Hearing impairment is the most common sensory disorder, with congenital hearing impairment present in ~1 in 1000 newborns1, and yet there is no cellular cure for deafness. Hereditary deafness is often mediated by the developmental failure or degeneration of cochlear hair cells2. Until now, it was not known whether such congenital failures could be mitigated by therapeutic intervention3-5. Here we show that hearing and vestibular function can be rescued in a mouse model of human hereditary deafness. An antisense oligonucleotide (ASO) was used to correct defective pre–mRNA splicing of transcripts from the mutated USH1C.216G>A gene, which causes human Usher syndrome (Usher), the leading genetic cause of combined deafness and blindness6,7. Treatment of neonatal mice with a single systemic dose of ASO partially corrects USH1C.216G>A splicing, increases protein expression, improves stereocilia organization in the cochlea, and rescues cochlear hair cells, vestibular function and hearing in mice. Our results demonstrate the therapeutic potential of ASOs in the treatment of deafness and provide evidence that congenital deafness can be effectively overcome by treatment early in development to correct gene expression.

The objectives of this review are to describe the acquired and hereditary causes of methemoglobinemia, to recommend the most sensitive diagnostic tests, and to enable critical care clinicians to rapidly detect and treat methemoglobinemia. To meet these objectives, Internet search engines were queried with the keywords to select articles for review that included case reports, case series, observational, longitudinal, and surveillance studies. The most common causes of methemoglobinemia include oxidizing reactions to cocaine-derived anesthetics, such as benzocaine and lidocaine, to antibiotics, such as dapsone and other sulfonamides, and to gases, such as nitric oxide. Additionally, CO-oximetry is superior to standard pulse oximetry in detecting methemoglobinemia. Finally, effective treatments for methemoglobinemia include intravenous administration of methylene blue, ascorbic acid, and riboflavin. In this manuscript we will discuss methemoglobinemia, how it occurs, and how to treat it.

This manuscript will outline the most recent trends in novel nonopioid pharmacotherapy development including tramadol/dexketoprofen, TrkA inhibitors, tapentadol, opioid agonists, Nektar 181, TRV 130, ßarrestin2, bisphosphonates, antibodies, sodium channel blockers, NMDA antagonists, TRP receptors, transdermal vitamin D, AAK1 kinase inhibition, calcitonin gene-related peptide (CGRP), TRPV4 antagonists, cholecystokinin, delta opioid receptor, neurokinin, and gene therapy. The pharmacotherapies discussed in this manuscript outline promising opioid alternatives which can change the future of chronic pain treatment.