Mayo Clinic

About: Mayo Clinic is a healthcare organization based out in Rochester, Minnesota, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 63387 authors who have published 169578 publications receiving 8114006 citations.

Osteoporosis in Men

Abstract: With the aging of the population, there is a growing recognition that osteoporosis and fractures in men are a significant public health problem, and both hip and vertebral fractures are associated with increased morbidity and mortality in men. Osteoporosis in men is a heterogeneous clinical entity: whereas most men experience bone loss with aging, some men develop osteoporosis at a relatively young age, often for unexplained reasons (idiopathic osteoporosis). Declining sex steroid levels and other hormonal changes likely contribute to age-related bone loss, as do impairments in osteoblast number and/or activity. Secondary causes of osteoporosis also play a significant role in pathogenesis. Although there is ongoing controversy regarding whether osteoporosis in men should be diagnosed based on female- or male-specific reference ranges (because some evidence indicates that the risk of fracture is similar in women and men for a given level of bone mineral density), a diagnosis of osteoporosis in men is generally made based on male-specific reference ranges. Treatment consists both of nonpharmacological (lifestyle factors, calcium and vitamin D supplementation) and pharmacological (most commonly bisphosphonates or PTH) approaches, with efficacy similar to that seen in women. Increasing awareness of osteoporosis in men among physicians and the lay public is critical for the prevention of fractures in our aging male population.

Exercise Hemodynamics Enhance Diagnosis of Early Heart Failure with Preserved Ejection Fraction

Abstract: Background—When advanced, heart failure with preserved ejection fraction (HFpEF) is readily apparent. However, diagnosis of earlier disease may be challenging because exertional dyspnea is not specific for heart failure, and biomarkers and hemodynamic indicators of volume overload may be absent at rest. Methods and Results—Patients with exertional dyspnea and ejection fraction >50% were referred for hemodynamic catheterization. Those with no significant coronary disease, normal brain natriuretic peptide assay, and normal resting hemodynamics (mean pulmonary artery pressure <25 mm Hg and pulmonary capillary wedge pressure [PCWP] <15 mm Hg) (n=55) underwent exercise study. The exercise PCWP was used to classify patients as having HFpEF (PCWP ≥25 mm Hg) (n=32) or noncardiac dyspnea (PCWP <25 mm Hg) (n=23). At rest, patients with HFpEF had higher resting pulmonary artery pressure and PCWP, although all values fell within normal limits. Exercise-induced elevation in PCWP in HFpEF was confirmed by greater incre...

Characterization of human plasma-derived exosomal RNAs by deep sequencing

Abstract: Exosomes, endosome-derived membrane microvesicles, contain specific RNA transcripts that are thought to be involved in cell-cell communication. These RNA transcripts have great potential as disease biomarkers. To characterize exosomal RNA profiles systemically, we performed RNA sequencing analysis using three human plasma samples and evaluated the efficacies of small RNA library preparation protocols from three manufacturers. In all we evaluated 14 libraries (7 replicates). From the 14 size-selected sequencing libraries, we obtained a total of 101.8 million raw single-end reads, an average of about 7.27 million reads per library. Sequence analysis showed that there was a diverse collection of the exosomal RNA species among which microRNAs (miRNAs) were the most abundant, making up over 42.32% of all raw reads and 76.20% of all mappable reads. At the current read depth, 593 miRNAs were detectable. The five most common miRNAs (miR-99a-5p, miR-128, miR-124-3p, miR-22-3p, and miR-99b-5p) collectively accounted for 48.99% of all mappable miRNA sequences. MiRNA target gene enrichment analysis suggested that the highly abundant miRNAs may play an important role in biological functions such as protein phosphorylation, RNA splicing, chromosomal abnormality, and angiogenesis. From the unknown RNA sequences, we predicted 185 potential miRNA candidates. Furthermore, we detected significant fractions of other RNA species including ribosomal RNA (9.16% of all mappable counts), long non-coding RNA (3.36%), piwi-interacting RNA (1.31%), transfer RNA (1.24%), small nuclear RNA (0.18%), and small nucleolar RNA (0.01%); fragments of coding sequence (1.36%), 5′ untranslated region (0.21%), and 3′ untranslated region (0.54%) were also present. In addition to the RNA composition of the libraries, we found that the three tested commercial kits generated a sufficient number of DNA fragments for sequencing but each had significant bias toward capturing specific RNAs. This study demonstrated that a wide variety of RNA species are embedded in the circulating vesicles. To our knowledge, this is the first report that applied deep sequencing to discover and characterize profiles of plasma-derived exosomal RNAs. Further characterization of these extracellular RNAs in diverse human populations will provide reference profiles and open new doors for the development of blood-based biomarkers for human diseases.

A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells.

Abstract: The variability in the prognosis of individuals with hepatocellular carcinoma (HCC) suggests that HCC may comprise several distinct biological phenotypes. These phenotypes may result from activation of different oncogenic pathways during tumorigenesis and/or from a different cell of origin. Here we address whether the transcriptional characteristics of HCC can provide insight into the cellular origin of the tumor. We integrated gene expression data from rat fetal hepatoblasts and adult hepatocytes with HCC from human and mouse models. Individuals with HCC who shared a gene expression pattern with fetal hepatoblasts had a poor prognosis. The gene expression program that distinguished this subtype from other types of HCC included markers of hepatic oval cells, suggesting that HCC of this subtype may arise from hepatic progenitor cells. Analyses of gene networks showed that activation of AP-1 transcription factors in this newly identified HCC subtype might have key roles in tumor development.