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.

Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment

Abstract: Half of patients with heart failure (HF) have a preserved left ventricular ejection fraction (HFpEF). Morbidity and mortality in HFpEF are similar to values observed in patients with HF and reduced EF, yet no effective treatment has been identified. While early research focused on the importance of diastolic dysfunction in the pathophysiology of HFpEF, recent studies have revealed that multiple non-diastolic abnormalities in cardiovascular function also contribute. Diagnosis of HFpEF is frequently challenging and relies upon careful clinical evaluation, echo-Doppler cardiography, and invasive haemodynamic assessment. In this review, the principal mechanisms, diagnostic approaches, and clinical trials are reviewed, along with a discussion of novel treatment strategies that are currently under investigation or hold promise for the future.

Thyroid Incidentalomas: Management Approaches to Nonpalpable Nodules Discovered Incidentally on Thyroid Imaging

Abstract: Background: The introduction of highly sensitive imaging techniques has made it possible to detect many nonpalpable nodules, or “incidentalomas,” in the thyroid. Discovery of these lesions raises c...

Secondary mutations as a mechanism of cisplatin resistance in BRCA2 -mutated cancers

Abstract: Ovarian carcinomas with mutations in the tumour suppressor BRCA2 are particularly sensitive to platinum compounds. However, such carcinomas ultimately develop cisplatin resistance. The mechanism of that resistance is largely unknown. Here we show that acquired resistance to cisplatin can be mediated by secondary intragenic mutations in BRCA2 that restore the wild-type BRCA2 reading frame. First, in a cisplatin-resistant BRCA2-mutated breast-cancer cell line, HCC1428, a secondary genetic change in BRCA2 rescued BRCA2 function. Second, cisplatin selection of a BRCA2-mutated pancreatic cancer cell line, Capan-1 (refs 3, 4), led to five different secondary mutations that restored the wild-type BRCA2 reading frame. All clones with secondary mutations were resistant both to cisplatin and to a poly(ADP-ribose) polymerase (PARP) inhibitor (AG14361). Finally, we evaluated recurrent cancers from patients whose primary BRCA2-mutated ovarian carcinomas were treated with cisplatin. The recurrent tumour that acquired cisplatin resistance had undergone reversion of its BRCA2 mutation. Our results suggest that secondary mutations that restore the wild-type BRCA2 reading frame may be a major clinical mediator of acquired resistance to platinum-based chemotherapy.

Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice

Abstract: We investigated synaptic communication and plasticity in hippocampal slices from mice overexpressing mutated 695-amino-acid human amyloid precursor protein (APP695SWE), which show behavioral and histopathological abnormalities simulating Alzheimer's disease. Although aged APP transgenic mice exhibit normal fast synaptic transmission and short term plasticity, they are severely impaired in in-vitro and in-vivo long-term potentiation (LTP) in both the CA1 and dentate gyrus regions of the hippocampus. The LTP deficit was correlated with impaired performance in a spatial working memory task in aged transgenics. These deficits are accompanied by minimal or no loss of presynaptic or postsynaptic elementary structural elements in the hippocampus, suggesting that impairments in functional synaptic plasticity may underlie some of the cognitive deficits in these mice and, possibly, in Alzheimer's patients.