Systematic in vitro optimization of antimicrobial peptides against Escherichia coli.

Objectives: Antimicrobial resistance is a growing concern and claims over 1 million lives per year. The discovery of new antimicrobial drugs is expensive and often generates low profitability, with very low success rates. One way to combat this is by the improvement of known antimicrobials, such as antimicrobial peptides (AMPs). The aim of this study was to improve the antimicrobial activities of two known AMPs, UyCT3 and indolicidin, with the use of peptide libraries and growth curves. Methods: Peptide permutation libraries were synthesized for two AMPs, indolicidin and UyCT3, which included 520 peptides. These peptides were subsequently tested against MG1655-K12, to which subsequent peptide design was performed, then tested against three clinically Gram-negative relevant drug-resistant isolates. Best-performing candidates were subjected to a haemolysis assay for toxicity validation. Results: Single amino acid permutations of UyCT3 and indolicidin were sufficient to inhibit growth of MG1655-K12, and subsequent generations of peptide design were able to inhibit growth of clinical isolates at concentrations as low as 5 µM. Our best-performing AMP, UyCT3I5A, W6Y, K10I, F13I, was not seen to be toxic towards sheep RBCs. Conclusions: The efficacy of the AMPs improved with the use of our peptide library technology, whereby an AMP was found that inhibited bacterial growth of clinical Gram-negative isolates 4-fold better than its WT counterpart.

Carbapenemase producing Enterobacterales at a large teaching hospital in Ohio: comparison to state surveillance and retrospective analysis of patient characteristics.

Background: The presence of carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) around the world is increasing, particularly in healthcare settings. Surveillance testing for plasmid-mediated carbapenemase genes is necessary to tracking CP-CRE infections. Aim: In the state of Ohio, surveillance of carbapenem-resistant Enterobacterales (CRE) began in 2018, and to the authors' knowledge data on these cases has not been published to date. This study analyzed data on CRE from a large teaching hospital in Ohio, and by the Ohio Department of Health Laboratory (ODHL). Methods: Carbapenemase production was detected using mCIM, and plasmid-mediated carbapenemase genes were detected using rtPCR. Data was collected on 344 standard-of-care isolates from a large teaching hospital in Ohio, including data collected from chart review. Deidentified surveillance data on 4,391 CRE isolates was provided by the ODHL. Statistical analysis was performed using binary logistic regression. Findings: While KPC was the most common carbapenemase gene (n=1590), NDM (n=98), VIM (n=10), IMP (n=39) and OXA-48 (n=35) were also detected in the isolates studied. Klebsiella pneumoniae and Enterobacter cloacae were the most common CRE, and carbapenemase genes were most commonly detected in K. pneumoniae. Inpatient hospital stays and long-term care were associated with CP-CRE and were more common in women. Conclusion: Surveillance data shows that CP-CRE are present in Ohio, most commonly in Klebsiella pneumoniae. A better understanding of the prevalence of CRE, plasmid-mediated carbapenemase genes present, and the populations affected are important when tracking the spread of disease. Further study and surveillance of carbapenem-resistant organisms can provide a better understanding of their prevalence in the state.

Predictors of Population Mental Health in Montana: An Occupational Justice Perspective.

Population-level analyses can demonstrate occupational injustices and their impact on population health. The objective of this article is to examine whether population-level occupational factors are related to the mental health of Montanans. We used linear regression models of the 2021 Montana County Health Rankings to examine the association between occupational justice and mental health, adjusting for covariates. Predictor variables were access to exercise, insufficient sleep, healthy food access, food insecurity, proximal jobs, and social support. Outcome variables were frequent mental health distress and poor mental health days. Adjusted models showed significant associations between both insufficient sleep (ß = 0.25, 95% confidence interval [CI] = [0.0.11, 0.40]; Table 2) and food insecurity (ß = 0.32, 95% CI = [0.22, 0.43]) and poor mental health days z scores. Adjusted models also showed significant associations between insufficient sleep (ß = 0.18, 95% CI = [0.10, 0.26]) and food insecurity (ß = 0.19, 95% CI = [0.12, 0.25]) and frequent mental health distress. Future research should study whether targeting sleep and food security can enhance Montanans's mental health.

Predictors of Population Mental Health in MontanaA population-level analysis of Montana County Health Rankings using an occupational justice perspective revealed that food insecurity and insufficient sleep were associated with poor mental health days and frequent mental health distress.

Dating of a large tool assemblage at the Cooper's Ferry site (Idaho, USA) to ~15,785 cal yr B.P. extends the age of stemmed points in the Americas.

The timing and character of the Pleistocene peopling of the Americas are measured by the discovery of unequivocal artifacts from well-dated contexts. We report the discovery of a well-dated artifact assemblage containing 14 stemmed projectile points from the Cooper's Ferry site in western North America, dating to ~16,000 years ago. These stemmed points are several thousand years older than Clovis fluted points (~13,000 cal yr B.P.) and are ~2300 years older than stemmed points found previously at the site. These points date to the end of Marine Isotope Stage 2 when glaciers had closed off an interior land route into the Americas. This assemblage includes an array of stemmed projectile points that resemble pre-Jomon Late Upper Paleolithic tools from the northwestern Pacific Rim dating to ~20,000 to 19,000 years ago, leading us to hypothesize that some of the first technological traditions in the Americas may have originated in the region.

Standardized Scoring Tool and Weaning Guideline to Reduce Opioids in Critically Ill Neonates.

Introduction: Pain impacts brain development for neonates, causing deleterious neurodevelopmental outcomes. Prescription opioids for analgesia or sedation are common; however, prolonged opioid exposure in neonates is associated with neurodevelopmental impairment. Balancing the impact of inadequate pain control against prolonged opioid exposure in neonates is a clinical paradox. Therefore, we sought to decrease the average days of opioids used for analgesia or sedation in critically ill neonates at a level IV Neonatal Intensive Care Unit by 10% within 1 year. Methods: A multidisciplinary quality improvement team used the model for improvement, beginning with a Pareto analysis, and identified a lack of consistent approach to weaning opioids as a primary driver for prolonged exposure. The team utilized 2 main interventions: (1) a standardized withdrawal assessment tool-1 and (2) a risk-stratified opioid weaning guideline. Results: We demonstrated a reduction in mean opioid duration from 34.3 to 14.1 days, an increase in nursing withdrawal assessment tool-1 documentation from 20% to 90%, and an increase in the documented rationale for daily opioid dose in provider notes from 20% to 70%. Benzodiazepine use did not change. Conclusion: Standardized withdrawal assessments combined with risk-stratified weaning guidelines can decrease opioid use in critically ill neonates.

A Life Course Perspective on Growing Older With Cerebral Palsy.

Despite most children with cerebral palsy (CP) now living within typical life spans, little is known about how the effects of CP unfold across the life course and impact participation in everyday life during adulthood. In this study, we explored the experiences of 38 adults growing older with CP. Data were gathered using semi-structured interviews focused on participants' engagement in activities in their community and analyzed using a life course perspective to deepen our understanding of the experiences of our participants. We found that individual agency, family and social contexts, as well as larger sociocultural contexts all shaped participants' experiences as they grew older. The findings highlight the usefulness of the life course perspective for understanding how the effects of a diagnosis of CP unfold over time. Further use of this perspective can better inform health care services to meet the needs of adults with CP aging with a lifelong disability.

The Motivational Thought Frequency Scales for increased physical activity and reduced high-energy snacking.

OBJECTIVES: The Motivational Thought Frequency (MTF) Scale has previously demonstrated a coherent four-factor internal structure (Intensity, Incentives Imagery, Self-Efficacy Imagery, Availability) in control of alcohol and effective self-management of diabetes. The current research tested the factorial structure and concurrent associations of versions of the MTF for increasing physical activity (MTF-PA) and reducing high-energy snacks (MTF-S). DESIGN: Study 1 examined the internal structure of the MTF-PA and its concurrent relationship with retrospective reports of vigorous physical activity. Study 2 attempted to replicate these results, also testing the internal structure of the MTF-S and examining whether higher MTF-S scores were found in participants scoring more highly on a screening test for eating disorder. METHODS: In Study 1, 626 participants completed the MTF-PA online and reported minutes of activity in the previous week. In Study 2, 313 participants undertook an online survey that also included the MTF-S and the Eating Attitudes Test (EAT-26). RESULTS: The studies replicated acceptable fit for the four-factor structure on the MTF-PA and MTF-S. Significant associations of the MTF-PA with recent vigorous activity and of the MTF-S with EAT-26 scores were seen, although associations were stronger in Study 1. CONCLUSIONS: Strong preliminary support for both the MTF-PA and MTF-S was obtained, although more data on their predictive validity are needed. Associations of the MTF-S with potential eating disorder illustrate that high scores may not always be beneficial to health maintenance.

Multicenter Evaluation of the BioFire FilmArray Pneumonia/Pneumonia Plus Panel for Detection and Quantification of Agents of Lower Respiratory Tract Infection.

The ability to provide timely identification of the causative agents of lower respiratory tract infections can promote better patient outcomes and support antimicrobial stewardship efforts. Current diagnostic testing options include culture, molecular testing, and antigen detection. These methods may require collection of various specimens, involve extensive sample treatment, and can suffer from low sensitivity and long turnaround times. This study assessed the performance of the BioFire FilmArray Pneumonia Panel (PN panel) and Pneumonia Plus Panel (PNplus panel), an FDA-cleared sample-to-answer assay that enables the detection of viruses, atypical bacteria, bacteria, and antimicrobial resistance marker genes from lower respiratory tract specimens (sputum and bronchoalveolar lavage [BAL] fluid). Semiquantitative results are also provided for the bacterial targets. This paper describes selected analytical and clinical studies that were conducted to evaluate performance of the panel for regulatory clearance. Prospectively collected respiratory specimens (846 BAL and 836 sputum specimens) evaluated with the PN panel were also tested by quantitative reference culture and molecular methods for comparison. The PN panel showed a sensitivity of 100% for 15/22 etiologic targets using BAL specimens and for 10/24 using sputum specimens. All other targets had sensitivities of ≥75% or were unable to be calculated due to low prevalence in the study population. Specificity for all targets was ≥87.2%, with many false-positive results compared to culture that were confirmed by alternative molecular methods. Appropriate adoption of this test could provide actionable diagnostic information that is anticipated to impact patient care and antimicrobial stewardship decisions.

Practical Comparison of the BioFire FilmArray Pneumonia Panel to Routine Diagnostic Methods and Potential Impact on Antimicrobial Stewardship in Adult Hospitalized Patients with Lower Respiratory Tract Infections.

Lower respiratory tract infections, including hospital-acquired and ventilator-associated pneumonia, are common in hospitalized patient populations. Standard methods frequently fail to identify the infectious etiology due to the polymicrobial nature of respiratory specimens and the necessity of ordering specific tests to identify viral agents. The potential severity of these infections combined with a failure to clearly identify the causative pathogen results in administration of empirical antibiotic agents based on clinical presentation and other risk factors. We examined the impact of the multiplexed, semiquantitative BioFire FilmArray Pneumonia panel (PN panel) test on laboratory reporting for 259 adult inpatients submitting bronchoalveolar lavage (BAL) specimens for laboratory analysis. The PN panel demonstrated a combined 96.2% positive percent agreement (PPA) and 98.1% negative percent agreement (NPA) for the qualitative identification of 15 bacterial targets compared to routine bacterial culture. Semiquantitative values reported by the PN panel were frequently higher than values reported by culture, resulting in semiquantitative agreement (within the same log10 value) of 43.6% between the PN panel and culture; however, all bacterial targets reported as >105 CFU/ml in culture were reported as ≥105 genomic copies/ml by the PN panel. Viral targets were identified by the PN panel in 17.7% of specimens tested, of which 39.1% were detected in conjunction with a bacterial target. A review of patient medical records, including clinically prescribed antibiotics, revealed the potential for antibiotic adjustment in 70.7% of patients based on the PN panel result, including discontinuation or de-escalation in 48.2% of patients, resulting in an average savings of 6.2 antibiotic days/patient.

Doing Occupational Justice: A Central Dimension of Everyday Occupational Therapy Practice.

BACKGROUND.: The Canadian Association of Occupational Therapists (CAOT) and the American Occupational Therapy Association (AOTA) state that occupational justice is part of the domain of occupational therapy and that occupational justice is "an aspect of contexts and environments and an outcome of intervention" (AOTA, 2014, p. S9). KEY ISSUES.: Despite the increasing focus on justice in the occupational therapy and the occupational science literature, many practitioners in traditional settings do not see its relevance to their everyday practice (Galvin, Wilding, & Whiteford, 2011) or have difficulty envisioning how to enact a justice-informed practice. PURPOSE.: This paper demonstrates how occupational justice is germane to all settings of occupational therapy, and how it can be enacted at micro, meso, and macro levels of occupational therapy practice. IMPLICATIONS.: We argue that occupational therapy is a justice-oriented profession at its core and will discuss how occupational justice can be enacted at all levels of practice.

Novel approaches to measuring community integration in adults with cerebral palsy.

Purpose: Rehabilitation goals often focus on increasing community integration for adults with disabilities and are measured by objective assessments. Research methods have lagged behind in capturing current conceptualizations of community integration as a multidimensional construct that incorporates participation, social supports, and feelings of belonging in the community. This paper addresses this challenge by describing a multi-method approach to assessing community integration for adults with cerebral palsy.Methods: Measures include standardized questionnaires, qualitative methods, measures of function and physical activity, and geospatial measures using Geographic Information System mapping and Global Positioning System tracking. These objective and subjective data are used to determine where adults spend time and are most active, and which activities and social connections are associated with feeling integrated into the community.Results: Two case examples highlight the importance of using a multi-method approach to assess community integration for adults with cerebral palsy. Results of objective clinical measures were comparable among case examples; however, actual experiences of feeling connected to the community were vastly different.Conclusions: Multiple measures are required to capture the complexity of community integration. Relying solely on objective measures may not provide a complete picture of community integration.IMPLICATIONS FOR REHABILITATIONCommunity integration is a complex construct that incorporates participation, socialization, and feelings of belonging in the community.New methods and measures are needed to assess the many aspects of community integration in adults with disabilities.A multi-method approach is recommended to provide a richer characterization of community integration in individuals with disabilities.A combination of quantitative and qualitative measures addressing the physical, social and psychological aspects of community integration should be used.

Plasmid persistence: costs, benefits, and the plasmid paradox.

Plasmids are extrachromosomal DNA elements that can be found throughout bacteria, as well as in other domains of life. Nonetheless, the evolutionary processes underlying the persistence of plasmids are incompletely understood. Bacterial plasmids may encode genes for traits that are sometimes beneficial to their hosts, such as antimicrobial resistance, virulence, heavy metal tolerance, and the catabolism of unique nutrient sources. In the absence of selection for these traits, however, plasmids generally impose a fitness cost on their hosts. As such, plasmid persistence presents a conundrum: models predict that costly plasmids will be lost over time or that beneficial plasmid genes will be integrated into the host genome. However, laboratory and comparative studies have shown that plasmids can persist for long periods, even in the absence of positive selection. Several hypotheses have been proposed to explain plasmid persistence, including host-plasmid co-adaptation, plasmid hitchhiking, cross-ecotype transfer, and high plasmid transfer rates, but there is no clear evidence that any one model adequately resolves the plasmid paradox.

Hospital-Treated Deliberate Self-Harm in the Western Area of Northern Ireland.

Background: The Northern Ireland Registry of Deliberate Self-Harm was established as an outcome of the Northern Ireland Suicide Prevention Strategy and Action Plan - Protect Life, beginning in the Western Health and Social Care Trust area. Aims: The study aimed to establish the incidence of hospital-treated deliberate self-harm in the Western Area of Northern Ireland, and to explore the profile of such presentations. Method: Deliberate self-harm presentations made to the three hospital emergency departments operating in the area during the period 2007-2012 were recorded. Results: There were 8,175 deliberate self-harm presentations by 4,733 individuals. Respectively, the total, male, and female age-standardized incidence rate was 342, 320, and 366 per 100,000 population. City council residents had a far higher self-harm rate. The peak rate for women was among 15-19-year-olds (837 per 100,000) and for men was among 20-24-year-olds (809 per 100,000). Risk of repetition was higher in 35-44-year-old patients if self-cutting was involved, but was most strongly associated with the number of previous self-harm presentations. Conclusion: The incidence of hospital-treated self-harm in Northern Ireland is far higher than in the Republic of Ireland and more comparable to that in England.

Characteristics of hospital-treated intentional drug overdose in Ireland and Northern Ireland.

OBJECTIVES: This study compared the profile of intentional drug overdoses (IDOs) presenting to emergency departments in Ireland and in the Western Trust Area of Northern Ireland between 2007 and 2012. Specifically the study aimed to compare characteristics of the patients involved, to explore the factors associated with repeated IDO and to report the prescription rates of common drug types in the population. METHODS: We utilised data from two comparable registries which monitor the incidence of hospital-treated self-harm, recording data from deliberate self-harm presentations involving an IDO to all hospital emergency departments for the period 1 January 2007 to 31 December 2012. RESULTS: Between 2007 and 2012 the registries recorded 56 494 self-harm presentations involving an IDO. The study showed that hospital-treated IDO was almost twice as common in Northern Ireland than in Ireland (278 vs 156/100 000, respectively). CONCLUSIONS: Despite the overall difference in the rates of IDO, the profile of such presentations was remarkably similar in both countries. Minor tranquillisers were the drugs most commonly involved in IDOs. National campaigns are required to address the availability and misuse of minor tranquillisers, both prescribed and non-prescribed.

Investigation of Seed Treatments for Management of Bacterial Leaf Spot of Lettuce.

Chemical seed treatments were evaluated for efficacy of disinfestation of lettuce seed that had been inoculated with Xanthomonas campestris pv. vitians. Three concentrations of each chemical were evaluated by treating seed lots for 5 or 15 min. In addition, the effects of each seed treatment on seed germination and early plant growth were examined by observing seed germination rates. Bacteria were not detected when seed were treated with 3 or 5% hydrogen peroxide for 5 or 15 min. Treatment of seed with 0.52% sodium hypochlorite was relatively ineffective at 5 and 15 min. When sodium hypochlorite was used at a 1% concentration for 15 min, the level of bacterial infestation was reduced to 2%. Suspensions of copper hydroxide plus mancozeb also reduced seedborne inoculum to ≤2%. Treatment of seed with copper hydroxide alone, benzoyl peroxide, or calcium peroxide did not reduce seed infestation levels significantly. Seed germination rates were 90% or greater for the majority of seed treatments tested in laboratory assays. Hydrogen peroxide treatments at a concentration of 5% reduced seed germination up to 28% compared with controls. However, no significant differences in germination were observed among control treatments (noninoculated, nontreated seed and inoculated, nontreated seed) and any of the chemical seed treatments when seed were sown in a pasteurized soil mix in the greenhouse.