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Cold sensitivity or cold intolerance is unusual discomfort felt by some people when in a cool environment. [ 1 ] Cold sensitivity may be a symptom of hypothyroidism , anemia , low body weight, iron deficiency , vitamin B 12 deficiency , fevers , fibromyalgia or vasoconstriction . [ 2 ]
Cold agglutinins, or cold autoantibodies, occur naturally in nearly all individuals. These natural cold autoantibodies occur at low titers, less than 1:64 measured at 4 °C, and have no activity at higher temperatures. Pathologic cold agglutinins occur at titers over 1:1000 and react at 28-31 °C and sometimes at 37 °C.
Secondary cold agglutinin syndrome occurs when autoantibodies bind to red blood cells, rendering them subject to attack by the complement system. [17] It is a result of an underlying condition potentially associated with either monoclonal cold-reacting autoantibodies or polyclonal cold-reacting autoantibodies [16] predominantly caused by infection or lymphoproliferative disorders. [16]
The ROMs of the game and its sequel were formerly offered by the owner Randel Reiss for free download. In 2021, however, the rights to both games were purchased by Piko Interactive, leding the download links for the ROMs to disappear from Technopop's website [121], but they are still available for free download on Zophar's Domain.
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Pernicious anemia is the most common cause of clinically evident vitamin B 12 deficiency worldwide. [14] Pernicious anemia due to autoimmune problems occurs in about one per 1000 people in the US. Among those over the age of 60, about 2% have the condition. [8] It more commonly affects people of northern European descent. [2]
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