Reassignment of the Structure of a Tryptophan-Containing Cyclic Tripeptide Produced by the Biarylitide Crosslinking Cytochrome P450blt.

The structure of the sidechain crosslinked Tyr-Leu-Trp peptide produced by the biarylitide crosslinking cytochrome P450Blt from Micromonospora sp. MW-13 has been reanalysed by a series of NMR, computational and isotope labelling experiments and shown to contain a C-N rather than a C-O bond. Additional in vivo experiments using such a modified peptide show there is a general tolerance of biarylitide crosslinking P450 enzymes for histidine to tryptophan mutations within their minimal peptide substrate sequences despite the lack of such residues noted in natural biarylitide gene clusters. This work further highlights the impressive ability of P450s from biarylitide biosynthesis pathways to act as biocatalysts for the formation of a range of sidechain crosslinked tripeptides.

An Engineered Biarylitide Cross-Linking P450 from RiPP Biosynthesis Generates Alternative Cyclic Peptides.

Cytochrome-P450-mediated cross-linking of ribosomally encoded peptides (RiPPs) is rapidly expanding and displays great potential for biocatalysis. Here, we demonstrate that active site engineering of the biarylitide cross-linking enzyme P450Blt enables the formation of His-X-Tyr and Tyr-X-Tyr cross-linked peptides, thus showing how such P450s can be further exploited to produce alternate cyclic tripeptides with controlled cross-linking states.

Aneurysm management in patients over 80 years old with good grade subarachnoid haemorrhage.

BACKGROUND: An increasing proportion of aneurysmal subarachnoid haemorrhage (aSAH) occurs in older patients, in whom there is widespread variability in treatment rates due to a different balance of risks. Our aim was to compare outcomes of patients over 80 years old with good grade aSAH who underwent treatment of their aneurysm with those who did not. METHODS: Adult patients with good grade aSAH admitted to tertiary regional neurosciences centres contributing to the UK and Ireland Subarachnoid Haemorrhage Database (UKISAH) and a cohort of consecutive patients admitted from three regional cohorts were included for analysis. Outcomes were functional outcome at discharge, three months and survival at discharge. RESULTS: In the UKISAH, patients whose aneurysm was treated were more likely to have a favourable outcome at discharge (OR 2.34, CI 1.12-4.91, p = .02), at three months (OR 2.29, CI 1.11-4.76, p = .04), and lower mortality (10% vs. 29%, OR 0.83, CI 0.72-0.94, p < .01). In the regional cohort, a similar pattern was seen, but after correction for frailty and comorbidity there was no difference in survival (HR 0.45, CI 0.12-1.68, p = .24) or favourable outcome at discharge (OR 0.83, CI 0.23-2.94, p = .77) and at three months (OR 1.03, CI 0.25-4.29, p = .99). CONCLUSIONS: Better early functional outcomes in those undergoing aneurysm treatment appear to be explained by differences in frailty and comorbidity. Therefore, treatment decisions in this patient group are finely balanced with no clear evidence overall of either benefit or harm in this cohort.

Suicidal ideation in veterans enrolled in evidence-based psychotherapy for posttraumatic stress disorder.

Suicidal ideation (SI) is a highly prevalent public health issue in the veteran population and is increasingly common in veterans who are diagnosed with other mental health conditions, such as posttraumatic stress disorder (PTSD; U.S. Department of Veterans Affairs, 2020). The present study has an initial aim of examining changes in SI over treatment, and it is hypothesized that SI will decrease across PTSD treatments. A second aim is to examine the association of SI status with PTSD symptoms across treatment, and it is hypothesized that PTSD symptomatology will decrease at similar rates over the course of treatment for those who did and did not endorse SI at pretreatment. Participants included 717 (86.3% male) veterans who participated in outpatient treatment within a Veterans Affairs Post Traumatic Stress Disorder (VA PTSD) specialty clinic between July 2014 and December 2017. Descriptive analyses found that 37.2% of veterans endorsed SI at pretreatment, while 18.6% endorsed SI at posttreatment. The relationship between pre- and posttreatment SI was significant, χ²(1, N = 247) = 23.77, p < .001. A significant proportion of veterans who endorsed SI at pretreatment no longer endorsed SI at posttreatment (64.7%). There were no differences in changes in PTSD Checklist for DSM-5 (PCL-5) scores across treatment for those with and without SI at pretreatment. While those who endorsed SI at pretreatment had higher PCL-5 scores throughout treatment, they experienced a similar rate of improvement in symptoms as those without SI at pretreatment. This finding suggests that the presence of SI does not reduce the effectiveness of PTSD treatment. Limitations include the use of a single-item measure of SI, lack of adequate power to detect difference among treatments, and a cross-sectional design. Clinical and research implications are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Psychometric evaluation of the Brief Experiential Avoidance Questionnaire among treatment-seeking veterans with posttraumatic stress disorder.

Objective: The present study aimed to explore the psychometric properties of the Brief Experiential Avoidance Questionnaire (BEAQ) among veterans seeking treatment for posttraumatic stress disorder (PTSD). Given that experiential avoidance (EA) is implicated in the development and maintenance of PTSD, it appears to be a possible clinical target for change across treatment. Method: The BEAQ was administered among two samples of military veterans seeking outpatient (n = 179) and residential (n = 257) treatment for PTSD at a Veterans Affairs specialty clinic. The BEAQ is a 15-item self-report measure intended to assess EA, and additional information regarding its psychometric properties is warranted. Results: Descriptive results of the BEAQ in veteran samples are presented. Confirmatory factor analyses of the BEAQ found poor fit in both samples, indicating the BEAQ is not a unidimensional construct, as has been proposed. Conclusions: Future research should consider whether the current structure of the BEAQ is appropriate for measuring EA in veteran samples. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

An Integrated Approach to Falls Prevention: A Model for Linking Clinical and Community Interventions through the Massachusetts Prevention and Wellness Trust Fund.

Older adult falls continue to be a public health priority across the United States-Massachusetts (MA) being no exception. The MA Prevention and Wellness Trust Fund (PWTF) program within the MA Department of Public Health aims to reduce the physical and economic burdens of chronic health conditions by linking evidence-based clinical care with community intervention programs. The PWTF partnerships that focused on older adult falls prevention integrated the Centers for Disease Control and Prevention's Stopping Elderly Accidents, Death and Injuries toolkit into clinical settings. Partnerships also offer referrals for home safety assessments, Tai Chi, and Matter of Balance programs. This paper describes the PWTF program implementation process involving 49 MA organizations, while highlighting the successes achieved and lessons learned. With the unprecedented expansion of the U.S. Medicare beneficiary population, and the escalating incidence of falls, widespread adoption of effective prevention strategies will become increasingly important for both public health and for controlling healthcare costs. The lessons learned from this PWTF initiative offer insights and recommendations for future falls prevention program development and implementation.

Implementing a state-based stroke quality improvement collaborative: the Massachusetts experience.

BACKGROUND: The Stroke Collaborative Reaching for Excellence is a voluntary stroke quality improvement (QI) collaborative led by a partnership between the Massachusetts Department of Public Health and the American Heart Association/American Stroke Association. Since 2005, the collaborative has assisted Massachusetts Primary Stroke Service hospitals in improving the quality of acute stroke care based on national clinical guidelines. We provide a general overview for states seeking to establish a public-private partnership to promote hospital stroke QI. METHODS: Based on the Institute for Healthcare Improvement's Collaborative model, the program enrolled hospitals, trained staff in data collection, and provided expertise on clinical QI. To assess the success of the model at engaging hospitals, rates of change in participation and case entry were calculated with descriptive statistics. RESULTS: From 2005 to 2010, 58 of 70 (83%) Primary Stroke Service hospitals participated in the collaborative, accounting for over 85% of the statewide annual stroke discharges. On average, 74% of hospital representatives attended learning sessions, 55% participated in data quality conference calls, and 54% attended regional meetings. Over 39,000 cases were entered into the registry from 2007 to 2010, with a 15% increase from 2007 (mean, 171 ± 136; n = 9425) to 2010 (mean, 197 ± 143; n = 10,809). CONCLUSION: Consistent participation and case entry confirm that a voluntary state-based hospital QI collaborative is feasible and sustainable. This occurred in the absence of continued hospital funding. Further research is needed to identify the relationship between program participation and improved patient care and the generalizability of the model.

Assessment of methodological quality of primary studies by systematic reviews: results of the metaquality cross sectional study.

OBJECTIVES: To describe how the methodological quality of primary studies is assessed in systematic reviews and whether the quality assessment is taken into account in the interpretation of results. DATA SOURCES: Cochrane systematic reviews and systematic reviews in paper based journals. STUDY SELECTION: 965 systematic reviews (809 Cochrane reviews and 156 paper based reviews) published between 1995 and 2002. DATA SYNTHESIS: The methodological quality of primary studies was assessed in 854 of the 965 systematic reviews (88.5%). This occurred more often in Cochrane reviews than in paper based reviews (93.9% v 60.3%, P < 0.0001). Overall, only 496 (51.4%) used the quality assessment in the analysis and interpretation of the results or in their discussion, with no significant differences between Cochrane reviews and paper based reviews (52% v 49%, P = 0.58). The tools and methods used for quality assessment varied widely. CONCLUSIONS: Cochrane reviews fared better than systematic reviews published in paper based journals in terms of assessment of methodological quality of primary studies, although they both largely failed to take it into account in the interpretation of results. Methods for assessment of methodological quality by systematic reviews are still in their infancy and there is substantial room for improvement.