The present invention concerns methods to identify RIPK1 modulators capable of modulating RIPK1 activity, RIPK1 interacting molecules that modulate RIPK1 activity and pharmaceutical compositions comprising RIPK1 modulators.

Disclosed herein are combinations of compounds for treating a disease or condition, such as cancer. A combination of compounds for treating a disease or condition can include a SERD inhibitor and another inhibitor (such as a CDK4/6 inhibitor, a selective aromatase inhibitor, a non-selective aromatase inhibitor, a mTOR inhibitor, a PI3K inhibitor, an ERK or a MEK inhibitor, AKT inhibitor, a BET inhibitor and an Aurora inhibitor), along with pharmaceutically acceptable salts of any of the foregoing.

Disclosed herein are combinations of compounds for treating a disease or condition, such as cancer. A combination of compounds for treating a disease or condition can include a SERD inhibitor and another inhibitor (such as a CDK4/6 inhibitor, a selective aromatase inhibitor, a non-selective aromatase inhibitor, a mTOR inhibitor, a PI3K inhibitor, an ERK or a MEK inhibitor, AKT inhibitor, a BET inhibitor and an Aurora inhibitor), along with pharmaceutically acceptable salts of any of the foregoing.

Disclosed herein are combinations of compounds for treating a disease or condition, such as cancer. A combination of compounds for treating a disease or condition can include a SERD inhibitor and another inhibitor (such as a CDK4/6 inhibitor, a selective aromatase inhibitor, a non-selective aromatase inhibitor, a mTOR inhibitor, a PI3K inhibitor, an ERK or a MEK inhibitor, AKT inhibitor, a BET inhibitor and an Aurora inhibitor), along with pharmaceutically acceptable salts of any of the foregoing.

An earplug (1) for administering a fluid agent into an ear canal is provided. The earplug (1) comprises a first part (10) adapted for insertion in the ear canal. The first part comprises an elongated member (11) having a chamber (12) for containing the fluid agent, the chamber (12) having at least one outlet (13) at a proximal end (14) of the elongated member (11); and a malleable member (17) disposed laterally of the elongated member (11). The earplug (1) further comprises a second part (20) comprising a piston (21). The piston (21) has a first end (22) which is insertable in the elongated member (11), and a second end (23) which has a push member (24). The piston (21) is displaceable from a first position (A) distally of the chamber (12) to a second position (B) within the chamber (12), such that the fluid agent is injected from the chamber (12) through the outlet (13) into the ear canal.

The present disclosure provides methods of treating a subject having decreased bone mineral density or at risk of developing decreased bone mineral density, and methods of identifying subjects having an increased risk of developing decreased bone mineral density.

The present disclosure provides methods of treating a subject having decreased bone mineral density or at risk of developing decreased bone mineral density, and methods of identifying subjects having an increased risk of developing decreased bone mineral density.

Provided herein, inter alia, are compositions for the modulation of epithelium function, the compositions comprising EphrinA3 protein or EphrinA2 protein, fusions thereof, fragments thereof, or oligonucleotides encoding the same. Also provided are methods for modulating epithelium function, the methods comprising administration of compositions provided herein, including embodiments thereof.

Provided herein, inter alia, are compositions for the modulation of epithelium function, the compositions comprising EphrinA3 protein or EphrinA2 protein, fusions thereof, fragments thereof, or oligonucleotides encoding the same. Also provided are methods for modulating epithelium function, the methods comprising administration of compositions provided herein, including embodiments thereof.

The present disclosure is directed to formulations and methods for treatment of disease such as chemoprevention of cancer, for example oral squamous cell carcinoma (OSCC), and for methods of preparing the formulations. Further, the disclosure relates to local administration in slow release dosage forms for treatment of disease. The extended-release formulations are comprised of biodegradable polymeric implants (for example millicylinders and microspheres as well as in situ forming gels) and therapeutic agents selected from an anti-interleukin 6 agent, a synthetic vitamin A analogue and/or metabolite, and/or an estradiol metabolite for the local delivery of therapeutic agents to a site where a cancer has been previously excised or to prevent progression of a precancerous lesion.