Heme Oxygenase-1, Cardiac Senescence, and Myocardial Infarction: A Critical Review of the Triptych.

PURPOSE: Heme oxygenase-1 (HO-1) is a crucial enzyme in heme metabolism, facilitating the breakdown of heme into biliverdin, carbon monoxide, and free iron. Renowned for its potent cytoprotective properties, HO-1 showcases notable antioxidant, anti-inflammatory, and anti-apoptotic effects. In this review, the authors aim to explore the profound impact of HO-1 on cardiac senescence and its potential implications in myocardial infarction (MI). RESULTS: Recent research has unveiled the intricate role of HO-1 in cellular senescence, characterized by irreversible growth arrest and functional decline. Notably, cardiac senescence has emerged as a pivotal factor in the development of various cardiovascular conditions, including MI. Notably, cardiac senescence has emerged as an important factor in the development of various cardiovascular conditions, including myocardial infarction (MI). The accumulation of senescent cells, spanning vascular endothelial cells, vascular smooth muscle cells, cardiomyocytes, and progenitor cells, poses a significant risk for cardiovascular diseases such as vascular aging, atherosclerosis, myocardial infarction, and ventricular remodeling. Inhibition of cardiomyocyte senescence not only reduces senescence-associated inflammation but also impacts other myocardial lineages, hinting at a broader mechanism of propagation in pathological remodeling. HO-1 has been shown to improve heart function and mitigate cardiomyocyte senescence induced by ischemic injury and aging. Furthermore, HO-1 induction has been found to alleviate H2O2-induced cardiomyocyte senescence. As we grow in our understanding of antiproliferative, antiangiogenic, anti-aging, and vascular effects of HO-1, we see the potential to exploit potential links between individual susceptibility to cardiac senescence and myocardial infarction. CONCLUSIONS: This review investigates strategies for upregulating HO-1, including gene targeting and pharmacological agents, as potential therapeutic approaches. By synthesizing compelling evidence from diverse experimental models and clinical investigations, this study elucidates the therapeutic potential of targeting HO-1 as an innovative strategy to mitigate cardiac senescence and improve outcomes in myocardial infarction, emphasizing the need for further research in this field.

The Role of Artificial Intelligence in Echocardiography: A Clinical Update.

PURPOSE OF REVIEW: In echocardiography, there has been robust development of artificial intelligence (AI) tools for image recognition, automated measurements, image segmentation, and patient prognostication that has created a monumental shift in the study of AI and machine learning models. However, integrating these measurements into complex disease recognition and therapeutic interventions remains challenging. While the tools have been developed, there is a lack of evidence regarding implementing heterogeneous systems for guiding clinical decision-making and therapeutic action. RECENT FINDINGS: Newer AI modalities have shown concrete positive data in terms of user-guided image acquisition and processing, precise determination of both basic and advanced quantitative echocardiographic features, and the potential to construct predictive models, all with the possibility of seamless integration into clinical decision support systems. AI in echocardiography is a powerful and ever-growing tool with the potential for revolutionary effects on the practice of cardiology. In this review article, we explore the growth of AI and its applications in echocardiography, along with clinical implications and the associated regulatory, legal, and ethical considerations.

Recurrent syncopal episodes in a pregnant patient with neurocysticercosis.

Neurocysticercosis (NCC) is the most common parasitic infection of the nervous system and acquired epilepsy in low-resource settings due to the pork tapeworm, Taenia solium. Humans contract the intestinal infection of the adult tapeworm (taeniasis) through the fecal-oral route after consuming undercooked food, particularly pork or water, contaminated with tapeworm eggs. When the larvae invades the central nervous system (CNS), the infection causes NCC, which often manifests as late-onset seizures, chronic headaches, and intracranial hypertension. We describe a 31-year-old Hispanic multigravida woman from Guatemala, at 33 weeks of gestation, who presented with multiple syncopal and hypotensive episodes prompting a Computed tomography (CT) image of the head revealing multiple small cerebral calcifications indicating NCC. In this article, we highlight the significance of early symptom recognition and diagnostic workup for NCC in areas with diverse immigrant populations. We also discuss the epidemiology, clinical manifestations, and current treatment modalities available for NCC.

Gender Bias in Clinical Trial Enrollment: Female Authorship Matters.

BACKGROUND: Despite initiatives to promote equal enrollment of human subjects in clinical trials, females continue to be underrepresented. The goal of this work is to determine if female enrollment in human clinical trials published in 3 high-impact journals from 2015 to 2019 is correlated with gender of first and/or senior authors. METHODS: Clinical trials published in the Journal of the American Medical Association (JAMA), The Lancet, and the New England Journal of Medicine (NEJM) from January 1, 2015, to December 31, 2019, were reviewed. Trials were excluded for ongoing enrollment, sex-specific disease research, or author name without gender assignment. One-sample χ2 pairwise comparisons and two-tailed proportion tests on the proportion of females between gender author pairings were done overall and for each subset analysis. RESULTS: In total, 1,427 articles enrolled a total of 2,104,509 females and 2,616,981 males (44.6% vs. 55.4%, P ≤ 0.0001) in clinical trials. Overall, more females were enrolled if both first and senior authors were female (51.7% vs. 48.3%, P ≤ 0.0001). Proportion of females enrolled decreased with the following first and senior author pairings: female-male (48.9%), male-female (48.6%), and male-male (40.5%, P ≤ 0.0001 compared to female-female authorship). Greater female enrollment in clinical trials with female-female compared to male-male authorship persisted in subset analyses by funding source, phase, randomization for study participants, drug and/or device trial, and geographic location. Female enrollment was higher in 3 surgical specialties: neurosurgery (all authors: 52%, P ≤ 0.01), ophthalmology (all authors: 53.6%, P ≤ 0.0001), and surgery (all authors: 54.4%, P ≤ 0.0001). The majority of surgical specialties did not publish trials with female-female authorship but when stratifying by author gender pairing, surgical oncology had the highest female enrollment with female-female authorship (98.4%, P ≤ 0.0001). CONCLUSIONS: Female authorship of clinical trial publications, specifically having both first and senior authors as female, was correlated with higher female enrollment in clinical trials when compared to male authorship and endured with multiple subset analyses.

Membrane Estrogen Receptor ß Is Sufficient to Mitigate Cardiac Cell Pathology.

Estrogen acting through estrogen receptor ß (ERß) has been shown to oppose the stimulation of cardiac myocytes and cardiac fibroblasts that results in cardiac hypertrophy and fibrosis. Previous work has implicated signal transduction from ERß as being important to the function of estrogen in this regard. Here we address whether membrane ERß is sufficient to oppose key mechanisms by which angiotensin II (AngII) stimulates cardiac cell pathology. To do this we first defined essential structural elements within ERß that are necessary for membrane or nuclear localization in cells. We previously determined that cysteine 418 is the site of palmitoylation of ERß that is required and sufficient for cell membrane localization in mice and is the same site in humans. Here we determined in Chinese hamster ovarian (CHO) cells, and mouse and rat myocytes and cardiac fibroblasts, the effect on multiple aspects of signal transduction by expressing wild-type (WT ) or a C418A-mutant ERß. To test the importance of the nuclear receptor, we determined a 4-amino acid deletion in the E domain of ERß that strongly blocked nuclear localization. Using these tools, we expressed WT and mutant ERß constructs into cardiomyocytes and cardiac fibroblasts from ERß-deleted mice. We determined the ability of estrogen to mitigate cell pathology stimulated by AngII and whether the membrane ERß is necessary and sufficient.

Programming Semiconductor Nanowire Composition with Sub-100 nm Resolution via the Geode Process.

We demonstrate the vapor-liquid-solid growth of single-crystalline i-Si, i-Si/n-Si, and SixGe1-x/SiyGe1-y nanowires via the Geode process. By enabling nanowire growth on the large internal surface area of a microcapsule powder, the Geode process improves the scalability of semiconductor nanowire manufacturing while maintaining nanoscale programmability. Here, we show that heat and mass transport limitations introduced by the microcapsule wall are negligible, enabling the same degree of compositional control for nanowires grown inside microcapsules and on conventional flat substrates. Efficient heat and mass transport also minimize the structural variations of nanowires grown in microcapsules with different diameters and wall thicknesses. Nanowires containing at least 16 segments and segment lengths below 75 nm are demonstrated.

Bottom-up nanoscale patterning and selective deposition on silicon nanowires.

We demonstrate a bottom-up process for programming the deposition of coaxial thin films aligned to the underlying dopant profile of semiconductor nanowires. Our process synergistically combines three distinct methods-vapor-liquid-solid nanowire growth, selective coaxial lithography via etching of surfaces (SCALES), and area-selective atomic layer deposition (AS-ALD)-into a cohesive whole. Here, we study ZrO2on Si nanowires as a model system. Si nanowires are first grown with an axially modulated n-Si/i-Si dopant profile. SCALES then yields coaxial poly(methyl methacrylate) (PMMA) masks on the n-Si regions. Subsequent AS-ALD of ZrO2occurs on the exposed i-Si regions and not on those masked by PMMA. We show the spatial relationship between nanowire dopant profile, PMMA masks, and ZrO2films, confirming the programmability of the process. The nanoscale resolution of our process coupled with the plethora of available AS-ALD chemistries promises a range of future opportunities to generate structurally complex nanoscale materials and electronic devices using entirely bottom-up methods.

COVID-19 and Pregnancy: Risk, Symptoms, Diagnosis, and Treatment.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel virus responsible for causing an infection known as COVID-19. Several pulmonary and systemic manifestations of the illness have been described since the discovery of this virus. However, there have been higher-risk populations in which this infection has not been well studied nor documented. One of these populations includes the pregnant cohort. The purpose of this article is to describe the clinical manifestations of COVID-19 infection in the pregnant population and review the implications and sequelae of the infection throughout pregnancy and outcomes of live births. Also, we summarize the understanding and safety of current treatments and vaccination in pregnancy. This comprehensive review article comprises several case reports, case series, cohort studies, retrospective studies, and randomized clinical trials. Findings regarding maternal morbidity included an increased risk of acquiring severe COVID-19 infection requiring a higher level of inpatient hospital care along with an increased risk of preterm labor and cesarean delivery. Neonatal COVID-19 vertical transmission was shown to have conflicting data as there was a presence of transmission in certain retrospective studies and absence in others. There was also no evidence of teratogenicity from maternal COVID-19 infection. In conclusion, in part due to the unique physiologic state of pregnancy and part due to unknown factors, pregnant patients are at increased risk for negative outcomes of COVID-19 infection and must be classified as a high-risk population.