Single-Molecule Stoichiometry of Supramolecular Complexes.

The use of single-molecule microscopy is introduced as a method to quantify the photophysical properties of supramolecular complexes rapidly at ultra low concentrations (<1 nM), previously inaccessible. Using a model supramolecular system based on the host-guest complexation of cucurbit[n]uril (CB[n]) macrocycles together with a fluorescent guest (Ant910Me), we probe fluorescent CB[n] host-guest complexes in the single molecule regime. We show quantification and differentiation of host-guest photophysics and stoichiometries, both in aqueous media and noninvasively in hydrogel, by thresholding detected photons. This methodology has wide reaching implications in aiding the design of next-generation materials with programmed and controlled properties.

RASP: Optimal Single Puncta Detection in Complex Cellular Backgrounds.

Super-resolution and single-molecule microscopies have been increasingly applied to complex biological systems. A major challenge of these approaches is that fluorescent puncta must be detected in the low signal, high noise, heterogeneous background environments of cells and tissue. We present RASP, Radiality Analysis of Single Puncta, a bioimaging-segmentation method that solves this problem. RASP removes false-positive puncta that other analysis methods detect and detects features over a broad range of spatial scales: from single proteins to complex cell phenotypes. RASP outperforms the state-of-the-art methods in precision and speed using image gradients to separate Gaussian-shaped objects from the background. We demonstrate RASP's power by showing that it can extract spatial correlations between microglia, neurons, and α-synuclein oligomers in the human brain. This sensitive, computationally efficient approach enables fluorescent puncta and cellular features to be distinguished in cellular and tissue environments, with sensitivity down to the level of the single protein. Python and MATLAB codes, enabling users to perform this RASP analysis on their own data, are provided as Supporting Information and links to third-party repositories.

Responsive neurostimulation of thalamic nuclei for regional and multifocal drug-resistant epilepsy in children and young adults.

OBJECTIVE: Responsive neurostimulation (RNS) is a US FDA-approved form of neuromodulation to treat patients with focal-onset drug-resistant epilepsy (DRE) who are ineligible for or whose condition is refractory to resection. However, the FDA approval only extends to use in patients with one or two epileptogenic foci. Recent literature has shown possible efficacy of thalamic RNS in patients with Lennox-Gastaut syndrome and multifocal epilepsy. The authors hypothesized that RNS of thalamic nuclei may be effective in seizure reduction for patients with multifocal or regionalized-onset DRE. METHODS: The authors performed a retrospective chart review of all patients who had an RNS device managed at Texas Children's Hospital between July 2016 and September 2023, with at least one active electrode in the thalamic nuclei and ≥ 12 months of postimplantation follow-up. Information conveyed by the patient or their caregiver provided data on the change in the clinical seizure frequency, quality of life (QOL), and seizure severity between the preimplantation baseline visit and the last office visit (LOV). RESULTS: Thirteen patients (ages 8-24 years) were identified with active RNS leads in thalamic nuclei (11 centromedian and 2 anterior nucleus). At LOV, 46% of patients reported 50%-100% clinical seizure reduction (classified as responders), 15% reported 25%-49% reduction, and 38% reported < 25% reduction or no change. Additionally, 42% of patients reported subjective improvement in QOL and 58% reported improved seizure severity. Patients with focal cortical dysplasia (FCD) responded strongly: 3 of 5 (60%) reported ≥ 80% reduction in seizure burden and improvement in seizure severity and QOL. Patients with multifocal epilepsy and bilateral thalamocortical leads also did well, with all 3 reporting ≥ 50% reduction in seizures. CONCLUSIONS: RNS of thalamic nuclei shows promising results in reducing seizure burden for patients with multifocal or regional-onset DRE, particularly in a bilateral thalamocortical configuration or when addressing an underlying FCD.

High-density volumetric super-resolution microscopy.

Volumetric super-resolution microscopy typically encodes the 3D position of single-molecule fluorescence into a 2D image by changing the shape of the point spread function (PSF) as a function of depth. However, the resulting large and complex PSF spatial footprints reduce biological throughput and applicability by requiring lower labeling densities to avoid overlapping fluorescent signals. We quantitatively compare the density dependence of single-molecule light field microscopy (SMLFM) to other 3D PSFs (astigmatism, double helix and tetrapod) showing that SMLFM enables an order-of-magnitude speed improvement compared to the double helix PSF by resolving overlapping emitters through parallax. We demonstrate this optical robustness experimentally with high accuracy ( > 99.2 ± 0.1%, 0.1 locs µm-2) and sensitivity ( > 86.6 ± 0.9%, 0.1 locs µm-2) through whole-cell (scan-free) imaging and tracking of single membrane proteins in live primary B cells. We also exemplify high-density volumetric imaging (0.15 locs µm-2) in dense cytosolic tubulin datasets.

Antibody agonists trigger immune receptor signaling through local exclusion of receptor-type protein tyrosine phosphatases.

Antibodies can block immune receptor engagement or trigger the receptor machinery to initiate signaling. We hypothesized that antibody agonists trigger signaling by sterically excluding large receptor-type protein tyrosine phosphatases (RPTPs) such as CD45 from sites of receptor engagement. An agonist targeting the costimulatory receptor CD28 produced signals that depended on antibody immobilization and were sensitive to the sizes of the receptor, the RPTPs, and the antibody itself. Although both the agonist and a non-agonistic anti-CD28 antibody locally excluded CD45, the agonistic antibody was more effective. An anti-PD-1 antibody that bound membrane proximally excluded CD45, triggered Src homology 2 domain-containing phosphatase 2 recruitment, and suppressed systemic lupus erythematosus and delayed-type hypersensitivity in experimental models. Paradoxically, nivolumab and pembrolizumab, anti-PD-1-blocking antibodies used clinically, also excluded CD45 and were agonistic in certain settings. Reducing these agonistic effects using antibody engineering improved PD-1 blockade. These findings establish a framework for developing new and improved therapies for autoimmunity and cancer.

Targeting the activated microenvironment with endosialin (CD248)-directed CAR-T cells ablates perivascular cells to impair tumor growth and metastasis.

BACKGROUND: Targeting of solid cancers with chimeric antigen receptor (CAR)-T cells is limited by the lack of suitable tumor-specific antigens and the immunosuppressive, desmoplastic tumor microenvironment that impedes CAR-T cell infiltration, activity and persistence. We hypothesized that targeting the endosialin (CD248) receptor, strongly expressed by tumor-associated pericytes and perivascular cancer-associated fibroblasts, would circumvent these challenges and offer an exciting antigen for CAR-T cell therapy due to the close proximity of target cells to the tumor vasculature, the limited endosialin expression in normal tissues and the lack of phenotype observed in endosialin knockout mice. METHODS: We generated endosialin-directed E3K CAR-T cells from three immunocompetent mouse strains, BALB/c, FVB/N and C57BL/6. E3K CAR-T cell composition (CD4+/CD8+ ratio), activity in vitro against endosialin+ and endosialin- cells, and expansion and activity in vivo in syngeneic tumor models as well as in tumor-naive healthy and wounded mice and tumor-bearing endosialin knockout mice was assessed. RESULTS: E3K CAR-T cells were active in vitro against both mouse and human endosialin+, but not endosialin-, cells. Adoptively transferred E3K CAR-T cells exhibited no activity in endosialin knockout mice, tumor-naive endosialin wildtype mice or in wound healing models, demonstrating an absence of off-target and on-target/off-tumor activity. By contrast, adoptive transfer of E3K CAR-T cells into BALB/c, FVB/N or C57BL/6 mice bearing syngeneic breast or lung cancer lines depleted target cells in the tumor stroma resulting in increased tumor necrosis, reduced tumor growth and a substantial impairment in metastatic outgrowth. CONCLUSIONS: Together these data highlight endosialin as a viable antigen for CAR-T cell therapy and that targeting stromal cells closely associated with the tumor vasculature avoids CAR-T cells having to navigate the harsh immunosuppressive tumor microenvironment. Further, the ability of E3K CAR-T cells to recognize and target both mouse and human endosialin+ cells makes a humanized and optimized E3K CAR a promising candidate for clinical development applicable to a broad range of solid tumor types.

The role of high-resolution ultrasound and MRI in the evaluation of peripheral nerves in the lower extremity.

Lower extremity peripheral neuropathy is a commonly encountered neurologic disorder, which can lead to chronic pain, functional disability, and decreased quality of life for a patient. As diagnostic imaging modalities have improved, imaging has started to play an integral role in the detection and characterization of peripheral nerve abnormalities by non-invasively and accurately identifying abnormal nerves as well as potential causes of neuropathy, which ultimately leads to precise and timely treatment. Ultrasound, which has high spatial resolution and can quickly and comfortably characterize peripheral nerves in real time along with associated denervation muscle atrophy, and magnetic resonance neurography, which provides excellent contrast resolution between nerves and other tissues and between pathologic and normal segments of peripheral nerves, in addition to assessing reversible and irreversible muscle denervation changes, are the two mainstay imaging modalities used in peripheral nerve assessment. These two modalities are complimentary, and one may be more useful than the other depending on the nerve and location of pathology. Imaging must be interpreted in the context of available clinical information and other diagnostic studies, such as electrodiagnostic tests. Here, we offer a comprehensive overview of the role of high-resolution ultrasound and magnetic resonance neurography in the evaluation of the peripheral nerves of the lower extremity and their associated neuropathies.

Role of high-resolution ultrasound and magnetic resonance neurography in the evaluation of peripheral nerves in the upper extremity.

Upper extremity entrapment neuropathies are common conditions in which peripheral nerves are prone to injury at specific anatomical locations, particularly superficial regions or within fibro-osseous tunnels, resulting in pain and potential disability. Although neuropathy is primarily diagnosed clinically by physical examination and electrophysiology, imaging evaluation with ultrasound and magnetic resonance neurography are valuable complementary non-invasive and accurate tools for evaluation and can help define the site and cause of nerve dysfunction which ultimately leads to precise and timely treatment. Ultrasound, which has higher spatial resolution, can quickly and comfortably characterize the peripheral nerves in real time and can evaluate for denervation related muscle atrophy. Magnetic resonance imaging on the other hand provides excellent contrast resolution between the nerves and adjacent tissues, also between pathologic and normal segments of peripheral nerves. It can also assess the degree of muscle denervation and atrophy. As a prerequisite for nerve imaging, radiologists and sonographers should have a thorough knowledge of anatomy of the peripheral nerves and their superficial and deep branches, including variant anatomy, and the motor and sensory territories innervated by each nerve. The purpose of this illustrative article is to review the common neuropathy and nerve entrapment syndromes in the upper extremities focusing on ultrasound and magnetic resonance neurography imaging.

scAAV2-Mediated Expression of Thioredoxin 2 and C3 Transferase Prevents Retinal Ganglion Cell Death and Lowers Intraocular Pressure in a Mouse Model of Glaucoma.

Elevated intraocular pressure (IOP) in glaucoma causes retinal ganglion cell (RGC) loss and damage to the optic nerve. Although IOP is controlled pharmacologically, no treatment is available to restore retinal and optic nerve function. In this paper, we aimed to develop a novel gene therapy for glaucoma using an AAV2-based thioredoxin 2 (Trx2)-exoenzyme C3 transferase (C3) fusion protein expression vector (scAAV2-Trx2-C3). We evaluated the therapeutic effects of this vector in vitro and in vivo using dexamethasone (DEX)-induced glaucoma models. We found that scAAV2-Trx2-C3-treated HeLa cells had significantly reduced GTP-bound active RhoA and increased phosphor-cofilin Ser3 protein expression levels. scAAV2-Trx2-C3 was also shown to inhibit oxidative stress, fibronectin expression, and alpha-SMA expression in DEX-treated HeLa cells. NeuN immunostaining and TUNEL assay in mouse retinal tissues was performed to evaluate its neuroprotective effect upon RGCs, whereas changes in mouse IOP were monitored via rebound tonometer. The present study showed that scAAV2-Trx2-C3 can protect RGCs from degeneration and reduce IOP in a DEX-induced mouse model of glaucoma, while immunohistochemistry revealed that the expression of fibronectin and alpha-SMA was decreased after the transduction of scAAV2-Trx2-C3 in murine eye tissues. Our results suggest that AAV2-Trx2-C3 modulates the outflow resistance of the trabecular meshwork, protects retinal and other ocular tissues from oxidative damage, and may lead to the development of a gene therapeutic for glaucoma.

Changes in Self-Reported Adult Health and Household Food Security With the 2021 Expanded Child Tax Credit Monthly Payments.

Importance: The 2021 Expanded Child Tax Credit (ECTC) provided families with children monthly payments from July 2021 to December 2021. The association of this policy with adult health is understudied. Objective: To examine changes in adult self-reported health and household food security before and during ECTC monthly payments. Design, Setting, and Participants: This repeated cross-sectional study used multivariable regression with a difference-in-differences estimator to assess adult health and food security for 39 479 respondents to the National Health Interview Survey (January 2019 to December 2021) before vs during monthly payments. Analyses were stratified by income to focus on low-income vs middle-income and upper-income households. Exposure: Eligibility for ECTC monthly payments from July 2021 to December 2021. Main Outcomes and Measures: Overall self-reported adult health and household food security as binary outcomes (excellent or very good health vs good, fair, or poor health; food secure vs food insecure). Results: In this nationally representative cross-sectional study of 39 479 US adults (mean [SD] age, 41.0 [13.0] years; 7234 [21.7%] Hispanic, 321 [0.9%] non-Hispanic American Indian/Alaska Native, 2205 [5.7%] non-Hispanic Asian, 5113 [13.7%] non-Hispanic Black, and 23 704 [55.8%] White individuals), respondents were predominantly female (21 511 [52.4%]), employed (33 035 [86.7%]), and married (19 838 [55.7%]). Before disbursement of ECTC monthly payments, 7633 ECTC-eligible adults (60.1%) reported excellent or very good health, and 10 950 (87.8%) reported having food security. Among ECTC-ineligible adults, 10 778 (54.9%) reported excellent or very good health and 17 839 (89.1%) reported food security. Following disbursement of monthly payments, ECTC-eligible adults experienced a 3.0 percentage point (pp) greater adjusted increase (95% CI, 0.2-5.7) in the probability of reporting excellent or very good health compared with ECTC-ineligible adults. Additionally, ECTC-eligible adults experienced a 1.9 pp greater adjusted increase (95% CI, 0.1-3.7) in the probability of food security than ECTC-ineligible adults. In income-stratified analyses, the association between ECTC eligibility and overall health was concentrated among middle-income and upper-income households (3.7-pp increase in excellent or very good health; 95% CI, 0.5-6.9). Conversely, the association between ECTC eligibility and food security was concentrated among low-income adults (3.9-pp increase in food security; 95% CI, 0-7.9). Conclusions and Relevance: The results of this cross-sectional study suggest that monthly ECTC payments were associated with improved adult overall health and food security. Cash transfer programs may be effective tools in improving adult health and household nutrition.

Antigen discrimination by T cells relies on size-constrained microvillar contact.

T cells use finger-like protrusions called 'microvilli' to interrogate their targets, but why they do so is unknown. To form contacts, T cells must overcome the highly charged, barrier-like layer of large molecules forming a target cell's glycocalyx. Here, T cells are observed to use microvilli to breach a model glycocalyx barrier, forming numerous small (<0.5 µm diameter) contacts each of which is stabilized by the small adhesive protein CD2 expressed by the T cell, and excludes large proteins including CD45, allowing sensitive, antigen dependent TCR signaling. In the absence of the glycocalyx or when microvillar contact-size is increased by enhancing CD2 expression, strong signaling occurs that is no longer antigen dependent. Our observations suggest that, modulated by the opposing effects of the target cell glycocalyx and small adhesive proteins, the use of microvilli equips T cells with the ability to effect discriminatory receptor signaling.

Age-related effects on the anterior and posterior hippocampal volumes in 6-21 year olds: A model selection approach.

Although recent studies support significant differences in intrinsic structure, function, and connectivity along the longitudinal axis of the hippocampus, few studies have investigated the normative development of this dimension. In addition, factors known to influence hippocampal structure, such as sex or puberty, have yet to be characterized when assessing age-related effects on its subregions. This study addresses this gap by investigating the relationship of the anterior (antHC) and posterior (postHC) hippocampus volumes with age, and how these are moderated by sex or puberty, in structural magnetic resonance imaging scans from 183 typically developing participants aged 6-21 years. Based on previous literature, we first anticipated that non-linear models would best represent the relationship between age and the antHC and postHC volumes. We found that age-related effects are region-specific, such that the antHC volume remains stable with increasing age, while the postHC shows a cubic function characterized by overall volume increase with age but a slower rate during adolescence. Second, we hypothesized that models, which include biological sex or pubertal status would best describe these relationships. Contrary to expectation, models comprising either biological sex or pubertal status did not significantly improve model performance. Further longitudinal research is needed to evaluate their effects on the antHC and postHC development.

Comparing the Effects of Self-Generated and Platform-Generated Whole Body Vibration on Vocal Fatigue.

OBJECTIVES: A whole body vibration platform using vertical oscillation has been shown to be efficacious in reducing vocal fatigue in adults. This study aimed to investigate whether this platform-generated whole body vibration was unique in reducing vocal fatigue by comparing it with self-generated whole body vibration. METHODS: Twenty-four female adults (mean age = 23.96 years) were randomly assigned to one of the following three groups: a machine-generated whole body vibration group (N = 8), a self-generated whole body vibration group (N = 8), and a placebo vocal resting group (N = 8). All participants performed a karaoke singing task for at least 95 minutes. Each participant received 10 minutes of platform-generated vibration, self-vibration, or sham localised vibration (placebo group with basically voice rest only), according to their group allocation. Vocal function ability, measured by the highest fundamental frequency produced, and a self-reported vocal fatigue score were evaluated at three time points: baseline (prefatigue), after the singing task (post-fatigue) and post-vibration. RESULTS: The study revealed that machine-generated whole body vibration was significantly better at improving vocal fatigue than self-generated whole body vibration or voice rest. CONCLUSION: The findings support previous research that machine-generated whole body vibration is effective in reducing vocal fatigue. The non-significant results of self-generated whole body vibration in terms of relieving vocal fatigue suggest that inadequate vibration frequency or amplitude together with leg muscle fatigue may have been the main factor of ineffectiveness.

Development of a microwave-based extraction for forensic biological samples.

In this study, a quick microwave-based treatment was developed as a front end for DNA analysis of forensic samples. The effect of microwave treatment is to cause cell disruption which can improve the release of DNA during direct PCR as well as with extraction methods. Exposure to microwave preprocessing improved the quality of rapid genotyping, particularly when used with low level samples. Optimal results were obtained when samples were microwaved at 300W for 40 s, resulting in improved allele detection. Overall, the addition of this simple preprocessing step improves sensitivity and allele recovery for low level DNA samples when combined with expedited DNA analysis workflows. Its main advantages include speed, low cost, compatibility with downstream DNA methods and application to a wide variety of samples.

Why study mechanisms of brain stimulation therapies? To modulate the right neurons, in the right way, at the right time.

Clinical applications of vagus nerve stimulation (VNS) are burgeoning, but mechanistic work lags behind. In this issue of Neuron, Bowles and colleagues show that VNS timed with positive reinforcement improves motor learning and cortical function by a cholinergic mechanism.

resPAINT: Accelerating Volumetric Super-Resolution Localisation Microscopy by Active Control of Probe Emission.

Points for accumulation in nanoscale topography (PAINT) allows practically unlimited measurements in localisation microscopy but is limited by background fluorescence at high probe concentrations, especially in volumetric imaging. We present reservoir-PAINT (resPAINT), which combines PAINT and active control of probe photophysics. In resPAINT, an activatable probe "reservoir" accumulates on target, enabling a 50-fold increase in localisation rate versus conventional PAINT, without compromising contrast. By combining resPAINT with large depth-of-field microscopy, we demonstrate super-resolution imaging of entire cell surfaces. We generalise the approach by implementing various switching strategies and 3D imaging techniques. Finally, we use resPAINT with a Fab to image membrane proteins, extending the operating regime of PAINT to include a wider range of biological interactions.

mTOR inhibition as a novel gene therapeutic strategy for diabetic retinopathy.

In addition to laser photocoagulation, therapeutic interventions for diabetic retinopathy (DR) have heretofore consisted of anti-VEGF drugs, which, besides drawbacks inherent to the treatments themselves, are limited in scope and may not fully address the condition's complex pathophysiology. This is because DR is a multifactorial condition, meaning a gene therapy focused on a target with broader effects, such as the mechanistic target of rapamycin (mTOR), may prove to be the solution in overcoming these concerns. Having previously demonstrated the potential of a mTOR-inhibiting shRNA packaged in a recombinant adeno-associated virus to address a variety of angiogenic retinal diseases, here we explore the effects of rAAV2-shmTOR-SD in a streptozotocin-induced diabetic mouse model. Delivered via intravitreal injection, the therapeutic efficacy of the virus vector upon early DR processes was examined. rAAV2-shmTOR-SD effectively transduced mouse retinas and therein downregulated mTOR expression, which was elevated in sham-treated and control shRNA-injected (rAAV2-shCon-SD) control groups. mTOR inhibition additionally led to marked reductions in pericyte loss, acellular capillary formation, vascular permeability, and retinal cell layer thinning, processes that contribute to DR progression. Immunohistochemistry showed that rAAV2-shmTOR-SD decreased ganglion cell loss and pathogenic Müller cell activation and proliferation, while also having anti-apoptotic activity, with these effects suggesting the therapeutic virus vector may be neuroprotective. Taken together, these results build upon our previous work to demonstrate the broad ability of rAAV2-shmTOR-SD to address aspects of DR pathophysiology further evidencing its potential as a human gene therapeutic strategy for DR.

Hyperphosphorylated tau self-assembles into amorphous aggregates eliciting TLR4-dependent responses.

Soluble aggregates of the microtubule-associated protein tau have been challenging to assemble and characterize, despite their important role in the development of tauopathies. We found that sequential hyperphosphorylation by protein kinase A in conjugation with either glycogen synthase kinase 3ß or stress activated protein kinase 4 enabled recombinant wild-type tau of isoform 0N4R to spontaneously polymerize into small amorphous aggregates in vitro. We employed tandem mass spectrometry to determine the phosphorylation sites, high-resolution native mass spectrometry to measure the degree of phosphorylation, and super-resolution microscopy and electron microscopy to characterize the morphology of aggregates formed. Functionally, compared with the unmodified aggregates, which require heparin induction to assemble, these self-assembled hyperphosphorylated tau aggregates more efficiently disrupt membrane bilayers and induce Toll-like receptor 4-dependent responses in human macrophages. Together, our results demonstrate that hyperphosphorylated tau aggregates are potentially damaging to cells, suggesting a mechanism for how hyperphosphorylation could drive neuroinflammation in tauopathies.

Predictive value of magnetic resonance imaging in outcomes of nonsurgical treatment of lateral epicondylitis.

BACKGROUND: The diagnosis of lateral epicondylitis is typically made on the basis of clinical history and examination. However, magnetic resonance imaging (MRI) is often used to supplement evaluation of the patient with a painful elbow and can identify extensor carpi radialis brevis (ECRB) tendon tears. The objective of this study was to determine if ECRB tear size on MRI could be used as a prognostic indicator for patients with recalcitrant lateral epicondylitis and partial ECRB tears. METHODS: Forty-one patients with recalcitrant lateral epicondylitis and a partial ECRB tear on MRI were identified (22 men and 19 women; age: 49 ± 8 years; height: 165 ± 36 mm; weight: 73 ± 18 kg). Patients were divided into two groups based on whether they underwent surgery or not. Nonsurgical treatment was evaluated by the Disabilities of the Arm, Shoulder, and Hand questionnaire, and surgery was considered a failure of nonsurgical treatment. Nonsurgical treatment was variable and included a mixture of physical therapy, rest, injection therapy, and splinting. RESULTS: Of the 41 patients, 5 patients opted for immediate surgery and 36 patients were treated nonsurgically. Of those 36 patients, 11 patients had symptom relief, 19 patients had subsequent surgery, and 6 patients chose not to have surgery despite continued symptoms. Tear size on MRI did not differ significantly between the patients who had symptom relief with nonsurgical treatment and the other patients (7.7 ± 4.3 mm vs. 9.7 ± 2.5 mm, P = .07). DISCUSSION: Only 11 of 41 patients (27%) with recalcitrant lateral epicondylitis and ECRB tear had symptom relief with nonsurgical treatment. However, ECRB tendon defect size on MRI did not predict success or failure of nonsurgical treatment.

Elbow Osteochondral Allograft Transplantation and Lateral Ulnar Collateral Ligament Repair with Internal Brace: A Case Report.

CASE: A 23-year-old woman with an Osborne-Cotterill lesion and posterolateral rotatory instability (PLRI) of the elbow was treated with osteochondral allograft transplantation (OCA) and lateral ulnar collateral ligament (LUCL) repair with internal brace. Two years after surgery, she reported resolution of pain and returned to all recreational activities. She reported no mechanical symptoms and no episodes of postoperative instability. CONCLUSION: PLRI can present with an Osborne-Cotterill lesion in addition to LUCL injury. The purpose of this case report was to describe the use of OCA to manage bony defects in the capitellum in addition to LUCL repair for patients with PLRI.