Octinoxate Instead, we used the E-to-Ea ratio to reflect the LV filling pressure. However, Geske reported that there was only a modest correlation between the estimated LV filling pressure with the use of the E-to-Ea ratio and the directly measured pressure in HCM patients. The small, medium, and largesegments encode the nucleocapsidprotein, 2 glycoproteins, and an RNA-dependent RNA polymerase, respectively. N interacts with host mRNA and viral RNA during viral replication. Gn and Gc oligomerize to form spikes on the virus particle, mediating receptor binding and fusion with target cells. The L protein is responsible for replicating and transcribing the viral genome. ANDV infection in humans occurs by exposure to excreta from the persistently-infected rodent reservoir. The disease is characterized initially by fever, muscle aches, and headaches, followed by pulmonary edema due to vascular leakage. Patients with severe disease quickly develop respiratory failure or shock, often leading to death. Levels of ANDV RNA peak at the time of pulmonary edema, and viremia levels correlate with HPS severity. Currently, no vaccines or antiviral drugs are approved to prevent or to treat HPS.Attempts to treat HPS with intravenous ribavirin have been ineffective after hospitalization, indicating that the final clinical stages of HPS progress too rapidly for ribavirin to exert an antiviral effect. However, no firm conclusions can be drawn from these studies given the low number of patients enrolled. RNA interferenceis a post-transcriptional, sequence-specific RNA degradation process observed in eukaryotic cells, and 
is considered a defense mechanism against viral infection. Upon recognizing exogenous double-stranded RNA, the cytosolic ribonuclease Dicer cleaves it into small interfering RNAs21�C25 nt in length. These siRNAs are incorporated into the RNA-induced silencing complex, in which siRNAs directly bind to complementary mRNA sequences to induce their cleavage, consequently silencing the expression of the targeted gene. The major advantage of siRNA treatment is its target specificity. It has been shown that RNAi targeting viral genes inhibits viral replication in vitro and has been explored as a strategy to combat viral infection caused by, e.g., HIV-1, poliovirus, nairovirus, and Lassa virus. RNAi-based therapy effectively reduces viral loads and increases survival rates in humans and animals infected with a number of other viruses. Here, we investigate the potential of using siRNA against ANDV infection. Our data suggest that siRNAs targeting the ANDV genome can efficiently lower virus titers, thus showing promise as potential in vivo therapeutic agents against HPS. To determine whether siRNA has potential as a therapeutic agent against ANDV, we tested pools of siRNAs targeting the ANDV genome. These pools were tested in vitro in both continuous and primary cell lines. The siS pool Butylhydroxyanisole targets the virus S segment, which encodes the virus N protein. Treatment with this siRNA pool very efficiently reduced virus protein levels, a result consistent with previous findings in other bunyaviruses. The N mRNA can be detected as early as 2 h post ANDV infection, and is the first viral RNA detected during infection. The N protein has several important roles in viral replication, as it encapsidates and protects viral RNA, and participates in initiating viral transcription and translation by binding cellular 59 mRNA caps.