR Residues as Molecular Cargo Delivery Tools.

Cell-impermeable and negatively charged compounds' cellular uptake across the cell membranes remains challenging. Herein, the synthesis of four linear [(WWRR), (WWRR), (WWRR), and (WWRR)] and four cyclic ([WWRR], [WWRR], [WWRR], and [WWRR]) peptides containing alternate two tryptophan (WW) and two arginine (RR) residues and their biological evaluation as molecular transporters are reported. The peptides did not show any significant cytotoxicity in different cell lines (MDA-MB-23, SK-OV-3, and HEK 293) at a concentration of 5 μM and after 3 h of incubation time.

The ethics of AI-assisted warfighter enhancement research and experimentation: Historical perspectives and ethical challenges.

The military applications of AI raise myriad ethical challenges. Critical among them is how AI integrates with human decision making to enhance cognitive performance on the battlefield. AI applications range from augmented reality devices to assist learning and improve training to implantable Brain-Computer Interfaces (BCI) to create bionic "super soldiers.

Is Russia's Research Ethics Culture Reliable?

The Russian invasion of Ukraine has led to the imposition of economic sanctions intended to isolate Russia from much of global commerce, which implicitly includes the medical research enterprise. The prospect of ongoing isolation of Russia's substantial research enterprise raises issues related to but distinct from the more familiar problem of corruption. In this paper, we identify reasons that the culture of research ethics in Russia may have been weak even before the war, contributing to hard questions about its future role in the global clinical research community.

Autonomy and Social Responsibility: The Post-Pandemic Challenge.

Over the last 80 years, a series of critical events has led to reconsideration of the basic premises of medical ethics. One of these events was the recognition of horrific medical experiments performed by German medical scientists in World War II concentration camps, resulting in intensified emphasis on a consent requirement, later understood as grounded in the bioethical principle of respect for autonomy, as well as on the moral accountability of the experimenter. Another important event that is forcing a reconsideration of respect for autonomy in medicine and health care is the COVID-19 pandemic.

Robust, Automated Analysis of Electrophysiology in Induced Pluripotent Stem Cell-Derived Micro-Heart Muscle for Drug Toxicity.

Drugs are often removed from clinical trials or market progression owing to their unforeseen effects on cardiac action potential and calcium handling. Induced pluripotent stem cell-derived cardiomyocytes and tissues fabricated from these cells are promising as screening tools for early identification of these potential cardiac liabilities. In this study, we describe an automated, open-source MATLAB-based analysis software for calculating cardiac action potentials and calcium transients from fluorescent reporters.

Oleyl Conjugated Histidine-Arginine Cell-Penetrating Peptides as Promising Agents for siRNA Delivery.

Recent approvals of siRNA-based products motivated the scientific community to explore siRNA as a treatment option for several intractable ailments, especially cancer. The success of approved siRNA therapy requires a suitable and safer drug delivery agent. Herein, we report a series of oleyl conjugated histidine-arginine peptides as a promising nonviral siRNA delivery tool.