Nociceptor-immune interactomes reveal insult-specific immune signatures of pain.

Inflammatory pain results from the heightened sensitivity and reduced threshold of nociceptor sensory neurons due to exposure to inflammatory mediators. However, the cellular and transcriptional diversity of immune cell and sensory neuron types makes it challenging to decipher the immune mechanisms underlying pain. Here we used single-cell transcriptomics to determine the immune gene signatures associated with pain development in three skin inflammatory pain models in mice: zymosan injection, skin incision and ultraviolet burn. We found that macrophage and neutrophil recruitment closely mirrored the kinetics of pain development and identified cell-type-specific transcriptional programs associated with pain and its resolution. Using a comprehensive list of potential interactions mediated by receptors, ligands, ion channels and metabolites to generate injury-specific neuroimmune interactomes, we also uncovered that thrombospondin-1 upregulated by immune cells upon injury inhibited nociceptor sensitization. This study lays the groundwork for identifying the neuroimmune axes that modulate pain in diverse disease contexts.

Propositive follow-up: Long-term immune responses to the 4CMenB and MenACWY vaccines in people living with HIV.

BACKGROUND: People living with HIV have an increased risk of meningococcal disease. The Propositive trial evaluated co-administration of two doses of a four-component recombinant protein-based MenB vaccine (4CMenB) and a quadrivalent conjugate polysaccharide MenACWY vaccine (MenACWY-CRM197) given 1 month apart in people with HIV. The follow-up trial assessed the immunogenicity of these vaccines at 1.5 and 2.5 years after primary vaccination. METHODS: Participants who completed the parent Propositive trial were invited to the follow-up study. Immunogenicity analysis was performed at 18 and 30 months after primary vaccination. Primary outcome measures were serum bactericidal antibody (SBA) geometric mean titres (GMTs) against three MenB reference strains and the proportion of participants maintaining a protective SBA titre of ≥4 at 18 and 30 months. Secondary outcome measures were SBA GMTs against MenA, C, W, and Y serogroups and the proportion of participants maintaining a protective SBA titre of ≥8 at 18 and 30 months. The trial is registered with Clinicaltrials.gov (NCT042394300). RESULTS: A total of 40 participants aged 22-47 years were enrolled. Geometric mean titres waned by 18 and 30 months but remained higher than pre-vaccination for all MenB strains and MenA, C, W, and Y. In total, 75%-85% of participants retained protective SBA titres by 30 months against individual MenB strains, whereas 68.8% of patients retained protective antibody titres against all three MenB strains. Antibodies against MenC waned more rapidly than did those against MenA, W, and Y. The proportion of participants with protective titres against MenC at 30 months was also lower (46.9%) than that with protective titres against MenA (87.5%), W (78.1%), and Y (87.5%). CONCLUSIONS: Immune responses against MenB in our cohort of people living with HIV at 2.5 years of follow-up were reassuring, with 68.8% of participants retaining protection against all three reference strains. However, responses against MenC were lower than those against MenA, W, and Y serogroups.

Prediction of Listeria monocytogenes Clonal Complexes from Multilocus Variable Number Tandem Repeat Analysis Patterns Using a Machine Learning Approach.

Multilocus variable number tandem repeat analysis (MLVA) is a molecular subtyping technique that remains useful for those without the resources to access whole genome sequencing for the tracking and tracing of bacterial contaminants. Unlike techniques such as multilocus sequence typing (MLST) and pulsed-field gel electrophoresis, MLVA did not emerge as a standardized subtyping method for Listeria monocytogenes, and as a result, there is no reference database of virulent or food-associated MLVA subtypes as there is for MLST-based clonal complexes (CCs). Having previously shown the close congruence of a 5-loci MLVA scheme with MLST, a predictive model was created using the XGBoost machine learning (ML) technique, which enabled the prediction of CCs from MLVA patterns with ∼85% (±4%) accuracy. As well as validating the model on existing data, a straightforward update protocol was simulated for if and when previously unseen subtypes might arise. This article illustrates how ML techniques can be applied with elementary coding skills to add value to previous-generation molecular subtyping data in-built food processing environments.

First Metatarsophalangeal Arthrodesis for Hallux Rigidus and Hallux Valgus: A Comparison of Patient Reported and Clinical Outcomes.

Few prior studies have compared the patient reported outcomes of first metatarsophalangeal arthrodesis between hallux rigidus and hallux valgus patients. Furthermore, we sought to examine the impact of postoperative radiographic hallux alignment on outcomes scores within each group. A retrospective review of 98 patients who a received primary metatarsophalangeal arthrodesis from January 2010 to March 2020. Clinical complications including nonunion were collected. Patient Reported Outcomes Measurement Information Systems (PROMIS) Physical Function, PROMIS Pain Interference, and the foot function index (FFI) revised short form scores were obtained via telephone. Patients were grouped based on review of preoperative radiographs of the foot and this grouping 37 hallux rigidus and 61 hallux valgus patients. Clinical and patient reported outcomes were compared between these pathologies. No differences in the rate of wound complications, radiographic union, and revision surgery were found between the 2 subgroups. At a median of 2.4 years (3.9 IQR) postoperatively, PROMIS and FFI scores did not vary by pathology group. For both groups, PROMIS scores were similar to the general population of the United States. The postoperative first MTP dorsiflexion angle in the hallux rigidus group was correlated with decreased FFI Pain, FFI Total, and PROMIS Pain Interference domain scores (|r| ≥ 0.40, p < .05 for all). When performing MTP arthrodesis in patients with hallux rigidus, increasing the first MTP dorsiflexion angle may correlate with improved intermediate term patient reported outcomes. However, further studies will need to be done to confirm this theoretical relationship.

The Impact of Surgical Timing After Ankle Fracture on Clinical and Long-Term Patient Reported Outcomes.

The goal of this study is to evaluate the effect of time-to-surgery following closed ankle fractures on long-term patient reported outcomes, fracture healing, and wound complications. To date, little research has been done focusing on the impact "time to definitive fixation" has on patient reported outcomes. We performed a retrospective analysis of 215 patient records who underwent open reduction and internal fixation (ORIF) for an ankle fracture from July 2011 to July 2018. A total of 86 patients completed the patient reported outcome measurement information systems (PROMIS) survey at long-term follow-up. Primary outcomes were the rate of delayed union, postoperative wound complications, patient reported outcome measurement information system (PROMIS) pain interference (PI), and physical function (PF) scores. No differences were found when comparing time to surgery on a continuous scale with rates of delayed union, nonunion, or wound complications (p = .84, .47, and .63, respectively). PROMIS scores were collected at a median of 4.5 years (2.0 interquartile range (IQR), range 2.5-12.3) postoperatively. The time from ankle fracture to surgery was independently associated with worse PROMIS PI scores (unstandardized ß 0.38, 95% CI 0.07-0.68) but not PROMIS PF scores. Severe Lauge-Hansen injuries were independently associated with decreased PROMIS PF scores (unstandardized ß -7.02, 95% CI -12.0 to -2.04). Increased time to surgical intervention and severe Lauge-Hansen injuries were independently associated with worse long-term patient reported outcomes. Surgical timing did not impact union rates or wound complications. Surgeons should be aware that delaying ankle fracture repair beyond 12 days after injury may negatively affect long-term patient reported pain scores.

Achilles tendon disorders: An overview of diagnosis and conservative treatment.

ABSTRACT: Achilles tendon-related pain affects up to 6% of the US population during their lifetime and is commonly encountered by primary care providers. An accurate diagnosis and early conservative management can improve patient quality of life and reduce unnecessary surgical consultations, saving healthcare dollars. Achilles tendon pathologies can be categorized into acute (pain lasting less than 6 weeks), chronic (pain lasting more than 6 weeks), and acute on chronic (worsening of pain with preexisting chronic Achilles tendon pathology). This article describes the diagnosis, conservative management, indications for imaging, and indications for surgical referral for acute and chronic Achilles tendon rupture, Achilles tendinitis, gastrocnemius strain, plantaris rupture, insertional Achilles tendinopathy, Haglund deformity, and noninsertional Achilles tendinopathy.

Infiltrative and drug-resistant slow-cycling cells support metabolic heterogeneity in glioblastoma.

Metabolic reprogramming has been described in rapidly growing tumors, which are thought to mostly contain fast-cycling cells (FCCs) that have impaired mitochondrial function and rely on aerobic glycolysis. Here, we characterize the metabolic landscape of glioblastoma (GBM) and explore metabolic specificities as targetable vulnerabilities. Our studies highlight the metabolic heterogeneity in GBM, in which FCCs harness aerobic glycolysis, and slow-cycling cells (SCCs) preferentially utilize mitochondrial oxidative phosphorylation for their functions. SCCs display enhanced invasion and chemoresistance, suggesting their important role in tumor recurrence. SCCs also demonstrate increased lipid contents that are specifically metabolized under glucose-deprived conditions. Fatty acid transport in SCCs is targetable by pharmacological inhibition or genomic deletion of FABP7, both of which sensitize SCCs to metabolic stress. Furthermore, FABP7 inhibition, whether alone or in combination with glycolysis inhibition, leads to overall increased survival. Our studies reveal the existence of GBM cell subpopulations with distinct metabolic requirements and suggest that FABP7 is central to lipid metabolism in SCCs and that targeting FABP7-related metabolic pathways is a viable therapeutic strategy.

Pediatric hallux valgus: An overview of history, examination, conservative, and surgical management.

Pediatric hallux valgus (PHV), while relatively rare, is still often encountered by general pediatricians. Herein, we concisely summarize the existing literature regarding the pathogenesis, associated conditions, clinical diagnosis, radiographic characteristics, conservative management, and surgical management of PVH. Though PHV is generally considered benign, the progression of hallux valgus can result in complications. The presence of an open physis in the pediatric age group delineates first line treatment choices, whenever possible, as nonoperative. The general exception to this recommendation is for children with neuromuscular and connective tissues disease who may benefit from earlier surgical management. If conservative approaches fail prior to skeletal maturity, the risk of recurrence and need for revision surgery should be discussed with patients and their families before surgical referral is made. The current review was conducted to aid primary care providers in better understanding the pathogenesis, associated conditions, and intervention options available to manage PHV.

Which surgical approach is optimal for joint preparation in talonavicular fusion - A cadaver study.

BACKGROUND: Fusion of the talonavicular joint has proven challenging in literature. The optimal surgical approach for talonavicular arthrodesis is still uncertain. This study compares the amount of physical joint preparation between dorsal and medial approaches to the talonavicular joint. METHODS: Twenty fresh frozen cadaver specimens were randomly assigned to receive either a dorsal or medial operative approach to the talonavicular joint. The joint surface was prepared, and the joint was disarticulated. Image analysis, using ImageJ, was performed by two blinded reviewers to assess the joint surface preparation and this was compared by surgical approach. RESULTS: The dorsal approach had a higher median percentage of talar and total talonavicular joint surface area prepared (75% vs. 59% (p = .007) and 82% vs. 70% (p = .005)). Irrespective of approach, the talus was significantly more difficult to prepare than the navicular (62% vs 88% (p = .001)). CONCLUSION: The dorsal approach provides superior talonavicular joint preparation. The lateral »th of the talar head was the most difficult surface to prepare, and surgeons performing double or triple arthrodesis may prepare the lateral talar head from the lateral approach. LEVEL OF EVIDENCE: Level V.

A randomized, controlled trial of an aerosolized vaccine against measles.

BACKGROUND: Aerosolized vaccine can be used as a needle-free method of immunization against measles, a disease that remains a major cause of illness and death. Data on the immunogenicity of aerosolized vaccine against measles in children are inconsistent. METHODS: We conducted an open-label noninferiority trial involving children 9.0 to 11.9 months of age in India who were eligible to receive a first dose of measles vaccine. Children were randomly assigned to receive a single dose of vaccine by means of either aerosol inhalation or a subcutaneous injection. The primary end points were seropositivity for antibodies against measles and adverse events 91 days after vaccination. The noninferiority margin was 5 percentage points. RESULTS: A total of 1001 children were assigned to receive aerosolized vaccine, and 1003 children were assigned to receive subcutaneous vaccine; 1956 of all the children (97.6%) were followed to day 91, but outcome data were missing for 331 children because of thawed specimens. In the per-protocol population, data on 1560 of 2004 children (77.8%) could be evaluated. At day 91, a total of 662 of 775 children (85.4%; 95% confidence interval [CI], 82.5 to 88.0) in the aerosol group, as compared with 743 of 785 children (94.6%; 95% CI, 92.7 to 96.1) in the subcutaneous group, were seropositive, a difference of -9.2 percentage points (95% CI, -12.2 to -6.3). Findings were similar in the full-analysis set (673 of 788 children in the aerosol group [85.4%] and 754 of 796 children in the subcutaneous group [94.7%] were seropositive at day 91, a difference of -9.3 percentage points [95% CI, -12.3 to -6.4]) and after multiple imputation of missing results. No serious adverse events were attributable to measles vaccination. Adverse-event profiles were similar in the two groups. CONCLUSIONS: Aerosolized vaccine against measles was immunogenic, but, at the prespecified margin, the aerosolized vaccine was inferior to the subcutaneous vaccine with respect to the rate of seropositivity. (Funded by the Bill and Melinda Gates Foundation; Measles Aerosol Vaccine Project Clinical Trials Registry-India number, CTRI/2009/091/000673.).

Small, mobile FcepsilonRI receptor aggregates are signaling competent.

Crosslinking of IgE-bound FcepsilonRI triggers mast cell degranulation. Previous fluorescence recovery after photobleaching (FRAP) and phosphorescent anisotropy studies suggested that FcepsilonRI must immobilize to signal. Here, single quantum dot (QD) tracking and hyperspectral microscopy methods were used for defining the relationship between receptor mobility and signaling. QD-IgE-FcepsilonRI aggregates of at least three receptors remained highly mobile over extended times at low concentrations of antigen that induced Syk kinase activation and near-maximal secretion. Multivalent antigen, presented as DNP-QD, also remained mobile at low doses that supported secretion. FcepsilonRI immobilization was marked at intermediate and high antigen concentrations, correlating with increases in cluster size and rates of receptor internalization. The kinase inhibitor PP2 blocked secretion without affecting immobilization or internalization. We propose that immobility is a feature of highly crosslinked immunoreceptor aggregates and a trigger for receptor internalization, but is not required for tyrosine kinase activation leading to secretion.

In-fiber Mach-Zehnder interferometer for gas refractive index measurements based on a hollow-core photonic crystal fiber.

We describe an in-fiber interferometer based on a gas-filled hollow-core photonic crystal fiber. Expressions for the sensitivity, figure of merit and refractive index resolution are derived, and values are experimentally measured and theoretically validated using mode field calculations. The refractive indices of nine monoatomic and molecular gases are measured with a resolution of δns < 10-6.

Quantification of different water species in acetone using a NIR-triple-wavelength fiber laser.

A fiber laser using a thulium-doped ZBLAN gain medium was used to generate laser radiation simultaneously at 1461, 1505 and 1874 nm, with > 5 mW output power at each of the wavelengths. The laser was used to quantify the near-infrared absorption of liquid water in acetone. Additionally, near-infrared spectra were recorded using a broad band source and were interpreted using parallel factor (PARAFAC) analysis to rationalize the concentration-dependent peak shifts.

Prevalence of clinical electroencephalography findings in stroke patients with delirium.

OBJECTIVE: Delirium is an acute cognitive disorder associated with multiple electroencephalographic (EEG) abnormalities in non-neurological patients, though specific EEG characteristics in patients with stroke remain unclear. We aimed to compare the prevalence of EEG abnormalities in stroke patients during delirium episodes with periods that did not correspond to delirium. METHODS: We retrospectively analyzed clinical EEG reports for stroke patients who received daily delirium assessments as part of a prospective study. We compared the prevalence of EEG features corresponding to patient-days with vs. without delirium, including focal and generalized slowing, and focal and generalized epileptiform abnormalities (EAs). RESULTS: Among 58 patients who received EEGs, there were 192 days of both EEG and delirium monitoring (88% [n = 169] corresponding to delirium). Generalized slowing was significantly more prevalent on days with vs. without delirium (96% vs. 57%, p = 0.03), as were bilateral or generalized EAs (38% vs. 13%, p = 0.03). In contrast, focal slowing (53% vs. 74%, p = 0.11) and focal EAs were less prevalent on days with delirium (38% vs. 48%, p = 0.37), though these differences were not statistically significant. CONCLUSIONS: We found a higher prevalence of generalized but not focal EEG abnormalities in stroke patients with delirium. SIGNIFICANCE: These findings may reinforce the diffuse nature of delirium-associated encephalopathy, even in patients with discrete structural lesions.

Validating the Utility of Multilocus Variable Number Tandem-repeat Analysis (MLVA) as a Subtyping Strategy to Monitor Listeria monocytogenes In-built Food Processing Environments.

Listeria monocytogenes is a serious human pathogen and an enduring challenge to control for the ready-to-eat food processing industry. Cost-effective tools that can be deployed by commercial or in-house laboratories to rapidly investigate and resolve contamination events in the built food processing environment are of value to the food industry. Multilocus variable number tandem-repeat analysis (MLVA) is a molecular subtyping method, which along with other same-generation methods such as pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) is being superseded in disease tracking and outbreak investigations by whole-genome sequencing (WGS). In this paper, it is demonstrated that MLVA can continue to play a valuable role as a valid, fast, simple, and cost-effective method to identify and track Listeria monocytogenes subtypes in factory environments, with the method being highly congruent with MLST. Although MLVA does not have the discriminatory power of WGS to identify truly persistent clones, with careful interpretation of results alongside isolate metadata, it remains a powerful tool in situations and locations where WGS may not be readily available to food business operators.

A Novel Plating System for First Metatarsophalangeal Joint Arthrodesis: A Retrospective Comparison of Hybrid and Traditional Locking Plate Constructs.

BACKGROUND: Dorsal plate fixation is commonly used for first metatarsophalangeal joint (1st MTPJ) arthrodesis and plate design continues to evolve. A new staple compression plate (SCP) design attempts to utilize the continuous compression of a nitinol staple across the fusion site while simultaneously providing the stability of a dorsal locked plate. Herein, we compare the radiographic, clinical, and patient-reported outcomes of 1st MTPJ joint arthrodesis using 2 dorsal locking plate constructs including a novel SCP construct. METHODS: Forty-four patients who underwent 1st MTPJ arthrodesis between 2016 and 2020 were retrospectively evaluated. There were 2 group cohorts. Group 1 cohort included 23 patients who received a CrossRoads Extremity SCP, and Group 2 cohort included 21 patients who received a Stryker dorsal locking precontoured titanium plate (LPP). All patients were evaluated with radiographs, Patient-Reported Outcomes Measures Information System (PROMIS) outcome scores, and Foot Function Index (FFI). RESULTS: The complication and union rates did not vary between groups with a fusion rate of 95.7% in the SCP group and 90.5 % in the LPP group. Similarly, we found no significant differences in PROMIS or FFI scores between the SCP and LPP plates. CONCLUSION: Use of either dorsal locking plate construct for 1st MTPJ arthrodesis was associated with high union rates and comparable functional outcomes. As locked plate technology continues to evolve for 1st MTPJ arthrodesis, it is important that clinical outcomes are reported. LEVELS OF EVIDENCE: Level IV.

Intravenous tranexamic acid decreases intraoperative transfusion requirements and does not increase incidence of symptomatic venous thromboembolic events in musculoskeletal sarcoma surgery.

BACKGROUND AND OBJECTIVES: Tranexamic acid (TXA) is poorly studied in patients with bone and musculoskeletal sarcoma due to perceived increased risk of venous thromboembolism (VTE). This study aims to assess the safety and efficacy of intravenous (IV) TXA for patients undergoing surgical resection of primary bone or soft-tissue sarcoma. METHODS: A retrospective, single center review of adult patients with pelvic or extremity sarcoma who underwent surgical resections between January 2005 and March 2020 was performed. Patients between 2005 and 2012 were included as a historical comparison prior to the routine use of IV TXA for all sarcoma resections at our institution. RESULTS: Thirty-nine non-TXA and 59 TXA resections were identified. Two non-TXA patients experienced symptomatic pulmonary embolism compared to zero VTEs amongst TXA patients. IV TXA administered at any dose significantly reduced the probability of intraoperative transfusion (p = 0.003) and the median units of blood transfused at the time of any perioperative transfusion (p = 0.007). Intraoperative times were significantly shorter for TXA patients (128 vs 190 min; p = 0.004). A subset of patients who underwent wide resection with endoprosthetic reconstruction and received TXA similarly showed decreased requirement for intraoperative transfusion (p = 0.014) and decreased procedure times (p = 0.009). CONCLUSIONS: During sarcoma resection, at least 1 g of IV TXA can safely decrease the need for any intraoperative transfusion and the median number of PRBCs transfused by 2 units when any perioperative transfusion is given.

Nociceptor neuroimmune interactomes reveal cell type- and injury-specific inflammatory pain pathways.

Inflammatory pain associated with tissue injury and infections, results from the heightened sensitivity of the peripheral terminals of nociceptor sensory neurons in response to exposure to inflammatory mediators. Targeting immune-derived inflammatory ligands, like prostaglandin E2, has been effective in alleviating inflammatory pain. However, the diversity of immune cells and the vast array of ligands they produce make it challenging to systematically map all neuroimmune pathways that contribute to inflammatory pain. Here, we constructed a comprehensive and updatable database of receptor-ligand pairs and complemented it with single-cell transcriptomics of immune cells and sensory neurons in three distinct inflammatory pain conditions, to generate injury-specific neuroimmune interactomes. We identified cell-type-specific neuroimmune axes that are common, as well as unique, to different injury types. This approach successfully predicts neuroimmune pathways with established roles in inflammatory pain as well as ones not previously described. We found that thrombospondin-1 produced by myeloid cells in all three conditions, is a negative regulator of nociceptor sensitization, revealing a non-canonical role of immune ligands as an endogenous reducer of peripheral sensitization. This computational platform lays the groundwork to identify novel mechanisms of immune-mediated peripheral sensitization and the specific disease contexts in which they act.

Analysis of risk factors for nonunion in pediatric lateral column lengthening.

The lateral column lengthening procedure is a commonly used osteotomy for correction of pes planus performed by inserting a graft in the anterior aspect of the calcaneus through a transverse osteotomy. Though nonunion and calcaneo-cuboid subluxation have been previously reported, these complications have not been extensively studied in pediatric patients. After IRB approval, 111 patients (151 feet) who underwent lateral column lengthening at a single institution were identified. Fifty-three females (70 feet) and 58 males (81 feet) with an average age of 11.4 years (2.6 SD; range 5-17) were analyzed. The primary outcome was nonunion defined as a lack of radiographic evidence of osteotomy healing by 9 months. Underlying diagnosis, pre and postoperative radiographic measurements, age, operative technique, fixation, calcaneo-cuboid subluxation, graft material and concomitant procedures were analyzed for their relationship to nonunion. Nonunion occurred in 7 of 151 feet (4.6%). Patient age at the time of surgery and calcaneo-cuboid subluxation trended toward a significant association with nonunion ( P = 0.053, 0.054, respectively). The degree of surgical correction, as determined by radiographic analysis, and the use of calcaneo-cuboid fixation were not significantly associated with nonunion. None of the other factors evaluated were significantly associated with nonunion. There were three cases of postoperative infections (2.0%), two were superficial and 1 (0.7%) was deep. Thirty-five of 151 feet disclosed radiographic evidence of subluxation. Excluding subluxation, the overall complication rate was 8.6%. Nonunion occurred in 4.6% of pediatric feet undergoing lateral column lengthening. Fixation type was not significantly associated with nonunion. Older age at the time of surgery and calcaneocuboid subluxation trended towards significance. The placement of a calcaneo-cuboid pin was not found to be a significant factor in preventing calcaneo-cuboid subluxation or nonunion.

Insights into cell membrane microdomain organization from live cell single particle tracking of the IgE high affinity receptor FcϵRI of mast cells.

Current models propose that the plasma membrane of animal cells is composed of heterogeneous and dynamic microdomains known variously as cytoskeletal corrals, lipid rafts and protein islands. Much of the experimental evidence for these membrane compartments is indirect. Recently, live cell single particle tracking studies using quantum dot-labeled IgE bound to its high affinity receptor FcϵRI, provided direct evidence for the confinement of receptors within micrometer-scale cytoskeletal corrals. In this study, we show that an innovative time-series analysis of single particle tracking data for the high affinity IgE receptor, FcϵRI, on mast cells provides substantial quantitative information about the submicrometer organization of the membrane. The analysis focuses on the probability distribution function of the lengths of the jumps in the positions of the quantum dots labeling individual IgE FcϵRI complexes between frames in movies of their motion. Our results demonstrate the presence, within the micrometer-scale cytoskeletal corrals, of smaller subdomains that provide an additional level of receptor confinement. There is no characteristic size for these subdomains; their size varies smoothly from a few tens of nanometers to a over a hundred nanometers. In QD-IGE labeled unstimulated cells, jumps of less than 70 nm predominate over longer jumps. Addition of multivalent antigen to crosslink the QD-IgE-FcϵRI complexes causes a rapid slowing of receptor motion followed by a long tail of mostly jumps less than 70 nm. The reduced receptor mobility likely reflects both the membrane heterogeneity revealed by the confined motion of the monomeric receptor complexes and the antigen-induced cross linking of these complexes into dimers and higher oligomers. In both cases, the probability distribution of the jump lengths is well fit, from 10 nm to over 100 nm, by a novel power law. The fit for short jumps suggests that the motion of the quantum dots can be modeled as diffusion in a fractal space of dimension less than two.