Medvedev expressed dismay at President Barack Obama's speech before the UN General Assembly in which he labeled Russia a key threat, second only to the deadly Ebola virus and ahead of the terrorist threat posed by Islamic State.
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"I don't want to dignify it with a response. It's sad, it's like some kind of mental aberration. We need to come back to a normal position, and only after that we can elaborate on how we are going to elaborate our positions in the future," he said.
He said the country hadn't closed its doors to anyone however.
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A recent pullback of Russian troops from the Ukraine border was not a signal to the U.S., he said, but an internal decision of the Russian federation.
"Real life is as follows: we are deeply concerned about the events in Ukraine. We would like the civil war unleashed by the coup earlier this year to end and Ukraine to return to calm and stability," the Russian prime minister said.
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He stressed that Ukraine could make "any choice," whether it wants to join the EU an another political union.
"Our current goal is to help restore peace in Ukraine," he said, adding that that could only be achieved by negotiations by central and eastern Ukraine.
Russia has been heavily criticized for its perceived military support of separatist rebels in eastern Ukraine. It denies such charges.
The crisis came to a head when what are believed to be Russian-supplied rebels shot down Malaysia Airlines Flight MH17 in July, killing all 298 people on the plane.