Molecular insights into the low complexity secreted venom of Calliactis polypus.

Sea anemones are venomous animals that rely on their venom for prey capture, defence against predators and intraspecific competition. Currently, comprehensive molecular and evolutionary analyses of the toxin repertoire for sea anemones are limited by a lack of proteomic data for most species. In this study, proteo-transcriptomic analyses were used to expand our knowledge of the proteinaceous components of sea anemone venom by determining the secreted venom proteome of Calliactis polypus. Electro-mechanical stimulation was used to obtain the secreted venom of C. polypus. We identified a low complexity proteome that was dominated by toxins with similarity to known neurotoxins, as well as six novel toxin candidates. The novel putative toxin candidates were found to be taxonomically restricted to species from the superfamily Metridioidea. Furthermore, the secreted venom of C. polypus had only three putative toxins in common with the venom of acontia from the same species, and little similarity with the secreted venom of closely-related species. Overall, this demonstrates that regionalised and lineage-specific variability in toxin abundance is common among sea anemone species. Moreover, the limited complexity of the toxin repertoire found in C. polypus supports the idea that peptide neurotoxins make up the dominant toxin arsenal found in the venom of sea anemones.

Improving Resident Physician Participation in Reporting Patient Safety and Quality Concerns.

Background: Reporting medical errors, near misses, and adverse events is an important component of improving patient safety and resident learning. Studies have revealed that event reporting rates can be low for physicians, resident physicians, and fellows. The objective of this quality improvement project was to improve resident reporting of patient safety and quality events and engage residents in the analysis of events at a community-based teaching hospital in the United States. Methods: We developed a program to engage 122 residents from 6 Accreditation Council for Graduate Medical Education-accredited residency programs using a multifaceted approach that included instructing residents how to use the hospital's adverse event reporting system; requiring first-year residents to submit at least 1 report; reviewing all resident reports during a monthly multidisciplinary meeting; and ensuring that each resident who submitted a report received feedback on how the concern was being addressed. Results: The program resulted in a 41.8% (95% CI 31%-53%) absolute increase in the number of residents reporting a concern, and resident submissions led to several documented improvements in patient care. A survey was administered to the residents who submitted reports, and the majority (76.0% response rate) expressed satisfaction with both the reporting system and the feedback about how their submission was being addressed. The responding residents agreed that they were more likely to submit reports because of their experience with the program and that they felt the program would improve safety and the quality of care at the institution. Conclusion: This quality improvement project successfully increased resident event reporting and engaged residents in the review of submitted events. The program can serve as a model for other teaching hospitals.

Characterization of Emergency Department Quality Assurance Cases Seen Within a Midwestern United States Health System.

BACKGROUND: Hospital quality-assurance (QA) processes, including peer-review committees, seek to identify high-risk areas. PURPOSE: To characterize emergency department (ED) cases sent for QA review. METHODS: A retrospective observational study was conducted of ED cases sent to a QA committee from November 2018 through July 2022 at three midwestern US hospitals. The QA records analyzed for these cases included the original incident report, case summary, and the committee determinations. RESULTS: One hundred and forty-seven cases were reviewed by the ED QA Committee. The most frequent referrals came from physicians. Common diagnostic categories included infectious (21%), cardiac (16%), gastrointestinal (11%), and neurologic (10%) concerns. Of the cases, 51% were considered nonpreventable, 33% were potentially preventable, and 9% were preventable. Inpatient boarding in the ED was explicitly implicated as a contributing factor in 6% of case reports. CONCLUSIONS: Peer physician reporting represent the largest referral source sent for review with the most frequent diagnostic categories, including infectious, cardiac, gastrointestinal, and neurological conditions. Preventable concerns were rare. IMPLICATIONS: This study provides a better understanding of the referral sources, diagnostic categories, and committee determinations in ED quality concerns. These results can target future investigations into case reporting and patient safety.

Impact of education and clinic site champion on extragenital testing for sexually transmitted infections.

BACKGROUND: Sexually transmitted infections (STIs) are on the rise in the United States. Infections at extragenital (EG) sites (throat or rectum) may serve as an overlooked reservoir for STIs. The aims of this project were to determine the proportion of patients receiving EG testing and to observe the impact of an educational intervention. METHODS: Phase I included four urgent care clinics and baseline data for adults receiving STI testing (Chlamydia trachomatis and Neisseria gonorrhoeae). Clinics received access to an educational presentation regarding the importance of EG testing. Two of these clinics served as pilot sites for the implementation of self-collection kits. Phase II involved further expansion and utilization of clinic site champions. RESULTS: Phase I baseline data indicated that less than 1% of samples from patients receiving STI testing were from EG sites. There was an increase in EG testing after the educational intervention and implementation of self-collection kits. A larger increase in EG testing was seen after utilization of a site champion in Phase II. CONCLUSION: EG infections serve as a potential source for STI transmission which makes multi-site testing necessary. Our interventions to improve EG testing were most effective in Phase II after implementing a clinic site champion.

Cluster of Nontoxigenic Corynebacterium diphtheriae Infective Endocarditis and Rising Background C. diphtheriae Cases-Seattle, Washington, 2020-2023.

BACKGROUND: Nontoxigenic Corynebacterium diphtheriae, often associated with wounds, can rarely cause infective endocarditis (IE). Five patients with C. diphtheriae IE were identified within 12 months at a Seattle-based hospital system. We reviewed prior C. diphtheriae-positive cultures to determine if detections had increased over time and evaluated epidemiologic trends. METHODS: We conducted a formal electronic health record search to identify all patients aged ≥18 years with C. diphtheriae detected in a clinical specimen (ie, wound, blood, sputum) between 1 September 2020 and 1 April 2023. We collected patient demographics, housing status, comorbidities, substance-use history, and level of medical care required at detection. We extracted laboratory data on susceptibilities of C. diphtheriae isolates and on other pathogens detected at the time of C. diphtheriae identification. RESULTS: Between 1 September 2020 and 1 April 2023, 44 patients (median age, 44 years) had a C. diphtheriae-positive clinical culture, with most detections occurring after March 2022. Patients were predominantly male (75%), White (66%), unstably housed (77%), and had a lifetime history of injecting drugs (75%). Most C. diphtheriae-positive cultures were polymicrobial, including wound cultures from 36 (82%) patients and blood cultures from 6 (14%) patients, not mutually exclusive. Thirty-four patients (77%), including all 5 patients with C. diphtheriae IE, required hospital admission for C. diphtheriae or a related condition. Of the 5 patients with IE, 3 died of IE and 1 from COVID-19. CONCLUSIONS: Findings suggest a high-morbidity outbreak disproportionately affecting patients who use substances and are unstably housed.

Adverse Childhood Experiences and Positive Childhood Experiences Among United States Military Children.

INTRODUCTION: Many facets of military life are contributors to child health including frequent mobility, family separation, and increased risk to parental physical and mental health, as well as strong social networks and military support systems; yet, there has not been an examination of adverse childhood experiences (ACEs) and positive childhood experiences (PCEs) among military children. MATERIALS AND METHODS: This study used the 2020-2021 National Survey of Children's Health, limited to children aged 6 to 17 years of age, to examine the association between a child who has ever had a caregiver on active duty and their exposure to ACEs and PCEs (n = 54,256 children). Bivariate analyses used Pearson's chi-squared tests and were weighted to be nationally representative. Multivariable regression models were used to examine the association between military status and selected ACEs. RESULTS: There were no statistically significant differences in PCEs between military and civilian children. Compared to children with a civilian caregiver, children who had a caregiver who had ever served on active duty had a higher odds of experiencing domestic violence (adjusted Odds Ratio (aOR), 1.61; 95% CI 1.23-2.11), mental health issues or depression in the household (aOR 1.28; 95% CI 1.07-1.52), and substance use (aOR 1.28; 95% CI 1.06-1.55). CONCLUSIONS: This study complements and extends previous research that has taken a deficit approach and focused exclusively on the hardships faced by children in military families. The findings from this study may be instructive for child welfare advocates and policymakers as they intervene in communities with programming that promotes PCEs among children and adolescents.

Change in Methicillin-Resistant Staphylococcus aureus Testing in the Intensive Care Unit as an Antimicrobial Stewardship Initiative.

Background: Methicillin-resistant Staphylococcus aureus (MRSA)-associated infections are a cause of morbidity and mortality in the intensive care unit (ICU). Vancomycin is a treatment option but is not without risks. Methods: A MRSA testing change-the switch from culture to polymerase chain reaction-was implemented at 2 adult (tertiary and community) ICUs located in a Midwestern US health system. Data from 2016 to 2020 were included in the study, and the median change in time to test results was examined. Results: During the study period, 71% of 19,975 patients seen at the 2 ICUs received MRSA testing. In the preintervention period, 91% and 99% of patients at the tertiary and community hospitals received testing via culture, respectively. Culture testing was used 1% and ∼0% of the time at the tertiary and community hospitals, respectively, in the postintervention period. A counterfactual estimate showed 36 (95% credible interval [CrI], 35, 37) and 32 (95% CrI, 31, 33) fewer hours until results were available at the tertiary and community hospitals, respectively. Conclusion: After the testing change, MRSA results were available in less time. Obtaining results sooner can assist with antimicrobial stewardship through the potential delay in initiating therapies such as vancomycin and/or quicker de-escalation of such therapies.

Interrater reproducibility of the Myoton and durometer devices to quantify sclerotic chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) is a severe complication in long-term survivors of allogeneic hematopoietic stem cell transplantation. This disease is challenging to manage clinically due to a lack of validated tools to quantitatively measure skin sclerosis. The current gold standard for measuring skin sclerosis is the NIH Skin Score which has only moderate agreement among clinicians and experts. To more accurately assess skin sclerosis in cGVHD, the Myoton and durometer devices can be used to directly measure biomechanical parameters of the skin. However, the reproducibility of these devices is not known in patients with cGVHD. To determine this reproducibility, three observers independently measured 10 anatomic sites in each of seven patients with sclerotic cGVHD using the Myoton and durometer. Clinical reproducibility was measured by mean pairwise differences (U-statistic) and intraclass correlation coefficients (ICCs) with 95% confidence intervals (CIs). Mean pairwise differences, expressed in true physical units, were used to report typical errors for each anatomic site and device. Mean pairwise differences were less than 11% of the average overall values for all five Myoton parameters and durometer hardness. These were lower for Myoton creep (4.1%), relaxation time (4.7%), and frequency (5.1%) than decrement (9.0%), stiffness (10.4%), and durometer hardness (9.0%). Myoton parameters creep, relaxation time, and frequency showed promise for capturing skin biomechanics more accurately than Myoton stiffness, decrement, or durometer hardness. Mean pairwise differences trended highest in the shin and volar forearm and lowest in the dorsal forearm. The interobserver ICC for overall (averaged across all measured body sites of a patient) creep (0.94; 95% CI 0.87-1.00), relaxation time (0.96; 95% CI 0.90-1.00), and frequency (0.95; 95% CI 0.88-1.00), trended higher than that for decrement (0.43; 95% CI 0.00-0.88), stiffness (0.92; 95% CI 0.81-1.00), and durometer hardness (0.82; 95% CI 0.61-1.00). Similar trends were observed in healthy participants. These findings can help clinicians design better studies to assess therapeutic response to new cGVHD treatments and support the interpretation of future measurements.

Genomic, functional and structural analyses elucidate evolutionary innovation within the sea anemone 8 toxin family.

BACKGROUND: The ShK toxin from Stichodactyla helianthus has established the therapeutic potential of sea anemone venom peptides, but many lineage-specific toxin families in Actiniarians remain uncharacterised. One such peptide family, sea anemone 8 (SA8), is present in all five sea anemone superfamilies. We explored the genomic arrangement and evolution of the SA8 gene family in Actinia tenebrosa and Telmatactis stephensoni, characterised the expression patterns of SA8 sequences, and examined the structure and function of SA8 from the venom of T. stephensoni. RESULTS: We identified ten SA8-family genes in two clusters and six SA8-family genes in five clusters for T. stephensoni and A. tenebrosa, respectively. Nine SA8 T. stephensoni genes were found in a single cluster, and an SA8 peptide encoded by an inverted SA8 gene from this cluster was recruited to venom. We show that SA8 genes in both species are expressed in a tissue-specific manner and the inverted SA8 gene has a unique tissue distribution. While the functional activity of the SA8 putative toxin encoded by the inverted gene was inconclusive, its tissue localisation is similar to toxins used for predator deterrence. We demonstrate that, although mature SA8 putative toxins have similar cysteine spacing to ShK, SA8 peptides are distinct from ShK peptides based on structure and disulfide connectivity. CONCLUSIONS: Our results provide the first demonstration that SA8 is a unique gene family in Actiniarians, evolving through a variety of structural changes including tandem and proximal gene duplication and an inversion event that together allowed SA8 to be recruited into the venom of T. stephensoni.

Acontia, a Specialised Defensive Structure, Has Low Venom Complexity in Calliactis polypus.

Phylum Cnidaria represents a unique group among venomous taxa, with its delivery system organised as individual organelles, known as nematocysts, heterogeneously distributed across morphological structures rather than packaged as a specialised organ. Acontia are packed with large nematocysts that are expelled from sea anemones during aggressive encounters with predatory species and are found in a limited number of species in the superfamily Metridioidea. Little is known about this specialised structure other than the commonly accepted hypothesis of its role in defence and a rudimentary understanding of its toxin content and activity. This study utilised previously published transcriptomic data and new proteomic analyses to expand this knowledge by identifying the venom profile of acontia in Calliactis polypus. Using mass spectrometry, we found limited toxin diversity in the proteome of acontia, with an abundance of a sodium channel toxin type I, and a novel toxin with two ShK-like domains. Additionally, genomic evidence suggests that the proposed novel toxin is ubiquitous across sea anemone lineages. Overall, the venom profile of acontia in Calliactis polypus and the novel toxin identified here provide the basis for future research to define the function of acontial toxins in sea anemones.

Targeting Lower Serum Trough Concentrations: A New Gentamicin Dosing Strategy for Suspected Neonatal Early-Onset Sepsis.

OBJECTIVE: Neonatal gentamicin dosing algorithms are not designed to achieve serum trough concentrations ≤1 mcg/mL. The purpose of our study was to evaluate a new gentamicin algorithm based on serum creatinine (SCr) and gestational age (GA) designed to achieve serum gentamicin trough concentrations ≤1 mcg/mL. METHODS: A retrospective cohort study was conducted in a level IIIB neonatal intensive care unit. The incidence of elevated serum gentamicin troughs for this study was compared with the center's previously published results to evaluate the proposed dosing algorithm. Patients were included if gentamicin was administered within the first 7 days of life and a serum gentamicin trough concentration and a baseline SCr concentration were obtained. Patients were further subdivided into groups based on GA for data analysis: ≤30 weeks (group 1), 30-34 weeks (group 2), and ≥35 weeks (group 3). The SCr was considered mildly elevated (0.81-0.99 mg/dL) or elevated (≥1 mg/dL). The respective outcomes between the post-algorithm and control groups were examined using intention-to-treat analysis and Bayesian modeling to calculate rate differences. RESULTS: Of the 2377 patients evaluated, 366 met the inclusion criteria. Significantly lower percentages of elevated serum gentamicin troughs were noted in groups 2 and 3 subsequent to the implementation of the dosing algorithm with 16% and 15% lower rate differences, respectively. Regardless of GA, there were significantly fewer elevated serum troughs in the post-implementation groups than in the control with mildly elevated and elevated SCr p < 0.001. CONCLUSIONS: Using a dosing algorithm based on SCr significantly reduced the number of elevated serum trough rates in neonates with a GA greater than 30 weeks.

Evaluation of computed tomography perfusion and angiogram use in stroke evaluation for thrombectomy at a community emergency department setting.

PURPOSE: Evaluate concordance of provider practices with clinical guidelines for thrombectomy screening in an emergency department (ED) via computed tomography perfusion and angiogram (CT-P/A). METHODS: A retrospective observational study was conducted for patients 18 years or older who received a CT-P/A of the head and neck in a US Midwestern ED between September 2019 through June 2021. Healthcare system records reviewed for patient information, CT-P/A findings, and treatment decisions. RESULTS: During study period, 68,403 patients presented to the ED with 718 (1.1%) receiving a CT-P/A. Of these patients, 105 (14.6%) were transferred to a regional facility for potential thrombectomy, with 74 (70.5%) receiving procedure, 28 (26.7%) not receiving procedure, and 3 (2.9%) with insufficient follow-up information. Of patients receiving CT-P/A, 23 met DAWN criteria for thrombectomy, with 21 (91.3%) transferred for potential thrombectomy and 20 (95.2%) receiving the procedure; in comparison, 81 patients (11.7%) did not meet all DAWN criteria and were transferred for potential thrombectomy, with 52 (64.2%) receiving procedure. Lastly, 55 patients met DEFUSE-3 criteria for thrombectomy with 49 (89.1%) being transferred for potential thrombectomy and 45 (91.8%) receiving procedure. In comparison, 53 patients who did not meet all DEFUSE-3 criteria were transferred for potential thrombectomy, with 27 (50.9%) receiving procedure. CONCLUSIONS: This study helps to understand CT-P/A usage, especially in patients that fall outside of treatment criteria in the current thrombectomy literature. Results may have value to institutions interested in using CT-P/A as a diagnostic tool as well as institutions already incorporating it in stroke assessments.

Reexploring Female Pathways to Incarceration: Assessing the Role of Mental Illness.

The pathways framework represents an emerging body of work that emphasizes gendered-based influences on crime and incarceration. To date, studies on female pathways often minimize or exclude the role of mental illness. The current study employs Life Course Theory and the use of Life History Calendar to examine the pathways of a sample of 15 female prison inmates diagnosed with serious and persistent mental health conditions. Findings indicate that mental illness carried criminogenic risk throughout the life course, with crucial transitions of risk leading these women toward long term incarceration. Self-reported pathways included repeated victimization, substance use, psychological trauma, delinquency, and/or crime. This study suggests that the pathway framework would benefit from the increased recognition of the role of mental illness on female criminality. Trauma-informed policy implications are provided and discussed.

Impact of Simulation Manikins to Train Pharmacy Students in Nasal, Throat, and Oral Fluid Swab Collection.

Introduction: A point-of-care testing (POCT) certificate was implemented in a required pharmacy skills-based course. The purpose of this study was to evaluate the impact of manikins on student confidence in performing POCT swabs for infectious diseases. Innovation: Manikins were used to train second-year pharmacy students on nasal swabs, throat swabs, and oral fluid swabs. Student skills were assessed on manikins first, then on a peer. Proficiency was defined as a score of 90% or higher. Students completed a pre- and post-training survey regarding their confidence performing swabs. Student confidence was based on Likert style responses (i.e., 'Strongly Disagree' [score: 1], to 'Strongly Agree' [score: 5]) performing the swabs. Median change in confidence was calculated using quantile regression. Findings: All students (n=63) demonstrated proficiency in performing swabs. Median confidence for nasal, throat, and oral fluid swabs changed by 2.0 (95% CI: 1.5, 2.5), 2.0 (95% CI: 1.5, 2.5), and 2.0 (95%CI: 1.3, 2.7), respectively. The majority of students reported time spent practicing was adequate for the nasal (n=51, 81%), throat (n=51, 81%), and oral fluid swab (n=59, 94%). All participating students reported manikins to be moderately (n=17, 27%) or extremely (n=46, 73%) valuable, and all students rated their overall experience with manikins as positive (n=63, 100%). Student comments revealed manikins helped to visualize anatomy, practice skills without peer discomfort, and minimize risk during the COVID-19 pandemic. Conclusion: This study demonstrated that inclusion of practice on manikins increased student confidence in performing POCT for infectious diseases. In addition, the majority of students indicated that the use of manikins was valuable to their learning and reported feeling prepared to perform POCT in practice after using the manikins.

Comparison of the performance of a clinical classification tree versus clinical gestalt in predicting sepsis with extended-spectrum beta-lactamase-producing gram-negative rods.

A clinical decision tree was developed using point-of-care characteristics to identify patients with culture-proven sepsis due to extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE). We compared its performance with the clinical gestalt of emergency department (ED) clinicians and hospital-based clinicians. The developed tree outperformed ED-based clinicians but was comparable to inpatient-based clinicians.

The Prison Rape Elimination Act (PREA): Snitching, Sexuality, and Normalizing Deviance.

The normalization of deviance in the form of prison rape finds common themes in media, rape myths, and common discourse. However, these portrayals fail to include real world policies and the perspectives of incarcerated populations. As such, the normalization of deviance is assessed in the context of the implementation of the Prison Rape Elimination Act (PREA). A thematic analysis was conducted using qualitative survey responses from 407 males incarcerated in three medium-level security state prisons in the Southern United States. Surprisingly, respondents rejected stereotypical notions of sexuality (institutional deviancy) and snitching (cultural deviancy) surrounding prison rape. Rather, respondents favored standardized safety procedures and institutional responses designed to reduced risk, while also endorsing views that traditional snitching codes were not applicable to prison rape. This study provides implications for researchers and practitioners, particularly in the context of the implementation of PREA.

A Functional Approach to the Assessment of Non-Suicidal Self-Injury on YouTube.

This research explores representations of non-suicidal self-injury (NSSI) on social media. The current study aims to examine the applicability of a functional model of NSSI to videos posted on YouTube by analyzing the 100 most viewed YouTube videos relating to NSSI at a point in time in 2018. Motivations for continued engagement in NSSI were examined for each content creator who posted one of the top 100 most viewed videos relating to NSSI. Categorizations of a content creator's motivation were based on Nock and Prinstein (2004) four-function model (FFM) of NSSI, in which the motivations, or functions, of NSSI are categorized by two dichotomous factors: (a) positive (i.e., involves the addition of a favorable stimulus) or negative (i.e., involves the removal of an aversive stimulus) and (b) automatic (i.e., intrapersonal) or social (i.e., interpersonal). Uploaders most endorsed automatic negative reinforcement (50%), followed by automatic positive (26%), social positive (3%), and social negative (3%). Considering the growing number of children and adolescents with near constant access to internet and social media, there may be implications for further development of safety measures for social media platforms.＿ The results of this study may be valuable for parents, health care professionals, and educators, who should be aware of available social media content relating to NSSI and consider implementing additional media-literacy and media-safety education in school curriculums and programming for children and adolescents. Furthermore, health care professional should be aware that misconceptions of NSSI may have an impact on patients' willingness to seek treatment, or the attitude with which treatment is sought.

Analysis of ingestion admissions in a midsized pediatric intensive care unit.

BACKGROUND: Pediatric ingestion of toxic substances is a complicated cause of morbidity. Currently, there is limited literature on toxic ingestions resulting in pediatric intensive care unit (PICU) admissions. METHODS: A retrospective study was conducted to quantify the number and financial costs of admissions for toxic ingestion. Secondary objectives were to determine common types of ingestions and interventions as well as examine the relationship between intentional ingestion status and patient age. Data were obtained from a retrospective review of records from April 2016 through August 2018 from a PICU located in the Midwestern USA. RESULTS: There were 360 unique patient encounters used in primary analyses. Intentional ingestion and suicidal ideation documented in 72% and 54% of patients, respectively.Patients younger than nine had an 87% (95% confidence interval: 80%, 92%) lower risk for intentional ingestion. The median lengths of stay were 1.0 (interquartile range [IQR]: 1.0, 1.0) days with a median cost of $2498 (IQR: $1870, $3592) USD. There was no patient mortality identified in the sample. CONCLUSION: The types of ingestions appeared to match those of the National Poison Control Database. Lengths of stay were short and had a non-nominal cost. A greater age was associated with an increased risk of intentional ingestions.