No abstract

Platelets are best known as mediators of hemostasis and thrombosis; however, their inflammatory effector properties are increasingly recognized. Atherosclerosis, a chronic vascular inflammatory disease, represents the interplay between lipid deposition in the artery wall and unresolved inflammation. Here, we reveal that platelets induce monocyte migration and recruitment into atherosclerotic plaques, resulting in plaque platelet-macrophage aggregates. In Ldlr−/− mice fed a Western diet, platelet depletion decreased plaque size and necrotic area and attenuated macrophage accumulation. Platelets drive atherogenesis by skewing plaque macrophages to an inflammatory phenotype, increasing myeloid suppressor of cytokine signaling 3 (SOCS3) expression and reducing the Socs1:Socs3 ratio. Platelet-induced Socs3 expression regulates plaque macrophage reprogramming by promoting inflammatory cytokine production (Il6, Il1b, and Tnfa) and impairing phagocytic capacity, dysfunctions that contribute to unresolved inflammation and sustained plaque growth. Translating our data to humans with cardiovascular disease, we found that women with, versus without, myocardial infarction have up-regulation of SOCS3, lower SOCS1:SOCS3, and increased monocyte-platelet aggregate. A second cohort of patients with lower extremity atherosclerosis demonstrated that SOCS3 and the SOCS1:SOCS3 ratio correlated with platelet activity and inflammation. Collectively, these data provide a causative link between platelet-mediated myeloid inflammation and dysfunction, SOCS3, and cardiovascular disease. Our findings define an atherogenic role of platelets and highlight how, in the absence of thrombosis, platelets contribute to inflammation.

Oral cancer is one of the most commonly diagnosed malignancies worldwide. Its dismal five-year survival rate of ~50% has barely changed for decades. A better understanding of the molecular basis of tumorigenesis - with particular emphasis on disease initiation and progression - is needed to improve clinical outcomes, since this will facilitate the development of drugs and management strategies based on the specific genetic changes underpinning disease behaviors. MicroRNAs (miRNAs), a class of short non-coding RNAs that down-regulate gene expression, have been demonstrated to play essential roles in human cancers. miRNA deregulation has been observed in many tumor types and is implicated in oncogenic cell processes, including proliferation, survival, apoptosis, metastasis, and chemoresistance. In addition, miRNA alterations have been associated with specific clinical phenotypes such as disease progression or recurrence, development of metastases, and post-operative survival. Recent studies have explored the utility of miRNAs as diagnostic and prognostic tools and as potential therapeutic targets. Herein, we discuss miRNA biology and provide a summary of the key findings on the role of miRNAs in oral malignancies.

AIBG and TM acetabular defect reconstructions achieve good clinical outcome but there is greater success with TM in higher grades of acetabular deficiency regardless of prior infection.

Background Transpedal access is increasingly utilized for the treatment of peripheral artery disease (PAD). Femoral-popliteal artery chronic total occlusions (CTOs) are some of the most difficult lesion subsets that sometimes require the use of re-entry support devices during percutaneous intervention. Limited data is available on the use of re-entry devices when treating femoral-popliteal CTOs via transpedal access. The aim of this study was to demonstrate the feasibility of using the Outback® Elite re-entry device for the treatment of femoral-popliteal CTOs via the transpedal approach in an outpatient based lab setting. Methods Seventeen patients presented with femoral-popliteal CTOs in which treatment required the use of the Outback® Elite re-entry device. All procedures were performed in a single outpatient based lab. Patients were followed at 1 week and 1 month post-procedure, with lower extremity arterial duplex ultrasound assessment during the 1 month follow-up. Results The average patient age was 78 years-old, with 71% being males. Most patients presented with Rutherford class IV symptoms. Procedural success was achieved in all patients with no requirement to convert to femoral artery access in any of the cases. No immediate post-procedural complications nor at any time during follow-up were observed. Ultrasonography at 1 month follow-up showed patent intervention sites and access site vessels in all patients. Conclusion The use of the Outback® Elite re-entry device for the treatment of femoral-popliteal CTOs via transpedal access is a feasible option and may have potential benefits by avoiding risks associated with traditional femoral artery access.