Acrolein and higher alpha,beta-unsaturated aldehydes are bifunctional genotoxins. The deoxyguanosine adduct of acrolein, 3-(2-deoxy-beta-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purin-10(3H)-one (8-hydroxy-1,N(2)-propanodeoxyguanosine, 2a), is a major DNA adduct formed by acrolein. The potential for oligodeoxynucleotide duplexes containing 2a to form interchain cross-links was evaluated by HPLC, CZE, MALDI-TOF, and melting phenomena. Interchain cross-links represent one of the most serious types of damage in DNA since they are absolute blocks to replication. In oligodeoxynucleotides containing the sequence 5'-dC-2a, cross-linking occurred in a slow, reversible manner to the extent of approximately 50%. Enzymatic digestion to form 3-(2-deoxy-beta-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-(N(2)-2'-deoxyguanosinyl)pyrimido[1,2-a]purin-10(3H)one (5a) and reduction with NaCNBH(3) followed by enzymatic digestion to give 1,3-bis(2'-deoxyguanosin-N(2)-yl)propane (6a) established that cross-linking had occurred with the exocyclic amino group of deoxyguanosine. It is concluded that the cross-link is a mixture of imine and carbinolamine structures. With oligodeoxynucleotide duplexes containing the sequence 5'-2a-dC, cross-links were not detected by the techniques enumerated above. In addition, (15)N-(1)H HSQC and HSQC-filtered NOESY spectra carried out with a duplex having (15)N-labeling of the target amino group established unambiguously that a carbinolamine cross-link was not formed. The potential for interchain cross-link formation by the analogous crotonaldehyde adduct (2b) was evaluated in a 5'-dC-2b sequence. Cross-link formation was strongly dependent on the configuration of the methyl group at C6 of 2b. The 6R diastereomer of 2b formed a cross-link to the extent of 38%, whereas the 6S diastereomer cross-linked only 5%.

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Background: A Veterans Health Administration (VHA) patient centered medical home, the Geriatric Patient-Aligned Care Team (GeriPACT). Methods: Plan-Do-Study-Act (PDSA) cycles regarding strategy, resource development, patient and caregiver experience of care, and clinical care process improvement. Stakeholder engagement for half-time operation with initial grant support for personnel who also had collateral duties. Tracking of operations data. Results: The clinic population grew from 200 to 627 over a 7-year period. GeriPACT patients were frail with multiple co-morbidities, including a mean age 84, a 19.4% yearly hospitalization rate, and 12.2% died yearly. Collaborative team management of these complex patients reduced mean number of outpatient medications from 11 to 9, and the 30day rehospitalization rate was 10%, approximately half the facility's rate. Estimated yearly

A particular challenge for specialist community public health nursing (SCPHN) programme leaders is developing assessment and evaluation processes for students. This article outlines a strategy of combining two competency frameworks for use as part of the SCPHN course at a higher education institute. The frameworks are required to assess students' attitudes, skills and knowledge in relation to this specialist field of nursing practice. Combining the strengths of two different frameworks has the potential to enable practice teachers to assess and evaluate students developmentally. Assessing a student's ability, knowledge, attitudes and skills has proven to be successful using this approach in Wales and is featured in the All Wales Clinical Portfolio (used at four Welsh universities). Students can reflect on and in practice while achieving specific learning outcomes, and practice teachers can use the frameworks to assess competence and proficiency effectively.

Background: The United States continues to confront an opioid crisis that also affects older adults. Best practices for prescription opioid management in older adults are challenging to implement in this population. We present our experience with a 1-year management of 48 high-risk older patients who received guideline-based best practices for chronic prescription opioid therapy at a US Department of Veterans Affairs (VA) patient aligned care team (PACT) patient-centered medical home. Methods: The GeriPACT population at the Nashville Campus of the VA Tennessee Valley Healthcare System has an enrollment of 745 patients of whom 48 (6.5%) receive chronic prescription opioid therapy. The practice is supported by the VA Computerized Patients Record System, including the electronic patient portal, My healtheVet, and telemedicine capabilities. Data were collected by chart review and operations data. Results: The mean (range) age of patients was 70.4 (66-93) years. Many patients had comorbid conditions, such as diabetes mellitus (35%), congestive heart failure (18.6%), and dementia (8.3%). More than half had an estimated glomer-ular filtration rates (eGFR) < 60 mL/min, indicating at least stage 3 chronic kidney disease, 41.7% used mental health services (41.7%), and 20.8% had a history of opioid use disorder. Most indications for chronic pain were for musculoskeletal pain (95.8%). The mean (range) morphine equivalent daily dose was 37 mg (10-109). More than half had been seen in the emergency department, and 20.8% had been hospitalized in the previous year for an opioid-related hospitalization, and 3% had expired. Over the year, dose reductions of benzodiazepines or narcotics was performed for 12.5% of patients, accidental overdoses occurred in 4.2%, and positive urine drug screens (UDSs) for cocaine and cannabinoid/tetrahydrocannabinol occurred in 10.4%. One patient was terminated from the program for multiple positive UDSs. Conclusions: Guideline-based patient-centered medical home management of patients with chronic pain who were treated with opioids can be an effective model contributing to the health and well-being of older patients. Complex older patients on chronic opioid treatment are best managed by an interdisciplinary team.