DNA hydrogels for bone regeneration.

DNA-based biomaterials have been proposed for tissue engineering approaches due to their predictable assembly into complex morphologies and ease of functionalization. For bone tissue regeneration, the ability to bind Ca2+ and promote hydroxyapatite (HAP) growth along the DNA backbone combined with their degradation and release of extracellular phosphate, a known promoter of osteogenic differentiation, make DNA-based biomaterials unlike other currently used materials. However, their use as biodegradable scaffolds for bone repair remains scarce. Here, we describe the design and synthesis of DNA hydrogels, gels composed of DNA that swell in water, their interactions in vitro with the osteogenic cell lines MC3T3-E1 and mouse calvarial osteoblast, and their promotion of new bone formation in rat calvarial wounds. We found that DNA hydrogels can be readily synthesized at room temperature, and they promote HAP growth in vitro, as characterized by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, atomic force microscopy, and transmission electron microscopy. Osteogenic cells remain viable when seeded on DNA hydrogels in vitro, as characterized by fluorescence microscopy. In vivo, DNA hydrogels promote the formation of new bone in rat calvarial critical size defects, as characterized by micro-computed tomography and histology. This study uses DNA hydrogels as a potential therapeutic biomaterial for regenerating lost bone.

Revisiting resistant hypertension: a comprehensive review.

Resistant hypertension (RHT) is typically defined as blood pressure that remains above guideline-directed targets despite the use of three anti-hypertensives, usually including a diuretic, at optimal or maximally tolerated doses. It is generally estimated to affect 10-30% of those diagnosed with hypertension, though the true incidence might be lower after one factor in the prevalence of non-adherence. Risk factors for its development include diabetes, obesity and other adverse lifestyle factors, and a diagnosis of RHT confers a greater risk of adverse cardiovascular outcomes, such as stroke, heart failure and mortality. It is essential to exclude pseudoresistance and secondary hypertension and to ensure non-pharmacologic management is optimised prior to consideration of fourth-line anti-hypertensive agents or advanced interventions, such as device therapies. In this review, we will cover the different definitions of RHT, along with the importance of careful diagnosis and management strategies, and discuss newer agents and research needs.

Quantized spiral-phase-modulation based deep learning for real-time defocusing distance prediction.

Whole slide imaging (WSI) has become an essential tool in pathological diagnosis, owing to its convenience on remote and collaborative review. However, how to bring the sample at the optimal position in the axial direction and image without defocusing artefacts is still a challenge, as traditional methods are either not universal or time-consuming. Until recently, deep learning has been shown to be effective in the autofocusing task in predicting defocusing distance. Here, we apply quantized spiral phase modulation on the Fourier domain of the captured images before feeding them into a light-weight neural network. It can significantly reduce the average predicting error to be lower than any previous work on an open dataset. Also, the high predicting speed strongly supports it can be applied on an edge device for real-time tasks with limited computational source and memory footprint.

Natural History of Cricopharyngeus Muscle Dysfunction Symptomatology.

Cricopharyngeus muscle dysfunction (CPMD) is a common cause for progressive dysphagia and can lead to dietary restriction, reduced nutrition, weight loss, and pneumonia. There is a continuum between small, non-obstructive cricopharyngeus bars representing mild disease and severely obstructive bars or Zenker's diverticulum forming late-stage disease, but the natural history of untreated CPMD and the associated time course for progression is unknown. Retrospective longitudinal cohort study from a tertiary outpatient dysphagia centre. Patients diagnosed with CPMD by fluoroscopy and either awaiting surgical treatment or electing non-operative management were evaluated through prospectively collected Eating Assessment Tool-10 (EAT-10) and Functional Oral Intake Scale (FOIS). Review of available imaging identified degree of CPMD. We identified 174 patients with CPMD diagnosed between July 1, 2016, and June 30, 2020; 52 patients had serial Eating Assessment Tool (EAT-10) measures obtained at time of diagnosis and follow up appointment without operative treatment. Mean EAT-10 scores increased from 17.1 to 20.6 (3.5 ± 8.1 points, p = 0.002) points. This change was related to those with a Zenker's diverticulum rather than an isolated cricopharyngeus bar. Dietary outcomes measured by FOIS were stable. While some patients showed fluoroscopic progression of bar size, no patients developed a Zenker's diverticulum from a pre-existing bar in this population. Our data indicate patients with a cricopharyngeus bar do not decline in subjective dysphagia score or diet tolerance, however those with a Zenker's diverticulum worsen over time. This has implications for treatment timing and counselling patients but also reflects a need to understand the pathophysiology behind CPMD and the subset of patients who show progression.

Understanding the Future Prospects of Synergizing Minimally Invasive Transforaminal Lumbar Interbody Fusion Surgery with Ceramics and Regenerative Cellular Therapies.

Transforaminal lumber interbody fusion (TLIF) is the last resort to address the lumber degenerative disorders such as spondylolisthesis, causing lower back pain. The current surgical intervention for these abnormalities includes open TLIF. However, in recent years, minimally invasive TLIF (MIS-TLIF) has gained a high momentum, as it could minimize the risk of infection, blood loss, and post-operative complications pertaining to fusion surgery. Further advancement in visualizing and guiding techniques along with grafting cage and materials are continuously improving the safety and efficacy of MIS-TLIF. These assistive techniques are also playing a crucial role to increase and improve the learning curve of surgeons. However, achieving an appropriate output through TLIF still remains a challenge, which might be synergized through 3D-printing and tissue engineering-based regenerative therapy. Owing to their differentiation potential, biomaterials such as stem/progenitor cells may contribute to restructuring lost or damaged tissues during MIS-TLIF, and this therapeutic efficacy could be further supplemented by platelet-derived biomaterials, leading to improved clinical outcomes. Thus, based on the above-mentioned strategies, we have comprehensively summarized recent developments in MIS-TLIF and its possible combinatorial regenerative therapies for rapid and long-term relief.

Differential Domain Distribution of gnomAD- and Disease-Linked Connexin Missense Variants.

Twenty-one human genes encode connexins, a family of homologous proteins making gap junction (GJ) channels, which mediate direct intercellular communication to synchronize tissue/organ activities. Genetic variants in more than half of the connexin genes are associated with dozens of different Mendelian inherited diseases. With rapid advances in DNA sequencing technology, more variants are being identified not only in families and individuals with diseases but also in people in the general population without any apparent linkage to Mendelian inherited diseases. Nevertheless, it remains challenging to classify the pathogenicity of a newly identified connexin variant. Here, we analyzed the disease- and Genome Aggregation Database (gnomAD, as a proxy of the general population)-linked variants in the coding region of the four disease-linked α connexin genes. We found that the most abundant and position-sensitive missense variants showed distinct domain distribution preference between disease- and gnomAD-linked variants. Plotting missense variants on topological and structural models revealed that disease-linked missense variants are highly enriched on the structurally stable/resolved domains, especially the pore-lining domains, while the gnomAD-linked missense variants are highly enriched in the structurally unstable/unresolved domains, especially the carboxyl terminus. In addition, disease-linked variants tend to be on highly conserved residues and those positions show evolutionary co-variation, while the gnomAD-linked missense variants are likely on less conserved residue positions and on positions without co-variation. Collectively, the revealed distribution patterns of disease- and gnomAD-linked missense variants further our understanding of the GJ structure-biological function relationship, which is valuable for classifying the pathogenicity of newly identified connexin variants.

Axially resolved volumetric two-photon microscopy with an extended field of view using depth localization under mirrored Airy beams.

It is a great challenge in two-photon microscopy (2PM) to have a high volumetric imaging speed without sacrificing the spatial and temporal resolution in three dimensions (3D). The structure in 2PM images could be reconstructed with better spatial and temporal resolution by the proper choice of the data processing algorithm. Here, we propose a method to reconstruct 3D volume from 2D projections imaged by mirrored Airy beams. We verified that our approach can achieve high accuracy in 3D localization over a large axial range and is applicable to continuous and dense sample. The effective field of view after reconstruction is expanded. It is a promising technique for rapid volumetric 2PM with axial localization at high resolution.

Nursing Students' Perceived Self-Efficacy and the Generation of Medication Errors with the Use of an Electronic Medication Administration Record (eMAR) in Clinical Simulation.

Medication errors continue to be a significant issue, posing substantial threats to the safety and well-being of patients. Through Bandura's theory of self-efficacy, nursing students' self-efficacy (confidence) related to medication administration was examined to investigate its influence on the generation of medication errors with the use of an Electronic Medication Administration Record (eMAR) in clinical simulation. This study examined the generation of medication errors and the differences that may exist based on nursing students' perceived confidence. The findings of this study demonstrated that nursing students continue to generate medication errors within clinical simulation. No differences in the generation of medication errors were found between nursing students with perceived high levels of confidence and those with perceived low levels of confidence (one exception noted). Further examination of the variables and contextual factors related to safe medication administration practices is required to inform nursing education and practice.

Analysis of decreases in systemic arterial pressure and heart rate in response to the hydrogen sulfide donor sodium sulfide.

The actions of hydrogen sulfide (H2S) on the heart and vasculature have been extensively reported. However, the mechanisms underlying the effects of H2S are unclear in the anesthetized rat. The objective of the present study was to investigate the effect of H2S on the electrocardiogram and examine the relationship between H2S-induced changes in heart rate (HR), mean arterial pressure (MAP), and respiratory function. Intravenous administration of the H2S donor Na2S in the anesthetized Sprague-Dawley rat decreased MAP and HR and produced changes in respiratory function. The administration of Na2S significantly increased the RR interval at some doses but had no effect on PR or corrected QT(n)-B intervals. In experiments where respiration was maintained with a mechanical ventilator, we observed that Na2S-induced decreases in MAP and HR were independent of respiration. In experiments where respiration was maintained by mechanical ventilation and HR was maintained by cardiac pacing, Na2S-induced changes in MAP were not significantly altered, whereas changes in HR were abolished. Coadministration of glybenclamide significantly increased MAP and HR responses at some doses, but methylene blue, diltiazem, and ivabradine had no significant effect compared with control. The decreases in MAP and HR in response to Na2S could be dissociated and were independent of changes in respiratory function, ATP-sensitive K+ channels, methylene blue-sensitive mechanism involving L-type voltage-sensitive Ca2+ channels, or hyperpolarization-activated cyclic nucleotide-gated channels. Cardiovascular responses observed in spontaneously hypertensive rats were more robust than those in Sprague-Dawley rats.NEW & NOTEWORTHY H2S is a gasotransmitter capable of producing a decrease in mean arterial pressure and heart rate. The hypotensive and bradycardic effects of H2S can be dissociated, as shown with cardiac pacing experiments. Responses were not blocked by diltiazem, ivabradine, methylene blue, or glybenclamide.

Early steroid withdrawal results in improved patient and graft survival and lower risk of post-transplant cardiovascular risk profiles: A single-center 10-year experience.

Long-term use of steroids results in predictable secondary effects that can lead to increased morbidity and mortality. In this study, we present 10 years worth of data of early steroid withdrawal (ESW) immunosuppression consisting of mycophenolate, sirolimus, and tacrolimus. From 2003 to 2013, 563 kidney transplant recipients were weaned off steroids prior to discharge. We compared outcomes with that of our 65 historical controls maintained on steroids. We analyzed graft and patient survival and determined the incidence of steroid-related comorbidities such as hypertension, hypercholesterolemia, diabetes, coronary artery disease, and weight gain. Patients on ESW maintenance immunosuppression had improved patient and graft survival compared to controls. (HR: 0.23; P≤.011, 0.57; P=.026). Rates of biopsy-proven acute rejection were not different among both groups (HR: 1.24; P=.610). Incidence of post-transplant diabetes were reduced but not statistically significant (OR: 0.67; P=.138). Additionally, the development of hypertension (OR: 0.86, P≤.01), hypercholesterolemia (RR: 0.82; P=.027), CAD (RR: 0.43; P=.002), and >20 lbs. weight gain (RR: 0.29; P≤.01) was significantly improved over 10 years following initiation of ESW protocols. Early steroid withdrawal in renal transplant recipients results in improved patient and graft survival as well as better rates of post-transplant comorbid conditions.

Clinical Impact of Changes in Left Ventricular Function After Aortic Valve Replacement: Analysis From 3112 Patients.

BACKGROUND: Our objectives were to identify correlates of mortality and congestive heart failure after aortic valve replacement (AVR) according to preoperative left ventricular (LV) function and to describe the incidence, time course, and correlates of LV recovery and mass regression postoperatively. METHODS AND RESULTS: A total of 3112 patients with AVR were assessed in a follow-up clinic with echocardiography (median follow-up, 6.0 years). At operation, their mean age was 67.8±13.4 years, one third were female, and 29% had LV dysfunction (ejection fraction <50%). In severe patients with severe aortic stenosis and LV dysfunction, transaortic valve mean pressure gradient <40 mm Hg, longer cardiopulmonary bypass duration, and prosthesis-patient mismatch (indexed effective orifice area ≤0.85 cm(2)/m(2)) were independent correlates of the composite outcome of death or congestive heart failure after AVR. In patients with severe aortic regurgitation and LV dysfunction, older age and higher preoperative LV mass were identified. LV recovery correlated with better survival and freedom from heart failure in patients with aortic stenosis. Maximum LV mass regression took 24 months in patients with aortic stenosis and nearly 5 years with aortic regurgitation; independent correlates included smaller LV end-systolic diameter in patients with aortic stenosis and low New York Heart Association class with aortic regurgitation. CONCLUSIONS: Incomplete LV recovery, prosthesis-patient mismatch, low transaortic valve pressure gradient, and higher LV mass are associated with increased mortality or heart failure after AVR in patients with LV dysfunction. Higher LV end-systolic diameter and symptoms correlate with less LV mass regression, which takes at least 2 years. These findings help surgeons and cardiologists refine the indications, timing, prognostication, and follow-up of patients before and after AVR.

Nebivolol has a beneficial effect in monocrotaline-induced pulmonary hypertension.

Pulmonary hypertension is a rare disorder that, without treatment, is progressive and fatal within 3-4 years. Current treatment involves a diverse group of drugs that target the pulmonary vascular bed. In addition, strategies that increase nitric oxide (NO) formation have a beneficial effect in rodents and patients. Nebivolol, a selective ß1 adrenergic receptor-blocking agent reported to increase NO production and stimulate ß3 receptors, has vasodilator properties suggesting that it may be beneficial in the treatment of pulmonary hypertension. The present study was undertaken to determine whether nebivolol has a beneficial effect in monocrotaline-induced (60 mg/kg) pulmonary hypertension in the rat. These results show that nebivolol treatment (10 mg/kg, once or twice daily) attenuates pulmonary hypertension, reduces right ventricular hypertrophy, and improves pulmonary artery remodeling in monocrotaline-induced pulmonary hypertension. This study demonstrates the presence of ß3 adrenergic receptor immunoreactivity in pulmonary arteries and airways and that nebivolol has pulmonary vasodilator activity. Studies with ß3 receptor agonists (mirabegron, BRL 37344) and antagonists suggest that ß3 receptor-mediated decreases in systemic arterial pressure occur independent of NO release. Our results suggest that nebivolol, a selective vasodilating ß1 receptor antagonist that stimulates ß3 adrenergic receptors and induces vasodilation by increasing NO production, may be beneficial in treating pulmonary hypertensive disorders.

3D tumor tissue analogs and their orthotopic implants for understanding tumor-targeting of microenvironment-responsive nanosized chemotherapy and radiation.

An appropriate representation of the tumor microenvironment in tumor models can have a pronounced impact on directing combinatorial treatment strategies and cancer nanotherapeutics. The present study develops a novel 3D co-culture spheroid model (3D TNBC) incorporating tumor cells, endothelial cells and fibroblasts as color-coded murine tumor tissue analogs (TTA) to better represent the tumor milieu of triple negative breast cancer in vitro. Implantation of TTA orthotopically in nude mice, resulted in enhanced growth and aggressive metastasis to ectopic sites. Subsequently, the utility of the model is demonstrated for preferential targeting of irradiated tumor endothelial cells via radiation-induced stromal enrichment of galectin-1 using anginex conjugated nanoparticles (nanobins) carrying arsenic trioxide and cisplatin. Demonstration of a multimodal nanotherapeutic system and inclusion of the biological response to radiation using an in vitro/in vivo tumor model incorporating characteristics of tumor microenvironment presents an advance in preclinical evaluation of existing and novel cancer nanotherapies. FROM THE CLINICAL EDITOR: Existing in-vivo tumor models are established by implanting tumor cells into nude mice. Here, the authors described their approach 3D spheres containing tumor cells, enodothelial cells and fibroblasts. This would mimic tumor micro-environment more realistically. This interesting 3D model should reflect more accurately tumor response to various drugs and would enable the design of new treatment modalities.

Vascular Access Considerations in Home Hemodialysis.

There is a global interest in expanding home dialysis utilization among patients with ESKD. Home hemodialysis (HHD) is an appealing KRT option for this population because of its multiple clinical and quality of life benefits. Central to successful HHD is the establishment and maintenance of a functioning vascular access that serves as a patient's lifeline while on therapy. While the selection of a vascular access type is influenced by individual patient circumstances, the arteriovenous fistula is generally the preferred access method. Training patients to use their dialysis access requires attention to safety, risk management, and monitoring for complications to minimize adverse events and technique failure. Policies incorporating systematic frameworks for quality improvement and assurance, in conjunction with the measurement of metrics relating to vascular access, are tools that should be used by HHD programs to enhance the value of care delivered. In this perspective, we aim to describe what is currently known about the various vascular access options in HHD and to elucidate what needs to be taken into consideration in the selection and care of this access.

Take-Home Naloxone Access and Use among Older Adults Living with Pain: A Scoping Review.

Background: Opioids are a common treatment for older adults living with pain. Given high rates of polypharmacy and chronic comorbidities, older adults are at risk of opioid overdose. Evidence is now available that take-home naloxone (THN) supports reduction of opioid-related harms. It is unknown what THN initiatives are available for older adults, especially those living with chronic pain. Objective: To summarize the literature regarding THN, with a focus on older adults using opioids for pain, including facilitators of and barriers to THN access, knowledge gaps, and pharmacist-led initiatives. Data Sources: A scoping review, guided by an established framework and PRISMA-ScR guidelines, was performed. Methods involved searching 6 bibliographic databases (MEDLINE, Embase, Scopus, APA PsycINFO, Web of Science Core Collection, and PubMed), reference harvesting, and citation tracking. Searches were conducted up to March 2023, with no date limits applied; only English publications were included. Study Selection and Data Extraction: Study eligibility was determined according to preset criteria, including age; discrepancies were resolved by discussion and consensus. Data were extracted and categorized through thematic analysis. Data Synthesis: Four studies met the eligibility criteria. All 4 studies detailed THN programs in primary care settings involving older adults taking opioids for pain management. Two of the studies highlighted patient-specific risk factors for opioid overdose, including concomitant use of benzodiazepines and/or gabapentinoids, mean morphine milligram equivalents per day of at least 50, and previous opioid overdose. Two of the studies assessed patient knowledge of opioid overdose management and attitudes toward THN. Educational programs increased patients' interest in THN. Conclusions: The literature about THN for older adults living with pain is limited, and no literature was found on pharmacist-led initiatives in this area. Future research on THN provision for older adults, including pharmacist-led initiatives, could help to optimize care for older adults living with pain.

Contexte: Les opioïdes sont un traitement courant pour les personnes âgées souffrant de douleur. Compte tenu des taux élevés de polypharmacie et de comorbidités chroniques, les personnes âgées courent un risque de surdose d'opioïdes. Il est désormais prouvé que la distribution de trousses de naloxone contribue à la réduction des méfaits liés aux opioïdes. On ne sait pas quelles initiatives de distribution de trousses de naloxone existent pour les personnes âgées, en particulier celles souffrant de douleurs chroniques. Objectif: Résumer la documentation concernant la distribution des trousses de naloxone chez les personnes âgées qui utilisent des opioïdes contre la douleur, y compris les facilitateurs et les obstacles à l'accès aux trousses, les lacunes dans les connaissances et les initiatives menées par les pharmaciens. Sources des données: Un examen de la portée, guidé par un cadre éprouvé et les lignes directrices PRISMA-ScR, a été réalisé. Les méthodes impliquaient la recherche dans 6 bases de données bibliographiques (MEDLINE, Embase, Scopus, APA PsycINFO, Web of Science Core Collection et PubMed), la récolte de références et le suivi des citations. Les recherches ont été effectuées jusqu'en mars 2023, sans limites quant à la date; seules les publications en anglais ont été incluses. Sélection des études et extraction des données: L'admissibilité à l'étude a été déterminée selon des critères prédéfinis, notamment l'âge; les divergences ont été résolues par discussion et consensus. Les données ont été extraites et catégorisées grâce à une analyse thématique. Synthèse des données: Quatre études répondaient aux critères d'admissibilité. Les 4 études ont détaillé des programmes de distribution de trousses de naloxone dans des établissements de soins primaires chez les personnes âgées prenant des opioïdes pour gérer la douleur. Deux des études ont mis en évidence des facteurs de risque spécifiques aux patients en matière de surdosage aux opioïdes, notamment l'utilisation concomitante de benzodiazépines et/ou de gabapentinoïdes, une moyenne d'équivalents en milligrammes de morphine par jour d'au moins 50 et un surdosage antérieur aux opioïdes. Deux des études ont évalué les connaissances des patients en matière de gestion des surdosages aux opioïdes et leur attitude envers la distribution de trousses de naloxone. Les programmes éducatifs ont accru l'intérêt des patients pour les trousses de naloxone. Conclusions: La documentation sur la distribution de trousses de naloxone chez les personnes âgées souffrant de douleur est limitée et aucune littérature n'a été trouvée sur les initiatives menées par les pharmaciens dans ce domaine. Les recherches futures sur la distribution de trousses de naloxone aux personnes âgées, y compris les initiatives menées par des pharmaciens, pourraient contribuer à optimiser les soins aux personnes âgées souffrant de douleur.

One-Year Follow-Up Study on Assessing the Range of Segmental Motion and Clinical Outcomes Following Cervical Disc Arthroplasty for Treatment of Severe Cervical Disc Degeneration.

BACKGROUND: Though previous studies have documented various clinical outcomes after cervical arthroplasty for degenerative cervical disc disease, none of them reported the impact of cervical arthroplasty on severe cervical disc degeneration (CDD). METHODS: This retrospective cohort study included severe 40 CDD (C3-C7) patients who underwent single-level cervical arthroplasty using ProDisc-C between January 2017 and December 2019. After surgical intervention, the range of motion (ROM) was determined, whereas clinical outcomes were measured in terms of the Visual Analogue Scale (VAS) and Neck Disability Index (NDI) to evaluate neck pain and disability, respectively. RESULTS: Compared to the mean preoperative ROM (6.57 ± 4.85°), the cervical dynamic ROM was increased 3 months after cervical arthroplasty, and the increment was maintained for at least 1 year. The increased ROM is attributed to the extension and not flexion components. The mean preoperative ROM of 6.57 ± 4.85° significantly increased to 11.67 ± 4.98° (P = 0.0005), 10.05 ± 5.18° (P = 0.0426) and 10.46 ± 4.73° (P = 0.0247) after 3 months, 6 months and 1 year, respectively. The extension ROM also revealed a similar trend. VAS for neck and arm decreased from 7.4 and 6.6 to 1.4 and 1.2, respectively. Consistently, the preoperative mean Neck Disability Index (NDI) score of 27.6 decreased to 14.6. We recorded a case of device subsidence, but without extrusion. CONCLUSIONS: Cervical arthroplasty can improve clinical outcomes and restore ROM in severe CDD patients.

A rapid review on current and potential uses of large language models in nursing.

BACKGROUND: The application of large language models across commercial and consumer contexts has grown exponentially in recent years. However, a gap exists in the literature on how large language models can support nursing practice, education, and research. This study aimed to synthesize the existing literature on current and potential uses of large language models across the nursing profession. METHODS: A rapid review of the literature, guided by Cochrane rapid review methodology and PRISMA reporting standards, was conducted. An expert health librarian assisted in developing broad inclusion criteria to account for the emerging nature of literature related to large language models. Three electronic databases (i.e., PubMed, CINAHL, and Embase) were searched to identify relevant literature in August 2023. Articles that discussed the development, use, and application of large language models within nursing were included for analysis. RESULTS: The literature search identified a total of 2028 articles that met the inclusion criteria. After systematically reviewing abstracts, titles, and full texts, 30 articles were included in the final analysis. Nearly all (93 %; n = 28) of the included articles used ChatGPT as an example, and subsequently discussed the use and value of large language models in nursing education (47 %; n = 14), clinical practice (40 %; n = 12), and research (10 %; n = 3). While the most common assessment of large language models was conducted by human evaluation (26.7 %; n = 8), this analysis also identified common limitations of large language models in nursing, including lack of systematic evaluation, as well as other ethical and legal considerations. DISCUSSION: This is the first review to summarize contemporary literature on current and potential uses of large language models in nursing practice, education, and research. Although there are significant opportunities to apply large language models, the use and adoption of these models within nursing have elicited a series of challenges, such as ethical issues related to bias, misuse, and plagiarism. CONCLUSION: Given the relative novelty of large language models, ongoing efforts to develop and implement meaningful assessments, evaluations, standards, and guidelines for applying large language models in nursing are recommended to ensure appropriate, accurate, and safe use. Future research along with clinical and educational partnerships is needed to enhance understanding and application of large language models in nursing and healthcare.

Detection of colonization by carbapenemase-producing Gram-negative Bacilli in patients by use of the Xpert MDRO assay.

Detecting colonization of patients with carbapenemase-producing bacteria can be difficult. This study compared the sensitivity and specificity of a PCR-based method (Xpert MDRO) for detecting blaKPC, blaNDM, and blaVIM carbapenem resistance genes using GeneXpert cartridges to the results of culture with and without a broth enrichment step on 328 rectal, perirectal, and stool samples. The culture method included direct inoculation of a MacConkey agar plate on which a 10-µg meropenem disk was placed and plating on MacConkey agar after overnight enrichment of the sample in MacConkey broth containing 1 µg/ml of meropenem. Forty-three (13.1%) samples were positive by PCR for blaKPC and 11 (3.4%) were positive for blaVIM; none were positive for blaNDM. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the PCR assay for blaKPC were 100%, 99.0%, 93.0%, and 100%, respectively, compared to broth enrichment culture and sequencing of target genes. The sensitivity, specificity, PPV, and NPV of the assay for blaVIM were 100%, 99.4%, 81.8%, and 100%, respectively. Since none of the clinical samples contained organisms with blaNDM, 66 contrived stool samples were prepared at various dilutions using three Klebsiella pneumoniae isolates containing blaNDM. The PCR assay showed 100% positivity at dilutions from 300 to 1,800 CFU/ml and 93.3% at 150 CFU/ml. The Xpert MDRO PCR assay required 2 min of hands-on time and 47 min to complete. Rapid identification of patients colonized with carbapenemase-producing organisms using multiplex PCR may help hospitals to improve infection control activities.