Project description:Upper respiratory tract infections ("common cold") are the most common acute illnesses in elite athletes. Numerous studies on exercise immunology have proposed that intense exercise may increase susceptibility to respiratory infections. Virological data to support that view are sparse, and several fundamental questions remain. Immunity to respiratory viral infections is highly complex, and there is a lack of evidence that minor short- or long-term alterations in immunity in elite athletes have clinical implications. The degree to which athletes are infected by respiratory viruses is unclear. During major sport events, athletes are at an increased risk of symptomatic infections caused by the same viruses as those in the general population. The symptoms are usually mild and self-limiting. It is anecdotally known that athletes commonly exercise and compete while having a respiratory viral infection; there are no virological studies to suggest that such activity would affect either the illness or the performance. The risk of myocarditis exists. Which simple mitigation procedures are crucial for effective control of seasonal respiratory viral infections is not known.
Project description:Monogenic autoinflammatory diseases (mAIDs) are inherited errors of innate immunity characterized by systemic inflammation recurring with variable frequency and involving the skin, serosal membranes, synovial membranes, joints, the gastrointestinal tube, and/or the central nervous system, with reactive amyloidosis as a potential severe long-term consequence. Although individually uncommon, all mAIDs set up an emerging chapter of internal medicine: recent findings have modified our knowledge regarding mAID pathophysiology and clarified that protean inflammatory symptoms can be variably associated with periodic fevers, depicting multiple specific conditions which usually start in childhood, such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, cryopyrin-associated periodic syndrome, and mevalonate kinase deficiency. There are no evidence-based studies to establish which potential genotype analysis is the most appropriate in adult patients with clinical phenotypes suggestive of mAIDs. This review discusses genetic and clinical hints for an ideal diagnostic approach to mAIDs in adult patients, as their early identification is essential to prompt effective treatment and improve quality of life, and also highlights the most recent developments in the diagnostic work-up for the most frequent hereditary periodic febrile syndromes worldwide.
Project description:BackgroundToll-like receptors (TLRs) are one of the first pattern recognition receptors (PRRs) found in the innate immune system. The TLR family has 12 members (TLR1-TLR9, TLR11-TLR13) in mice and 10 members (TLR1-TLR10) in humans, with TLR10 being the latest identified.SummaryConsiderable research has been performed on TLRs, however, TLR10 is known as an orphan receptor for the lack of information on its signalling, role, and ligands. Even though there are recent studies pointing towards the potential TLR10 ligands, its function and signalling pathway are yet to be determined.Key messagesThis review gives an insight into recent findings on TLR10 pro- and anti-inflammatory properties, with the goal of outlining existing results and indicating future research topics on this receptor.
Project description:Cardiovascular (CV) complications represent the first non-graft-related cause of death and the third overall cause of death among patients undergoing liver transplantation (LT). History of coronary artery disease is related to increased CV mortality following LT. Although it is of paramount importance to stratify CV risk in pre-LT patients, there is no consensus regarding the choice of the optimal non-invasive cardiac imaging test. Algorithms proposed by scientific associations include non-traditional risk factors, which are associated with increased cardiac risk profiles. Thus, an individualized pre-LT evaluation protocol should be followed. As the average age of patients undergoing LT and the number of candidates continue to rise, the "3 W" questions still remain unanswered, Who, Which and When? Who should be screened for coronary artery disease (CAD), which screening modality should be used and when should the asymptomatic waitlisted patients repeat cardiac evaluation? Prospective studies with large sample sizes are warranted to define an algorithm that can provide better risk stratification and more reliable survival prediction.
Project description:The term asthma-COPD overlap (ACO) has been used to identify a heterogeneous condition in which patients present with airflow limitation that is not completely reversible and clinical and inflammatory features of both asthma and chronic obstructive pulmonary disease (COPD). ACO diagnosis may be difficult in clinical practice, while controversy still exists regarding its definition, pathophysiology, and impact. Patients with ACO experience a greater disease burden compared to patients with asthma or COPD alone, but in contrast they show better response to inhaled corticosteroid treatment than other COPD phenotypes. Current management recommendations focus on defining specific and measurable treatable clinical traits, according to disease phenotypes and underlying biological mechanisms for every single patient. In this publication, we review the current knowledge on definition, pathophysiology, clinical characteristics, and management options of ACO.
Project description:Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine that is involved in various innate and adaptive immune processes related to infection, inflammation, and autoimmunity. Therefore, it is described as a key mediator of autoinflammatory diseases associated with the development of macrophage activation syndrome (MAS), including systemic juvenile idiopathic arthritis and adult-onset Still's disease. This review focuses on the role of IL-18 in inflammatory responses, placing emphasis on autoinflammatory diseases associated with chronic excess of serum IL-18, which correlate with clinical and biological signs of the disease. Therefore, it is useful for the diagnosis and monitoring of disease activity. Researchers are currently investigating IL-18's role as a therapeutic target for the treatment of inflammatory diseases. The inhibition of IL-18 signaling through recombinant human IL-18BP (IL-18 binding protein) seems to be an effective therapeutic strategy, though further studies are necessary to clarify its importance as a therapeutic target.
Project description:Monogenic autoinflammatory disorders are a group of conditions defined by systemic or localized inflammation without identifiable causes, such as infection. In contrast to classical primary immunodeficiencies that manifest with impaired immune responses, these disorders are due to defects in genes that regulate innate immunity leading to constitutive activation of pro-inflammatory signaling. Through studying patients with rare autoinflammatory conditions, novel mechanisms of inflammation have been identified that bare on our understanding not only of basic signaling in inflammatory cells, but also of the pathogenesis of more common inflammatory diseases and have guided treatment modalities. Autoinflammation has further been implicated as an important component of cardiovascular, neurodegenerative, and metabolic syndromes. In this review, we will focus on a subset of inherited enzymatic deficiencies that lead to constitutive inflammation, and how these rare diseases have provided insights into diverse areas of cell biology not restricted to immune cells. In this way, Mendelian disorders of the innate immune system, and in particular loss of catalytic activity of enzymes in distinct pathways, have expanded our understanding of the interplay between many seemingly disparate cellular processes. We also explore the overlap between autoinflammation, autoimmunity, and immunodeficiency, which has been increasingly recognized in patients with dysregulated immune responses.
Project description:BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) represents a current threat to the Arabian Peninsula, and potential pandemic disease. As of June 3, 2014, MERS CoV has reportedly infected 688 people and killed 282. We briefly summarize the state of the outbreak, and highlight unanswered questions and various explanations for the observed epidemiology. FINDINGS: The continuing but infrequent cases of MERS-CoV reported over the past two years have been puzzling and difficult to explain. The epidemiology of MERS-CoV, with many sporadic cases and a few hospital outbreaks, yet no sustained epidemic, suggests a low reproductive number. Furthermore, a clear source of infection to humans remains unknown. Also puzzling is the fact that MERS-CoV has been present in Saudi Arabia over several mass gatherings, including the 2012 and 2013 Hajj and Umrah pilgrimages, which predispose to epidemics, without an epidemic arising. CONCLUSIONS: The observed epidemiology of MERS-CoV is quite distinct and does not clearly fit either a sporadic or epidemic pattern. Possible explanations of the unusual features of the epidemiology of MERS-CoV include sporadic ongoing infections from a non-human source; human to human transmission with a large proportion of undetected cases; or a combination of both. The virus has been identified in camels; however the mode of transmission of the virus to humans remains unknown, and many cases have no history of animal contact. In order to gain a better understanding of the epidemiology of MERS CoV, further investigation is warranted.