Reporting Peripheral Artery Disease in Claudicants: Lessons Learned From the TASC-Ability Study.

BACKGROUND: The Trans-Atlantic Inter-Society Consensus Document (TASC II) aims to comprehensively describe the case scenarios of aortoiliac and femoropopliteal lesions to suggest an endovascular or a surgical approach. Over time, it has become a guide for describing the gravity of arterial lesions. PURPOSE: To assess the revised TASC II system for classifying arterial lesions in a large database of patients presenting with claudication. MATERIALS AND METHODS: This study was a retrospective review of the arteriograms of patients with intermittent claudication. Aortoiliac and femoropopliteal lesions were classified according to the TASC II. When no consensus was reached, the lesion was rated as unTASCable. RESULTS: In total, 1454 patients were included (male: 62.1%, 66.8±9.3 years). There were 39% aortoiliac lesions (n=960/2462) and 61% femoropopliteal lesions (n=1502/2462); 33.6% of the patients (n=489/1454) were associated with aortoiliac and femoropopliteal lesions. In addition, 20% of the lesions (n=493/2462) were unTASCable, and 26.7% of the patients (n=388/1454) had at least 1 unTASCable lesion. There were 4 categories of unTASCable lesions: (1) association with a common femoral artery lesion in 53.1% (n=262/493); (2) iliac artery lesions in 23.1% (n=114/493); (3) femoropopliteal lesions whose lengths did not fit into any category in 16.6% (n=82/493); and (4) association with an aortic lesion in 7.1% (n=35/493). The interobserver agreement was 0.97 for anatomically describing the infrarenal arterial tree and 0.85 for TASCing, with the lesions lowering to 0.69 for aortoiliac lesions. CONCLUSION: Using the revised TASC II case scenario, 26.7% of the patients had at least 1 unTASCable lesion. Reporting peripheral artery disease using a comprehensive anatomical description of the infrarenal arterial tree showed better interobserver reproducibility.

Pan-retroviral Nucleocapsid-Mediated Phase Separation Regulates Genomic RNA Positioning and Trafficking.

The duality of liquid-liquid phase separation (LLPS) of cellular components into membraneless organelles defines the nucleation of both normal and disease processes including stress granule (SG) assembly. From mounting evidence of LLPS utility by viruses, we discover that HIV-1 nucleocapsid (NC) protein condenses into zinc-finger (ZnF)-dependent LLPSs that are dynamically influenced by cytosolic factors. ZnF-dependent and Zinc (Zn2+)-chelation-sensitive NC-LLPS are formed in live cells. NC-Zn2+ ejection reverses the HIV-1 blockade on SG assembly, inhibits NC-SG assembly, disrupts NC/Gag-genomic RNA (vRNA) ribonucleoprotein complexes, and causes nuclear sequestration of NC and the vRNA, inhibiting Gag expression and virus release. NC ZnF mutagenesis eliminates the HIV-1 blockade of SG assembly and repositions vRNA to SGs. We find that NC-mediated, Zn2+-coordinated phase separation is conserved among diverse retrovirus subfamilies, illustrating that this exquisitely evolved Zn2+-dependent feature of virus replication represents a critical target for pan-antiretroviral therapies.