Aventis Pasteur discovered a stockpile from the 1950s and donated it to the U.S. government.Stockpiles of newer vaccines must be repurchased periodically since they carry expiration dates. The United States had received 269 million doses of ACAM2000 and 28 million doses of MVA-BN by 2019, but only 100 million doses of ACAM2000 and 65,000 doses of MVA-BN were still available from the stockpile at the start of the 2022 monkeypox outbreak. First-generation vaccines have no specified expiration date and remain viable indefinitely in deep freeze. The U.S. stockpile of WetVax was manufactured in 1956–1957 and maintained since then at −4 °F (−20 °C), and it was still effective when tested in 2004. Replicating vaccines also remain effective even at 1:10 dilution, so a limited number of doses can be stretched to cover a much larger population. History
Variolation
The mortality of the severe form of smallpox – variola major – was very high without vaccination, up to 35% in some outbreaks. A method of inducing immunity known as inoculation, insufflation or "variolation" was practiced before the development of a modern vaccine and likely occurred in Africa and China well before the practice arrived in Europe. It may also have occurred in India, but this is disputed; other investigators contend the ancient Sanskrit medical texts of India do not describe these techniques. The first clear reference to smallpox inoculation was made by the Chinese author Wan Quan (1499–1582) in his Douzhen xinfa (痘疹心法) published in 1549.
Breast pain is the symptom of discomfort in the breast. Pain that involves both breasts and which occurs repeatedly before the menstrual period is generally not serious. Pain that involves only one part of a breast is more concerning. It is particularly concerning if a hard mass or nipple discharge is also present.Causes may be related to the menstrual cycle, birth control pills, hormone therapy, or psychiatric medication. Pain may also occur in those with large breasts, during menopause, and in early pregnancy. In about 2% of cases breast pain is related to breast cancer. Diagnosis involves examination, with medical imaging if only a specific part of the breast hurts.In more than 75% of people the pain resolves without any specific treatment. Otherwise treatments may include paracetamol or NSAIDs. A well fitting bra may also help. In those with severe pain tamoxifen or danazol may be used. About 70% of women have breast pain at some point in time. Breast pain is one of the most common breast symptoms, along with breast masses and nipple discharge. Causes
Cyclical breast pain is often associated with fibrocystic breast changes or duct ectasia and thought to be caused by changes of prolactin response to thyrotropin. Some degree of cyclical breast tenderness is normal in the menstrual cycle, and is usually associated with menstruation and/or premenstrual syndrome (PMS).Noncyclical breast pain has various causes and is harder to diagnose and frequently the root cause is outside the breast.