Plos One
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Randomized Controlled Trial Multicenter Study
Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy.
Mipomersen, an antisense oligonucleotide targeting apolipoprotein B synthesis, significantly reduces LDL-C and other atherogenic lipoproteins in familial hypercholesterolemia when added to ongoing maximally tolerated lipid-lowering therapy. Safety and efficacy of mipomersen in patients with severe hypercholesterolemia was evaluated. ⋯ Mipomersen significantly reduced LDL-C, apolipoprotein B, total cholesterol and non-HDL-cholesterol, and lipoprotein(a). Mounting evidence suggests it may be a potential pharmacologic option for lowering LDL-C in patients with severe hypercholesterolemia not adequately controlled using existing therapies. Future studies will explore alternative dosing schedules aimed at minimizing side effects.
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Both gastric and colorectal cancers (CRC) are the most frequently occurring malignancies worldwide with the overall survival of these patients remains unsatisfied. Identification of tumor suppressor genes (TSG) silenced by promoter CpG methylation uncovers mechanisms of tumorigenesis and identifies new epigenetic biomarkers for early cancer detection and prognosis assessment. Cystathionine-beta-synthase (CBS) functions in the folate metabolism pathway, which is intricately linked to methylation of genomic DNA. Dysregulation of DNA methylation contributes substantially to cancer development. ⋯ A novel finding from this study is that the folate metabolism enzyme CBS mRNA levels are frequently downregulated through CpG methylation of the CBS gene in gastric cancer and CRC, suggesting that CBS functions as a tumor suppressor gene. These findings warrant further study of CBS as an epigenetic biomarker for molecular diagnosis of gastrointestinal cancers.
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Randomized Controlled Trial
A pilot randomized, placebo controlled, double blind phase I trial of the novel SIRT1 activator SRT2104 in elderly volunteers.
SRT2104 has been developed as a selective small molecule activator of SIRT1, a NAD(+)-dependent deacetylase involved in the regulation of energy homeostasis and the modulation of various metabolic pathways, including glucose metabolism, oxidative stress and lipid metabolism. SIRT1 has been suggested as putative therapeutic target in multiple age-related diseases including type 2 diabetes and dyslipidemias. We report the first clinical trial of SRT2104 in elderly volunteers. ⋯ SRT2104 can be safely administered in elderly individuals and has biological effects in humans that are consistent with SIRT1 activation. The results of this study support further development of SRT2104 and may be useful in dose selection for future clinical trials in patients.
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Randomized Controlled Trial
Risk factors for vascular occlusive events and death due to bleeding in trauma patients; an analysis of the CRASH-2 cohort.
Vascular occlusive events can complicate recovery following trauma. We examined risk factors for venous and arterial vascular occlusive events in trauma patients and the extent to which the risk of vascular occlusive events varies with the severity of bleeding. ⋯ Patients with severe traumatic bleeding are at greatly increased risk of venous and arterial vascular occlusive events. Older age and blunt trauma are also risk factors for vascular occlusive events. Effective treatment of bleeding may reduce venous and arterial vascular occlusive complications in trauma patients.
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Research has shown that people with chronic pain have difficulty directing their attention away from pain. A mental strategy that incorporates focused attention and distraction has been found to modulate the perception of pain intensity. That strategy involves placing attention on the nociceptive stimulus felt and shifting attention to a self-generated sub-nociceptive image and rehearsing it. Event-related potential was used to study the possible processes associated with the focus-then-orient strategy. ⋯ Focus-and-orient attention across nociceptive and sub-nociceptive images appears to be related to response inhibition. Mental rehearsal of the sub-nociceptive images was found to modulate the perception of the nociceptive sensation felt prior to the imagery. Such modulation seems to be mediated by generating and maintaining sub-nociceptive images in working memory. Future studies should explore the mental processes associated with orienting attention for pain modulation among people with pathological pain and frontal lobe dysfunction.