In those with 8 or fewer repeats, symptoms are more likely than in those with 9 - 10 repeats, leading to diagnosis regardless of an additional SMCHD1 mutation.The apparent frequency of FSHD1/FSHD2 cases in the 9 - 10 repeat range, combined with the FSHD2-like methylation pattern, suggest the 9 - 10 repeat size to be an overlap zone between FSHD1 and FSDH2. Pathophysiology
Molecular
As of 2020, there seems to be a consensus that aberrant expression of DUX4 in muscle is the cause of FSHD. DUX4 is expressed in extremely small amounts, detectable in 1 out of every 1000 immature muscle cells (myoblast), which appears to increase after myoblast maturation, in part because the cells fuse as they mature, and a single nucleus expressing DUX4 can provide DUX4 protein to neighboring nuclei from fused cells.It remains an area of active research how DUX4 protein causes muscle damage. DUX4 protein is a transcription factor that regulates many other genes. Some of these genes are involved in apoptosis, such as p53, p21, MYC, and β-catenin, and indeed it seems that DUX4 protein makes muscle cells more prone to apoptosis. Other DUX4 protein-regulated genes are involved in oxidative stress, and indeed it seems that DUX4 expression lowers muscle cell tolerance of oxidative stress. Variation in the ability of individual muscles to handle oxidative stress could partially explain the muscle involvement patterns of FSHD.
Just when he has recovered his well-being, he hears her misreading recipes for dinner the next night: "Marshmallowed meatballs," "medium salad snails," and "pouched (actually poached) oysters". He returns to the bathroom for more Alka-Seltzer. The catchphrase, Howie Cohen told the Los Angeles Times, was inspired when he ate too much of the food at a London commercial shoot because "I am a nice Jewish kid from the Bronx, so I ate everything," and when he told his wife "I cant believe I ate the whole thing", she said, "Theres your next Alka-Seltzer commercial. "A 1971 commercial featured another catch-phrase from Cohen (along with Bob Pasqualina), "Try it, youll like it!" It was remade with Kathy Griffin in 2006. In 1972, an actor (Milt Moss) spent the commercial moaning, "I cant believe I ate that who-o-o-o-o-ole thing," while his wife (Lynn Whinic) made sarcastic comments and finally advised him to take some Alka-Seltzer. In 2005, this ad was also remade, featuring Peter Boyle and Doris Roberts from the 1996–2005 TV sitcom Everybody Loves Raymond.Sammy Davis, Jr. recorded two versions of the "Plop Plop Fizz Fizz" jingle in 1978, one of which (the "big band" version) was featured on a television commercial. Both the big band and rock versions had additional lyrics (with at least one verse unique to each song) written by Tom Dawes, former lead singer of The Cyrkle who wrote the original jingle.