F1000 Medicine Reports

Telomeres and telomere repair are basic molecular features of cells possessing linear DNA chromosomes and defects in them result in various diseases. This review examines recent advances in understanding these diseases, particularly at a molecular level, and in relating telomere dysfunction to clinical diseases. We also discuss the potential role of telomere elongation as a therapy in diseases, and more controversially, the prevention/reversal of aging.

Helicobacter pylori infects about 50% of the world's population and inevitably results in the development of gastritis. Of those infected, about 10% develop peptic ulcer disease and roughly 1% develop gastric cancer. Conversely, some take the view that H. pylori infection provides some protection against gastro-esophageal reflux disease and possibly asthma. This review aims to explore the case for and against eradication of the bacterium using a "test and treat" approach amongst the general population.

Schizophrenia is one of the major and potentially severe mental illnesses. Even with best practices, there are limitations to the effectiveness of treatments that include medications for this disorder. Relapse rates are high and often those with the illness remain symptomatic and functionally impaired. All the evidence suggests that individuals with schizophrenia do best with a combination of pharmacological and psychosocial intervention. One psychosocial treatment that has received much attention is cognitive behaviour therapy (CBT)...

Protein kinases are fundamental components of diverse signaling pathways, including immune cells. Their essential functions have made them effective therapeutic targets. Initially, the expectation was that a high degree of selectivity would be critical; however, with time, the use of "multikinase" inhibitors has expanded. Moreover, the spectrum of diseases in which kinase inhibitors are used has also expanded to include not only malignancies but also immune-mediated diseases. At present, thirteen kinase inhibitors have been approved in the United States, all for oncologic indications...

Methicillin-resistant S. aureus (MRSA) has emerged as the most common hospital-acquired pathogen and is associated with increased morbidity and mortality compared with other strains. Vancomycin has been the cornerstone of treatment of patients with serious MRSA infections for some decades and while more than 99% of clinical S. aureus isolates remain susceptible to vancomycin, we are beginning to see strains of MRSA with reduced susceptibility. This review discusses this phenomenon, the predictors of infection with such forms of MRSA, and current and future management options...

Endoscopic imaging is in part responsible for the recent drop in deaths from gastrointestinal cancers and also for detecting pre-cancerous and non-cancerous conditions and allowing them to be treated effectively, although techniques are far from perfect. Endoscopic imaging has evolved considerably from fiber optic systems 50 years ago to high resolution and high definition systems used at present. Moreover, image enhancement using filters and processors has led to the technique of 'electronic chromoendoscopy' to visualize mucosal blood vessels and surface pit patterns clearly...

Acute Respiratory Distress Syndrome (ARDS) constitutes a spectrum of severe acute respiratory failure in response to a variety of inciting stimuli that is the leading cause of death and disability in the critically ill. Despite decades of research, there are no therapies for ARDS, and management remains supportive. A growing understanding of the complexity of the pathophysiology of ARDS, coupled with advances in stem cell biology, has lead to a renewed interest in the therapeutic potential of mesenchymal stem cells for ARDS...

Vascular endothelial growth factor (VEGF) plays a central role in angiogenesis. A number of studies have focused on its role in health and disease and discussed the possibility of VEGF as both a therapeutic tool and target based on its specific actions on vascular proliferation and cell survival. On one side, anti-VEGF therapies are at the fore-front of treatment of many solid tumors, but blockade of VEGF carries collateral effects such as hypertension and renal damage largely due to abnormalities in the microvasculature...

Ichthyosis vulgaris is a common genetic skin disorder characterized by dry, scaly skin. About 1% of the European population have the full presentation of ichthyosis vulgaris; up to 10% have a milder, subclinical form. Atopic eczema is the most common, inflammatory skin condition, affecting 20% of children. It is often accompanied by a number of other allergies, including atopic asthma. Atopic eczema is a complex trait, where predisposing genes in combination with environmental stimuli produce the disease. Recently, we reported the first loss-of-function genetic mutations in the filaggrin gene as the cause of ichthyosis vulgaris...

Mounting evidence shows that inflammation plays a critical role in causing Alzheimer's disease. Over the last few decades we have gone from a situation where inflammation was generally believed to have no role in the disease to the current picture where chronic activation of IL-1 inflammation has been shown to account for many of the hallmarks of the disease. This review is a personal account of the quest to prove that inflammation plays a critical role in causing Alzheimer's disease.

It has been suggested that, at least in some forms of cancer, a sub-population of slow-cycling, therapy-resistant cancer stem cells exists that has the ability to reconstitute the tumor in its entirety. If true, this model implies that conventional therapies based on targeting highly cycling cells within the tumor will leave the slow-cycling stem cell population intact, giving them the opportunity to reinitiate the tumor at a later date. This review discusses the evidence for this model and the likely implications for cancer treatment...

Ovarian cancer has a disproportionately high mortality rate because patients typically present with late-stage metastatic disease. The vast majority of these deaths are from high-grade serous carcinoma. Recent studies indicate that many of these tumors arise from the fallopian tube and subsequently metastasize to the ovary. This may explain why such tumors have not been detected at early stage as detection efforts have been focused purely on the ovary. In keeping with this leap in understanding other advances such as the development of ex-vivo models and immortalization of human fallopian tube epithelial cells, and the use of integrated genomic analyses to identify hundreds of novel candidate oncogenes and tumor suppressors potentially involved in tumorigenesis now engender hope that we can begin to truly define the differences in pathogenesis between fallopian tube and ovarian-derived tumors...

For many years treatment for advanced or metastatic non-small cell lung cancer (NSCLC) has employed chemotherapy regimens for patient care, with limited effect. Five-year survival rates for these patients are not encouraging. However, for a subgroup of these patients, there have been radical changes over recent years. Our understanding of the basic pathology behind NSCLC at the molecular level has offered up a host of new molecularly targeted therapies, which are revolutionizing this area of cancer care. Results from recent clinical trials provide hope for NSCLC patients harboring oncogenic translocations involving the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase...

Despite intensive efforts to eradicate it, addiction to both legal and illicit drugs continues to be a major worldwide medical and social problem. Anti-addiction vaccines can produce the antibodies to block the effects of these drugs on the brain, and have great potential to ameliorate the morbidity and mortality associated with illicit drug intoxications. This review provides a current overview of anti-addiction vaccines that are under clinical trial and pre-clinical research evaluation. It also outlines the development challenges, ethical concerns, and likely future intervention for anti-addiction vaccines...

Resolvins are a group of molecules derived from omega-3 fatty acids. They are part of a biochemical program that allows inflamed tissues to return to homeostasis once the need for the inflammatory response is over. Resolvins act in very low dose ranges in vitro and in vivo. New data suggest that they might have the potential to become very potent analgesic drugs in inflammatory pain.

Technological advances, while providing many benefits, often create circumstances that differ from the conditions in which we evolved. With the wide-spread adoption of electrical lighting during the 20(th) century, humans became exposed to bright and unnatural light at night for the first time in their evolutionary history. Electrical lighting has led to the wide-scale practice of 24-hour shift-work and has meant that what were once just "daytime" activities now run throughout the night; in many ways Western society now functions on a 24-hour schedule...

Gene therapy is a promising new therapeutic strategy that has been explored in a wide variety of diseases, ranging from cancer to hemophilia, and ocular disorders to autoimmune diseases, among others. Proof of concept of gene transfer approaches has been shown in over 100 studies of animal models of disease, although only a few are under development for clinical application. The US Food and Drug Administration and the European Medicines Agency have not approved any viral human gene therapy products for sale so far, but the amount of gene-related research and development occurring in the United States and Europe continues to grow at a fast rate...

Antigenic variability of immunodominant antigens is a common mechanism used by pathogens to escape the immune response. Frequently, the proposed solution is a universal vaccine based on conserved antigens present on all strains of the pathogen. Indeed, a lot of progress has been made in the development of vaccines that induce broad immune responses. However, truly universal vaccines are not easy to produce and still face many challenges, mostly because in those pathogens that use antigenic variability to escape the immune response, conserved antigens have been selected by evolution to be poorly immunogenic...

The exocrine pancreas synthesizes all the enzymes needed for intestinal breakdown of proteins, fats, and carbohydrates in our diet. Unfortunately, the proteases needed for the digestion of the meat we eat can, if inappropriately activated inside the acinar cells, also digest the pancreas itself as well as the surrounding tissues, which is what happens in the sometimes fatal human disease acute pancreatitis. The disease is currently untreatable, but significant progress has recently been made in understanding the fundamental processes initiating the pathological changes underlying pancreatic autodigestion...

Invasive fungal infections are infections of importance and are increasing in incidence in immunocompromised hosts such as patients who have had hematopoietic stem cell and solid organ transplants. Despite our expanded antifungal armamentarium, these infections cause considerable morbidity and mortality. Indeed, certain trends have emerged in these invasive fungal infections: a rise in the incidence of invasive mold infections, an increase in the non-albicans strains of Candida spp. causing invasive disease and, finally, the emergence of less susceptible fungal strains that are resistant to the broader-spectrum antifungal agents due to overutilization of these agents...