Sodium (Na⁺) is a ubiquitous and important inorganic salt mediating many critical biological processes such as neuronal excitation, signaling, and facilitation of various transporters. The hydration states of Na⁺ are proposed to play critical roles in determining the conductance and the selectivity of Na⁺ channels, yet they are rarely captured by conventional structural biology means. Here we use the emerging cryo-electron microscopy (cryoEM) method micro-electron diffraction (MicroED) to study the structure of a prototypical tetrameric Na⁺-conducting channel, NaK, to 2.5 Å resolution from nano-crystals. Two new conformations at the external site of NaK are identified, allowing us to visualize a partially hydrated Na⁺ ion at the entrance of the channel pore. A process of dilation coupled with Na⁺ movement is identified leading to valuable insights into the mechanism of ion conduction and gating. This study lays the ground work for future studies using MicroED in membrane protein biophysics.

Background

Few studies have examined threshold improvements in health-related quality of life (HRQOL) by measuring minimal clinically important differences (MCIDs) in treatment of adult spinal deformity. We hypothesized that patients undergoing operative treatment would be more likely to achieve MCID threshold improvement compared with those receiving nonoperative care, although a subset of nonoperative patients may still reach threshold.

Methods

We analyzed a multicenter, prospective, consecutive case series of 464 patients: 225 nonoperative and 239 operative. To be included in the study, patients had to have adult spinal deformity, be older than 18 years, and have both baseline and 1-year follow-up HRQOL measures (Oswestry Disability Index [ODI], Short Form-36 [SF-36] health survey, and Scoliosis Research Society-22 [SRS-22] questionnaire). We compared the percentages of patients achieving established MCID thresholds between operative and nonoperative groups using risk ratios (RR) with a 95% confidence interval (CI).

Results

Compared to nonoperative patients, surgical patients demonstrated significant mean improvement (P<0.01) and were more likely to achieve threshold MCID improvement across all HRQOL scores (ODI RR = 7.37 [CI 4.45, 12.21], SF-36 physical component score RR = 2.96 [CI 2.11, 4.15], SRS Activity RR = 3.16 [CI 2.32, 4.31]). Furthermore, operative patients were more likely to reach threshold MCID improvement in 2 or more HRQOL measures simultaneously and were less likely to deteriorate.

Conclusion

Patients in both the operative and nonoperative treatment groups demonstrated improvement in at least one HRQOL measure at 1 year. However, surgical treatment was more likely to result in threshold improvement and more likely to lead to simultaneous improvement across multiple measures of ODI, SF-36, and SRS-22. Although a subset of nonoperative patients achieved threshold improvement, nonoperative patients were significantly less likely to improve in multiple HRQOL measures and more likely to sustain MCID deterioration or no change.