Advances in biomimetic AIE nanoparticles for diagnosis and phototherapy.

This minireview provides an overview of the recent advancements in the development of biomimetic Aggregation-Induced Emission (AIE) nanoparticles and their applications in disease diagnosis, phototherapy, and photoimmunotherapy. AIE nanoparticles can be engineered to enable efficient image-guided photodynamic and photothermal therapies, however, challenges related to immune defense and target specificity persist. To overcome these, coating biomimetic materials on the surface of AIE nanoparticles, which mimic the features and functions of native cells, have emerged as a promising solution. This minireview will highlight the synthesis strategies and discuss the biomedical application of biomimetic AIE nanoparticles.

Recyclable and Environmentally Friendly Magnetic Nanoparticles with Aggregation-Induced Emission Photosensitizer for Sustainable Bacterial Inactivation in Water.

Bacterial photodynamic inactivation based on the combined actions of photosensitizers, light, and oxygen presents a promising alternative for eliminating bacteria compared to conventional water disinfection methods. However, a significant challenge in this approach is the inability to retrieve photosensitizers after phototreatment, posing potential adverse environmental impacts. Additionally, conventional photosensitizers often exhibit limited photostability and photodynamic efficiency. This study addresses these challenges by employing an aggregation-induced emission (AIE) photosensitizer, iron oxide magnetic nanoparticles (Fe3O4 MNPs), and Pluronic F127 to fabricate AIE magnetic nanoparticles (AIE MNPs). AIE MNPs not only exhibit fluorescence imaging capabilities and superior photosensitizing ability but also demonstrate broad-spectrum bactericidal activities against both Gram-positive and Gram-negative bacteria. The controlled release of TPA-Py-PhMe and magnetic characteristics of the AIE MNPs facilitate reuse and recycling for multiple cycles of bacterial inactivation in water. Our findings contribute valuable insights into developing environmentally friendly disinfectants, emphasizing the full potential of AIE photosensitizers in photodynamic inactivation beyond biomedical applications.

The Role of Structural Hydrophobicity on Cationic Amphiphilic Aggregation-Induced Emission Photosensitizer-Bacterial Interaction and Photodynamic Efficiency.

The aggregation-induced emission photosensitizer (AIE PS) has stood out as an alternative and competent candidate in bacterial theranostics, particularly with the use of cationic AIE PS in bacterial discrimination and elimination. Most reported work emphasizes the role of electrostatic interaction between cationic AIE PS and negatively charged bacterial surfaces, enabling broad applications from bacterial discrimination to bacterial killing. However, the underlying targeting mechanism and the design rationale of the cationic AIE PS for effective bacterial labeling remain poorly investigated. In this Article, we designed and synthesized a series of cationic amphiphilic AIE PSs with different calculated log P values. Then, we systemically studied the relationship between the hydrophobicity variation of AIE PS and bacterial targeting outcomes, the dose of AIE PS needed to label various species of bacteria, and their photodynamic antibacterial efficiency. The findings in this work provide a better understanding of the unclear AIE PS-bacterial interaction mechanism and some insights into the structural design strategies of cationic amphiphilic AIE PS for better development in bacterial theranostics.

Evaluation of Outpatient Antibiotic Prescribing for Urinary Tract Infection in Pediatric Patients Ages 2 Months to 18 Years.

OBJECTIVE: To characterize the diagnosis and management of urinary tract infection (UTI) in pediatric patients at the University of Illinois Hospital and Health Sciences System (UIH), with an emphasis on antibiotic prescribing; in addition, to characterize pediatric uropathogen patterns to help guide future empiric therapy choices. METHODS: We used a retrospective, descriptive study of pediatric patients ages 2 months to ≤18 years seen at the UIH emergency department or clinic from January 1, 2014, to August 31, 2018, with ICD-9 or ICD-10 discharge diagnosis of UTI. Data collected included presenting symptoms, urinalysis, details of antibiotic regimens, urine culture, and susceptibility results. RESULTS: Of the 207 patients included, the median age was 5.7 years (IQR, 3.2-9.4), and 183 patients (88.4%) were female. Common symptoms included dysuria (57%) and fever (37%). Empiric antibiotics were p-rescribed in 96.1% of cases, most commonly cefdinir (42%), cephalexin (22%), and sulfamethoxazole-trimethoprim (14%). Urine cultures were collected in 161 patients (77.8%), with 81 growing >50,000 colony-forming units bacteria. Escherichia coli was the most commonly isolated organism (82.1%), showing susceptibility to third-generation cephalosporins (97%), nitrofurantoin (95%), and sulfamethoxazole-trimethoprim (84%). Although 25 urine cultures showed no growth, antibiotics were discontinued in only 4 cases. CONCLUSIONS: Pediatric patients with UTI symptoms were often empirically prescribed cefdinir, possibly an unnecessarily broad choice because many E coli isolates were susceptible to narrower agents. Both urinalysis and urine cultures should be obtained during the diagnostic evaluation of UTI, with better follow-up of negative cultures to potentially discontinue antibiotics. This study highlights areas for improvement in the diagnosis, treatment, and antimicrobial stewardship in pediatric UTI.

Tailoring the Amphiphilic Structure of Zwitterionic AIE Photosensitizers to Boost Antitumor Immunity.

Although photodynamic therapy (PDT) for thorough cancer treatment is hindered by the limited generation of reactive oxygen species (ROS) with short lifetime from photosensitizers, PDT-induced antitumor immune response remedies the defects. Previous studies show that inducing immunogenic cell deaths is an attractive approach to activate antitumor immunity, which confers a robust adjuvanticity to dying cancer cells. In this work, amphiphilic luminogens with aggregation-induced emission characteristics (AIEgens) are rationally designed and synthesized. By modulating the hydrophobic π-bridge and zwitterionic functional groups, these AIEgens exhibit tunable organelle specificity to lysosome, endoplasmic reticulum, and plasma membrane and enhance ROS generation ability. Notably, the membrane-targeting AIEgen namely TPS-2 induces cell death and membrane rupture via PDT to facilitate the release of antigens and activation of immune cells. Furthermore, the size-controlled TPS-2 nanoaggregates are found to serve as an adjuvant, promoting antigen accumulation and delivery to sufficiently boost the in vivo antitumor immunity by only one dose injection in a prophylactic tumor vaccination model. This work thus provides new insights into optimizing AIE photosensitizers via a hydrophobicity-hydrophilicity balance strategy for evoking an antitumor immunity and directly suppressing the distanced tumor. A single small-molecular system for PDT-stimulated antitumor immunity is envisioned.

Adipocyte-Targeting Type I AIE Photosensitizer for Obesity Treatment via Photodynamic Lipid Peroxidation.

Obesity is a surging public health risk and is often associated with fatal diseases, including diabetes, stroke, and myocardial infarction. Common methods for obesity treatment include diet control, weight-loss medicine, and bariatric surgery, but these methods are often ineffective or unsafe. Herein, we introduce a minimally invasive and effective approach to reduce excessive fat accumulation by utilizing red/near-infrared emissive and lipid droplet targeting aggregation-induced emissive luminogens (AIEgens), namely, TTMN and MeTTMN, for specific targeting and photoinduced peroxidation of large lipid droplets in adipocytes. The reported AIEgens can trace and monitor the formation process of adipocytes from pre-adipocytes with a high signal-to-noise ratio. In addition, the presented AIEgens act as Type I photosensitizer that generates highly reactive hydroxyl radicals and superoxides under white light to eliminate mature adipocytes through the chain reactions of lipid peroxidation, even under low oxygen supply. We also demonstrate the use of AIEgens for in vivo photodynamic therapy (PDT) for subcutaneous fat reduction treatment. This work demonstrates the use of AIEgen as a dual imaging and Type I photosensitizer for photodynamic therapeutics to induce adipocyte apoptosis, involving a simple fabrication and treatment process. The suggested in vivo photodynamic obesity treatment processes have negligible toxicity toward nontargeted normal tissues, providing an alternative approach for effective and relatively safer obesity treatment in the future.

The clinical spectrum of SMA-PME and in vitro normalization of its cellular ceramide profile.

OBJECTIVE: The objectives of this study were to define the clinical and biochemical spectrum of spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and to determine if aberrant cellular ceramide accumulation could be normalized by enzyme replacement. METHODS: Clinical features of 6 patients with SMA-PME were assessed by retrospective chart review, and a literature review of 24 previously published cases was performed. Leukocyte enzyme activity of acid ceramidase was assessed with a fluorescence-based assay. Skin fibroblast ceramide content and was assessed by high performance liquid chromatography, electrospray ionization tandem mass spectroscopy. Enzyme replacement was assessed using recombinant human acid ceramidase (rhAC) in vitro. RESULTS: The six new patients showed the hallmark features of SMA-PME, with variable initial symptom and age of onset. Five of six patients carried at least one of the recurrent SMA-PME variants observed in two specific codons of ASAH1. A review of 30 total cases revealed that patients who were homozygous for the most common c.125C > T variant presented in the first decade of life with limb-girdle weakness as the initial symptom. Sensorineural hearing loss was associated with the c.456A > C variant. Leukocyte acid ceramidase activity varied from 4.1%-13.1% of controls. Ceramide species in fibroblasts were detected and total cellular ceramide content was elevated by 2 to 9-fold compared to controls. Treatment with rhAC normalized ceramide profiles in cultured fibroblasts to control levels within 48 h. INTERPRETATION: This study details the genotype-phenotype correlations observed in SMA-PME and shows the impact of rhAC to correct the abnormal cellular ceramide profile in cells.

Inspiration from nature: BioAIEgens for biomedical and sensing applications.

Owing to high sensitivity, selectivity, and non-invasiveness, fluorescence has been widely applied in the biomedical and sensing fields. Among the pool of fluorescent probes, luminogens with aggregation-induced emission (AIE) characteristic exhibit unique strengths in biological applications. However, most reported AIE luminogens (AIEgens) require complicated synthetic procedures, which raise the costs and biocompatibility concerns, especially in biomedical imaging and therapy. In contrast, bioproduct-inspired AIEgens (BioAIEgens) can compensate for the weakness of synthetic AIEgens in terms of their high biocompatibility, low costs, and easy preparation. This review highlights the latest development of BioAIEgens discovered from natural herbs, as well as their potential biomedical and sensing applications. As nature is full of potential resources, studying AIEgens from natural herbs can facilitate the strength of AIE properties in diverse applications and offer more inspiration to the future BioAIEgen structural design and development.

A ratiometric theranostic system for visualization of ONOO- species and reduction of drug-induced hepatotoxicity.

Peroxynitrite (ONOO-) is a potent reactive nitrogen species that plays a role as a critical mediator in liver injury elicited by drugs such as acetaminophen (APAP). At a therapeutic dosage, most APAP is metabolized by liver cells and then excreted in the urine. However, excessive APAP intake can cause an acute production of ONOO-, which induces mitochondrial oxidative stress and necrosis of the liver cells. Therefore, the ONOO- levels in hepatocytes have been considered as an early sign of hepatotoxicity associated with drug overdosage. Herein, a ratiometric theranostic system based on aggregation-induced emission luminogens (AIEgens) for the visualization of ONOO- and reduction of drug-induced hepatotoxicity is developed. The AIEgen ATV-PPB shows a ratiometric fluorescence response from red to green upon cleavage of arylboronic ester moieties by ONOO- with high sensitivity and selectivity. Meanwhile, experiments reveal that ATV-PPB not only acts as a fluorescent probe for ONOO- but also as an intracellular ONOO- scavenger to reduce the hepatotoxicity under overdose APAP treatment.

Stereotypes About Political Attitudes and Coalitions Among U.S. Racial Groups: Implications for Strategic Political Decision-Making.

What are people's expectations of interracial political coalitions? This research reveals expectations of flexible interracial coalitions stemming from how policies and racial groups are viewed in terms of perceived status and foreignness. For policies seen as changing societal status (e.g., welfare), people expected Black-Hispanic political coalitions and viewed Asian Americans as more likely to align with Whites than with other minorities. For policies seen as impacting American identity (e.g., immigration), people expected Asian-Hispanic coalitions and that Black Americans would align with Whites more than other minorities. Manipulating a novel group's alleged status and cultural assimilation influenced coalitional expectations, providing evidence of causality. These expectations appear to better reflect stereotypes than groups' actual average policy attitudes and voting behavior. Yet these beliefs may have implications for a diversifying electorate as White Americans strategically amplified the political voice of a racial group expected to agree with their personal preferences on stereotyped policies.

Interventions involving spiritual and religious themes in pharmacy student patient encounters during advanced practice rotations.

INTRODUCTION: Patient spiritual and religious beliefs can impact their health care choices and outcomes. Pharmacists and other health care providers need to be prepared when these beliefs present changes from usual medical care. The objective of this research brief was to describe interventions related to spirituality and/or religion that are encountered by students during advanced pharmacy practice experience (APPE) patient care activities. METHODS: Fourth-year pharmacy students were asked to complete a web-based questionnaire defining the frequency and setting of patient care activities that incorporated spiritual beliefs during APPEs. Data analysis utilized descriptive statistics. RESULTS: Sixty-three students completed the questionnaire. The most common theme encountered was that of patient refusal of specific therapy based on patient's spiritual or religious beliefs. This result remained consistent across multiple practice settings, except in the community practice setting, where product substitution due to a religious forbidden ingredient was the most common theme encountered. CONCLUSIONS: Training for future and current pharmacists should provide them with the tools needed to navigate spiritual and religious-focused barriers, such as patient refusal of care and substitutes for religiously forbidden ingredients.

A Facile Strategy of Boosting Photothermal Conversion Efficiency through State Transformation for Cancer Therapy.

Improving photothermal conversion efficiency (PCE) is critical to facilitate therapeutic performance during photothermal therapy (PTT). However, current strategies of prompting PCE always involve complex synthesis or modification of photothermal agents, thereby significantly inhibiting the practical applications and fundamental understanding of photothermal conversion. A facile strategy is herein present for boosting PCE by transforming photothermal agents from aggregated state to dispersed state. Compared to aggregated state, the developed photothermal agents with semiconducting nature can rotate freely in dispersed state, which allows for an efficient nonradiative dissipation through twisted intramolecular charge transfer (TICT) effect, consequentially offering excellent photothermal performance. Noteworthy, the state transformation can be achieved by virtue of releasing photothermal molecules from nanoparticles on the basis of a pH-responsive polymer nanocarrier, and the PCE is elevated from 43% to 60% upon changing the pH values from 7.4 to 5.0. Moreover, the nanoparticle disassembly and state transformation behaviors can also smoothly proceed in lysosome of cancer cells, demonstrating a distinct photothermal therapeutic performance for cancer ablation. It is hoped that this strategy of transforming state to boost PCE would be a new platform for practical applications of PTT technique.

Fabrics Attached with Highly Efficient Aggregation-Induced Emission Photosensitizer: Toward Self-Antiviral Personal Protective Equipment.

Personal protective equipment (PPE) is vital for the prevention and control of SARS-CoV-2. However, conventional PPEs lack virucidal capabilities and arbitrarily discarding used PPEs may cause a high risk for cross-contamination and environmental pollution. Recently reported photothermal or photodynamic-mediated self-sterilizing masks show bactericidal-virucidal abilities but have some inherent disadvantages, such as generating unbearable heat during the photothermal process or requiring additional ultraviolet light irradiation to inactivate pathogens, which limit their practical applications. Here, we report the fabrication of a series of fabrics (derived from various PPEs) with real-time self-antiviral capabilities, on the basis of a highly efficient aggregation-induced emission photosensitizer (namely, ASCP-TPA). ASCP-TPA possesses facile synthesis, excellent biocompatibility, and extremely high reactive oxygen species generation capacity, which significantly outperforms the traditional photosensitizers. Meanwhile, the ASCP-TPA-attached fabrics (ATaFs) show tremendous photodynamic inactivation effects against MHV-A59, a surrogate coronavirus of SARS-CoV-2. Upon ultralow-power white light irradiation (3.0 mW cm-2), >99.999% virions (5 log) on the ATaFs are eliminated within 10 min. Such ultralow-power requirement and rapid virus-killing ability enable ATaFs-based PPEs to provide real-time protection for the wearers under indoor light irradiation. ATaFs' virucidal abilities are retained after 100 washings or continuous exposure to office light for 2 weeks, which offers the benefits of reusability and long-term usability. Furthermore, ATaFs show no toxicity to normal skin, even upon continuous high-power light illumination. This self-antiviral ATaFs-based strategy may also be applied to fight against other airborne pathogens and holds huge potential to alleviate global PPE supply shortages.

Frequency, setting and influential factors associated with pharmacy student-patient encounters involving spirituality and religiosity during advanced practice rotations.

INTRODUCTION: To identify (1) how often and in what settings pharmacy students include spirituality and religion and (2) what factors may influence how often students incorporate spirituality in patient care plans. METHODS: Fourth-year pharmacy students completed a questionnaire defining the frequency and setting of patient care activities that incorporated spiritual beliefs during advanced pharmacy practice experiences. Demographics, prior spirituality and health coursework, and self-identified measures of religiosity and spirituality were collected. Data analysis utilized descriptive statistics with nonparametric exploratory analysis. RESULTS: Sixty-three students completed the survey (31.7% response rate). While 11% of students asked patients about spiritual needs, 25.4% reported inclusion of spiritual factors in therapeutic plan creation. The general medicine rotation was the most common setting identified. Student frequency of religious service attendance, self-identified religiosity, and self-reported spirituality were associated with perceived importance of asking patients about spiritual needs (P < .05 for all). This did not impact whether students asked about or incorporated these topics (P > .05 for all). Students who did ask about or incorporate spiritual and religious issues had significantly greater comfort in discussing these and referring patients to a chaplain (P < .05 for all). CONCLUSIONS: Students are considering patients' spiritual needs in patient care activities. Greater student spiritual and religious practices positively influenced attitudes toward importance of asking about patient needs but did not influence student-reported behavior in patient care. Results highlight the need for instructors to consider how students' comfort levels and patient care setting influence addressing spiritual concerns.

Highly efficient phototheranostics of macrophage-engulfed Gram-positive bacteria using a NIR luminogen with aggregation-induced emission characteristics.

Although phagocytosis serves as the front line to attack invading pathogens, its low bacterial encounter and killing rates leads to an ineffective bactericidal output. In view of this, developing multifunctional theranostic probe to effectively discriminate and ablate intracellular bacteria is highly desirable. However, the shielding effect of the host macrophages put the detection and elimination of macrophage-engulfed bacteria into a challenging task. Herein, we utilize a luminogen with aggregation-induced emission (AIE) characteristics, namely TTVP, as a simple and effective probe for simultaneous tracing and photodynamic killing of intracellular Gram-positive bacteria. With the help of the AIE property, excellent water solubility, near-infrared (NIR) emission and strong reactive oxygen species (ROS) generating ability, TTVP performed ideally to be a targeting agent to intracellular Gram-positive bacteria with high signal contrast, as well as to be a photosensitizer to effectively ablate intracellular bacteria without attacking host macrophages. This work thus provides insights for the next generation antibiosis theranostic application for potential clinical trials.

Programmed Self-Assembly of Protein-Coated AIE-Featured Nanoparticles with Dual Imaging and Targeted Therapy to Cancer Cells.

Modifying different functional moieties into one platform is a conventional strategy for constructing theranostic systems. However, this strategy usually suffers from the unsatisfied efficiency of each individual function. Herein, a programmed self-assembly strategy is presented to fabricate theranostic nanoparticles, which significantly exhibit a dual-modality imaging function involving fluorescence imaging and magnetic resource imaging (MRI), and an efficient targeted therapy to cancer cells. Fluorescent vesicles are first self-assembled by aggregation-induced emission (AIE)-active molecules. Gd3+, serving as an MRI agent, is subsequently bound to the vesicles to provide highly positive charges, which have been realized to be anticancer active. Thereafter, transferrin (Tf) protein is introduced onto the surface of Gd3+ coordinated vesicles, shielding the positive charges and making the nanoparticles nontoxic to cells. With the assistance of Tf protein, the constructed nanoparticles are specifically targeted to cancer cells. Moreover, Tf proteins further peel off from nanoparticles in lysosomes due to their charge reversion, resulting in highly positive charges and heavy toxicity of nanoparticles to kill cancer cells. In the nanoparticles, each of the functional components acts as double-sided adhesive tape to glue the next layer, so that the abilities of functional components are not compromised. This strategy holds great potential for theranostic nanomedicine.

Human embryoid bodies as a 3D tissue model of the extracellular matrix and α-dystroglycanopathies.

The basal lamina is a specialized sheet of dense extracellular matrix (ECM) linked to the plasma membrane of specific cell types in their tissue context, which serves as a structural scaffold for organ genesis and maintenance. Disruption of the basal lamina and its functions is central to many disease processes, including cancer metastasis, kidney disease, eye disease, muscular dystrophies and specific types of brain malformation. The latter three pathologies occur in the α-dystroglycanopathies, which are caused by dysfunction of the ECM receptor α-dystroglycan. However, opportunities to study the basal lamina in various human disease tissues are restricted owing to its limited accessibility. Here, we report the generation of embryoid bodies from human induced pluripotent stem cells that model the basal lamina. Embryoid bodies cultured via this protocol mimic pre-gastrulation embryonic development, consisting of an epithelial core surrounded by a basal lamina and a peripheral layer of ECM-secreting endoderm. In α-dystroglycanopathy patient embryoid bodies, electron and fluorescence microscopy reveal ultrastructural basal lamina defects and reduced ECM accumulation. By starting from patient-derived cells, these results establish a method for the in vitro synthesis of patient-specific basal lamina and recapitulate disease-relevant ECM defects seen in the α-dystroglycanopathies. Finally, we apply this system to evaluate an experimental ribitol supplement therapy on genetically diverse α-dystroglycanopathy patient samples.This article has an associated First Person interview with the first author of the paper.

Single AIEgen for multiple tasks: Imaging of dual organelles and evaluation of cell viability.

Fully understanding the complicated interplays among various chemical species and organelles is greatly important to unravel the mystery of life. However, fluorescent probes capable of visualizing multiple targets discriminatively are severely deficient, which extremely limit the investigation on intracellular interplays among various species. Towards this end and in consideration of the unique advantages of aggregation-induced emission luminogens (AIEgens), here we rationally designed and presented a single AIEgen, named TVQE, bearing lipophilic, cationic and hydrolyzable moieties, and this AIEgen was capable of illuminating mitochondria and lipid droplets with red and blue emission, respectively. In addition, TVQE was successfully used for evaluating cell viability due to its distinct two-color emission changes tuned by esterase-mediated hydrolysis. Of particular importance is that TVQE can selectively differentiate live, early apoptotic, late apoptotic, and dead cells by confocal microscopy and quantify cell viability statistically by flow cytometry.

Three-Pronged Attack by Homologous Far-red/NIR AIEgens to Achieve 1+1+1>3 Synergistic Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) has long been shown to be a powerful therapeutic modality for cancer. However, PDT is undiversified and has become stereotyped in recent years. Exploration of distinctive PDT methods is thus highly in demand but remains a severe challenge. Herein, an unprecedented 1+1+1>3 synergistic strategy is proposed and validated for the first time. Three homologous luminogens with aggregation-induced emission (AIE) characteristics were rationally designed based on a simple backbone. Through slight structural tuning, these far-red/near-infrared AIE luminogens are capable of specifically anchoring to mitochondria, cell membrane, and lysosome, and effectively generating reactive oxygen species (ROS). Notably, biological studies demonstrated combined usage of three AIE photosensitizers gives multiple ROS sources simultaneously derived from several organelles, which gives superior therapeutic effect than that from a single organelle at the same photosensitizers concentration. This strategy is conceptually and operationally simple, providing an innovative approach and renewed awareness of improving therapeutic effect through three-pronged PDT.

Evaluating the Transition From Dexmedetomidine to Clonidine for the Prevention of Withdrawal in Critically Ill Pediatric Patients.

OBJECTIVES: To evaluate clonidine for preventing withdrawal from dexmedetomidine infusions and describe the incidence of withdrawal symptoms and adverse cardiovascular effects in critically ill pediatric patients. METHODS: Retrospective, descriptive study of patients in Advocate Children's Hospital-Park Ridge PICU who received dexmedetomidine infusion for ≥72 hours, followed by clonidine for ≥48 hours, between January 1, 2015, and August 31, 2017. RESULTS: Thirty-eight patients (median age 4.3 years; IQR, 2-11.5) received 39 dexmedetomidine courses. The median duration of dexmedetomidine exposure was 7.6 days (IQR, 5-11.5) at an average dose of 1 mcg/kg/hr. The median dose of clonidine at initiation was 8.3 mcg/kg/day (for <50 kg) and 4.1 mcg/kg/day (for ≥50 kg). The most common oral administration frequency was every 8 hours. Dexmedetomidine infusions for 7 days or longer and a higher dexmedetomidine dose 24 hours prior to clonidine transition both correlated with increased initial clonidine doses. Fourteen patients (37%) had at least 1 WAT-1 score of ≥3 during the transition between dexmedetomidine and clonidine, with 7 (18%) requiring an increase in sedation. Adverse cardiovascular events were possibly attributable to dexmedetomidine and/or clonidine in 4 patients. CONCLUSIONS: Patients receiving prolonged infusions of dexmedetomidine may transition to clonidine to help prevent withdrawal symptoms. Duration of dexmedetomidine infusion of 7 days or longer and higher average dexmedetomidine dose 24 hours prior to the transition are important considerations when determining the initial clonidine dose. Transition from dexmedetomidine to clonidine was found to be safe and efficacious in our patients, with minimal adverse effects.