Human morbidity

About: Human morbidity is a research topic. Over the lifetime, 802 publications have been published within this topic receiving 31604 citations.

Hidden Killers: Human Fungal Infections

Abstract: Although fungal infections contribute substantially to human morbidity and mortality, the impact of these diseases on human health is not widely appreciated. Moreover, despite the urgent need for efficient diagnostic tests and safe and effective new drugs and vaccines, research into the pathophysiology of human fungal infections lags behind that of diseases caused by other pathogens. In this Review, we highlight the importance of fungi as human pathogens and discuss the challenges we face in combating the devastating invasive infections caused by these microorganisms, in particular in immunocompromised individuals.

Clearing the air: a review of the effects of particulate matter air pollution on human health.

Abstract: The World Health Organization estimates that particulate matter (PM) air pollution contributes to approximately 800,000 premature deaths each year, ranking it the 13th leading cause of mortality worldwide. However, many studies show that the relationship is deeper and far more complicated than originally thought. PM is a portion of air pollution that is made up of extremely small particles and liquid droplets containing acids, organic chemicals, metals, and soil or dust particles. PM is categorized by size and continues to be the fraction of air pollution that is most reliably associated with human disease. PM is thought to contribute to cardiovascular and cerebrovascular disease by the mechanisms of systemic inflammation, direct and indirect coagulation activation, and direct translocation into systemic circulation. The data demonstrating PM's effect on the cardiovascular system are strong. Populations subjected to long-term exposure to PM have a significantly higher cardiovascular incident and mortality rate. Short-term acute exposures subtly increase the rate of cardiovascular events within days of a pollution spike. The data are not as strong for PM's effects on cerebrovascular disease, though some data and similar mechanisms suggest a lesser result with smaller amplitude. Respiratory diseases are also exacerbated by exposure to PM. PM causes respiratory morbidity and mortality by creating oxidative stress and inflammation that leads to pulmonary anatomic and physiologic remodeling. The literature shows PM causes worsening respiratory symptoms, more frequent medication use, decreased lung function, recurrent health care utilization, and increased mortality. PM exposure has been shown to have a small but significant adverse effect on cardiovascular, respiratory, and to a lesser extent, cerebrovascular disease. These consistent results are shown by multiple studies with varying populations, protocols, and regions. The data demonstrate a dose-dependent relationship between PM and human disease, and that removal from a PM-rich environment decreases the prevalence of these diseases. While further study is needed to elucidate the effects of composition, chemistry, and the PM effect on susceptible populations, the preponderance of data shows that PM exposure causes a small but significant increase in human morbidity and mortality. Most sources agree on certain “common sense” recommendations, although there are lonely limited data to support them. Indoor PM exposure can be reduced by the usage of air conditioning and particulate filters, decreasing indoor combustion for heating and cooking, and smoking cessation. Susceptible populations, such as the elderly or asthmatics, may benefit from limiting their outdoor activity during peak traffic periods or poor air quality days. These simple changes may benefit individual patients in both short-term symptomatic control and long-term cardiovascular and respiratory complications.

Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure.

Abstract: Cardiovascular disease is the leading cause of human morbidity and mortality. Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy associated with heart failure. Here, we report that cardiac-specific knockout of Dicer, a gene encoding a RNase III endonuclease essential for microRNA (miRNA) processing, leads to rapidly progressive DCM, heart failure, and postnatal lethality. Dicer mutant mice show misexpression of cardiac contractile proteins and profound sarcomere disarray. Functional analyses indicate significantly reduced heart rates and decreased fractional shortening of Dicer mutant hearts. Consistent with the role of Dicer in animal hearts, Dicer expression was decreased in end-stage human DCM and failing hearts and, most importantly, a significant increase of Dicer expression was observed in those hearts after left ventricle assist devices were inserted to improve cardiac function. Together, our studies demonstrate essential roles for Dicer in cardiac contraction and indicate that miRNAs play critical roles in normal cardiac function and under pathological conditions.

MicroRNAs Add a New Dimension to Cardiovascular Disease

Abstract: Cardiovascular disease is the predominant cause of human morbidity and mortality in developed countries. Thus, extraordinary effort has been devoted to determining the molecular and pathophysiological characteristics of the diseased heart and vasculature with the goal of developing novel diagnostic and therapeutic strategies to combat cardiovascular disease. The collective work of multiple research groups has uncovered a complex transcriptional and posttranscriptional regulatory circuit, the integrity of which is essential for the maintenance of cardiac homeostasis. Mutations in or aberrant expression of various transcriptional and posttranscriptional regulators have now been correlated with human cardiac disease, and pharmacological modulation of the activity of these target genes is a major focus of ongoing research. Recently, a novel class of small noncoding RNAs, called microRNAs (miRNAs), was identified as important transcriptional and posttranscriptional inhibitors of gene expression thought to “fine tune” the translational output of target messenger RNAs (mRNAs).1,2 miRNAs are implicated in the pathogenesis of various cardiovascular diseases and have become an intriguing target for therapeutic intervention. This review focuses on the basic biology and mechanism of action of miRNAs specifically pertaining to cardiovascular disorders and addresses the potential for miRNAs to be targeted therapeutically in the treatment of cardiovascular disease. miRNAs originate from longer precursor RNAs called primary miRNAs that are regulated by conventional transcription factors and transcribed by RNA polymerase II. Primary miRNAs are hundreds to thousands of nucleotides long and are processed in the nucleus into an ≈70- to 100-nucleotide hairpin-shaped precursor miRNA by the RNase III enzyme Drosha and the double-stranded RNA binding protein DGCR8. The precursor miRNA is then transported into the cytoplasm by the nuclear export factor exportin 5 and further processed into an ≈19- to 25-nucleotide double-stranded RNA by the RNaseIII enzyme Dicer. This duplex miRNA is then incorporated into the RNA-induced silencing complex. One …

Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species

Abstract: Regulated production of reactive oxygen species (ROS)/reactive nitrogen species (RNS) adequately balanced by antioxidant systems is a prerequisite for the participation of these active substances in physiological processes, including insulin action. Yet, increasing evidence implicates ROS and RNS as negative regulators of insulin signaling, rendering them putative mediators in the development of insulin resistance, a common endocrine abnormality that accompanies obesity and is a risk factor of type 2 diabetes. This review deals with this dual, seemingly contradictory, function of ROS and RNS in regulating insulin action: the major processes for ROS and RNS generation and detoxification are presented, and a critical review of the evidence that they participate in the positive and negative regulation of insulin action is provided. The cellular and molecular mechanisms by which ROS and RNS are thought to participate in normal insulin action and in the induction of insulin resistance are then described. Finally, we explore the potential usefulness and the challenges in modulating the oxidant-antioxidant balance as a potentially promising, but currently disappointing, means of improving insulin action in insulin resistance-associated conditions, leading causes of human morbidity and mortality of our era.