The present invention provides, among other things, effective methods and compositions for delivering messenger RNA (mRNA) via rectal delivery. The present invention is, in part, based on unexpected observation that mRNA may be effectively delivered to the circulation, liver, kidney, colon and/or rectum via rectal delivery despite the barriers such as RNase and mucus layer.

The present invention provides, among other things, effective methods and compositions for delivering messenger RNA (mRNA) via rectal delivery. The present invention is, in part, based on unexpected observation that mRNA may be effectively delivered to the circulation, liver, kidney, colon and/or rectum via rectal delivery despite the barriers such as RNase and mucus layer.

A topical treatment for anorectal disorders with and without utilization of a contoured seat cushion with a temperature-adapted or electrical stimulation element that can provide hot or cold temperatures or electrical stimulation to the anorectal region.

Disclosed herein are compositions and methods for ovulation induction in females in need thereof. Current methods for inducing ovulation have unpleasant side effects and are expensive. The disclosed compositions and methods are safe, efficacious, and inexpensive. An exemplary method of inducing ovulation includes steps of monitoring ovarian follicle development and size during the follicular phase of the menstrual cycle; and administering to the subject a pharmaceutical composition including progesterone or ioidentical progesterone in an amount effective to increase the plasma concentration of progesterone to between about 0.1 ng/ml to about 1 ng/ml when the follicle reaches a size of at least 15 mm.

Disclosed herein are compositions and methods for ovulation induction in females in need thereof. Current methods for inducing ovulation have unpleasant side effects and are expensive. The disclosed compositions and methods are safe, efficacious, and inexpensive. An exemplary method of inducing ovulation includes steps of monitoring ovarian follicle development and size during the follicular phase of the menstrual cycle; and administering to the subject a pharmaceutical composition including progesterone or ioidentical progesterone in an amount effective to increase the plasma concentration of progesterone to between about 0.1 ng/ml to about 1 ng/ml when the follicle reaches a size of at least 15 mm.

The invention relates to vaginal composition comprising a combination of estrogen and vitamin D or a vitamin D analog at a daily dosage delivery of (i) estrogen ranging from 1 μg to 100 μg estrogen of estradiol equivalent and (ii) vitamin D or analog ranging from 7.5 μg to 100 μg of vitamin D equivalent.

The invention relates to vaginal composition comprising a combination of estrogen and vitamin D or a vitamin D analog at a daily dosage delivery of (i) estrogen ranging from 1 μg to 100 μg estrogen of estradiol equivalent and (ii) vitamin D or analog ranging from 7.5 μg to 100 μg of vitamin D equivalent.

The present invention provides compounds which are selective allosteric inhibitors of T790M and C797S containing EGFR mutants, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances.

The present invention provides compounds which are selective allosteric inhibitors of T790M and C797S containing EGFR mutants, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances.

Provided are fused ring compounds of Formula (I), Formula (II), or Formula (III), as further detailed herein, which are used for the inhibition of Ras proteins, as well as compositions comprising these compounds and methods treatment by their administration.

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