XP unable to open files after ~2 hours

Interesting issue that's cropped up on my machine the last couple days, and I'm trying to narrow it down to software, malware, or memory.

After a couple hours up and running, nothing will open except folders. Anything else - program shortcuts, shortcuts from the start menu, anything - clocks for a second, then never opens. Can't even shut down - the shutdown/sleep/logoff dialogue comes up from the start menu, but clicking any of the buttons clocks for a second, then nothing.

Antivirus, Malwarebytes, Spybot, and AdAware all come up empty on scans, both in normal and safe mode.

Recent system changes include installing AdAware, a version update on Avast, and turning off MDM.exe in msconfig - subesquently turned back on as a test for the boot before I got online here; will see if it snags again.