Vaccination-Associated Myocarditis and Myocardial Injury.

SARS-CoV-2 vaccine-associated myocarditis/myocardial injury should be evaluated in the contexts of COVID-19 infection, other types of viral myocarditis, and other vaccine-associated cardiac disorders. COVID-19 vaccine-associated myocardial injury can be caused by an inflammatory immune cell infiltrate, but other etiologies such as microvascular thrombosis are also possible. The clinical diagnosis is typically based on symptoms and cardiac magnetic resonance imaging. Endomyocardial biopsy is confirmatory for myocarditis, but may not show an inflammatory infiltrate because of rapid resolution or a non-inflammatory etiology. Myocarditis associated with SARS-COVID-19 vaccines occurs primarily with mRNA platform vaccines, which are also the most effective. In persons aged >16 or >12 years the myocarditis estimated crude incidences after the first 2 doses of BNT162b2 and mRNA-1273 are approximately 1.9 and 3.5 per 100 000 individuals, respectively. These rates equate to excess incidences above control populations of approximately 1.2 (BNT162b2) and 1.9 (mRNA-1273) per 100 000 persons, which are lower than the myocarditis rate for smallpox but higher than that for influenza vaccines. In the studies that have included mRNA vaccine and SARS-COVID-19 myocarditis measured by the same methodology, the incidence rate was increased by 3.5-fold over control in COVID-19 compared with 1.5-fold for BNT162b2 and 6.2-fold for mRNA-1273. However, mortality and major morbidity are less and recovery is faster with mRNA vaccine-associated myocarditis compared to COVID-19 infection. The reasons for this include vaccine-associated myocarditis having a higher incidence in young adults and adolescents, typically no involvement of other organs in vaccine-associated myocarditis, and based on comparisons to non-COVID viral myocarditis an inherently more benign clinical course.

Tenofovir-Diphosphate and Emtricitabine-Triphosphate Adherence Benchmarks in Dried Blood Spots for Persons with HIV Receiving Tenofovir Alafenamide and Emtricitabine-based Antiretroviral Therapy (QUANTI-TAF).

BACKGROUND: QUANTI-TAF aimed to establish tenofovir-diphosphate/emtricitabine-triphosphate (TFV-DP/FTC-TP) adherence benchmarks in dried blood spots (DBS) for persons with HIV (PWH) receiving tenofovir alafenamide/emtricitabine (TAF/FTC)-based antiretroviral therapy (ART). METHODS: During a 16-week pharmacokinetic study, PWH received TAF/FTC-based ART co-encapsulated with an ingestible sensor to directly measure cumulative (enrollment to final visit) and 10-day adherence. At monthly visits, intraerythrocytic concentrations of TAF/FTC anabolites (TFV-DP/FTC-TP) in DBS were quantified by LC-MS/MS and summarized at steady-state (week 12 or 16) as median (IQR). Linear mixed-effects models evaluated factors associated with TFV-DP/FTC-TP. RESULTS: 84 participants (86% male, 11% female, and 4% transgender), predominantly receiving bictegravir/TAF/FTC (73%) enrolled. 92% completed week 12 or 16 (94% receiving unboosted ART). TFV-DP for <85% (7/72), ≥85%-<95% (9/72), and ≥95% (56/72) cumulative adherence was 2696 (2039-4108), 3117 (2332-3339), and 3344 (2605-4293) fmol/punches. All participants with ≥85% cumulative adherence had TFV-DP ≥1800 fmol/punches. Adjusting for cumulative adherence, TFV-DP was higher with boosted ART, lower BMI, and in non-Blacks. FTC-TP for <85% (14/77), ≥85%-<95% (6/77), and ≥95% (57/77) 10-day adherence was 3.52 (2.64-4.48), 4.58 (4.39-5.06), and 4.96 (4.21-6.26) pmol/punches. All participants with ≥85% 10-day adherence had FTC-TP ≥2.5 pmol/punches. Low-level viremia (HIV-1 RNA ≥20-<200 copies/mL) occurred at 60/335 (18%) visits in 33/84 (39%) participants (range: 20-149 copies/mL), with similar TFV-DP (3177 [2494-4149] fmol/punches) compared with HIV-1 RNA <20 copies/mL visits (3279 [2580-4407] fmol/punches). CONCLUSIONS: We propose PK-based TFV-DP (≥1800 fmol/punches)/FTC-TP (≥2.5 pmol/punches) benchmarks in DBS for PWH receiving unboosted TAF/FTC-based ART with ≥85% adherence. In the setting of high adherence, low-level viremia was common.

Impact of Clinical Demands on the Educational Mission in Hospital Medicine at 17 Academic Medical Centers : A Qualitative Analysis.

BACKGROUND: Clinical growth is outpacing the growth of traditional educational opportunities at academic medical centers (AMCs). OBJECTIVE: To understand the impact of clinical growth on the educational mission for academic hospitalists. DESIGN: Qualitative study using semistructured interviews that were analyzed using a mixed inductive and deductive method at the semantic level. SETTING: Large AMCs across the United States that experienced clinical growth in the past 5 years. PARTICIPANTS: Division heads, section heads, and other hospital medicine (HM) leaders who oversaw and guided academic and clinical efforts of HM programs. MEASUREMENTS: Themes and subthemes. RESULTS: From September 2021 to January 2022, HM leaders from 17 AMCs participated in the interviews, and 3 key themes emerged. First, AMCs' disproportionate clinical growth highlighted the tension between clinical and educational missions. This included a mismatch in supply and demand for traditional teaching time, competing priorities, and clinical growth being seen as both an opportunity and a threat. Second, amid the shifting landscape of high clinical demands and evolving educational opportunities, hospitalists still strongly prefer traditional teaching. To address this mismatch, HM groups have had to alter recruitment strategies and create innovative solutions to help build academic careers. Third, participants noted a need to reimagine the role and identity of an academic hospitalist, emphasizing tailored career pathways and educational roles spanning well beyond traditional house staff teaching teams. LIMITATION: The study focused on large AMCs. CONCLUSION: Although HM groups have implemented many creative strategies to address clinical growth and keep education front and center, challenges remain, particularly heavy clinical workloads and a continued dilution of traditional teaching opportunities. PRIMARY FUNDING SOURCE: Society of Hospital Medicine Student Scholar Grant.

Mycobacterium abscessus Meningitis Associated with Stem Cell Treatment During Medical Tourism.

Mycobacterium abscessus infections have been reported as adverse events related to medical tourism. We report M. abscessus meningitis in a patient who traveled from Colorado, USA, to Mexico to receive intrathecal stem cell injections as treatment for multiple sclerosis. We also review the management of this challenging central nervous system infection.

A Pilot Study of Telehealth Mindfulness-Based Cognitive Therapy for Depression in Parkinson's Disease.

Introduction: Parkinson's disease (PD) is characterized by high-rates of depression with limited evidence-based treatment options to improve mood. Objective: To expand therapeutic options, we evaluated the feasibility and effect of a telehealth mindfulness-based cognitive therapy intervention adapted for PD (MBCT-PD) in a sample of participants with DSM-5 depressive disorders. Methods: Fifteen participants with PD and clinically-significant depression completed 9 sessions of MBCT-PD. Depression, anxiety, and quality of life were evaluated at baseline, endpoint, and 1-month follow-up. Results: Telehealth MBCT-PD was feasible and beneficial. Completion rates exceeded 85% and treatment satisfaction rates were high. Notable improvements were observed for depression, anxiety, and quality of life over the course of the trial. Conclusion: Telehealth MBCT-PD shows promise and warrants further evaluation via randomized clinical trial with more diverse participants. Such research holds the potential to expand the range of therapeutic options for depression in PD, thereby setting the stage for personalized care.

The effect of a telehealth exercise intervention on balance in adults with Down syndrome.

BACKGROUND: People with Down syndrome often present with balance deficits, which compromise safety during daily activity. While evidence shows that exercise can improve balance in the Down syndrome population, it is unclear if a telehealth method will elicit similar benefits. We aimed to examine the effects of a virtual exercise program on balance in adults with Down syndrome. METHODS: Eighteen low-active participants with Down syndrome completed a 12-week telehealth exercise program based on the Mann Method. Balance testing took place before and after the intervention, which included: TUG, MCTSIB, FICSIT-4, and FRT. This study was registered as a clinical trial on ClinicalTrials.gov, identifier: NCT04647851. RESULTS: Significant improvement was seen in the TUG (p = .043), FICSIT-4 (p = .019) and FRT (p = .019). All participants achieved maximum scores on the MCTSIB in pre- and post-testing. CONCLUSIONS: Balance in low-active adults with Down syndrome significantly improved following the telehealth exercise program, which we attribute to the tailored exercises that address visual/vestibular deficits and hip muscle weakness.

Criticism in the Parkinson's Caregiving Relationship: A Key Target for Intervention.

INTRODUCTION: Caregiver distress is prevalent in Parkinson's disease (PD) and predictive of negative health outcomes for both people with PD and caregivers. To identify future intervention targets, it is important to better elucidate the specific processes, such as criticism, that perpetuate burden. OBJECTIVE: Evaluate the frequency and impact of criticism and reactivity to criticism in PD caregiving dyads. METHODS: Eighty-three people with PD and their caregivers independently completed measures of criticism and physical and emotional health. RESULTS: Criticism in the caregiving relationship was reported by 71.1% (n = 59) of people with PD and 80.7% (n = 67) of caregivers. Both perceived criticism and emotional reactivity to criticism were significant predictors of caregiver distress, adjusting for PD motor and non-motor symptom severity. In contrast, criticism was not related to PD depression. CONCLUSION: Criticism in the PD caregiving relationship is a clear target for psychotherapeutic intervention and may improve caregiver health and quality of life.

Biological causal beliefs and depression stigma: the moderating effects of first- and second-hand experience with depression.

BACKGROUND: Essentialist theory (ET) links biological attributions for mental illnesses to pessimistic prognostic beliefs and stigma. The commonsense model (CSM) provides a nuanced framework for studying illness beliefs as shaped by experience. AIMS: ET-informed hypotheses linking causal and prognostic beliefs and stigmatizing attitudes concerning depression were tested using CSM constructs with a focus on the moderating effects of self-reported experience with this disorder. METHODS: U.S. adults (N = 319) completed online questionnaires assessing depression-related beliefs, attitudes and experience. Multiple regression analysis focused on predictive effects of neurobiological and genetic attributions. Potential mediators (prognosis) and moderators (experience) of the biological attribution-stigma link also were tested. RESULTS: Neurobiological attributions predicted viewing depression as more consequential, longer lasting, and unexpectedly, more treatable. Neurobiological attributions were inversely related to stigma, a link partially mediated by beliefs about depression's consequences and duration. However, both biological attributions' relationships to stigma were moderated by experience. Stronger biological attributions predicted less stigma specifically among participants reporting first- or second-hand experience with depression. CONCLUSION: Experience with depression may shape the relationships of specific causal and prognostic beliefs with depression stigma. Psychoeducation in clinical and public health contexts may be informed by further research using CSM constructs.

Innovating Parkinson's Care: A Randomized Controlled Trial of Telemedicine Depression Treatment.

BACKGROUND: For several decades, a myriad of factors have contributed to the inadequate diagnosis and management of depression in Parkinson's disease (PD), leaving up to 60% of significantly symptomatic patients untreated. Poor access to evidence-based neuropsychiatric care is one major barrier to achieving optimal Parkinson's outcomes. OBJECTIVE: The goal of this study was to compare the efficacy of individual Parkinson's-informed, video-to-home cognitive-behavioral therapy (experimental group), to clinic-based treatment as usual (control group), for depression in PD. METHOD: Ninety United States military veterans with clinical diagnoses of both depression and PD were computer-randomized (1:1) to either the experimental or control group; randomization was stratified by baseline antidepressant use and blind to all other baseline data. The acute treatment period spanned 10 weeks and was followed by a 6-month extension phase. The Hamilton Depression Rating Scale was the a priori primary outcome. Depression treatment response was defined as a score ≤2 on the Clinical Global Impression Improvement Scale. All statistical analyses were intent to treat. RESULTS: Video-to-home cognitive-behavioral therapy outperformed clinic-based treatment as usual across three separate depression measures (P < 0.001). Effects were observed at the end of acute treatment and maintained through 6-month follow-up. Number needed to treat (based on treatment response classification) was 2.5 with an absolute risk reduction of 40%. CONCLUSION: Video-to-home cognitive-behavioral therapy may be an effective intervention to bypass access barriers to specialized, evidence-based depression care in PD and to address the unmet neuropsychiatric treatment needs of the Parkinson's community. © 2021 International Parkinson and Movement Disorder Society.

Histone H4-based peptoids are inhibitors of protein arginine methyltransferase 1 (PRMT1).

Methylation of arginine residues occurs on a number of protein substrates, most notably the N-terminal tails of histones, and is catalyzed by a family of enzymes called the protein arginine methyltransferases (PRMTs). This modification can lead to transcriptional activation or repression of cancer-related genes. To date, a number of inhibitors, based on natural peptide substrates, have been developed for the PRMT family of enzymes. However, because peptides are easily degraded in vivo, the utility of these inhibitors as potential therapeutics is limited. The use of peptoids, which are peptide mimetics where the amino acid side chain is attached to the nitrogen in the amide backbone instead of the α-carbon, may circumvent the problems associated with peptide degradation. Given the structural similarities, peptoid scaffolds may provide enhanced stability, while preserving the mechanism of action. Herein, we have identified that peptoids based on natural peptide substrates are not catalyzed to the product by PRMT1, but instead are inhibitors of this enzyme. Reducing the length of the peptoid reduces inhibition and suggest the residues distal from the site of modification are important for binding. Furthermore, a positive charge on the N-terminus helps promote binding and improves inhibition. Selectivity among family members is likely possible based on inhibition being moderately selective for PRMT1 over PRMT5 and provides a scaffold that can be used to develop pharmaceuticals against this class of enzymes.

Structure Effects on the Ionicity of Protic Ionic Liquids.

We report on the characterisation of 16 protic ionic liquids (PILs) prepared by neutralisation of primary or tertiary amines with a range of simple carboxylic acids, or salicylic acid. The extent of proton transfer was greater for simple primary amine ILs compared to tertiary amines. For the latter case, proton transfer was increased by providing a better solvation environment for the ions through the addition of a hydroxyl group, either on the tertiary amine, or by formation of PIL/molecular solvent mixtures. The library of PILs was characterised by differential scanning calorimetry and a range of transport properties (i. e. viscosity, conductivity and diffusivity) were measured. Using the (fractional) Walden rule, the conductivity and viscosity results were analysed with respect to their deviation from ideal behaviour. The validity of the Walden plot for PILs containing ions of varying sizes was also verified for a number of samples by directly measuring self-diffusion coefficients using pulsed-field gradient spin-echo (PGSE) NMR. Ionicity was found to decrease as the alkyl chain length and degree of branching of both the cations and anions was increased. These results aim to develop a better understanding of the relationship between PIL properties and structure, to help design ILs with optimal properties for applications.

Revealing Intermolecular Hydrogen Bonding Structure and Dynamics in a Deep Eutectic Pharmaceutical by Magic-Angle Spinning NMR Spectroscopy.

Liquid forms of pharmaceuticals (ionic liquids and deep eutectic solvents) offer a number of potential advantages over solid-state drugs; a key question is the role of intermolecular hydrogen bonding interactions in enabling membrane transport. Characterization is challenging since high sample viscosities, typical of liquid pharmaceutical formulations, hamper the use of conventional solution NMR at ambient temperature. Here, we report the application of magic-angle spinning (MAS) NMR spectroscopy to the deep eutectic pharmaceutical, lidocaine ibuprofen. Using variable temperature MAS NMR, the neat system, at a fixed molar ratio, can be studied over a wide range of temperatures, characterized by changing mobility, using a single experimental setup. Specific intermolecular hydrogen bonding interactions are identified by two-dimensional 1H-1H NOESY and ROESY MAS NMR experiments. Hydrogen-bonding dynamics are quantitatively determined by following the chemical exchange process between the labile protons by means of line-width analysis of variable temperature 1H MAS NMR spectra.

Cryptococcal pericarditis in a heart transplant recipient.

We present a case of Cryptococcus neoformans pericarditis in a cardiac transplant recipient. This article reviews the diagnosis, treatment, and complications of cryptococcosis specifically in transplant patients. While pericarditis is a rare manifestation of Cryptococcus infection, this case highlights that cryptococcosis should be considered in the differential diagnosis for solid organ transplant and immunocompromised patients presenting with pericardial effusions.

Exploring the impact of providing men with information about potential prostate cancer treatment options prior to receiving biopsy results.

PURPOSE: There is little research assessing the impact of providing men with information about prostate cancer (PCa) treatment options at the time of referral for a prostate biopsy. Study objectives were to determine whether receiving an information booklet about PCa treatment options prior to receiving biopsy results was acceptable to patients, and if receiving this information influenced levels of anxiety, depression, distress, and treatment decisional conflict. METHODS: Between June 2016 and September 2017, a randomised block design was used to allocate patients from an Australian urology practice into the intervention or control group. Patients in the intervention group were provided with written information about treatment options for localised PCa prior to their biopsy. Outcome measures including the Distress Thermometer, Generalised Anxiety Disorder-7, Patient Health Questionnaire-9, and Decisional Conflict Scale were completed pre-biopsy and 2-3 weeks post-biopsy. Ninety-eight patients referred for an initial prostate biopsy for an elevated PSA test or suspicious digital rectal exam participated in the study (response rate = 78%). RESULTS: Multimodal repeated-measures analyses showed no significant differences between control and intervention groups in changes in distress, anxiety, or depression from pre- to post-biopsy, and in decisional conflict post-diagnosis (all p > .05). Thirty-five (87%) patients believed that the resource made it easier to understand subsequent explanation of treatment options, and 51 patients (98%) who received the intervention preferred to be given information at that time. CONCLUSIONS: Providing patients with information about treatment options prior to biopsy did not impact on changes in psychological distress and decisional conflict post-biopsy. However, the majority of patients preferred to be given such information at this time point.

The development and characterization of a chemical probe targeting PRMT1 over PRMT5.

Protein arginine methyltransferases (PRMTs) are a family of mammalian enzymes catalyzing the symmetric dimethylation (Type I), asymmetric dimethylation (Type II), or monomethylation (Type III) of arginine residues within proteins. This family is composed of 11 isozymes, however the vast majority of asymmetric and symmetric dimethylation in mammals is completed by either PRMT1 or PRMT5, respectively. In recent years, a number of chemical probes targeting this family of enzymes have been developed, but the majority of these probes lack isozyme specificity. Herein, we report the development of a chemical probe, based on a non-natural peptide sequence, which specifically labels PRMT1 over PRMT5 with high selectivity and sensitivity.

Cognitive behavioral therapy improves diverse profiles of depressive symptoms in Parkinson's disease.

OBJECTIVE: Depression is among the most common and debilitating nonmotor complaints in Parkinson's disease (PD), yet there is a paucity of controlled research to guide treatment. Little research has focused on the extent to which specific depressive symptom profiles may dictate unique clinical recommendations to ultimately improve treatment outcomes. The current study examined the impact of cognitive behavioral therapy (CBT) on different types of depressive symptoms in PD. It was hypothesized that the cognitive (eg, guilt, rumination, and negative attitudes towards self) and behavioral (eg, avoidance and procrastination) symptoms targeted most intensively by the treatment protocol would show the most robust response. The extent to which stabilized antidepressant use moderated specific symptom change was examined on an exploratory basis. METHOD: Eighty depressed people with PD participated in a randomized controlled trial of CBT plus clinical management, versus clinical management only. Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI) subscale scores, reflecting depressive symptom heterogeneity in PD, were the focus of this investigation. RESULTS: CBT response was associated with significant improvements in mood, sleep, anxiety, and somatic symptoms (HAMD), and negative attitudes toward self, performance impairment, and somatic symptoms (BDI). As hypothesized, the largest effect sizes were observed for cognitive and behavioral (vs somatic) symptoms of depression. Stabilized antidepressant use moderated the effect of CBT on somatic complaints (HAMD and BDI). CONCLUSIONS: CBT may improve a diverse array of depressive symptoms in PD. Cognitive and behavioral (vs somatic) symptoms showed the greatest change. Combining CBT with antidepressants may help optimize the management of somatic complaints in depression in PD (dPD).

Quality of Life, Psychological Functioning, and Treatment Satisfaction of Men Who Have Undergone Penile Prosthesis Surgery Following Robot-Assisted Radical Prostatectomy.

BACKGROUND: Penile prosthesis surgery is last-line treatment to regaining erectile function after radical prostatectomy (RP) for localized prostate cancer. AIMS: To assess quality of life, psychological functioning, and treatment satisfaction of men who underwent penile implantation after RP; the psychosocial correlates of treatment satisfaction and sexual function after surgery; and the relation between patients' and partners' ratings of treatment satisfaction. METHODS: 98 consecutive patients who underwent penile implantation after RP from 2010 and 2015 and their partners were invited to complete a series of measures at a single time point. Of these, 71 patients and 43 partners completed measures assessing sexual function, psychological functioning, and treatment satisfaction. Proportions of patients who demonstrated good sexual function and satisfaction with treatment and clinical levels of anxiety and depression were calculated. Hierarchical regression analyses were conducted to determine psychosocial factors associated with patient treatment satisfaction and sexual function and patient-partner differences in treatment satisfaction. OUTCOMES: Patients completed the Expanded Prostate Cancer Index Composite Short Form (EPIC-26), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Prostate Cancer-Related Quality of Life Scale, Self-Esteem and Relationship Questionnaire (SEAR), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). Partners completed the GAD-7, PHQ-9, EDITS (partner version), and SEAR. RESULTS: 94% of men reported satisfaction with treatment (EDITS score > 50). 77% of men reported good sexual function (EPIC-26 score > 60). Lower depression scores were associated with higher sexual confidence and sexual intimacy, and these were correlated with better treatment satisfaction and sexual function. Patients experienced higher sexual relationship satisfaction (median score = 90.6) than their partners (median score = 81.2), but there was no difference in treatment satisfaction between groups. Higher patient treatment satisfaction was more likely to be reported for couples whose depression scores were more similar. CLINICAL IMPLICATIONS: It is important to provide preoperative penile implant counseling and encourage patients to seek postoperative counseling if needed. STRENGTHS AND LIMITATIONS: This is one of the first Australian-based studies comprehensively assessing treatment satisfaction and psychosocial health of men after penile prosthesis surgery after RP. This was a retrospective cross-sectional study, so there is a possibility of recall bias, and causal associations could not be determined. CONCLUSION: Men in this Australian series who underwent penile prosthesis surgery after RP generally reported good sexual function and treatment satisfaction. Nevertheless, patient and partner mental health influenced their reported experience of the treatment. Pillay B, Moon D, Love C, et al. Quality of Life, Psychological Functioning, and Treatment Satisfaction of Men Who Have Undergone Penile Prosthesis Surgery Following Robot-Assisted Radical Prostatectomy. J Sex Med 2017;14:1612-1620.

Zero hospital admissions for infection after 577 transperineal prostate biopsies using single-dose cephazolin prophylaxis.

PURPOSE: To determine the rate of hospital admissions for infection after transperineal biopsy of prostate (TPB) with single-dose cephazolin prophylaxis using a prospective database. METHOD: Between April 2013 and February 2016, 577 patients undergoing TPB had 2 g of cephazolin given intravenously at induction of anaesthesia. Data collected from these patients included age, PSA, prostate volume, number of cores taken and post-operative complications. RESULTS: No patients were readmitted to hospital with infection post-TPB. Seven patients developed acute urinary retention, and one patient developed clinical prostatitis that was treated with oral antibiotics in the community. CONCLUSION: It is safe to use single-dose cephazolin only as antibiotic prophylaxis prior to TPB, negating the need for quinolones. This study supports Australia's current Therapeutic Guidelines recommendation for TPB prophylaxis and the existing evidence that sepsis post-TPB is a rare complication. Whether any antibiotic prophylaxis is needed at all for TPB is the subject of a future study.

Quantifying Nanoparticle Internalization Using a High Throughput Internalization Assay.

PURPOSE: The internalization of nanoparticles into cells is critical for effective nanoparticle mediated drug delivery. To investigate the kinetics and mechanism of internalization of nanoparticles into cells we have developed a DNA molecular sensor, termed the Specific Hybridization Internalization Probe - SHIP. METHODS: Self-assembling polymeric 'pHlexi' nanoparticles were functionalized with a Fluorescent Internalization Probe (FIP) and the interactions with two different cell lines (3T3 and CEM cells) were studied. The kinetics of internalization were quantified and chemical inhibitors that inhibited energy dependent endocytosis (sodium azide), dynamin dependent endocytosis (Dyngo-4a) and macropinocytosis (5-(N-ethyl-N-isopropyl) amiloride (EIPA)) were used to study the mechanism of internalization. RESULTS: Nanoparticle internalization kinetics were significantly faster in 3T3 cells than CEM cells. We have shown that ~90% of the nanoparticles associated with 3T3 cells were internalized, compared to only 20% of the nanoparticles associated with CEM cells. Nanoparticle uptake was via a dynamin-dependent pathway, and the nanoparticles were trafficked to lysosomal compartments once internalized. CONCLUSION: SHIP is able to distinguish between nanoparticles that are associated on the outer cell membrane from nanoparticles that are internalized. This study demonstrates the assay can be used to probe the kinetics of nanoparticle internalization and the mechanisms by which the nanoparticles are taken up by cells. This information is fundamental for engineering more effective nanoparticle delivery systems. The SHIP assay is a simple and a high-throughput technique that could have wide application in therapeutic delivery research.