Antisense Technology: An Emerging Platform for Cardiovascular Disease Therapeutics

Antisense oligonucleotides and small interfering RNAs, which suppress the translation of specific mRNA target proteins, are emerging as important therapeutic modalities for the treatment of cardiovascular disease. Over the last 25 years, the advances in all aspects of antisense technology, as well as a detailed understanding of the mechanism of action of antisense drugs, have enabled their use as therapeutic agents. These advancements culminated in the FDA approval of the first chronically administered cardiovascular antisense therapeutic, mipomersen, which targets hepatic apolipoprotein B mRNA. This review provides a brief history of antisense technology, highlights the progression of mipomersen from preclinical studies to multiple Phase III registration trials, and gives an update on the status of other cardiovascular antisense therapeutics currently in the clinic.     

Cine computerized tomography

Ultrafast (Cine) CT scanning provides cross-sectional millisecond tomography, and therefore combines digital imaging and high resolution without the need for either cardiac catheterization or any form of ECG gating. Fifty millisecond multilevel scanning at rates of 17 scans per second allows quantitation of left ventricular (LV) function at each tomographic level during a cardiac cycle. Calculations of global and regional ejection fraction can be obtained, and in addition ultrafast CT also has the potential for providing unique data concerning regional wall thickening, mass and even regional myocardial perfusion. Interventional studies with exercise and pharmacological agents have commenced and are currently being evaluated.     

Immunoblotting: An Emerging Technique in Immunohematology

Protein blotting is a technique of transferring and immobilizing the original protein patterns from gel matrices to a suitable solid phase. It can be employed in identifying the protein antigens in complex biological mixtures, since each protein is accessible to its corresponding antibody. This method, called immunoblotting, is also applicable to define the specificity of a given antibody. The perspective of immunoblotting has already found wide application in basic research. Some features of the immunoblotting and recent improvements of the original procedures will be discussed. To justify a wider application in clinical research I will summarize some applications with respect to immunohematology.     

COVID-19 Myocarditis: An Emerging Clinical Conundrum

Coronavirus Disease 2019 (COVID-19) has been a significant cause of global mortality and morbidity since it was first reported in December 2019 in Wuhan, China. COVID19 like previous coronaviruses primarily affects the lungs causing pneumonia, interstitial pneumonitis, and severe acute respiratory distress syndrome (ARDS). However, there is increasing evidence linking COVID-19 to cardiovascular complications such as arrhythmias, heart failure, cardiogenic shock, fulminant myocarditis, and cardiac death. Given the novelty of this virus, there is paucity of data on some cardiovascular complications of COVID-19, specifically myocarditis. Myocarditis is an inflammatory disease of the heart muscle with a heterogenous clinical presentation and progression. It is mostly caused by viral infections and is the result of interaction of the virus and the host's immune system. There have been several case reports linking COVID-19 with myocarditis, however the true mechanism of cardiac injury remains under investigation. In this paper we review the clinical presentation, proposed pathophysiology, differential diagnoses and management of myocarditis in COVID-19 patients.     

Rhodococcus Equi: An Emerging Opportunistic Pathogen?

Human infection with Rhodococcus equi is apparently rare with most published reports describing the development of lung abscesses in immunocompromised hosts. Of only 18 cases of infection previously recorded, four have recently occurred in patients with the acquired immune deficiency syndrome (AIDS). In Australasia, R. equi has frequently been isolated from soil and infected farm animals yet no human infections have been reported thus far. Three cases of R. equi infection have occurred in New Zealand and, collectively, they cover a wider spectrum of disease than that previously recognised. The natural history of R. equi infections, their clinical features and treatment are described in the light of our recent experience. (Aust NZ J Med 1989; 19: 103–107.)     

Usutu Virus: An Emerging Flavivirus in Europe

Usutu virus (USUV) is an African mosquito-borne flavivirus belonging to the Japanese encephalitis virus serocomplex. USUV is closely related to Murray Valley encephalitis virus, Japanese encephalitis virus, and West Nile virus. USUV was discovered in South Africa in 1959. In Europe, the first true demonstration of circulation of USUV was reported in Austria in 2001 with a significant die-off of Eurasian blackbirds. In the subsequent years, USUV expanded to neighboring countries, including Italy, Germany, Spain, Hungary, Switzerland, Poland, England, Czech Republic, Greece, and Belgium, where it caused unusual mortality in birds. In 2009, the first two human cases of USUV infection in Europe have been reported in Italy, causing meningoencephalitis in immunocompromised patients. This review describes USUV in terms of its life cycle, USUV surveillance from Africa to Europe, human cases, its cellular tropism and pathogenesis, its genetic relationship with other flaviviruses, genetic diversity among USUV strains, its diagnosis, and a discussion of the potential future threat to Asian countries.     

Strongyloidiasis: An Emerging Infectious Disease in China

Since the first case of strongyloidiasis reported in China in 1973, there have been 330 confirmed cases as of 2011. The present study conducted a meta-analysis on 106 cases for which detailed information on clinical symptoms, diagnosis, and outcome was available. Most (63%) cases were from the past decade. Immunocompromised patients and those given cortical hormones accounted for 68% of the cases, and case-fatality rate was 38%. General clinical symptoms included abdominal pain (53%), diarrhea (46%), fever (40%), and vomiting (39%). The parasite positivity rate in feces, sputum, and urine by microscopic diagnosis was 75%, 24%, and 8%, respectively, and gastrointestinal endoscopy or other biopsy detection rates were 17%. A lack of specific clinical manifestations makes early diagnosis and correct treatment difficult. Strongyloidiasis is an emerging disease in China, and public and clinical awareness needs to be raised to improve prevention and control.     

Diabetic Foot Disease: Emerging Technologies: Applying 21st Century Imaging Technology to Wound Healing: An Avant-Gardist Approach

A significant arising complication in the care of patients with diabetes is increased susceptibility to chronic wounds, including diabetic foot ulcers and pressure sores. This is driven by, e.g., neuropathy and peripheral arterial disease. It is well recognized that best practice in wound care requires wound assessment, including measurement, on presentation and regularly throughout the treatment program. Proper assessment is necessary to ensure that the most appropriate and cost-effective therapy is used at all times, with quantitative measurement necessary to track the efficacy of the chosen approach. A documented assessment can also assist patient–clinician dialog and discussion within the multidisciplinary team. Remote evaluation and assessment of the wound is also of increasing importance and practicality through the use of a telemedicine approach. There has been considerable progress in the space of imaging for wounds, including systems that include three-dimensional measurement and telemedicine features. This literature review examines the available options and reviews the clinical evidence for measurement accuracy, scope for remote assessment, and published user feedback on the systems.     

Overlap Syndromes: An Emerging Diagnostic and Therapeutic Challenge

Overlap syndrome in hepatology is emerging as a diagnostic and therapeutic challenge, which is further complicated by the present gaps in the information regarding the immunopathogenesis of these diseases. The present review represents a concise review of literature on overlap syndromes with emphasis on prevalence, etiopathogenesis, clinical presentation, diagnosis, and management of true overlap syndromes.     

Women and Heart Failure: An Emerging Venus-Mars Concept

Some of the most profound sex differences in cardiovascular disease are evident in the syndrome of heart failure. Certain heart failure conditions have a unique predilection for women, such as heart failure with preserved ejection fraction and apical ballooning syndrome; or are exclusive to women, such as peripartum cardiomyopathy. Overall, there are notable differences between women and men in terms heart failure disease burden, risk factors, clinical presentation and prognosis. Yet, women remain under-represented in heart failure clinical trials. Important knowledge gaps exist in our understanding of the pathophysiologic basis for these sex differences and potential for effective sex-specific management strategies.     

Batai Orthobunyavirus: An Emerging Mosquito-Borne Virus in Europe

Batai virus (BATV) is a zoonotic orthobunyavirus transmitted by a wide range of mosquito vectors. The virus is distributed throughout Asia and parts of Africa and has been sporadically detected in several European countries. There is increasing evidence that BATV is emerging in Europe as a potential threat to both animal and human health, having been detected in mosquitoes, mammals, birds and humans. In recent years, serological surveillance in cattle, sheep and goats has suggested an antibody prevalence of up to 46% in European livestock, although human serological prevalence remains generally low. However, the recent and continued spread of invasive mosquito species into Europe may facilitate the establishment of competent populations of mosquitoes leading to increased BATV transmission. Migratory birds may also potentially facilitate the emergence of BATV in geographical locations where it was previously undetected. Although BATV has the potential to cause disease in humans and livestock, our understanding of the impact in wild animal populations is extremely limited. Therefore, there is a need for increased surveillance for BATV in mosquitoes, livestock, wild mammals and birds in Europe to understand the true impact of this virus.     

Balamuthia Mandrillaris Amoebic Encephalitis: An Emerging Parasitic Infection

Balamuthia mandrillaris is a free living amoeba that can be isolated from soil. It is an emerging pathogen causing skin lesions as well as CNS involvement with a fatal outcome if untreated. The infection has been described more commonly in inmunocompetent individuals, mostly males, many children, and with a predilection for population with Hispanic background in cases occurring in the United States. Except for Africa, all continents have reported the disease, although a majority of cases are seen in North and South America. In published reported cases from North America, most patients will debut with neurological symptoms, where as in countries like Peru, a skin lesion will precede other symptoms. The classical skin lesion is a plaque, mostly located on face or knee. Diagnosis requires a high level of suspicion. Therapeutic strategies require a multidrug approach, than includes at least one amebicidal drug, and prolonged periods of treatment.