Medical multimorbidity and drug use among adults in the United States.

Adults with medical multimorbidity (≥2 chronic conditions) present challenges for health care systems to provide coordinated care. Substance use can complicate the management of chronic medical conditions, but little research has focused on the intersection of medical multimorbidity and substance use. This study uses cross-sectional analysis of 115,335 adult respondents of the 2012-2014 administrations of the National Survey on Drug Use and Health to estimate the prevalence and correlates of past-year drug use among adults with multimorbidity. The prevalence of past-year drug use was compared between individuals reporting 0, 1, and ≥2 chronic medical conditions. We used multivariable logistic regression to determine correlates of past-year drug use among adults with ≥2 chronic medical conditions. 53.1% reported no chronic conditions, 29.5% reported one chronic condition, and 17.4% reported ≥2 chronic conditions. Past-year drug use was reported by 18.3% of those with no chronic conditions, 14.8% with 1 chronic condition, and 11.6% with ≥2 chronic conditions. Cannabis and opioid analgesics (nonmedical use) were the most common drugs used across all three groups. In the adjusted model, among adults with medical multimorbidity, adults with past-year drug use were more likely to be younger, male, have lower income, and report current tobacco use, alcohol dependence, past-year depression, and having received mental health treatment in the past year. In this national cohort, fewer adults with multimorbidity reported substance use compared to adults with no or one chronic condition, however, this population with high multimorbidity may be particularly vulnerable to the negative effects of drug use.

Zooming in on Cadherin-23: Structural Diversity and Potential Mechanisms of Inherited Deafness.

Cadherin-23 (CDH23) is an essential component of hair-cell tip links, fine filaments that mediate inner-ear mechanotransduction. The extracellular domain of CDH23 forms about three-fourths of the tip link with 27 extracellular cadherin (EC) repeats that are structurally similar but not identical to each other. Calcium (Ca2+) coordination at the EC linker regions is key for tip-link elasticity and function. There are ∼116 sites in CDH23 affected by deafness-causing mutations, many of which alter conserved Ca2+-binding residues. Here we present crystal structures showing 18 CDH23 EC repeats, including the most and least conserved, a fragment carrying disease mutations, and EC repeats with non-canonical Ca2+-binding motif sequences and unusual secondary structure. Complementary experiments show deafness mutations' effects on stability and affinity for Ca2+. Additionally, a model of nine contiguous CDH23 EC repeats reveals helicity and potential parallel dimerization faces. Overall, our studies provide detailed structural insight into CDH23 function in mechanotransduction.