Construction of Isoquinolone Scaffolds on DNA via Rhodium(III)-Catalyzed C-H Activation.

Isoquinolone is one of the most common heterocyclic core structures in countless natural products and many bioactive compounds. Here, a highly efficient approach to synthesize isoquinolone scaffolds on DNA via rhodium(III)-catalyzed C-H activation has been described. This chemistry transformation is robust and has shown good compatibility with DNA, which is suitable for DNA-encoded library synthesis.

Fully Implantable Peripheral Nerve Stimulation for Hemiplegic Shoulder Pain: A Multi-Site Case Series With Two-Year Follow-Up.

OBJECTIVE: To explore the feasibility and safety of a single-lead, fully implantable peripheral nerve stimulation system for the treatment of chronic shoulder pain in stroke survivors. PARTICIPANTS: Participants with moderate to severe shoulder pain not responsive to conservative therapies for six months. METHODS: During the trial phase, which included a blinded sham introductory period, a percutaneous single-lead peripheral nerve stimulation system was implanted to stimulate the axillary nerve of the affected shoulder. After a three-week successful trial, participants received an implantable pulse generator with an electrode placed to stimulate the axillary nerve of the affected shoulder. Outcomes included pain, pain interference, pain-free external rotation range of motion, quality of life, and safety. Participants were followed for 24 months. RESULTS: Twenty-eight participants underwent trial stimulation and five participants received an implantable pulse generator. The participants who received the implantable generator experienced an improvement in pain severity (p = 0.0002). All five participants experienced a 50% or greater pain reduction at 6 and 12 months, and four experienced at least a 50% reduction at 24 months. There was an improvement in pain interference (p < 0.0001). There was an improvement in pain-free external ROM (p = 0.003). There were no serious adverse events related to the device or to the procedure. CONCLUSIONS: This case series demonstrates the safety and efficacy of a fully implantable axillary PNS system for chronic HSP. Participants experienced reduction in pain, reduction in pain interference, and improved pain-free external rotation ROM. There were no serious adverse events associated with the system or the procedure.

Fully implantable peripheral nerve stimulation for the treatment of hemiplegic shoulder pain: a case report.

This case report describes the first participant treated with a fully implantable, single-lead peripheral nerve stimulation system for refractory hemiplegic shoulder pain. During the 6-wk trial stage, a temporary lead was placed percutaneously near the terminal branches of the axillary nerve to the deltoid. The primary outcome measure was the Brief Pain Inventory-Short Form Question 3, a 0-10 pain numeric rating scale. The participant experienced 75% pain reduction and proceeded to the implantation stage, where he received a single-lead, implantable pulse generator. After 3 wks, the participant became pain-free. However, 7 wks after implantation, the system was turned off because of an unrelated acute medical illness. Hemiplegic shoulder pain reemerged with a Brief Pain Inventory-Short Form Question 3 score of 9. After 11 wks of recovery, peripheral nerve stimulation was reinitiated and the participant became pain-free through the 9-mo follow-up. At 12 mos, Brief Pain Inventory-Short Form Question 3 score was 1. This case report demonstrates the feasibility of a single-lead, fully implantable peripheral nerve stimulation system for refractory hemiplegic shoulder pain.

Hole wave functions and transport with deazaadenines replacing adenines in DNA.

Transport of a hole along the base stack of DNA is relatively facile for a series of adenines (As) paired with thymines (Ts) or for a series of guanines (Gs) paired with cytosines (Cs). However, the speed at which a hole was found to travel was much too small to make useful semiconductor-type devices. Quite recently it was found that replacing one of the electronegative nitrogens (N3 or N7) with a carbon and a hydrogen, thus turning A into deazaadenine, increased the hole speed in what was A/T by a factor 30. To study the effect of the substitution we have carried out simulations for the wave function of a hole on an A/T oligomer with As modified by replacing N3 or N7, or both, with C-H's. The simulations were carried out using QM/MM and the code CP2K. We find, for either N, or both, replaced, the wave function of the hole behaves similarly to that of a hole on A/T in being delocalized immediately after hole insertion for up to ∼20 fs, and then becoming localized on one of the modified As. The time for localization could be decreased by placing additional water within ∼1.8 Šof N3 or N7, encouraging the formation of hydrogen bonds with these nitrogens. Because of their positive charge the hydrogen bonds tend to repel holes. However, these bonds were found to decay on a femtosecond time scale, thus unlikely to affect the hole hopping, which occurs on approximately a nanosecond scale in A/T. Replacement with a C-H of one or both of the electronegative Ns, along with the structural changes that result, is expected to decrease the activation energy and thus account for the larger hole hopping rate in the deaza-modified DNA.

A descriptive analysis of patient education courses in undergraduate and graduate health education programs.

Patient education is a necessary component of quality health care, yet little attention has been given to the preparation of health educators to work in that setting. This study seeks to determine the status of and content in patient education courses offered in professional preparation programs. Results show that 9% of respondents offered a patient education course in their academic unit, whereas 18% indicated that such a course was offered in another unit on campus. It appears there is not agreement between university faculty members and practicing patient educators on what should be taught in such a course. In addition, no significant relationship is found between (a) programs with accreditation or approval and offering a patient education course and (b) programs that prepared students for the Certified Health Education Specialist examination and offering a patient education course. Recommendations are offered for improving the preparation of health educators for the medical care setting.

Optimization of pyrrolidinone based HIV protease inhibitors.

Optimization of P1-substituted pyrrolidinone based HIV protease inhibitors has yielded analogs with very potent antiviral activity.