Bundling implementation strategies supports outcome measure adoption in stroke rehabilitation: preliminary findings.

BACKGROUND: Over 80% of people who experience a stroke present with residual impairment of the upper extremity, such as the shoulder, elbow, wrist, and hand. However, rarely do stroke rehabilitation practitioners (e.g., occupational therapists) use standardized outcome measures to objectively evaluate upper extremity function. Accordingly, the purpose of this project was to develop a bundle of implementation strategies that supports practitioners' adoption of the Fugl-Meyer Assessment of the Upper Extremity in stroke rehabilitation practice. METHODS: We used tenets of Implementation Mapping to guide the development of our implementation strategy bundle. We partnered with one, large academic health system serving over 200 stroke patients annually through intensive rehabilitation care. Strategies were selected and developed through a multi-method process that included a review of the literature, qualitative input from our health system's practitioners and managers, and expert consultation. We also specified the hypothesized implementation "mechanisms" our strategies intended to change. Practitioners' adoption (yes/no) of the Fugl-Meyer Assessment was calculated by analyzing electronic health record documentation of the 6-month time frame before strategies were deployed compared to the 6-month time frame after deployment. RESULTS: Practitioners were exposed to the following implementation strategies to support Fugl-Meyer adoption: conduct educational meetings, prepare outcome measure champions, provide equipment, develop training materials, and adapt documentation systems. In the 6-months before deployment of our implementation strategies, practitioners implemented the Fugl-Meyer with 14.8% of stroke patients. In the six months after deployment, adoption of the Fugl-Meyer increased to 73.8% (p < .001). CONCLUSIONS: When systematically developed in collaboration with health system partners, a bundle of implementation strategies may support outcome measure adoption in stroke rehabilitation. Improving the use of standardized outcome measures is of paramount importance in stroke rehabilitation to objectively monitor patients' progress or decline, to demonstrate the value of rehabilitation services for enhancing patients' recovery, and to advocate for continued reimbursement for rehabilitation care. Future opportunities lie in further specifying the mechanisms through which implementation strategies are intended to work and how those mechanisms contribute to strategy effectiveness. TRIAL REGISTRATION: NCT registration: NCT04888416; May 06, 2021.

Substitution of the mononuclear, non-heme iron cofactor in lipoxygenases for structural studies.

This Chapter describes methods for the biosynthetic substitution of the mononuclear, non-heme iron in plant and animal lipoxygenases (LOXs). Substitution of this iron center for a manganese ion results in an inactive, yet faithful structural surrogate of the LOX enzymes. This metal ion substitution permits structural and dynamical studies of enzyme-substrate complexes in solution and immobilized on lipid membrane surfaces. Representative procedures for two LOXs, soybean lipoxygenase (SLO) from plants and human epithelial 15-lipoxygenase-2 (15-LOX-2) from mammals, are described as examples.

Extensive exploration of structure activity relationships for the SARS-CoV-2 macrodomain from shape-based fragment merging and active learning.

The macrodomain contained in the SARS-CoV-2 non-structural protein 3 (NSP3) is required for viral pathogenesis and lethality. Inhibitors that block the macrodomain could be a new therapeutic strategy for viral suppression. We previously performed a large-scale X-ray crystallography-based fragment screen and discovered a sub-micromolar inhibitor by fragment linking. However, this carboxylic acid-containing lead had poor membrane permeability and other liabilities that made optimization difficult. Here, we developed a shape-based virtual screening pipeline - FrankenROCS - to identify new macrodomain inhibitors using fragment X-ray crystal structures. We used FrankenROCS to exhaustively screen the Enamine high-throughput screening (HTS) collection of 2.1 million compounds and selected 39 compounds for testing, with the most potent compound having an IC50 value equal to 130 µM. We then paired FrankenROCS with an active learning algorithm (Thompson sampling) to efficiently search the Enamine REAL database of 22 billion molecules, testing 32 compounds with the most potent having an IC50 equal to 220 µM. Further optimization led to analogs with IC50 values better than 10 µM, with X-ray crystal structures revealing diverse binding modes despite conserved chemical features. These analogs represent a new lead series with improved membrane permeability that is poised for optimization. In addition, the collection of 137 X-ray crystal structures with associated binding data will serve as a resource for the development of structure-based drug discovery methods. FrankenROCS may be a scalable method for fragment linking to exploit ever-growing synthesis-on-demand libraries.

A climate threshold for ocean deoxygenation during the Early Cretaceous.

Oceanic anoxic events (OAEs) are historical intervals of global-scale ocean deoxygenation associated with hyperthermal climate states and biological crises1,2. Massive volcanic carbon dioxide (CO2) emissions frequently associated with these events are thought to be a common driver of ocean deoxygenation through several climate-warming-related mechanisms1,3,4. The Early Cretaceous OAE1a is one of the most intense ocean deoxygenation events, persisting for more than 1 Myr (refs. 5,6). However, existing records of marine chemistry and climate across OAE1a are insufficient to fully resolve the timing and dynamics of the underlying processes, thus obscuring cause-and-effect relationships between climate forcing and ocean oxygenation states. Here we show that rapid ocean deoxygenation during OAE1a is linked to volcanic CO2 emissions and the crossing of an associated climate threshold, after which the sluggish pace of the silicate-weathering feedback and climate recovery delayed reoxygenation for >1 Myr. At the end of OAE1a, recrossing this threshold allowed for ocean reoxygenation. Following OAE1a, however, the Earth system remained sufficiently warm such that orbitally forced climate dynamics led to continued cyclic ocean deoxygenation on approximately 100-kyr timescales for another 1 Myr. Our results thus imply a tight coupling between volcanism, weathering and ocean oxygen content that is characterized by a climate threshold.

Stent vs Stent-Less Ileal Conduits After Radical Cystectomy: Is There a Difference in Early Postoperative Outcomes?

INTRODUCTION: Placing ureteral stents at the uretero-ileal anastomosis for radical cystectomy with ileal conduit (RCIC) has long been common practice. Recently, some providers have begun omitting stents. We sought to investigate differences in perioperative and 30-day outcomes between patients who underwent radical cystectomy with ileal conduit (RCIC) with and without stents placed at the uretero-ileal anastomosis. METHODS: We identified RCICs performed between 2019 to 2021 in the National Surgical Quality Improvement Program database and corresponding Cystectomy-Targeted Participant Use File. Baseline demographics, comorbidities, and operative parameters were compared via Pearson's chi-square and t-tests between stented and stent-less RCICs. Outcomes of interest, including rates of urinary tract infections (UTIs), acute kidney injury (AKI), renal failure requiring dialysis, ileoileal anastomotic leaks, ureteral obstruction, urinary leak or fistula formation, reoperations, and 30-day hospital readmissions were compared using Pearson's chi-square. All statistical tests were 2 tailed with P < .05 considered significant. RESULTS: Five Thousand Four Hundred Eighteen RCICs were identified. Four hundred ninety-eight (9.2%) were stent-less. There were no differences in baseline demographics or comorbidities. Significantly fewer stented patients had robotic-assisted operations (23% vs 29%, P < .01). Stented patients had lower rates of urinary leak or fistula formation (3.1% vs 4.8%, P = .04). There was no significant difference in 30-day rates of UTIs, AKIs, renal failure, ileoileal anastomotic leaks, ureteral obstruction, reoperations, and readmissions. Limitations include retrospective design and lack of longitudinal tracking past 30 days. CONCLUSIONS: Stent-less patients had non-inferior outcomes compared to stented patients in most important 30-day outcomes. Our analysis suggests that stents may not be necessary in ileal conduit urinary diversion procedures.

Assessment of the HIV Enhanced Access Testing in the Emergency Department (HEATED) program in Nairobi, Kenya: a quasi-experimental prospective study.

BACKGROUND: Persons seeking emergency injury care are often from higher-risk and underserved key populations (KPs) and priority populations (PPs) for HIV programming. While facility-based HIV Testing Services (HTS) in Kenya are effective, emergency department (ED) delivery is limited, despite the potential to reach underserved persons. METHODS: This quasi-experimental prospective study evaluated implementation of the HIV Enhanced Access Testing in Emergency Departments (HEATED) at Kenyatta National Hospital ED in Nairobi, Kenya. The HEATED program was designed as a multi-component intervention employing setting appropriate strategies for HIV care sensitization and integration, task shifting, resource reorganization, linkage advocacy, skills development and education to promote ED-HTS with a focus on higher-risk persons. KPs included sex workers, gay men, men who have sex with men, transgender persons and persons who inject drugs. PPs included young persons (18-24 years), victims of interpersonal violence, persons with hazardous alcohol use and persons never HIV tested. Data were obtained from systems-level records, enrolled injured patient participants and healthcare providers. Systems and patient-level data were collected during a pre-implementation period (6 March - 16 April 2023) and post-implementation (period 1, 1 May - 26 June 2023). Additional, systems-level data were collected during a second post-implementation (period 2, 27 June - 20 August 2023). HTS data were evaluated as facility-based HIV testing (completed in the ED) and distribution of HIV self-tests independently, and aggregated as ED-HTS. Evaluation analyses were completed across reach, effectiveness, adoption, implementation and maintenance framework domains. RESULTS: All 151 clinical staff were reached through trainings and sensitizations on the HEATED program. Systems-level ED-HTS among all presenting patients increased from 16.7% pre-implementation to 23.0% post-implementation periods 1 and 2 (RR = 1.31, 95% CI: 1.21-1.43; p < 0.001). Among 605 enrolled patient participants, facilities-based HTS increased from 5.7% pre-implementation to 62.3% post-implementation period 1 (RR = 11.2, 95%CI: 6.9-18.1; p < 0.001). There were 440 (72.7%) patient participants identified as KPs (5.6%) and/or PPs (65.3%). For enrolled KPs/PPs, facilities-based HTS increased from 4.6% pre-implementation to 72.3% post-implementation period 1 (RR = 13.8, 95%CI: 5.5-28.7, p < 0.001). Systems and participant level data demonstrated successful adoption and implementation of the HEATED program. Through 16 wk post-implementation a significant increase in ED-HTS delivery was maintained as compared to pre-implementation. CONCLUSIONS: The HEATED program increased overall ED-HTS and augmented delivery to KPs/PPs, suggesting that broader implementation could improve HIV services for underserved persons already in contact with health systems.

Mindfulness meditation alters neural oscillations independently of arousal.

Neuroscience has identified that mindfulness meditation induces a state of relaxed alertness, characterised by changes in theta and alpha oscillations and reduced sympathetic arousal, although the underlying mechanisms remain unclear. This study aims to address this gap by examining changes in neural oscillations and arousal during mindfulness meditation using both traditional and data-driven methods. Fifty-two healthy young adults underwent electroencephalography (EEG) and skin conductance level (SCL) recordings during resting baseline and mindfulness meditation conditions, both conducted with eyes closed. The EEG data revealed a significant decrease in traditional alpha (8-13 Hz) amplitude during mindfulness meditation compared to rest. However, no significant differences were observed between conditions in traditional delta, theta, beta, or gamma amplitudes. Frequency Principal Components Analysis (fPCA) was employed as a data-driven approach, identifying six components consistent across conditions. A complex delta-theta-alpha component significantly increased during mindfulness meditation. In contrast, low alpha (~9.5 Hz) and low alpha-beta (~11 Hz) components decreased significantly during mindfulness meditation. No significant differences were observed between conditions in the delta, high alpha, and high alpha-beta components. Additionally, there were no significant differences in SCL between conditions, nor were there correlations between traditional alpha or fPCA components and SCL. These findings support the conceptualisation of mindfulness meditation as a state of relaxed alertness, characterised by changes in neural oscillations likely associated with attention and awareness. However, the observed changes do not appear to be driven by arousal.

Improving rigor and reproducibility in western blot experiments with the blotRig analysis.

Western blot is a popular biomolecular analysis method for measuring the relative quantities of independent proteins in complex biological samples. However, variability in quantitative western blot data analysis poses a challenge in designing reproducible experiments. The lack of rigorous quantitative approaches in current western blot statistical methodology may result in irreproducible inferences. Here we describe best practices for the design and analysis of western blot experiments, with examples and demonstrations of how different analytical approaches can lead to widely varying outcomes. To facilitate best practices, we have developed the blotRig tool for designing and analyzing western blot experiments to improve their rigor and reproducibility. The blotRig application includes functions for counterbalancing experimental design by lane position, batch management across gels, and analytics with covariates and random effects.

Global alpha power fluctuations in a self-caught mind-wandering paradigm are independent of arousal.

Mind-wandering is characterised as the emergence of thought and emotions which shift attention away from a primary task. It is thought to consume up to 50 % of our waking lives and has several negative implications. Breath-counting is one task that has been utilised in conjunction with electroencephalography (EEG) to examine the brain states associated with mind-wandering. Research has consistently found reductions in alpha oscillations during periods of mind-wandering relative to breath-focus. It is possible that such fluctuations reflect an arousal mechanism warranting further investigation. Thirty-seven participants completed a 15 min breath-counting task, with simultaneous recording of EEG and skin conductance level (SCL). During this task participants were required to self-identify periods of mind-wandering via button-press. Event-related spectral perturbation (ERSP) analysis was used to quantify changes in global alpha power (8-13 Hz) relative to the button press. The -8 to -4 s period prior to button-press was assessed as mind-wandering, and the 4 to 8 s period following the button-press as breath-focus. Relative to breath-focus, mind-wandering was associated with a significant decrease in global alpha power and significant increase in SCL, consistent with perceptual decoupling theory. However, changes in global alpha power and SCL did not correlate. These results suggest arousal is not the primary mechanism underlying alpha changes observed during breath-counting, thus additional processes should be considered.

Enhanced radiosensitivity of pancreatic cancer achieved through inhibition of Cyclin-dependent kinase 1.

BACKGROUND AND PURPOSE: Overcoming radioresistance is a critical challenge in pancreatic ductal adenocarcinoma (PDAC). Our study investigates the targeting of Cyclin-dependent kinase-1 (CDK1) through genetic and pharmaceutical inhibition to radiosensitize PDAC cells. MATERIALS AND METHODS: Mass spectrometry and phosphoproteomics were used to analyze engineered radiation-resistant PDAC cell lines (MIA PaCa-2 and PANC-1) compared to parental controls. The TCGA PDAC database was queried for clinical outcomes and patients were dichotomized based on the median CDK1 mRNA expression. We generated a microRNA-based TET-on inducible shRNA to inhibit CDK1 expression in two PDAC cell lines. We used an orthotopic model of PDAC to test the radiation sensitivity of PDAC tumors with or without doxycycline treatment. We targeted CDK1 activation with a selective CDK1 inhibitor, RO-3306, followed by in vitro experiments employing immunoblotting, immunocytochemistry, and clonogenic assays. RESULTS: Phosphoproteomics analysis revealed that phospho-CDK1 (Tyr15) was significantly elevated in the resistant clones. We found that high CDK1 expression was associated with worse OS in PDAC patients. Radiation exposure increased CDK1 phosphorylation. In MIA PaCa-2 and PANC-1 cells, CDK1 inhibition synergized with radiation therapy to delay tumor growth in vivo. CDK1 inhibition via. RO-3306 resulted in a significant shift of cells into the G2/M phase and disrupted DNA repair after radiation exposure. In vitro, pre-treatment with RO-3306 led to enhanced radiosensitivity of PDAC cells. CONCLUSION: CDK1 plays a crucial role in PDAC radioresistance. Targeting CDK1 with radiotherapy holds promise for further investigation in PDAC treatment.

Sinonasal Tumors: What the Multidisciplinary Cancer Care Board Wants to Know.

Sinonasal neoplasms are a remarkably heterogeneous group, reflecting the numerous tissue types present in the nasal cavity and paranasal sinuses. These entities can be relatively benign (ie, respiratory epithelial adenomatoid hamartoma) or can be exceedingly aggressive (ie, NUT carcinoma). Certain sinonasal tumors have a propensity to spread through local invasion and destruction, while others have a high likelihood of perineural spread. The genetic and molecular mechanisms underlying sinonasal tumor behavior have recently become better understood, and new tumor types have been described using these genetic and molecular data. This has prompted an expansion in the number of tumors included in the World Health Organization fifth edition classification system for head and neck tumors, along with a new classification structure. Radiologists' familiarity with this classification structure is crucial to understanding the expected behavior of these tumors and to collaboration with the multidisciplinary cancer care board in making decisions for optimal patient care. ©RSNA, 2024.

Recurrence following ptosis repair surgery: a multivariate analysis of risk factors.

PURPOSE: To identify and evaluate the risk factors for ptosis repair failure. METHODS: Retrospective, case-controlled study evaluating adult patients with ptosis who underwent ptosis surgery by external levator advancement/resection (ELR) or Müller muscle conjunctival resection (MMCR) with at least 3 months postoperative follow-up. Regression analyses were performed of ptosis repair outcomes comparing preoperative and perioperative risk factors for failure. RESULTS: A total of 240 patients (404 eyelids) met the inclusion criteria for the study. Surgical outcomes were measured categorically by success rate and measured quantitively over time using Kaplan-Meier survival analysis. Success was categorically achieved in 101/112 (90%) eyelids after MMCR and 231/292 (79%) eyelids after ELR (p = .0088). Success as measured over 5 years of follow-up was significantly better in eyelids following MMCR compared to ELR (p = .0469). In terms of surgical failure, the following variables were found to be predictive in order of decreasing risk: chronic topical prostaglandin use, chronic topical corticosteroid use, surgical approach, lower preoperative margin reflex distance 1, prior intraocular surgery, age, lower preoperative levator function, concomitant blepharoplasty, presence of a glaucoma filtering bleb, and female gender. CONCLUSIONS: Ptosis repair surgery is a complex and challenging procedure. This study provides the largest comparative analysis of ELR versus MMCR to date with findings suggesting MMCR to be more a successful surgery than ELR. Topical prostaglandin analogue use appears to be the highest known risk factor for MMCR and ELR ptosis repair failure.

Using Implementation Science in Surgical Care: A Scoping Review.

OBJECTIVE: Improvement of surgical care is dependent upon evidence-based practices (EBPs), policies, procedures, and innovations. The objective of this study was to understand and synthesize the use of implementation science (IS) in surgical care. SUMMARY BACKGROUND DATA: This article summarizes the existing literature to identify the frequency and types of EBPs selected for surgical care, IS frameworks that guided the published research, and prominent facilitators and barriers. METHODS: A modified version of the Arksey and O'Malley framework and the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews Checklist were used to provide the guidance and standards to conduct this scoping review. We queried: Ovid MEDLINE; American Psychological Association PsycINFO; Embase; Cumulated Index to Nursing and Allied Health Literature; Web of Science; and Google Scholar for manuscripts published January 2001 - June 2023. RESULTS: The initial search found 3,674 citations of which 129 met inclusion criteria. The heterogeneity and volume of innovations within the surgical IS field were vast. The most frequent innovations were in peri-operative care, safety in surgery, and Enhanced Recovery After Surgery. Six constructs were identified as both major facilitators and barriers: support from leadership; surgeon and staff knowledge regarding EBPs; relationship/team building; environmental context; data; and resources. CONCLUSION: Identifying these implementation factors used in the surgical field enables us to determine variables that support and inhibit the adoption and implementation of new practices, support practice change, enhance quality and equity of surgical care, and identify research gaps for future IS in surgical care.

The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2.

SARS-CoV-2 continues to pose a threat to public health. Current therapeutics remain limited to direct acting antivirals that lack distinct mechanisms of action and are already showing signs of viral resistance. The virus encodes an ADP-ribosylhydrolase macrodomain (Mac1) that plays an important role in the coronaviral lifecycle by suppressing host innate immune responses. Genetic inactivation of Mac1 abrogates viral replication in vivo by potentiating host innate immune responses. However, it is unknown whether this can be achieved by pharmacologic inhibition and can therefore be exploited therapeutically. Here we report a potent and selective lead small molecule, AVI-4206, that is effective in an in vivo model of SARS-CoV-2 infection. Cellular models indicate that AVI-4206 has high target engagement and can weakly inhibit viral replication in a gamma interferon- and Mac1 catalytic activity-dependent manner; a stronger antiviral effect for AVI-4206 is observed in human airway organoids. In an animal model of severe SARS-CoV-2 infection, AVI-4206 reduces viral replication, potentiates innate immune responses, and leads to a survival benefit. Our results provide pharmacological proof of concept that Mac1 is a valid therapeutic target via a novel immune-restoring mechanism that could potentially synergize with existing therapies targeting distinct, essential aspects of the coronaviral life cycle. This approach could be more widely used to target other viral macrodomains to develop antiviral therapeutics beyond COVID-19.

Predicting Recovery After Concussion in Pediatric Patients: A Meta-Analysis.

CONTEXT: Prognostic prediction models (PPMs) can help clinicians predict outcomes. OBJECTIVE: To critically examine peer-reviewed PPMs predicting delayed recovery among pediatric patients with concussion. DATA SOURCES: Ovid Medline, Embase, Ovid PsycInfo, Web of Science Core Collection, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Google Scholar. STUDY SELECTION: The study had to report a PPM for pediatric patients to be used within 28 days of injury to estimate risk of delayed recovery at 28 days to 1 year postinjury. Studies had to have at least 30 participants. DATA EXTRACTION: The Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies checklist was completed. RESULTS: Six studies of 13 PPMs were included. These studies primarily reflected male patients in late childhood or early adolescence presenting to an emergency department meeting the Concussion in Sport Group concussion criteria. No study authors used the same outcome definition nor evaluated the clinical utility of a model. All studies demonstrated high risk of bias. Quality of evidence was best for the Predicting and Preventing Postconcussive Problems in Pediatrics (5P) clinical risk score. LIMITATIONS: No formal PPM Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) process exists. CONCLUSIONS: The 5P clinical risk score may be considered for clinical use. Rigorous external validations, particularly in other settings, are needed. The remaining PPMs require external validation. Lack of consensus regarding delayed recovery criteria limits these PPMs.

Blood-based multivariate methylation risk score for cognitive impairment and dementia.

INTRODUCTION: The established link between DNA methylation and pathophysiology of dementia, along with its potential role as a molecular mediator of lifestyle and environmental influences, positions blood-derived DNA methylation as a promising tool for early dementia risk detection. METHODS: In conjunction with an extensive array of machine learning techniques, we employed whole blood genome-wide DNA methylation data as a surrogate for 14 modifiable and non-modifiable factors in the assessment of dementia risk in independent dementia cohorts. RESULTS: We established a multivariate methylation risk score (MMRS) for identifying mild cognitive impairment cross-sectionally, independent of age and sex (P = 2.0 × 10-3). This score significantly predicted the prospective development of cognitive impairments in independent studies of Alzheimer's disease (hazard ratio for Rey's Auditory Verbal Learning Test (RAVLT)-Learning = 2.47) and Parkinson's disease (hazard ratio for MCI/dementia = 2.59). DISCUSSION: Our work shows the potential of employing blood-derived DNA methylation data in the assessment of dementia risk. HIGHLIGHTS: We used whole blood DNA methylation as a surrogate for 14 dementia risk factors. Created a multivariate methylation risk score for predicting cognitive impairment. Emphasized the role of machine learning and omics data in predicting dementia. The score predicts cognitive impairment development at the population level.

Intracellular Trafficking Defects in Congenital Intestinal and Hepatic Diseases.

Enterocytes and liver cells fulfill important metabolic and barrier functions and are responsible for crucial vectorial secretive and absorptive processes. To date, genetic diseases affecting metabolic enzymes or transmembrane transporters in the intestine and the liver are better comprehended than mutations affecting intracellular trafficking. In this review, we explore the emerging knowledge on intracellular trafficking defects and their clinical manifestations in both the intestine and the liver. We provide a detailed overview including more investigated diseases such as the canonical, variant and associated forms of microvillus inclusion disease, as well as recently described pathologies, highlighting the complexity and disease relevance of several trafficking pathways. We give examples of how intracellular trafficking hubs, such as the apical recycling endosome system, the trans-Golgi network, lysosomes, or the Golgi-to-endoplasmic reticulum transport are involved in the pathomechanism and lead to disease. Ultimately, understanding these processes could spark novel therapeutic approaches, which would greatly improve the quality of life of the affected patients.

Vanadium-dependent haloperoxidases from diverse microbes halogenate exogenous alkyl quinolone quorum sensing signals.

Site-selective vanadium-dependent haloperoxidases (VHPOs) are a unique enzyme family that catalyze selective halogenation reactions previously characterized within bacterial natural product biosynthetic pathways. However, the broader chemical roles and biological distribution of these halogenases remains to be explored. Using bioinformatic methods, we have defined a VHPO subfamily that regioselectively brominates alkyl quinolone (AQ) quorum sensing molecules. In vitro AQ halogenation activity was demonstrated from phylogenetically distinct bacteria lacking established AQ biosynthetic pathways and sourced from diverse environments. AQ-VHPOs show high sequence and biochemical similarities with negligible genomic synteny or biosynthetic gene cluster co-localization. Exposure of VHPO-containing microbes to synthetic AQs or established bacterial producers identifies the chemical and spatial response to subvert their bacteriostatic effects. The characterization of novel homologs from bacterial taxa without previously demonstrated vanadium enzymology suggests VHPO-mediated AQ bromination is a niche to manipulate the chemical ecology of microbial communities.

Risk-adjusted discrete increases in length of stay by complication following anatomic lung resection: an analysis of 32 133 cases across the USA.

OBJECTIVES: Prior studies have associated morbidity following anatomic lung resection with prolonged postoperative length of stay; however, each complication's individual impact on length of stay as a continuous variable has not been studied. The purpose of this study was to determine the risk-adjusted increase in length of stay associated with each individual postoperative complications following anatomic lung resection. METHODS: Patients who underwent anatomic lung resection cataloged in the prospectively collected American College of Surgeons National Surgical Quality Improvement Program participant use file, 2005-2018, were targeted. The association between preoperative characteristics, postoperative complications and length of stay in days was tested. A negative binomial model adjusting for the effect of preoperative characteristics and 18 concurrent postoperative complications was used to generate incidence rate ratios. This model was fit to generate risk-adjusted increases in length of stay by complication. RESULTS: Of 32 133 patients, 5065 patients (15.8%) experienced at least one post-operative complication. The most frequent complications were pneumonia (n = 1829, 5.7%), the need for transfusion (n = 1794, 5.6%) and unplanned reintubation (n = 1064, 3.3%). The occurrence of each of the 18 individual complications was associated with significantly increased length of stay. This finding persisted after risk-adjustment, with the greatest risk-adjusted increases being associated with prolonged ventilation (+17.4 days), followed by septic shock (+17.2 days), acute renal failure (+16.5 days) and deep surgical site infection (+13.2 days). CONCLUSIONS: All 18 postoperative complications studied following anatomic lung resection were associated with significant risk-adjusted increases in length of stay, ranging from an increase of 17.4 days with prolonged ventilation to 2.6 days following the need for transfusion.

Strategies for Coping with Minority Stress among Queer Young Adults: Usage Frequency, Associations with Demographics, and Mental Health.

Queer young adults report significantly higher levels of anxiety and depression than their heterosexual counterparts, which is linked to sexual minority stress. Therefore, it is important to understand the coping strategies employed by this population to navigate minority stress and how coping strategies may impact mental health outcomes. Drawing from a U.S. national diverse sample of 387 queer young adults (ages 18-39 years), we analyzed descriptive results of 11 behavioral strategies to cope with minority stress and used ordered logistic and linear regression to examine the following objectives: the frequency of the use of each coping strategy, and the associations between each strategy and demographic characteristics as well as depression and anxiety. Results revealed that avoidance and talking with friends were the most frequently utilized coping strategies, while prayer/religious activities and counseling/psychotherapy/support groups were infrequently used. We examined utilization preferences of coping strategies across demographic factors (e.g., assigned sex at birth and sexual orientation). The use of counseling/psychotherapy/support group was positively associated with mental health symptoms, while exercise and mindfulness/mediation were associated with lower mental health symptoms. Our findings provide insights for mental health researchers and professionals in selecting appropriate coping strategies for queer young adults in prevention and intervention efforts.