Search

Background: To address unknown risk for readmission among patients with COVID-19 and persistent capacity strain, hospital systems used postdischarge contact and monitoring to facilitate safe discharge and recovery. However, little work has systematically documented how hospitals implemented changes to hospitalization postdischarge contact practices during COVID-19. Research Question: How did hospitals’ innovate and adapt postdischarge telephone follow-up and remote monitoring strategies to assess discharged patients with COVID-19 for risk of readmission and recovery progress? Study Design and Methods: Semistructured interviews were conducted (January 2022 to March 2023) with 70 inpatient and outpatient providers and administrators (5-12 per site) in nine health systems that varied by size, region, rurality, proportion of Medicaid patients, and estimated scale of post-COVID-19 care organization. Participants described innovation in and implementation of discharge and postdischarge care processes used to assess patients with COVID-19 for readmission risk and recovery progress. The primary analysis was site-level case comparative analysis. Results: Respondents described hospital systems’ motivations for adapting preexisting resources and innovating new postdischarge programs, including postdischarge telephone follow-up and remote monitoring programs, to facilitate safe hospital discharge and transitions to ambulatory care for patients with COVID-19. Respondents also explained various factors that influenced the implementation and use of postdischarge contact practices. Participants perceived that these practices mitigated postdischarge risks and alleviated capacity strain. Respondents described retiring or adapting remote monitoring programs for other conditions as COVID-19 demands declined. Interpretation: Our results show that hospitals implemented and adapted postdischarge practices to help facilitate recovery and address unknown risk for readmission during the pandemic. Some efforts may present opportunities to manage readmission concerns and capacity strain more generally.

Radiotherapy (RTx) is an essential and efficacious oncologic treatment, however, post-RTx bone fragility fractures present a challenging clinical problem. Cancer survivors treated with RTx are at variable risk for these late-onset, complex fragility fractures. Little data exists regarding the effects of RTx on bone fatigue properties despite the likelihood of fatigue loading as a mechanism leading up to atraumatic fracture. In this study, femurs collected from adult male rats were irradiated ex vivo with a therapeutic dose of x-irradiation (20 Gy), and then fatigued using a three-point bend setup. Femurs positioned in an isotonic bath at room temperature were loaded to a range of prescribed initial strain levels (based on beam theory equations, prior to any fatigue damage) at 3 Hz in force control. The goals of this study were to determine the feasibility of assessing RTx-induced alterations in 1) femur fatigue strength, 2) structural microdamage (creep and stiffness), and 3) tissue damage (diffuse damage and/or linear microcracking). Mid-diaphyseal morphology and tissue mineral density were not different between the RTx and Sham groups (p ≥ 0.35). With increasing applied apparent strain, the number of cycles to failure was reduced for the RTx femurs when compared to the Sham femurs (treatment x ε app , p = 0.041). RTx femurs had a greater phase II (steady state) creep rate (p = 0.0462) compared to Sham femurs. For femurs that reached 500k cycles, the RTx group had greater diffuse damage area (p = 0.015) than the Sham. This study provides evidence that radiation at therapeutic doses can directly diminish bone fatigue properties. This loss of fatigue properties is associated with increased structural fatigue damage and diffuse microdamage, without alterations in morphology or tissue mineral density, indicating a reduction in bone quality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Progressive osteolysis can occur at the cement-bone interface of joint replacements and the associated loss of fixation can lead to clinical loosening. We previously developed a rat hemiarthroplasty model that exhibited progressive loss of fixation with the development of cement-bone gaps under the tibial tray that mimicked patterns found in human arthroplasty retrievals. Here we explored the ability of a bisphosphonate (zoledronic acid, ZA) to attenuate cement-bone osteolysis and maintain implant stability. Sprague-Dawley rats (n = 59) received a poly(methylmethacrylate) cemented tibial component and were followed for up to 12 weeks. Treatment groups included peri-operative administration of ZA (ZA group), administration of ZA at 6 weeks postop (late ZA group), or vehicle (Veh group). There was a 60% reduction in the rate of cement-bone gap formation for the ZA group (0.15 mm 3 /week) compared to Veh group (0.38 mm 3 /week, p = 0.016). Late ZA prevented further progression of gap formation but did not reverse bone loss to the level achieved in the ZA group. Micromotion from five times body weight toggle loading was positively correlated with cement-bone gap volume (p = 0.009) and negatively correlated with the amount of cement in the metaphysis (p = 0.005). Reduced new bone formation and enduring nonviable bone in the epiphysis for the ZA group were found. This suggests that low bone turnover in the epiphysis may suppress the early catabolic response due to implantation, thereby maintaining better fixation in the epiphysis. This preclinical model presents compelling supporting data documenting improved maintenance of the cement-bone fixation with the use of peri-operative bisphosphonates., (© 2024 Orthopaedic Research Society.)

Florida, USA is a hotspot of biological invasions with over 500 non-native species reported. Reptiles encompass most of the non-native wildlife with over 50 species established, many of which are sympatric and are identified as invasive due to their impacts to the environment, economy, and human health and safety. Reports of new non-native reptiles occur, and many established non-native reptiles continue to expand their ranges in Florida, increasing the need for multitaxa detection and monitoring capabilities. Invasive constrictor snakes are a primary focus of management efforts due to life history traits that favor successful establishment and dispersal in Florida as well as their impacts to native wildlife and Everglades restoration efforts. While traditional survey methods that rely on visual detections fail to reliably detect invasive constrictors, environmental DNA (eDNA) has proven to be a promising method for detection of cryptic and rare species across the landscape. To address emerging needs for multispecies detection and monitoring in Florida, we developed the first tetraplex dPCR assay designed for detection of four species of invasive constrictor snakes, including Burmese pythons ( Python bivittatus ), northern African pythons ( P. sebae ), boa constrictors ( Boa constrictor ), and rainbow boas ( Epicrates cenchria ). In this tetraplex assay, no cross-amplification across species was documented. This assay serves as a valuable tool for faster and more accurate monitoring efforts of these invasive species in South Florida. Additionally, eDNA samples comprised of soil and water both tested positive for Burmese python DNA under controlled and semicontrolled conditions with DNA being detectable up to 2-weeks post removal in soil samples. Water samples yielded positive detection as quickly as 5 min after exposure to the organism. These data highlight the utility and sensitivity of this protocol for eDNA monitoring., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Leadless pacemakers (LPs) are self-contained pacemakers implanted inside the heart, providing a clinical strategy of pacing without pacemaker leads or a subcutaneous pocket. From an experimental therapy first used clinically in 2012, a decade later this technology is an established treatment option. Because of technologic advances and growing evidence, LPs are increasingly being used. Herein, the experience gained from a decade of leadless pacing is reviewed. We cover the safety and efficacy of single-chamber LPs, including comparisons with transvenous pacemakers and various models, and the initial clinical results of the first dual-chamber LP system. Furthermore, evidence and considerations regarding the optimal replacement strategy will be covered. Finally, we discuss future device developments that may broaden indications, such as LPs communicating with subcutaneous implantable cardiac defibrillators and energy-harvesting LPs., Competing Interests: Funding Support and Author Disclosures Dr Breeman has received an unrestricted research grant from Medtronic. Dr Tjong has received consulting honoraria and research funding from Abbott and Boston Scientific, paid to her institution (no personal financial gain); and is supported by the Dutch Research Council (NWO Rubicon grant no. 452019308), Amsterdam Cardiovascular Sciences, and Health Holland. Dr Miller has served as a consultant for Medtronic and Boston Scientific. Dr Neuzil has received consulting honoraria and research grants from Abbott, Boston Scientific and Medtronic. Dr Dukkipati is a consultant for Biosense Webster; has equity in Manual Surgical Sciences; has received payments from Boston Scientific for the Farapulse acquisition. Dr Knops has received consulting honoraria from Abbott, Boston Scientific, Medtronic, and Cairdac; and has stock options from AtaCor Medical. Dr Reddy is a consultant to Abbott, Boston Scientific, Cairdac, and Medtronic; and has served as a consultant for and has equity in Ablacon, Acutus Medical, Affera-Medtronic, Anumana, Apama Medical-Boston Scientific, APN Health, Append Medical, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, Cardiofocus, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Epix Therapeutics–Medtronic, EpiEP, Eximo, Farapulse-Boston Scientific, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, Laminar Medical, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, and Valcare, unrelated to this paper; has served as a consultant for Adagio Medical, AtriAN, Biosense-Webster, BioTel Heart, Biotronik, Cardionomic, CoreMap, Fire1, Gore and Associates, Impulse Dynamics, Novartis, Novo Nordisk, Philips, and Pulse Biosciences, unrelated to this paper; and has equity in DRS Vascular, Manual Surgical Sciences, Newpace, Nyra Medical, Surecor, and Vizaramed, unrelated to this paper., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) was developed to overcome the risk of lead-related complications associated with the transvenous implantable cardioverter-defibrillator (TV-ICD). In contrast to the TV-ICD, the S-ICD is a completely extrathoracic device. Subsequently, complications differ between these 2 implantable cardioverter-defibrillators, which might impact patient perceptions of the therapies. This prespecified secondary analysis of the PRAETORIAN trial evaluates differences in quality of life., Methods: The PRAETORIAN trial (A Prospective, Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator Therapy) randomized patients with an implantable cardioverter-defibrillator indication, without the need for pacing to S-ICD or TV-ICD therapy. Two questionnaires were collected at baseline, discharge, 12 months, and 30 months. The Duke Activity Status Index measures cardiac-specific physical functioning, and the 36-Item Short Form Health Survey measures physical and mental well-being, with the subscales bodily pain and mental health being of interest in this analysis. Mann-Whitney U tests were used to compare study arms, and a mixed model was used to describe the questionnaire outcomes over time., Results: Patients were randomized to S-ICD (n=426) and TV-ICD (n=423). In the S-ICD group, 20% were women versus 19% in the TV-ICD group. The median age was 63 (interquartile range, 54-69) years in the S-ICD group versus 64 (interquartile range, 56-69) years in the TV-ICD group. There were no significant differences in the Duke Activity Status Index and 36-Item Short Form Health Survey subscales for bodily pain and mental health between the groups at any time point. Patients with a shock in the last 90 days had significantly lower scores for social functioning ( P =0.008) and role limitations due to emotional problems ( P =0.001) than patients without a shock, but this effect did not differ between treatment arms., Conclusions: In a large randomized cohort of patients with an S-ICD or TV-ICD, no difference in overall quality of life was observed. However, implantable cardioverter-defibrillator shocks resulted in a reduction in quality of life, regardless of the device type or appropriateness., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01296022., Competing Interests: Dr Knops reports consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cairdac and has stock options from AtaCor Medical, Inc. Dr El Chami reports consultancy fees from Boston Scientific and Medtronic. Dr Mittal reports consultancy fees from Boston Scientific and Medtronic. K.M. Kooiman reports consultancy fees from Boston Scientific. Dr Lambiase reports educational and research grants from and is in the research board of Boston Scientific, and reports research grants from Abbott. Dr Vernooy reports consultancy fees from Medtronic and Abbott. M.C. Burke is a consultant and receives honoraria, as well as research grants from Boston Scientific and has equity in and is chief medical officer for AtaCor Medical, Inc. Dr Wright has consultancy arrangements with Boston Scientific and Medtronic and iRhythm and a research grant from Boston Scientific. Dr Nordbeck reports modest speaker honoraria from Biotronik, Boston Scientific, and Medtronic. Dr Miller reports consultancy fees from Boston Scientific. Dr Whinnett is an advisor for Boston Scientific and is on the advisory board for Medtronic and Abbot and reports speaker fees from Medtronic. The other authors report no conflicts.

There is an ongoing debate in the United Kingdom and in other countries about whether twice-yearly changes into and out of Daylight Saving Time should be abolished. Opinions are divided about whether any abolition of Daylight Saving Time should result in permanent Standard Time, or year-long Daylight Saving Time. The British Sleep Society concludes from the available scientific evidence that circadian and sleep health are affected negatively by enforced changes of clock time (especially in a forward direction) and positively by the availability of natural daylight during the morning. Thus, our recommendation is that the United Kingdom should abolish the twice-yearly clock change and reinstate Standard Time throughout the year., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Background: The subcutaneous implantable cardioverter-defibrillator (ICD) is associated with fewer lead-related complications than a transvenous ICD; however, the subcutaneous ICD cannot provide bradycardia and antitachycardia pacing. Whether a modular pacing-defibrillator system comprising a leadless pacemaker in wireless communication with a subcutaneous ICD to provide antitachycardia and bradycardia pacing is safe remains unknown., Methods: We conducted a multinational, single-group study that enrolled patients at risk for sudden death from ventricular arrhythmias and followed them for 6 months after implantation of a modular pacemaker-defibrillator system. The safety end point was freedom from leadless pacemaker-related major complications, evaluated against a performance goal of 86%. The two primary performance end points were successful communication between the pacemaker and the ICD (performance goal, 88%) and a pacing threshold of up to 2.0 V at a 0.4-msec pulse width (performance goal, 80%)., Results: We enrolled 293 patients, 162 of whom were in the 6-month end-point cohort and 151 of whom completed the 6-month follow-up period. The mean age of the patients was 60 years, 16.7% were women, and the mean (±SD) left ventricular ejection fraction was 33.1±12.6%. The percentage of patients who were free from leadless pacemaker-related major complications was 97.5%, which exceeded the prespecified performance goal. Wireless-device communication was successful in 98.8% of communication tests, which exceeded the prespecified goal. Of 151 patients, 147 (97.4%) had pacing thresholds of 2.0 V or less, which exceeded the prespecified goal. The percentage of episodes of arrhythmia that were successfully terminated by antitachycardia pacing was 61.3%, and there were no episodes for which antitachycardia pacing was not delivered owing to communication failure. Of 162 patients, 8 died (4.9%); none of the deaths were deemed to be related to arrhythmias or the implantation procedure., Conclusions: The leadless pacemaker in wireless communication with a subcutaneous ICD exceeded performance goals for freedom from major complications related to the leadless pacemaker, for communication between the leadless pacemaker and subcutaneous ICD, and for the percentage of patients with a pacing threshold up to 2.0 V at a 0.4-msec pulse width at 6 months. (Funded by Boston Scientific; MODULAR ATP ClinicalTrials.gov NCT04798768.)., (Copyright © 2024 Massachusetts Medical Society.)

Introduction: Contraceptive care is an opportunity for providers to help clients achieve their reproductive health goals. Client-centeredness is a core element of quality care; however, evidence suggests that the provision of client-centered contraceptive counseling needs improvement. This systematic review summarizes recent evidence on client preferences related to contraceptive care, including how client-centered approaches inform outcomes., Methods: A systematic review was conducted in PubMed, Cochrane Database of Systematic Reviews, and Scopus to identify articles published between December 1, 2016 and May 1, 2023. Studies that explored client preferences related to contraceptive counseling, education, and/or care, and how client-centered approaches impact clients' perceived experiences with their care were included., Results: Thirty-nine unique studies met inclusion criteria. Clients want a range of information about contraceptive methods tailored to their preferences through a variety of formats, before, during, and after their appointment. Clients desired providers with similar demographic backgrounds (gender, race, ethnicity) and life experiences (menstruation, contraceptive use, carceral system encounters) to themselves, and who are willing to offer continuous care. Clients reported greater satisfaction when providers engaged in shared decision-making, utilized decision support tools, and supported their autonomy, including prioritizing their family-building goals. When providers shared personal preferences or pressured clients to select one method over another, clients in turn, reported feeling conflicted about which method to select and some subsequently declined using any method., Discussion: The variation in client preferences highlight the importance of offering tailored, comprehensive information that supports decision-making, prioritizes client autonomy, and recognizes positive interpersonal relationships with providers., Trial Registration: Prospero: CRD42023414456 https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=414456., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Sequencing of messenger RNA (mRNA) found in extracellular vesicles (EVs) in liquid biopsies can provide clinical information such as somatic mutations, resistance profiles and tumor recurrence. Despite this, EV mRNA remains underused due to its low abundance in liquid biopsies, and large sample volumes or specialized techniques for analysis are required. Here we introduce Self-amplified and CRISPR-aided Operation to Profile EVs (SCOPE), a platform for EV mRNA detection. SCOPE leverages CRISPR-mediated recognition of target RNA using Cas13 to initiate replication and signal amplification, achieving a sub-attomolar detection limit while maintaining single-nucleotide resolution. As a proof of concept, we designed probes for key mutations in KRAS, BRAF, EGFR and IDH1 genes, optimized protocols for single-pot assays and implemented an automated device for multi-sample detection. We validated SCOPE's ability to detect early-stage lung cancer in animal models, monitored tumor mutational burden in patients with colorectal cancer and stratified patients with glioblastoma. SCOPE can expedite readouts, augmenting the clinical use of EVs in precision oncology., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: Contraceptive care is critical piece of quality sexual reproductive healthcare. Providers directly impact client experiences and clinical outcomes; it is important to understand how providers offer contraceptive care and the factors influencing this care. This systematic review summarizes recent research on providers, their perspectives, experiences, barriers, and facilitators to offering contraceptive counseling, education, and care., Methods: In May 2023, a systematic review was conducted in PubMed, Cochrane Database of Systematic Reviews, and Scopus to identify articles published between December 1, 2016, and May 1, 2023. Studies that explored the barriers and facilitators providers experience when offering contraceptive counseling, education, and/or care and how those differ by clinic setting, provider characteristics, and/or client demographics were included., Results: A total of 22 studies met the inclusion criteria. Only three studies reported provider demographic characteristics. Most studies were conducted in urban locations with five delivering care to clients with low income. Care provision varied based on clinic setting, provider characteristics, and client characteristics. Care also included client-centered, efficacy-based, shared decision-making, and directive counseling approaches. Providers identified real or perceived challenges among their clients as a barrier to quality care provision, in addition to insufficient time; inability to offer same-day method insertion; and a lack of training in cultural humility, long-acting methods, and providing care to clients with intellectual disabilities., Discussion: Despite intentions to provide client-centered care and prioritize client autonomy, providers face numerous barriers that impact their ability to offer quality care in alignment with client needs and desires., Trial Registration: Prospero-CRD42023414456 crd.york.ac.uk/PROSPERO/display_record.php?RecordID=414456., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Roughly one in six patients receiving conventional transvenous pacemaker systems experience significant complications within 1 year of implant, mainly due to the transvenous lead and subcutaneous pocket. A new helix-fixation single-chamber ventricular leadless pacemaker (LP) system capable of pre-deployment exploratory electrical mapping is commercially available. Such an LP may mitigate complications while streamlining the implantation. In this study, the initial real-world implant experience of the helix-fixation LP was evaluated following its commercial release., Methods: In patients indicated for single-chamber right ventricular pacing, helix-fixation Aveir VR LPs (Abbott, Abbott Park, IL) were implanted using the dedicated loading tool, introducer, and delivery catheter. Implant procedural characteristics, electrical parameters, and any 30-day procedure-related adverse events of consecutive implant attempts were retrospectively evaluated., Results: A total of 167 patients with Class I indication for permanent pacing received implants in four North American centers (57% male, 70 years old). Pre-fixation electrical mapping of potential sites allowed repositioning to be avoided in 95.7% of patients. Median [interquartile range] LP procedure and fluoroscopy durations were 25.5 min [20.0, 35.0] and 5.7 min [4.0, 9.2], respectively. Pacing capture threshold, sensed R-wave amplitude, and impedance were 0.8 V [0.5, 1.3], 9.0 mV [6.0, 12.0], and 705 Ω [550, 910], respectively. Implantation was successful in 98.8% of patients, with 98.2% free from acute adverse events., Conclusions: The initial, real-world experience of the helix-fixation ventricular leadless pacemaker demonstrated safe and efficient implantation with minimal repositioning, viable electrical metrics, and limited acute complications., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Intraoperative implantation of leadless cardiac pacemakers (LCPs) under direct visualization during cardiac surgery is a novel strategy to provide pacing to patients with an elevated risk of postoperative conduction disorders or with a preexisting pacing indication undergoing valve surgery., Objectives: This study sought to evaluate the long-term safety and efficacy of intraoperative LCP implantation in 100 consecutive patients., Methods: Retrospective single-center cohort study of consecutive patients (n = 100) who underwent intraoperative LCP implantation during valve surgery. Safety and efficacy were assessed at implantation and follow-up visits., Results: A total of 100 patients (age 68 ± 13 years, 47% female) underwent intraoperative LCP implantation. The surgery involved the tricuspid valve in 99 patients (99%), including tricuspid valve repair in 59 (59%) and tricuspid valve replacement in 40 (40%). Most of the patients (78%) underwent multivalve surgery. The indication for LCP implantation was elevated risk of postoperative atrioventricular block in 54% and preexisting bradyarrhythmias in 46%. LCP implantation was successful in all patients. During a median of 10.6 months (IQR: 2.0-22.7 months) of follow-up, no device-related complications occurred. At 12-month follow-up, the pacing thresholds were acceptable (≤2.0 V at 0.24 milliseconds) in 95% of patients., Conclusions: Intraoperative LCP implantation under direct visualization is a safe strategy to provide permanent pacing in patients undergoing valve surgery, with a postoperative electrical performance comparable to percutaneously placed LCPs., Competing Interests: Funding Support and Author Disclosures Dr Reddy has received research grants and served as a consultant for Medtronic, the manufacturer of the leadless pacemaker used in this series. Dr Miller has served as a consultant for Medtronic. Dr Adams declares that The Icahn School of Medicine at Mount Sinai receives royalty payments from Medtronic for intellectual property related to the development of 2 tricuspid valve repair rings. Medtronic is the manufacturer of the leadless pacemaker used in this study. Dr Breeman has received an unrestricted research grant from Medtronic and funding from the KNAW Medical Sciences Fund, Royal Netherlands Academy of Arts & Sciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Non-equilibrium clustering and percolation are investigated in an archetypal model of two-dimensional active matter using dynamic simulations of self-propelled Brownian repulsive particles. We concentrate on the single-phase region up to moderate levels of activity, before motility-induced phase separation (MIPS) sets in. Weak activity promotes cluster formation and lowers the percolation threshold. However, driving the system further out of equilibrium partly reverses this effect, resulting in a minimum in the critical density for the formation of system-spanning clusters and introducing re-entrant percolation as a function of activity in the pre-MIPS regime. This non-monotonic behaviour arises from competition between activity-induced effective attraction (which eventually leads to MIPS) and activity-driven cluster breakup. Using an adapted iterative Boltzmann inversion method, we derive effective potentials to map weakly active cases onto a passive (equilibrium) model with conservative attraction, which can be characterised by Monte Carlo simulations. While the active and passive systems have practically identical radial distribution functions, we find decisive differences in higher-order structural correlations, to which the percolation threshold is highly sensitive. For sufficiently strong activity, no passive pairwise potential can reproduce the radial distribution function of the active system.

We successfully employed targeted outreach to communities in Palm Beach County, Florida, to enhance detection of invasive reptiles. We defined targeted outreach as delivering a specific message to a specific audience, at a specific location, to obtain a specific result. These efforts improved our ability to solicit community involvement focused on target species of interest in locations at risk of potential establishment of incipient populations. From 2018 through 2020, we reached over 112,000 individuals who reported over 50 nonnative lizard sightings to EDDMapS, a web-based mapping system for documenting invasive species, and the State-managed IVE-GOT1 reporting hotline. We considered reports to be directly attributed to our outreach efforts when the reporter indicated our outreach method as the source from which they obtained information on reporting large invasive lizards. We found print media elicited the most reports, while social media reached the largest audience both in direct shares and spillover to additional communities outside our target area. We concluded that to help improve invasive species management programs, three tactics could be employed: (1) using multiple forms of media, (2) additional educational support to improve the accuracy of public reports, and (3) rapid, dedicated capability to respond to reported sightings., (© 2024. The Author(s).)

The human colon is home to trillions of microorganisms that modulate gastrointestinal physiology. Our understanding of how this gut ecosystem impacts human health, although evolving, has been slowed by the lack of accessible tools suitable to studying complex host-mucus-microbe interactions. Here, we report a synthetic gel-like material capable of recapitulating the varied structural, mechanical, and biochemical profiles of native human colonic mucus to develop compositionally simple microbiome screening platforms with utility in microbiology and drug discovery. The viscous fibrillar material is realized through templated assembly of a fluorine-rich amino acid at liquid-liquid interphases. The fluorine-assisted mucus surrogate (FAMS) can be decorated with mucins to serve as a habitat for microbial colonization and integrated with human colorectal cells to generate artificial mucosae, referred to as a microbiome organoid. Notably, FAMS are made with inexpensive and commercially available materials, and can be generated using simple protocols and standard laboratory hardware. As a result, this platform can be broadly incorporated into various laboratory settings to advance probiotic research and inform in vivo approaches. If implemented into high throughput screening approaches, FAMS may represent a valuable tool to study compound metabolism and gut permeability, with an exemplary demonstration of this utility presented here.

Background: 18 F-Fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/magnetic resonance (MR) can identify inflammation and fibrosis, which are high-risk features in cardiac sarcoidosis., Objective: The purpose of this study was to evaluate whether the involvement of certain myocardial segments is associated with higher risk compared to others., Methods: One hundred twenty-four patients with suspected clinical sarcoidosis underwent 18 F-FDG-PET/MR. Late gadolinium enhancement (LGE) and focal 18 F-FDG uptake were evaluated globally and in the 16 myocardial segments. Presence of LGE was defined when the percentage of LGE exceeded 5.7% globally (relative to myocardial volume) and in each myocardial segment. Patients were followed up for 5.5 years. Events were defined as ventricular arrhythmia (VA) (including sustained ventricular tachycardia, ventricular fibrillation, and appropriate implantable cardioverter-defibrillator discharge), heart failure hospitalization, or all-cause death., Results: Mean age was 57.1 ± 8.9 years, and 39.5% were female. Twenty-two patients (17.6%) had an event during follow-up, and 9 (7.2%) presented with VA. LGE and 18 F-FDG uptake were more frequent in patients with than without events (36.4% vs 7.8%, P = .001). Presence of LGE and 18 F-FDG in the basal anterior segment were independent predictors for events after adjustment for left ventricular ejection fraction and relative enhanced volume (LGE: odds ratio [1.2-92.4], P = .034; 18 F-FDG: odds ratio 5.5 [1.1-27.5], P = .038). LGE presence in basal to mid-anterior, mid-anteroseptal, and basal to mid-inferoseptal segments was an independent predictor of VA. Presence of 18 F-FDG in basal to mid-anterior, mid-inferoseptal and mid-inferior segments was an independent predictor of VA., Conclusion: Involvement of specific myocardial segments, particularly basal to mid-anterior and mid-septal segments, is associated with higher rates of events in patients with suspected cardiac sarcoidosis., Competing Interests: Disclosures The authors have no conflicts to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Positron emission tomography (PET) imaging methods have advanced our understanding of human biology, while targeted radiotherapeutic drug treatments are now routinely used clinically. The field is expected to grow considerably based on an expanding repertoire of available affinity ligands, radionuclides, conjugation chemistries, and their FDA approvals. With this increasing use, strategies for dose reduction have become of high interest to protect patients from unnecessary and off-target toxicity. Here, we describe a simple and powerful method, scission-enhanced molecular imaging (SEMI). The technique allows for rapid corporeal elimination of radionuclides once imaging or theranostic treatment is completed and relies on "click-to-release" bioorthogonal linkers.

Radionuclides used for imaging and therapy can show high molecular specificity in the body with appropriate targeting ligands. We hypothesized that local energy delivered by molecularly targeted radionuclides could chemically activate prodrugs at disease sites while avoiding activation in off-target sites of toxicity. As proof-of-principle, we tested whether this strategy of " RA dionuclide i nduced D rug E ngagement for R elease" ( RAiDER ) could locally deliver combined radiation and chemotherapy to maximize tumor cytotoxicity while minimizing exposure to activated chemotherapy in off-target sites., Methods: We screened the ability of radionuclides to chemically activate a model radiation-activated prodrug consisting of the microtubule destabilizing monomethyl auristatin E caged by a radiation-responsive phenyl azide ("caged-MMAE") and interpreted experimental results using the radiobiology computational simulation suite TOPAS-nBio. RAiDER was evaluated in syngeneic mouse models of cancer using fibroblast activation protein inhibitor (FAPI) agents 99m Tc-FAPI-34 and 177 Lu-FAPI-04, the prostate-specific membrane antigen (PSMA) agent 177 Lu-PSMA-617, combined with caged-MMAE or caged-exatecan. Biodistribution in mice, combined with clinical dosimetry, estimated the relationship between radiopharmaceutical uptake in patients and anticipated concentrations of activated prodrug using RAiDER., Results: RAiDER efficiency varied by 250-fold across radionuclides ( 99m Tc> 177 Lu> 64 Cu> 68 Ga> 223 Ra> 18 F), yielding up to 1.22µM prodrug activation per Gy of exposure from 99m Tc. Computational simulations implicated low-energy electron-mediated free radical formation as driving prodrug activation. Clinically relevant radionuclide concentrations chemically activated caged-MMAE restored its ability to destabilize microtubules and increased its cytotoxicity by up to 600-fold compared to non-irradiated prodrug. Mice treated with 99m Tc-FAPI-34 and caged-MMAE accumulated up to 3000× greater concentrations of activated MMAE in tumors compared to other tissues. RAiDER with 99m Tc-FAPI-34 or 177 Lu-FAPI-04 delayed tumor growth, while monotherapies did not ( P <0.03). Clinically-guided dosimetry suggests sufficient radiation doses can be delivered to activate therapeutically meaningful levels of prodrug., Conclusion: This proof-of-concept study shows that RAiDER is compatible with multiple radionuclides commonly used in nuclear medicine and has the potential to improve the efficacy of radiopharmaceutical therapies to treat cancer safely. RAiDER thus shows promise as an effective strategy to treat disseminated malignancies and broadens the capability of radiopharmaceuticals to trigger diverse biological and therapeutic responses.

Background: Merkel cell carcinoma (MCC) is an aggressive cancer with often poor outcomes. Limited biomarkers exist for predicting clinical outcomes. The Merkel cell polyomavirus (MCPyV) serum antibody test (AMERK) has shown potential for indicating better recurrence-free survival in a single-institution study. The study aimed to evaluate the link between initial AMERK serostatus and survival. Secondary objectives included examining the relationship between initial AMERK titer levels and tumor burden., Methods: A retrospective cohort study across two institutions analyzed patients tested with AMERK within 90 days of MCC diagnosis. Regression models assessed the association of survival outcomes with serostatus, considering various factors. The relationship between AMERK titer and tumor burden indicators was evaluated using ANOVA. Significance testing was exploratory, without a fixed significance level., Results: Of 261 MCC patients tested, 49.4% were initially seropositive (titer ≥75). Multivariable analysis showed that seropositivity improved recurrence, event-free, overall, and MCC-specific survival rates. Strong associations were found between initial AMERK titer and clinical, tumor, and nodal stages, tumor size, and disease extent. Notably, improved survival with seropositivity was observed only in patients with localized disease at initial presentation., Conclusion: Circulating antibodies to MCPyV oncoproteins, as indicated by the AMERK test, are linked with better survival in MCC patients with localized disease at presentation. This could enhance patient risk profiling and treatment personalization. The study's retrospective nature and exploratory analysis are key limitations., Plain Language Summary: Merkel cell carcinoma (MCC) is a potentially aggressive skin cancer, and tools to predict patient outcomes are limited. A blood test called anti-Merkel cell panel (AMERK), which checks for specific antibodies related to this cancer, might give us some clues. In this study, we looked at 261 MCC patients who took the AMERK test within 90 days of diagnosis. We found that patients with an initial positive AMERK result tended to have better outcomes, especially if their cancer was in the early stages. However, it is important to note that this study has limitations, including using retrospective data and exploratory analyses., (© 2024 American Cancer Society.)

Animal tuberculosis significantly challenges global health, agriculture, and wildlife conservation efforts. Mycobacterial cultures are resource-intensive, time-consuming, and challenged by heterogeneous populations. In this study, we employed a culture-independent approach, using targeted long-read-based next-generation sequencing (tNGS), to investigate the mycobacterial composition in 60 DNA samples extracted from Mycobacterium bovis infected culture-confirmed African buffalo tissue. We detected mycobacterial DNA in 93.3% of the samples and the sensitivity for detecting Mycobacterium tuberculosis complex (MTBC) was 91.7%, demonstrating a high concordance of our culture-independent tNGS approach with mycobacterial culture results. In five samples, we identified heterogenous mycobacterial populations with various non-tuberculous mycobacteria, including members of the Mycobacterium avium complex (MAC), M. smegmatis, and M. komaniense. The latter Mycobacterium species was described in South Africa from bovine nasal swabs and environmental samples from the Hluhluwe-iMfolozi Park, which was the origin of the buffalo samples in the present study. This finding suggests that exposure to environmental mycobacteria may confound detection of MTBC in wildlife. In conclusion, our approach represents a promising alternative to conventional methods for detecting mycobacterial DNA. This high-throughput technique enables rapid differentiation of heterogeneous mycobacterial populations, which will contribute valuable insights into the epidemiology, pathogenesis, and microbial synergy during mycobacterial infections., (© 2024. The Author(s).)

Introduction: Obstructive sleep apnoea (OSA) is a common, but underdiagnosed, sleep disorder. If untreated, it leads to poor health outcomes, including Alzheimer's disease, cancer, cardiovascular disease and all-cause mortality. Our aim is to determine the feasibility and cost-effectiveness of moving the testing for OSA into general practice and how general practitioner (GP)-based screening affects overall detection rates., Methods and Analysis: Randomised controlled trial of case finding of OSA in general practice using a novel Medicines and Healthcare products Regulatory Agency-registered device (AcuPebble SA100) compared with usual care with internal feasibility phase. A diverse sample of general practices (approximately 40) from across the West Midlands Clinical Research Network will identify participants from their records. Eligible participants will be aged 50-70 years with body mass index >30 kg/m 2 and diabetes (type 1 or 2) and/or hypertension (office blood pressure >145/90 mm Hg or on treatment). They will exclude individuals with known OSA or chronic obstructive pulmonary disease, or those they deem unable to take part. After eligibility screening, consent and baseline assessment, participants will be randomised to either the intervention or control group. Participants in the intervention arm will receive by post the AcuPebble sleep test kit. Those in the control arm will continue with usual care. Follow-up questionnaires will be completed at 6 months. The study is powered (90%) to detect a 5% difference and will require 606 patients in each arm (713 will be recruited to each arm to allow for attrition). Due to the nature of the intervention, participants and GPs will not be blinded to the allocation., Outcomes: Primary: Detection rate of moderate-to-severe OSA in the intervention group versus control group. Secondary: Time to diagnosis and time to treatment for intervention versus control group for mild, moderate and severe OSA; cost-effectiveness analysis comparing the different testing pathways., Ethics and Dissemination: The trial started on 1 November 2022. Ethical approval was granted from the South Central Oxford A Research Ethics Committee on 9 June 2023 (23/SC/0188) (protocol amendment version 1.3; update with amendment and approval to renumber to V2.0 on 29 August 2023). Patient recruitment began on 7 January 2024; initial planned end date will be on 31 April 2025.Results will be uploaded to the ISRCTN register within 12 months of the end of the trial date, presented at conferences, submitted to peer-reviewed journals and distributed via our patient and public involvement networks.The University of Warwick will act as the trial sponsor. The trial will be conducted in accordance with the Sponsor and Primary Care Clinical Trials Unit standard operating procedures., Trial Registration Number: ISRCTN 16982033., Competing Interests: Competing interests: MAM and FPC receive royalties from Oxford University Press for the publication of two books on Sleep, Health and Society., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Antimicrobial resistance among Enterobacterales continues to be a growing problem, particularly in those with urinary infections. Previous studies have demonstrated safety and efficacy with the use of single-dose aminoglycosides in uncomplicated cystitis. However, data in complicated infections are limited. Single-dose aminoglycosides may provide a convenient alternative for those with or at risk for resistant pathogens causing complicated urinary infections, especially when oral options are unavailable due to resistance, allergy, intolerance, or interactions with other medications. This study evaluated the safety and effectiveness of single-dose aminoglycosides in treatment of complicated cystitis in the emergency department (ED)., Methods: This was a multicenter, prospective study performed between July 2022 and March 2023 of patients who met criteria for complicated cystitis and were otherwise stable for discharge at an academic ED. Primary outcomes were clinical or microbiologic failure within 14 days of treatment. Safety was assessed by review of adverse events. Descriptive statistics were used., Results: Thirteen patients were included. Complicating factors were male sex (n = 4), kidney stone (n = 2), urinary catheter (n = 6), recent urologic procedure (n = 1), urinary hardware (n = 1), antibiotic allergy precluding use of alternate oral options (n = 4), immunocompromised status (n = 2), and <1-year history of multidrug-resistant organisms on urine culture (n = 8). Eleven patients (85%) had positive urine cultures in the preceding 12 months with no oral antimicrobial option. Eight patients (62%) received amikacin (median dose 15 mg/kg), four patients (31%) received gentamicin (median dose 5 mg/kg), and one patient (8%) received tobramycin (5 mg/kg) for treatment. Ten patients (77%) reported resolved urinary symptoms after treatment and 11 patients (85%) reported no new urinary symptoms since discharge. No patient required hospital admission for treatment failure, and no adverse events were noted., Conclusions: Single-dose aminoglycosides appear to be a reasonably effective and safe treatment for complicated cystitis, which avoided hospital admission in this cohort., (© 2024 Society for Academic Emergency Medicine.)

Hypervariable region sequencing of the 16S ribosomal RNA (rRNA) gene plays a critical role in microbial ecology by offering insights into bacterial communities within specific niches. While providing valuable genus-level information, its reliance on data from targeted genetic regions limits its overall utility. Recent advances in sequencing technologies have enabled characterisation of the full-length 16S rRNA gene, enhancing species-level classification. Although current short-read platforms are cost-effective and precise, they lack full-length 16S rRNA amplicon sequencing capability. This study aimed to evaluate the feasibility of a modified 150 bp paired-end full-length 16S rRNA amplicon short-read sequencing technique on the Illumina iSeq 100 and 16S rRNA amplicon assembly workflow by utilising a standard mock microbial community and subsequently performing exploratory characterisation of captive (zoo) and free-ranging African elephant (Loxodonta africana) respiratory microbiota. Our findings demonstrate that, despite generating assembled amplicons averaging 869 bp in length, this sequencing technique provides taxonomic assignments consistent with the theoretical composition of the mock community and respiratory microbiota of other mammals. Tentative bacterial signatures, potentially representing distinct respiratory tract compartments (trunk and lower respiratory tract) were visually identified, necessitating further investigation to gain deeper insights into their implication for elephant physiology and health., (© 2024. The Author(s).)

Radiotherapy is commonly used to treat cancer, and localized energy deposited by radiotherapy has the potential to chemically uncage prodrugs; however, it has been challenging to demonstrate prodrug activation that is both sustained in vivo and truly localized to tumors without affecting off-target tissues. To address this, we developed a series of novel phenyl-azide-caged, radiation-activated chemotherapy drug-conjugates alongside a computational framework for understanding corresponding pharmacokinetic and pharmacodynamic (PK/PD) behaviors. We especially focused on an albumin-bound prodrug of monomethyl auristatin E (MMAE) and found it blocked tumor growth in mice, delivered a 130-fold greater amount of activated drug to irradiated tumor versus unirradiated tissue, was 7.5-fold more efficient than a non albumin-bound prodrug, and showed no appreciable toxicity compared to free or cathepsin-activatable drugs. These data guided computational modeling of drug action, which indicated that extended pharmacokinetics can improve localized and cumulative drug activation, especially for payloads with low vascular permeability and diffusivity and particularly in patients receiving daily treatments of conventional radiotherapy for weeks. This work thus offers a quantitative PK/PD framework and proof-of-principle experimental demonstration of how extending prodrug circulation can improve its localized activity in vivo ., Competing Interests: The authors declare the following competing financial interest(s): M.A.M. has received unrelated support from Genentech/Roche and Pfizer and research funding from Ionis Pharmaceuticals. R.W. has consulted for Boston Scientific, ModeRNA, Earli, and Accure Health, none of whom contributed to or were involved in this research. Patents are pending and/or awarded with the authors and Massachusetts General Hospital., (© 2024 The Authors. Published by American Chemical Society.)

Clinical treatment of cancer commonly incorporates X-ray radiation therapy (XRT), and developing spatially precise radiation-activatable drug delivery strategies may improve XRT efficacy while limiting off-target toxicities associated with systemically administered drugs. Nevertheless, achieving this has been challenging thus far because strategies typically rely on radical species with short lifespans, and the inherent nature of hypoxic and acidic tumor microenvironments may encourage spatially heterogeneous effects. It is hypothesized that the challenge could be bypassed by using scintillating nanoparticles that emit light upon X-ray absorption, locally forming therapeutic drug depots in tumor tissues. Thus a nanoparticle platform (Scintillating nanoparticle Drug Depot; SciDD) that enables the local release of cytotoxic payloads only after activation by XRT is developed, thereby limiting off-target toxicity. As a proof-of-principle, SciDD is used to deliver a microtubule-destabilizing payload MMAE (monomethyl auristatin E). With as little as a 2 Gy local irradiation to tumors, MMAE payloads are released effectively to kill tumor cells. XRT-mediated drug release is demonstrated in multiple mouse cancer models and showed efficacy over XRT alone (p < 0.0001). This work shows that SciDD can act as a local drug depot with spatiotemporally controlled release of cancer therapeutics., (© 2024 Wiley‐VCH GmbH.)

Background: The PRAETORIAN score estimates the risk of failure of subcutaneous implantable cardioverter-defibrillator (S-ICD) therapy by using generator and lead positioning on bidirectional chest radiographs. The PRospective randomized compArative trial of subcutanEous implanTable cardiOverter-defibrillatoR ImplANtation with and without DeFibrillation Testing (PRAETORIAN-DFT) investigates whether PRAETORIAN score calculation is noninferior to defibrillation testing (DFT) with regard to first shock efficacy in spontaneous events., Objective: This prespecified subanalysis assessed the predictive value of the PRAETORIAN score for defibrillation success in induced ventricular arrhythmias., Methods: This multicenter investigator-initiated trial randomized 965 patients between DFT and PRAETORIAN score calculation after de novo S-ICD implantation. Successful DFT was defined as conversion of induced ventricular arrhythmia in <5 seconds from shock delivery within 2 attempts. Bidirectional chest radiographs were obtained after implantation. The predictive value of the PRAETORIAN score for DFT success was calculated for patients in the DFT arm., Results: In total, 482 patients were randomized to undergo DFT. Of these patients, 457 (95%) underwent DFT according to protocol, of whom 445 (97%) had successful DFT and 12 (3%) had failed DFT. A PRAETORIAN score of ≥90 had a positive predictive value of 25% for failed DFT, and a PRAETORIAN score of <90 had a negative predictive value of 99% for successful DFT. A PRAETORIAN score of ≥90 was the strongest independent predictor for failed DFT (odds ratio 33.77; confidence interval 6.13-279.95; P < .001)., Conclusion: A PRAETORIAN score of <90 serves as a reliable indicator for DFT success in patients with S-ICD, and a PRAETORIAN score of ≥90 is a strong predictor for DFT failure., Competing Interests: Disclosures Dr Knops reports consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cardiac and has stock options from AtaCor Medical Inc. Dr El-Chami reports consultancy fees from Medtronic and Boston Scientific. Dr Marquie reports consultancy fees from Boston Scientific.Dr Tilz reports consultancy fees from Boston Scientific, Biotronik, Biosense Webster, and Abbott Medical; speaker’s honoraria from Boston Scientific, Biotronik, Biosense Webster, Abbott Medical, and LifeTech; and research grants from Abbott, Biosense Webster, and LifeTech. Dr Lambiase reports research contracts with Boston Scientific and is a member of the advisory board of Boston Scientific. Dr Manyam reports consultancy fees from Janssen and Abbott. Dr Betts received honoraria for speaking and proctoring from Boston Scientific. Dr Bijsterveld presented at a conference of Abbott and gave a presentation sponsored by AstraZeneca. Dr Field reports being a speaker and proctor for Boston Scientific. Dr Golovchiner reports being a proctor for Boston Scientific. Dr de Jong reports consultancy fees from Medtronic. Dr Lewis reported to receive travel grants and honoraria from Abbott, Boston Scientific, and Medtronic. Dr Martin reported to receive research grants, honoraria, and speaker’s fees from Boston Scientific and honoraria and speaker’s fees from Medtronic and Biosense Webster. Dr Miller reported to receive consultancy fees from Boston Scientific. Dr Shaik reported to receive consultancy fees from Boston Scientific, Medtronic, and Biotronik. Dr Kuschyk reported to receive consultancy fees and honoraria from Boston Scientific, consultancy fees from Impulse Dynamics, and honoraria fees from Medtronic. Dr Boveda reported to receive consultancy fees from Medtronic, Boston Scientific, MicroPort, and Zoll. Dr Kaiser is a proctor for Boston Scientific. Dr Maass reported to receive consultancy fees from Boston Scientific and Medtronic, with all fees going to the department of Cardiology of the University Medical Center Groningen. Dr Wilde is a consultant for ARMGO and Thyrvv Therapeutics. The rest of the authors report no conflicts of interest., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: In a recent trial, tricuspid annuloplasty (TA) during mitral valve surgery (MVS) for degenerative mitral regurgitation and moderate or less tricuspid regurgitation (TR) reduced the composite rate of death, reoperation for TR, or TR progression at 2 years. However, this benefit was counterbalanced by an increase in implantation of permanent pacemakers (PPMs). In this study, we analyzed the timing, indications, and risk factors for these implantations., Methods: We randomized 401 patients (MVS alone = 203; MVS + TA = 198). Potential risk factors for PPMs were assessed using multivariable time-to-event models with death and PPM implantation for heart failure indications as competing risks., Results: A PPM was implanted in 36 patients (9.6; 95% CI, 6.8-13.0) within 2 years of randomization, with 30/187 (16.0%) in the MVS + TA and 6/188 (3.2%) in the MVS groups (rate ratio, 5.08; 95% CI, 2.16-11.94; P < .001). Most (29/36; 80.6%) implantations occurred within 30 days postoperatively. Independent risk factors for PPM implantation within 2 years were TA (hazard ratio [HR], 5.94; 95% CI, 2.27-15.53; P < .001), increasing age (5 years, HR, 1.23; 95% CI, 1.01-1.52; P = .04), and left ventricular ejection fraction (LVEF; HR, 0.96; 95% CI, 0.92-0.99; P = .02). In the subset of TA recipients (n = 197), age (5 years, HR, 1.05; 95% CI, 1.00-1.10; P = .04) and LVEF (HR, 0.95; 95% CI, 0.91-0.99; P = .01) were associated with PPM within 2 years., Conclusions: Concomitant TA, age, and baseline LVEF were risk factors for PPM implantation in patients who underwent MVS for degenerative mitral regurgitation. Although TA was effective in preventing progression of TR, innovation is needed to identify ways to decrease PPM implantation rates., (Copyright © 2022 The American Association for Thoracic Surgery. All rights reserved.)

Background: The goal of antibiotic stewardship programs (ASPs) is to ensure that patients receive effective therapy while minimizing adverse events. To overcome barriers commonly faced in implementing successful ASPs, the Agency for Healthcare Research and Quality (AHRQ) established a multifaceted, nationwide Safety Program for Improving Antibiotic Use in 2018. This report summarizes the lessons learned from the implementation of this initiative based on structured interviews of personnel from participating sites., Methods: At the completion of the one-year initiative, semistructured exit interviews were conducted with site leaders at 151 of the 402 hospitals that participated. These interviews consisted of open-ended questions about the perceived effectiveness of components of the Safety Program. Qualitative analyses incorporated both deductive coding themes (based on existing literature) and an iteratively developed inductive coding framework (based on salient themes that emerged from a subset of interviews)., Results: Several components of the Safety Program were identified as effective in expanding local stewardship activities, including techniques and strategies to implement sustainable ASPs, access to Implementation Advisors to keep sites engaged, provision of local benchmarked antibiotic use data to compare to similar hospitals, and Safety Program materials such as the antibiotic time-out tool to integrate stewardship techniques into daily work flows. The biggest challenges to greater effectiveness were suboptimal frontline staff engagement and difficulty changing antibiotic prescribing culture. Some approaches used to overcome these barriers (peer-to-peer communication and education through team huddles, identifying physician champions, informal rounds to enhance collegiality and buy-in, and engagement of hospital leadership) were identified., Conclusion: Lessons learned from the Safety Program can be applied by other teams looking to promote an effective ASP at their hospital or system. The themes that emerged in this study likely also have relevance across a wide range of large-scale quality improvement initiatives., (Copyright © 2024 The Joint Commission. All rights reserved.)

Background and Purpose: Mindfulness has been associated with many positive psychological benefits. It is usually measured by self-report, and there are numerous questionnaires available to measure mindfulness in this way. The purpose of this review is to offer a summary of the available self-assessment questionnaires for measuring mindfulness, their appropriate uses, and psychometrics. Methods: CINAHL, PubMed, and PsychINFO databases were queried along with hand searching reference lists based on the indicated criteria, including Mindfulness-Based Stress Reduction-related mindfulness measurement tools, based on self-report and designed for use in adults. Results: Fourteen tools, published between 2001 and 2021, were included in this review. The tools varied in their orientation and have been created to measure mindfulness as a state, trait, and process. Conclusions: There is a wide variety of available tools, and each conceptualizes mindfulness in a distinct way. Understanding these details is crucial to choosing the proper tool., (© 2024 Springer Publishing Company.)

MEK signaling pathway targeting has emerged as a valuable addition to the options available for the treatment of advanced cancers including melanoma and non-small cell lung cancer. Ophthalmologic monitoring of patients taking part in clinical trials of MEK inhibitors has shown that while ocular effects are common, generally emerging during the first days to weeks of treatment, the majority are either asymptomatic or have minimal visual impact and are benign, resolving without intervention or the need to reduce or stop MEK inhibitor therapy. However rare cases of serious, potentially vision-threatening ocular toxicities have been reported during MEK inhibitor therapy. There is currently no recommendation for routine ophthalmologic screening or monitoring of patients with advanced cancer who are initiating MEK inhibitor therapy. However, baseline ophthalmologic examination may be useful for all patients initiating MEK inhibitor therapy to allow the differentiation of preexisting pathology versus the development of MEK inhibitor-associated retinopathy in the event of the emergence of symptomatic ocular events. Regular ophthalmologic examination may be appropriate for patients at increased risk for ocular events, such as patients with a history of ocular inflammation, infection, or underlying macular/retinal disease. All patients reporting visual disturbance should be referred for prompt ophthalmologic review to determine the potential seriousness of any underlying abnormalities and whether there is a need for treatment modification or specific intervention. Understanding the potential consequences of ocular toxicities is of particular importance in the context of decision-making for the continuation of potentially life-prolonging medications such as MEK inhibitors., (© The Author(s) 2024. Published by Oxford University Press.)

Importance: Unprecedented increases in hospital occupancy rates during COVID-19 surges in 2020 caused concern over hospital care quality for patients without COVID-19., Objective: To examine changes in hospital nonsurgical care quality for patients without COVID-19 during periods of high and low COVID-19 admissions., Design, Setting, and Participants: This cross-sectional study used data from the 2019 and 2020 Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project State Inpatient Databases. Data were obtained for all nonfederal, acute care hospitals in 36 states with admissions in 2019 and 2020, and patients without a diagnosis of COVID-19 or pneumonia who were at risk for selected quality indicators were included. The data analysis was performed between January 1, 2023, and March 15, 2024., Exposure: Each hospital and week in 2020 was categorized based on the number of COVID-19 admissions per 100 beds: less than 1.0, 1.0 to 4.9, 5.0 to 9.9, 10.0 to 14.9, and 15.0 or greater., Main Outcomes and Measures: The main outcomes were rates of adverse outcomes for selected quality indicators, including pressure ulcers and in-hospital mortality for acute myocardial infarction, heart failure, acute stroke, gastrointestinal hemorrhage, hip fracture, and percutaneous coronary intervention. Changes in 2020 compared with 2019 were calculated for each level of the weekly COVID-19 admission rate, adjusting for case-mix and hospital-month fixed effects. Changes during weeks with high COVID-19 admissions (≥15 per 100 beds) were compared with changes during weeks with low COVID-19 admissions (<1 per 100 beds)., Results: The analysis included 19 111 629 discharges (50.3% female; mean [SD] age, 63.0 [18.0] years) from 3283 hospitals in 36 states. In weeks 18 to 48 of 2020, 35 851 hospital-weeks (36.7%) had low COVID-19 admission rates, and 8094 (8.3%) had high rates. Quality indicators for patients without COVID-19 significantly worsened in 2020 during weeks with high vs low COVID-19 admissions. Pressure ulcer rates increased by 0.09 per 1000 admissions (95% CI, 0.01-0.17 per 1000 admissions; relative change, 24.3%), heart failure mortality increased by 0.40 per 100 admissions (95% CI, 0.18-0.63 per 100 admissions; relative change, 21.1%), hip fracture mortality increased by 0.40 per 100 admissions (95% CI, 0.04-0.77 per 100 admissions; relative change, 29.4%), and a weighted mean of mortality for the selected indicators increased by 0.30 per 100 admissions (95% CI, 0.14-0.45 per 100 admissions; relative change, 10.6%)., Conclusions and Relevance: In this cross-sectional study, COVID-19 surges were associated with declines in hospital quality, highlighting the importance of identifying and implementing strategies to maintain care quality during periods of high hospital use.

Interfacial self-assembly describes the directed organization of molecules and colloids at phase boundaries. Believed to be fundamental to the inception of primordial life, interfacial assembly is exploited by a myriad of eukaryotic and prokaryotic organisms to execute physiologic activities and maintain homeostasis. Inspired by these natural systems, chemists, engineers, and materials scientists have sought to harness the thermodynamic equilibria at phase boundaries to create multi-dimensional, highly ordered, and functional nanomaterials. Recent advances in our understanding of the biophysical principles guiding molecular assembly at gas-solid, gas-liquid, solid-liquid, and liquid-liquid interphases have enhanced the rational design of functional bio-nanomaterials, particularly in the fields of biosensing, bioimaging and biotherapy. Continued development of non-canonical building blocks, paired with deeper mechanistic insights into interphase self-assembly, holds promise to yield next generation interfacial bio-nanomaterials with unique, and perhaps yet unrealized, properties. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies., (© 2024 The Authors. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals LLC.)

Objective: The effect of mitral valve (MV) surgery on the natural history of ventricular arrhythmia (VA) in patients with arrhythmic MV prolapse remains unknown. We sought to evaluate the cumulative incidence of VA at 1 year after surgical mitral repair., Methods: A retrospective review of progressively captured data identified 204 consecutive patients who underwent elective MV repair for significant degenerative mitral regurgitation as a first-time cardiovascular intervention in a quaternary reference center between January 2018 and December 2020. A subset of 62 consecutive patients with diagnosed arrhythmic MV prolapse was further evaluated for recurrent VA after MV repair., Results: The median age was 62 years (range, 27-77 years) and 26 of 62 (41.9%) were female. The median time from initial mitral regurgitation/MV prolaspe diagnosis-to-referral was 13.8 years (interquartile range [IQR], 5.4-25) and from VA diagnosis-to-referral was 8 years (IQR, 3-10.6). Using the Lown-Wolf classification, complex VA (Lown grade ≥3) was identified in 36 of 62 patients (58%) at baseline, whereas 8 of 62 (13%) had a cardioverter/defibrillator implanted for primary (4/8) or secondary (4/8) prevention. Left ventricular myocardial scar was confirmed in 23 of 34 (68%) of patients scanned at baseline. The prevailing valve phenotype was bileaflet Barlow (59/62; 95.2%). All patients underwent surgical MV repair by the same team. Surgical repair was stabilized with an annuloplasty prosthesis (median size 36 mm [IQR, 34-38]). Concomitant procedures included tricuspid valve repair (51/62; 82.3%), cryo-maze ± left atrial appendage exclusion (14/62, 23%), and endocardial cryoablation of VA ectopy (4/62; 6.5%). The 30-day and 1-year freedom from recurrent VA were 98.4% and 75.9%, respectively. Absent VA after mitral repair was uniformly observed in patients with minor VA at baseline. Absent VA after mitral repair was uniformly observed in patients with minor VA preoperatively. Complex baseline VA was the strongest predictor of recurrent VA (hazard ratio, 10.8; 95% confidence interval, 1.4-84.2; P  = .024), irrespective of myocardial fibrosis., Conclusions: In a series of 62 consecutive patients operated electively for arrhythmic mitral prolapse, VA remained undetected in 75.9% of patients at 1 year. Freedom from recurrent VA was greater among patients without complex VA preoperatively, whereas baseline Lown grade ≥3 was the strongest independent risk factor for recurrent VA at 1 year. These findings attest to the importance of early recognition and prompt referral of patients with mitral prolapse and progressive VA to specialty interdisciplinary care., Competing Interests: D.P. received nonfinancial support from TOMTEC Imaging Systems GmbH (PI - research license for myocardial strain analysis software). M.M. has served as a consultant to Boston Scientific. D.A. is the National co-Principal Investigator for the Triluminate-II US Pivotal Trials, the Medtronic Apollo and CoreValve US Pivotal Trials, and ReChord US Pivotal Trial, respectively. The Icahn School of Medicine at Mount Sinai receives royalty payments from Edwards Lifesciences and Medtronic for intellectual property related to D.A.’s involvement in the development of 3 mitral valve repair rings and a tricuspid valve repair ring. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

A number of studies have demonstrated the role of sex in regulating immune responses to vaccination. However, these findings have been limited to adults for both human and animal models. As a result, our understanding of the impact of sex on vaccine responses in the newborn is highly limited. Here, we probe this important question using a newborn non-human primate model. We leveraged our prior analysis of two cohorts of newborns, with one being mother-reared and one nursery-reared. This provided adequate numbers of males and females to interrogate the impact of sex on the response to inactivated influenza vaccines alone or adjuvanted with R848, flagellin, or both. We found that, in contrast to what has been reported in adults, the non-adjuvanted inactivated influenza virus vaccine induced similar levels of virus-specific IgG in male and female newborns. However, the inclusion of R848, either alone or in combination with flagellin, resulted in higher antibody titers in females compared to males. Sex-specific increases in the neutralizing antibody were only observed when both R848 and flagellin were present. These data, generated in the highly translational NHP newborn model, provide novel insights into the role of sex in the immune response of newborns.

Bridging molecular information to ecosystem-level processes would provide the capacity to understand system vulnerability and, potentially, a means for assessing ecosystem health. Here, we present an integrated dataset containing environmental and metagenomic information from plant-associated microbial communities, plant transcriptomics, plant and soil metabolomics, and soil chemistry and activity characterization measurements derived from the model tree species Populus trichocarpa. Soil, rhizosphere, root endosphere, and leaf samples were collected from 27 different P. trichocarpa genotypes grown in two different environments leading to an integrated dataset of 318 metagenomes, 98 plant transcriptomes, and 314 metabolomic profiles that are supported by diverse soil measurements. This expansive dataset will provide insights into causal linkages that relate genomic features and molecular level events to system-level properties and their environmental influences., (© 2024. UT-Battelle, LLC, Pacific Northwest National Laboratory and The Author(s).)

Purpose: This study aimed to assess both nonsurgical and operative treatment outcomes of pediatric and young adult patients with thoracic outlet syndrome (TOS) at a tertiary care pediatric hospital., Methods: A retrospective chart review of patients diagnosed with TOS, who were seen between January 2010 and August 2022 at a tertiary care pediatric hospital, was conducted. Collected pre- and postoperative data included symptoms, provocative testing (ie, Roo's, Wright's, and Adson's tests), participation in sports or upper-extremity activities, additional operations, and surgical complications. Assessment of operative treatment efficacy was based on pre- and post-provocative testing, pain, venogram results, alleviation of symptoms, and return to previous activity level 6 months after surgery., Results: Ninety-six patients, (70 females and 26 males) with an average age at onset of 15 ± 4 (4-25) years, met the inclusion criteria for TOS. Among them, 27 had neurogenic TOS, 29 had neurogenic and vasculogenic TOS, 20 had vasculogenic TOS, 19 had Paget-Schroetter Syndrome, and one was asymptomatic. Twenty-six patients were excluded because of less than 6 months of follow-up. Of the remaining 70, 6 (8.6%) patients (4 bilateral and 2 unilateral) underwent nonoperative management with activity modification and physical therapy only, and one was fully discharged because of complete relief of symptoms. Sixty-four (90.1%) patients (45 bilateral and 19 unilateral) underwent surgery. A total of 102 operations were performed. Substantial improvements were observed in provocative maneuvers after surgery. Before surgery, 79.7% were involved in sports or playing musical instruments with repetitive overhead activity, and after surgery, 86.2% of these patients returned to their previous activity level., Conclusions: Few patients were successfully managed with nonoperative activity modification and physical therapy. In those requiring surgical intervention, first or cervical rib resection with scalenectomy using a supraclavicular approach provided resolution of symptoms with 86.2% of patients being able to return to presymptom sport or activity level., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: Imaging with late gadolinium enhancement (LGE) magnetic resonance (MR) and 18 F-fluorodeoxyglucose ( 18 F-FDG) PET allows complementary assessment of myocardial injury and disease activity and has shown promise for improved characterization of active cardiac sarcoidosis (CS) based on the combined positive imaging outcome, MR(+)PET(+)., Objectives: This study aims to evaluate qualitative and quantitative assessments of hybrid MR/PET imaging in CS and to evaluate its association with cardiac-related outcomes., Methods: A total of 148 patients with suspected CS underwent hybrid MR/PET imaging. Patients were classified based on the presence/absence of LGE (MR+/MR-), presence/absence of 18 F-FDG (PET+/PET-), and pattern of 18 F-FDG uptake (focal/diffuse) into the following categories: MR(+)PET(+) FOCAL , MR(+)PET(+) DIFFUSE , MR(+)PET(-), MR(-)PET(+) FOCAL , MR(-)PET(+) DIFFUSE , MR(-)PET(-). Further analysis classified MR positivity based on %LGE exceeding 5.7% as MR(+/-) 5.7% . Quantitative values of standard uptake value, target-to-background ratio, target-to-normal-myocardium ratio (TNMRmax), and T2 were measured. The primary clinical endpoint was met by the occurrence of cardiac arrest, ventricular tachycardia, or secondary prevention implantable cardioverter-defibrillator (ICD) before the end of the study. The secondary endpoint was met by any of the primary endpoint criteria plus heart failure or heart block. MR/PET imaging results were compared between those meeting or not meeting the clinical endpoints., Results: Patients designated MR(+) 5.7% PET(+) FOCAL had increased odds of meeting the primary clinical endpoint compared to those with all other imaging classifications (unadjusted OR: 9.2 [95% CI: 3.0-28.7]; P = 0.0001), which was higher than the odds based on MR or PET alone. TNMRmax achieved an area under the receiver-operating characteristic curve of 0.90 for separating MR(+)PET(+) FOCAL from non-MR(+)PET(+) FOCAL , and 0.77 for separating those reaching the clinical endpoint from those not reaching the clinical endpoint., Conclusions: Hybrid MR/PET image-based classification of CS was statistically associated with clinical outcomes in CS. TNMRmax had modest sensitivity and specificity for quantifying the imaging-based classification MR(+)PET(+) FOCAL and was associated with outcomes. Use of combined MR and PET image-based classification may have use in prognostication and treatment management in CS., Competing Interests: Funding Support and Author Disclosures This work was supported by National Institutes of Health (NIH) grant R01 HL071021 (ZAF), NIH grant KL2 TR001435 (MGT), and AHA grant 20CDA35310099 (MGT). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Urinary tract infections (UTIs) are one of the most common infections and are frequently caused by Gram-negative organisms. The rise of resistant isolates has prompted evaluation of alternative therapies, including amoxicillin-clavulanate which has potent activity against Ambler class A enzymes. This study sought to evaluate clinical outcomes of patients with ceftriaxone non-susceptible UTIs receiving amoxicillin-clavulanate or standard of care (SOC). This was a single-center, retrospective, cohort study of adult patients with urinary tract infections caused by a ceftriaxone non-susceptible pathogen who received amoxicillin-clavulanate or SOC. The primary outcome was clinical failure at 90 days. Secondary outcomes included time to failure, isolation of a resistant organism, and hospital length of stay. Fifty-nine patients met study inclusion: 26 received amoxicillin/clavulanate and 33 received SOC. Amoxicillin-clavulanate recipients did not have higher failure rates compared to SOC recipients. For patients requiring hospital admission, hospital length of stay was numerically shorter with amoxicillin-clavulanate. The frequency of amoxicillin-clavulanate and carbapenem-resistant organisms did not differ significantly between groups. Amoxicillin-clavulanate may be a useful alternative therapy for the treatment of ceftriaxone non-susceptible Enterobacterales UTIs.

Nature-based Solutions (NbS) are integral to efforts to keep global warming below 2°C in accordance with the United Nations' 2015 Paris Agreement on Climate Change. Yet the transboundary governance dimensions of NbS remain unclear and largely undocumented. In Southeast Asia, NbS have emphasised the conservation and/ or sustainable commodification of carbon sinks found in terrestrial and mangrove forests, seagrass meadows, peatlands and agricultural soils. Mostly project-driven and fixed-term, these "solutions" have often failed to meet their social and ecological objectives. Increasingly, they have added to cross-border problems of: (1) displaced carbon emissions; and (2) economic migration and societal dispossession. This perspective paper delineates a transboundary governance research agenda to mitigate these trade-offs and enhance the co-benefits of NbS in carbon sinks. Building on NbS literature, it identifies cross-sector, multi-scalar and interdisciplinary pathways to improve transboundary cooperation, inclusion and equity in carbon sink governance in varying Southeast Asian contexts., (© 2023. The Author(s).)

Introduction and Background: Recent medical advances, including closure of myelomeningocele defects, shunting of hydrocephalus, and focusing on renal preservation have led to many individuals with spina bifida (SB) living into adulthood. This has led to more individuals with SB transitioning their care from pediatric-based to adult-based care models., Objective: We seek to explore the process of transition, with a focus on difficulties in transitioning individuals with SB. Additionally, we explore new problems that arise during the period of transition related to sexual function and dysfunction. We also discuss some of the difficulties managing neurogenic bladder and the sequalae of their prior urologic surgeries., Study Design: Each of the authors was asked to provide a summary, based on current literature, to highlight the challenges faced in their area of expertise., Conclusions: Transitioning care for individuals with SB is especially challenging due to associated neurocognitive deficits and neuropsychological functioning issues. Sexual function is an important component of transition that must be addressed in young adults with SB. Management of neurogenic bladder in adults with SB can be challenging due to the heterogeneity of the population and the sequelae of their prior urologic surgeries. The aim is to ensure that all individuals with SB receive appropriate, evidence-based care throughout their lifetime., (Copyright © 2023 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

This study investigated the presence of Mycobacterium bovis ( M. bovis ) DNA in archived human sputum samples previously collected from residents who reside adjacent to the M. bovis -endemic Hluhluwe-iMfolozi wildlife park, South Africa (SA). Sixty-eight sputum samples were GeneXpert MTB/RIF Ultra-positive for M. tuberculosis complex (MTBC) DNA but culture negative for M. tuberculosis . Amplification and Sanger sequencing of hsp65 and rpoB genes from DNA extracted from stored heat-inactivated sputum samples confirmed the presence of detectable amounts of MTBC from 20 out of the 68 sputum samples. Region of difference PCR, spoligotyping and gyrB long-read amplicon deep sequencing identified M. bovis ( n  = 10) and M. tuberculosis ( n  = 7). Notably, M. bovis spoligotypes SB0130 and SB1474 were identified in 4 samples, with SB0130 previously identified in local cattle and wildlife and SB1474 exclusively in African buffaloes in the adjacent park. M. bovis DNA in sputum, from people living near the park, underscores zoonotic transmission potential in SA. Identification of spoligotypes specifically associated with wildlife only and spoligotypes found in livestock as well as wildlife, highlights the complexity of TB epidemiology at wildlife-livestock-human interfaces. These findings support the need for integrated surveillance and control strategies to curb potential spillover and for the consideration of human M. bovis infection in SA patients with positive Ultra results., Competing Interests: All authors declare no competing financial and/or non-financial interests in relation to the work described., (© 2024 The Authors.)

Background: The introduction of intraoperative cytology revolutionized neurosurgical procedures in human medicine, providing real-time diagnostic guidance to surgeons and contributing to improved patient outcomes. In the realm of veterinary medicine, the understanding of pituitary tumors in dogs and cats remains limited due to challenges in obtaining antemortem samples of central nervous system lesions., Objectives: The aim of this study was to describe the cytologic features of pituitary adenomas in 12 dogs that underwent hypophysectomy., Methods: The series included nine melanotroph adenomas and three corticotroph adenomas. Definitive diagnosis was based on histopathology and immunohistochemistry., Results: Cytologically, the adenomas had high numbers of bare nuclei and intact cells that were round to polygonal and situated individually or in small clusters. The intact cells had round to oval, eccentric nuclei with finely stippled chromatin and one to three prominent nucleoli and ample to abundant lightly basophilic to amphophilic, grainy cytoplasm with distinct borders, and variable numbers of discrete vacuoles. Mild-to-moderate anisocytosis and anisokaryosis, occasional binucleation, rare and atypical mitotic figures, and nuclear molding were also observed., Conclusions: The results suggest that intraoperative cytology of canine pituitary adenomas holds promise as a valuable diagnostic tool, aiding swift differentiation from other sellar masses before histologic confirmation. Cytologic characterization of pituitary adenomas in dogs is exceptionally rare in the scientific literature, making this study one of the first to offer a comprehensive description of these cytologic features., (© 2024 The Authors. Veterinary Clinical Pathology published by Wiley Periodicals LLC on behalf of American Society for Veterinary Clinical Pathology.)

Several adverse cutaneous reactions have been reported in the literature after SARS-CoV-2 vaccination with emerging reports on chronic spontaneous urticaria (CSU). However, there is little literature of chronic urticaria after COVID-19 boosters in a military population and the impact on operational readiness. We present a retrospective case series of CSU following Moderna COVID-19 booster vaccinations at the US Naval Academy (USNA). Demographics, clinical features, and impact on readiness were evaluated. Forty-nine students from the USNA were evaluated for urticaria after their third COVID-19 booster vaccination. Seventeen individuals were diagnosed with CSU. The median age was 20 years and predominantly male; the median time interval between vaccination and the onset of urticaria was 11 days. Out of 13 referred to Allergy, 7 patients had CU index performed and 2 were positive. Four patients received a second booster vaccination subsequently and did not have any exacerbation of symptoms. Symptoms were controlled with antihistamines, and none required immunomodulator or immunosuppressive therapies. All students were able to complete their commissioning, and none were referred for a medical board. In this series, USNA students who developed CSU after the mRNA COVID-19 Moderna booster vaccine did not have limitations from commissioning, duty status, or issues with subsequent COVID-19 vaccinations., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Animal tuberculosis, caused by Mycobacterium bovis , presents a significant threat to both livestock industries and public health. Mycobacterium bovis tests rely on detecting antigen specific immune responses, which can be influenced by exposure to non-tuberculous mycobacteria, test technique, and duration and severity of infection. Despite advancements in direct M. bovis detection, mycobacterial culture remains the primary diagnostic standard. Recent efforts have explored culture-independent PCR-based methods for identifying mycobacterial DNA in respiratory samples. This study aimed to detect M. bovis in nasal swabs from goats ( Capra hircus ) cohabiting with M. bovis -infected cattle in KwaZulu-Natal, South Africa. Nasal swabs were collected from 137 communal goats exposed to M. bovis -positive cattle and 20 goats from a commercial dairy herd without M. bovis history. Swabs were divided into three aliquots for analysis. The first underwent GeneXpert® MTB/RIF Ultra assay (Ultra) screening. DNA from the second underwent mycobacterial genus-specific PCR and Sanger sequencing, while the third underwent mycobacterial culture followed by PCR and sequencing. Deep sequencing identified M. bovis DNA in selected Ultra-positive swabs, confirmed by region-of-difference (RD) PCR. Despite no other evidence of M. bovis infection, viable M. bovis was cultured from three communal goat swabs, confirmed by PCR and sequencing. Deep sequencing of DNA directly from swabs identified M. bovis in the same culture-positive swabs and eight additional communal goats. No M. bovis was found in commercial dairy goats, but various NTM species were detected. This highlights the risk of M. bovis exposure or infection in goats sharing pastures with infected cattle. Rapid Ultra screening shows promise for selecting goats for further M. bovis testing. These techniques may enhance M. bovis detection in paucibacillary samples and serve as valuable research tools., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cooke, Clarke, Kerr, Warren, Witte, Miller and Goosen.)

Campylobacter jejuni and Campylobacter coli are well known for their natural competence, i.e., their capacity for the uptake of naked DNA with subsequent transformation. This study identifies non-transformable C. jejuni and C. coli strains from domestic animals and employs genomic analysis to investigate the strain genotypes and their associated genetic mechanisms. The results reveal genetic associations leading to a non-transformable state, including functional DNase genes from bacteriophages and mutations within the cts -encoded DNA-uptake system, which impact the initial steps of the DNA uptake during natural transformation. Interestingly, all 38 tested C. jejuni ST-50 strains from the United States exhibit a high prevalence of non-transformability, and the strains harbor a variety of these genetic markers. This research emphasizes the role of these genetic markers in hindering the transfer of antimicrobial resistance (AMR) determinants, providing valuable insights into the genetic diversity of Campylobacter . As ST-50 is a major clone of C. jejuni globally, we additionally determined the prevalence of the genetic markers for non-transformability among C. jejuni ST-50 from different regions of the world, revealing distinct patterns of evolution and a strong selective pressure on the loss of competence in ST-50 strains, particularly in the agricultural environment in the United States. Our findings contribute to a comprehensive understanding of genetic exchange mechanisms within Campylobacter strains, and their implications for antimicrobial resistance dissemination and evolutionary pathways within specific lineages.

Erysipelothrix spp., including E. rhusiopathiae , are zoonotic bacterial pathogens that can cause morbidity and mortality in mammals, fish, reptiles, birds, and humans. The southern sea otter (SSO; Enhydra lutris nereis ) is a federally-listed threatened species for which infectious disease is a major cause of mortality. We estimated the frequency of detection of these opportunistic pathogens in dead SSOs, described pathology associated with Erysipelothrix infections in SSOs, characterized the genetic diversity and antimicrobial susceptibility of SSO isolates, and evaluated the virulence of two novel Erysipelothrix isolates from SSOs using an in vivo fish model. From 1998 to 2021 Erysipelothrix spp. were isolated from six of >500 necropsied SSOs. Erysipelothrix spp. were isolated in pure culture from three cases, while the other three were mixed cultures. Bacterial septicemia was a primary or contributing cause of death in five of the six cases. Other pathology observed included suppurative lymphadenopathy, fibrinosuppurative arteritis with thrombosis and infarction, bilateral uveitis and endophthalmitis, hypopyon, petechia and ecchymoses, mucosal infarction, and suppurative meningoencephalitis and ventriculitis. Short to long slender Gram-positive or Gram-variable bacterial rods were identified within lesions, alone or with other opportunistic bacteria. All six SSO isolates had the spaA genotype-four isolates clustered with spaA E. rhusiopathiae strains from various terrestrial and marine animal hosts. Two isolates did not cluster with any known Erysipelothrix spp.; whole genome sequencing revealed a novel Erysipelothrix species and a novel E. rhusiopathiae subspecies. We propose the names Erysipelothrix enhydrae sp. nov. and Erysipelothrix rhusiopathiae ohloneorum ssp. nov. respectively. The type strains are E. enhydrae UCD-4322-04 and E. rhusiopathiae ohloneorum UCD-4724-06, respectively. Experimental injection of tiger barbs ( Puntigrus tetrazona ) resulted in infection and mortality from the two novel Erysipelothrix spp. Antimicrobial susceptibility testing of Erysipelothrix isolates from SSOs shows similar susceptibility profiles to isolates from other terrestrial and aquatic animals. This is the first description of the pathology, microbial characteristics, and genetic diversity of Erysipelothrix isolates recovered from diseased SSOs. Methods presented here can facilitate case recognition, aid characterization of Erysipelothrix isolates, and illustrate assessment of virulence using fish models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chang, Miller, Tekedar, Rose, García, LaFrentz, Older, Waldbieser, Pomaranski, Shahin, Camus, Batac, Byrne, Murray, Griffin and Soto.)