Lundgaardshore8647

The incidence of pediatric cancers is rising steadily across the world, along with the challenges in understanding the molecular mechanisms and devising effective therapeutic strategies. Pediatric cancers are presented with diverse molecular characteristics and more distinct subtypes when compared to adult cancers. Recent studies on the genomic landscape of pediatric cancers using next-generation sequencing (NGS) approaches have redefined this field by providing better subtype characterization and novel actionable targets. Since early identification and personalized treatment strategies influence therapeutic outcomes, survival, and quality of life in pediatric cancer patients, the quest for actionable biomarkers is of great value in this field. Fusion genes that are prevalent and recurrent in several pediatric cancers are ideally suited in this context due to their disease-specific occurrence. In this review, we explore the current status of fusion genes in pediatric cancer subtypes and their use as biomarkers for diagnosis and personalized therapy. We discuss the technological advancements made in recent years in NGS sequencing and their impact on fusion detection algorithms that have revolutionized this field. Finally, we also discuss the advantages of pairing liquid biopsy protocols for fusion detection and their eventual use in diagnosis and treatment monitoring.The Epstein-Barr Virus (EBV) is a gamma-herpesvirus involved with a variety of human cancers, notably the endemic Burkitt lymphoma and nasopharyngeal carcinoma. In 2004, EBV was described as one the first known human oncoviruses to encode viral microRNAs (miRNAs), and these molecules were found to interact with viral and host targets. EBV miRNAs modulate biological processes that are critical for carcinogenesis, contributing to cell transformation and tumor progression of EBV-associated cancers. click here Herein we review and discuss EBV miRNAs as modulators of viral biology and carcinogenesis, as well as their usefulness as putative markers to monitor the onset, progression, and recurrence of cancers associated with the EBV infection.The COVID-19-related pandemic has resulted in profound health, financial, and societal impacts. Organized sporting events, from recreational to the Olympic level, have been cancelled to both mitigate the spread of COVID-19 and protect athletes and highly active individuals from potential acute and long-term infection-associated harms. COVID-19 infection has been associated with increased cardiac morbidity and mortality. Myocarditis and late gadolinium enhancement as a result of COVID-19 infection have been confirmed. Correspondingly, myocarditis has been implicated in sudden cardiac death of athletes. A pragmatic approach is required to guide those who care for athletes and highly active persons with COVID-19 infection. Members of the Community and Athletic Cardiovascular Health Network (CATCHNet) and the writing group for the Canadian Cardiovascular Society/Canadian Heart Rhythm Society Joint Position Statement on the Cardiovascular Screening of Competitive Athletes recommend that highly active persons with suspected or confirmed COVID-19 infection refrain from exercise for 7 days after resolution of viral symptoms before gradual return to exercise. We do not recommend routine troponin testing, resting 12-lead electrocardiography, echocardiography, or cardiac magnetic resonance imaging before return to play. However, medical assessment including history and physical examination with consideration of resting electrocardiography and troponin can be considered in the athlete manifesting new active cardiac symptoms or a marked reduction in fitness. If concerning abnormalities are encountered at the initial medical assessment, then referral to a cardiologist who cares for athletes is recommended.Microglial cells interact with all components of the central nervous system (CNS) and are increasingly recognized to play essential roles during brain development, homeostasis and disease pathologies. Functions of microglia include maintaining tissue integrity, clearing cellular debris and dead neurons through the process of phagocytosis, and providing tissue repair by releasing anti-inflammatory cytokines and neurotrophic factors. Changes of microglial ionic homeostasis (Na+, Ca2+, K+, H+, Cl-) are important for microglial activation, including proliferation, migration, cytokine release and reactive oxygen species production, etc. These are mediated by ion channels and ion transporters in microglial cells. Here, we review the current knowledge about the role of major microglial ion channels and transporters, including several types of Ca2+ channels (store-operated Ca2+ entry (SOCE) channels, transient receptor potential (TRP) channels and voltage-gated Ca2+ channels (VGCCs)) and Na+ channels (voltage-gated Na+ channels (Nav) and acid-sensing ion channels (ASICs)), K+ channels (inward rectifier K+ channels (Kir), voltage-gated K+ channels (KV) and calcium-activated K+ channels (KCa)), proton channels (voltage-gated proton channel (Hv1)), and Cl- channels (volume (or swelling)-regulated Cl- channels (VRCCs) and chloride intracellular channels (CLICs)). In addition, ion transporter proteins such as Na+/Ca2+ exchanger (NCX), Na+-K+-Cl- cotransporter (NKCC1), and Na+/H+ exchanger (NHE1) are also involved in microglial function in physiology and brain diseases. We discussed microglial activation and neuroinflammation in relation to the ion channel/transporter stimulation under brain disease conditions and therapeutic aspects of targeting microglial ion channels/transporters for neurodegenerative disease, ischemic stroke, traumatic brain injury and neuropathic pain.Intracerebral hemorrhage (ICH) is a major public health problem characterized by cerebral bleeding. Despite recent advances in preclinical studies, there is no effective treatment for ICH making it the deadliest subtype of stroke. The lack of effective treatment options partly attributes to the complexity as well as poorly defined pathophysiology of ICH. The emerging evidence indicates the potential of targeting secondary brain damage and hematoma resolution for improving neurological outcomes after ICH. Herein, we provide an overview of our understanding of the functional roles of activated microglia and brain-infiltrating monocyte-derived macrophages in brain injury and repair after ICH. The clinical and preclinical aspects that we discuss in this manuscript are related to ICH that occurs in adults, but not in infants. Also, we attempt to identify the knowledge gap in the field for future functional studies given the potential of targeting microglia and brain-infiltrating macrophages for therapeutic intervention after ICH.