New Drugs and Therapies in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension is a chronic, progressive disorder of the pulmonary vasculature with associated pulmonary and cardiac remodeling. PAH was a uniformly fatal disease until the late 1970s, but with the advent of targeted therapies, the life expectancy of patients with PAH has now considerably improved. Despite these advances, PAH inevitably remains a progressive disease with significant morbidity and mortality. Thus, there is still an unmet need for the development of new drugs and other interventional therapies for the treatment of PAH. One shortcoming of currently approved vasodilator therapies is that they do not target or reverse the underlying pathogenesis of the disease process itself. A large body of evidence has evolved in the past two decades clarifying the role of genetics, dysregulation of growth factors, inflammatory pathways, mitochondrial dysfunction, DNA damage, sex hormones, neurohormonal pathways, and iron deficiency in the pathogenesis of PAH. This review focuses on newer targets and drugs that modify these pathways as well as novel interventional therapies in PAH.

Molecular Pathways in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension is a multifactorial, chronic disease process that leads to pulmonary arterial endothelial dysfunction and smooth muscular hypertrophy, resulting in impaired pliability and hemodynamics of the pulmonary vascular system, and consequent right ventricular dysfunction. Existing treatments target limited pathways with only modest improvement in disease morbidity, and little or no improvement in mortality. Ongoing research has focused on the molecular basis of pulmonary arterial hypertension and is going to be important in the discovery of new treatments and genetic pathways involved. This review focuses on the molecular pathogenesis of pulmonary arterial hypertension.

Novel B-DNA dermatophyte assay for demonstration of canonical DNA in dermatophytes: Histopathologic characterization by artificial intelligence.

We describe a novel assay and artificial intelligence-driven histopathologic approach identifying dermatophytes in human skin tissue sections (ie, B-DNA dermatophyte assay) and demonstrate, for the first time, the presence of dermatophytes in tissue using immunohistochemistry to detect canonical right-handed double-stranded (ds) B-DNA. Immunohistochemistry was performed using anti-ds-B-DNA monoclonal antibodies with formalin-fixed paraffin-embedded tissues to determine the presence of dermatophytes. The B-DNA assay resulted in a more accurate identification of dermatophytes, nuclear morphology, dimensions, and gene expression of dermatophytes (ie, optical density values) than periodic acid-Schiff (PAS), Grocott methenamine silver (GMS), or hematoxylin and eosin (H&E) stains. The novel assay guided by artificial intelligence allowed for efficient identification of different types of dermatophytes (eg, hyphae, microconidia, macroconidia, and arthroconidia). Using the B-DNA dermatophyte assay as a clinical tool for diagnosing dermatophytes is an alternative to PAS, GMS, and H&E as a fast and inexpensive way to accurately detect dermatophytosis and reduce the number of false negatives. Our assay resulted in superior identification, sensitivity, life cycle stages, and morphology compared to H&E, PAS, and GMS stains. This method detects a specific structural marker (ie, ds-B-DNA), which can assist with diagnosis of dermatophytes. It represents a significant advantage over methods currently in use.

Preventive Therapies in Peripheral Arterial Disease.

Atherosclerosis, while initially deemed a bland proliferative process, is now recognized as a multifactorial-lipoprotein-mediated inflammation-driven pathway. With the rising incidence of atherosclerotic disease of the lower extremity arteries, the healthcare burden and clinical morbidity and mortality due to peripheral artery disease (PAD) are currently escalating. With a healthcare cost burden of over 21 billion USD and 200 million patients afflicted worldwide, accurate knowledge regarding the pathophysiology, presentation, and diagnosis of the disease is crucial. The role of lipoproteins and their remnants in atherosclerotic vessel occlusion and plaque formation and progression has been long established. This review paper discusses the epidemiology, pathophysiology, and presentation of PAD. PAD has been repeatedly noted to portend to poor cardiovascular and limb outcomes. We discuss major therapeutic avenues for the prevention of major cardiovascular adverse events and major limb adverse events in patients with PAD.

A Case of Ticagrelor-Induced Sinus Pause.

Ticagrelor is an oral antiplatelet agent commonly used following percutaneous coronary intervention (PCI). There have been many reports describing bradyarrhythmias in the setting of ticagrelor use, most notably sinus pauses. This process is thought to be related to ticagrelor's inhibition of human equilibrative nucleoside transporter (hENT1), which reduces cellular uptake of adenosine. We present a case of a 58-year-old male who experienced prolonged sinus pauses 38 hours after starting ticagrelor following ST-elevation myocardial infarction with subsequent PCI and stent placement.

Role of Lipid-Lowering Therapy in Peripheral Artery Disease.

Atherosclerosis is a multifactorial, lipoprotein-driven condition that leads to plaque formation within the arterial tree, leading to subsequent arterial stenosis and thrombosis that accounts for a large burden of cardiovascular morbidity and mortality globally. Atherosclerosis of the lower extremities is called peripheral artery disease and is a major cause of loss in mobility, amputation, and critical limb ischemia. Peripheral artery disease is a common condition with a gamut of clinical manifestations that affects an estimated 10 million people in the United States of America and 200 million people worldwide. The role of apolipoprotein B-containing lipoproteins, such as LDL and remnant lipoproteins in the development and progression of atherosclerosis, is well-established. The focus of this paper is to review existing data on lipid-lowering therapies in lower extremity atherosclerotic peripheral artery disease.

Psychosocial and Behavioral Effects of the COVID-19 Pandemic in the Indian Population: Protocol for a Cross-sectional Study.

BACKGROUND: During the year 2020, the COVID-19 pandemic spread from China to the rest of the world, which prompted the world to implement a widespread mandated quarantine or social isolation. The impending uncertainty of the pandemic must have resulted in a variety of widespread mental health maladies. There has been documentation in the literature about a lot of these in small populations of the world but limited studies have been conducted in India, leading to limited evidence in the literature. OBJECTIVE: The main objective of our study is to investigate the mental health effects that the COVID-19 pandemic has had on the general population in India both quantitatively and qualitatively. These results will help contribute to reducing the knowledge gap that is recognized in the literature, which is the result of the unprecedented and novel nature of the pandemic. METHODS: We designed and validated our own questionnaire and used the method of circulating the questionnaire via WhatsApp (Facebook Inc). WhatsApp is a social media app that is very popularly used in India; hence, it turned out to be an effective medium for gathering pilot data. We analyzed the pilot data and used them to validate the questionnaire. This was done with the expertise of our mentor, Nilima Shah, MD (psychiatry). We gathered pilot data on 545 subjects and used the results to determine the changes that were needed for the questionnaire while simultaneously validating the questionnaire. RESULTS: The study protocol was approved in September 2020 by the institutional review board at Vadilal Sarabhai General Hospital, Ahmedabad, Gujarat, India. CONCLUSIONS: The following preliminary assumptions can be made about the study based on the pilot data: the majority of the survey respondents were male (289/545, 53%), most of them were educated and employed as health care workers (199/545, 36.5%). The majority of the responders were self-employed (185/545, 33.9%), single (297/545, 54.5%), and stayed with their families (427/541, 79%) for the lockdown, which helped them psychologically. Findings that are specific to mental health have been elaborated upon in the manuscript. It is evident from the data collected in previous literature that the pandemic has had significant detrimental effects on the mental health of a vast proportion of the Indian population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29896.