Comparison of coagulation and fibrinolysis in Irish Wolfhounds and age-matched control dogs using tissue plasminogen activator-augmented viscoelastic testing.

OBJECTIVE: To determine if Irish Wolfhounds (IWs), like other sighthounds, are hyperfibrinolytic compared with nonsighthound dogs using 2 native and tissue plasminogen activator (tPA)-enhanced viscoelastic assays, one that is whole blood-based (viscoelastic coagulation monitor [VCM]) and the other that is plasma-based thromboelastography (TEG). DESIGN: Cohort study. SETTING: University teaching hospital. ANIMALS: A convenience sample of 27 IWs recruited from the Irish Wolfhound Association of New England Specialty and the local community, and 27 healthy, age-matched, large-breed control dogs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples including CBC, biochemistry, traditional coagulation, and viscoelastic testing were collected from IWs and control dogs. Twelve IWs had viscoelastic testing. IWs had lower fibrinogen concentrations (215.5 ± 57.8 vs 251.4 ± 64.5 mg/dL, P = 0.034) and formed weaker clots on both whole-blood VCM and plasma TEG assays (maximum clot firmness [VCM-MCF] = 39.4 [25.1-48.8] vs 48.5 [34.6-57.3], P = 0.0042; maximum amplitude [TEG-MA] = 22.7 [14.7-33.6] vs 32.2 [26.9-42.0], P < 0.0001). IWs were hyperfibrinolytic compared with control dogs on VCM whole-blood assays, with 25 U/mL tPA (lysis at 30 min [VCM-LI30] = 68.1 [0-100] vs\ 99.9 [63.3-100], P = 0.0009; lysis at 45 min [VCM-LI45] = 31.0 [0-100] vs 98.1 [38.4-100], P = 0.0002) but hypofibrinolytic compared with controls on TEG plasma assays with 50 U/mL tPA (lysis at 30 min [TEG-LY30] = 45.7 [4.6-94.6] vs 93.7 [12.3-96.5], P = 0.0004; lysis at 60 min [TEG-LY60] = 68.7 [29.7-96.8] vs 95.7 [34.4-97.6], P = 0.0003). Minimal fibrinolysis was measured on whole-blood VCM or plasma TEG assays without the addition of tPA, and there were no differences between the 2 groups. CONCLUSIONS: Weaker clots were found in IWs than control dogs. With the addition of tPA, IWs had evidence of hyperfibrinolysis on whole-blood VCM assays and hypofibrinolysis on plasma TEG assays compared with control dogs. Without the addition of tPA, however, both groups of dogs showed minimal fibrinolysis on viscoelastic testing.

A quality and readability comparison of artificial intelligence and popular health website education materials for common hand surgery procedures.

INTRODUCTION: ChatGPT and its application in producing patient education materials for orthopedic hand disorders has not been extensively studied. This study evaluated the quality and readability of educational information pertaining to common hand surgeries from patient education websites and information produced by ChatGPT. METHODS: Patient education information for four hand surgeries (carpal tunnel release, trigger finger release, Dupuytren's contracture, and ganglion cyst surgery) was extracted from ChatGPT (at a scientific and fourth-grade reading level), WebMD, and Mayo Clinic. In a blinded and randomized fashion, five fellowship-trained orthopaedic hand surgeons evaluated the quality of information using a modified DISCERN criteria. Readability and reading grade level were assessed using Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level (FKGL) equations. RESULTS: The Mayo Clinic website scored higher in terms of quality for carpal tunnel release information (p = 0.004). WebMD scored higher for Dupuytren's contracture release (p < 0.001), ganglion cyst surgery (p = 0.003), and overall quality (p < 0.001). ChatGPT - 4th Grade Reading Level, ChatGPT - Scientific Reading Level, WebMD, and Mayo Clinic written materials on average exceeded recommended reading grade levels (4th-6th grade) by at least four grade levels (10th, 14th, 13th, and 11th grade, respectively). CONCLUSIONS: ChatGPT provides inferior education materials compared to patient-friendly websites. When prompted to provide more easily read materials, ChatGPT generates less robust information compared to patient-friendly websites and does not adequately simplify the educational information. ChatGPT has potential to improve the quality and readability of patient education materials but currently, patient-friendly websites provide superior quality at similar reading comprehension levels.

A Novel Classification of Intraoperative Ulnar Nerve Instability to Aid Transposition Surgery.

HYPOTHESIS: The purpose of this study was to compare inter-and intraobserver agreement of a novel intraoperative subluxation classification for patients undergoing ulnar nerve surgery at the elbow. We hypothesize there will be strong inter- and intraobserver agreement of the four-category classification system and reviewers will have substantial confidence while reviewing the classification system. METHODS: Four blinded fellowship-trained orthopedic hand surgeons reviewed 25 videos in total on two separate viewings, 21 days apart. Variables collected were ulnar subluxation classification (A, B, C or D) and a confidence metric. Subsequent to primary data collection, classification grading was stratified into A/B or C/D subgroups for further analysis. Cohen's kappa scores were used to evaluate all variables collected in this study. The interpretation of kappa scores included ≤0.0 as no agreement, 0.01-0.20 as none to slight, 0.21-0.40 as fair, 0.41-0.60 as moderate, 0.61-0.80 as substantial, and 0.81-1.0 as almost perfect agreement. RESULTS: Interobserver agreement of subluxation classification as a four-category scale demonstrated a moderate agreement on first viewing, second viewing, and when both viewings were combined (kappa=0.51, 0.51, and 0.51 respectively). Seventy-five percent (3 out of 4) of reviewers had moderate intraobserver agreement for ulnar nerve subluxation classification while one reviewer had substantial intraobserver classification (kappa= 0.72). Overall, there was high confidence in 65% of classification scores in the second round of viewing, which improved from 58% in the first viewing round. When ulnar subluxation classification selections were regrouped into classes A/B or C/D, 100% of reviewers had substantial interobserver (kappa=0.74 - 0.75) and substantial to almost perfect intraobserver (kappa=0.71 to 0.91) agreement. CONCLUSIONS: The four-category classification was reproducible within and between reviewers. Agreement appeared to increase when simplifying the classification to two categories, which may provide guidance to surgical decision making. The validation of a reproducible classification scheme for intraoperative ulnar subluxation may aid with decision making and further postoperative outcomes research.

Approaching future rewards or waiting for them to arrive: Spatial representations of time and intertemporal choice.

Our mental representation of the passage of time is structured by concepts of spatial motion, including an ego-moving perspective in which the self is perceived as approaching future events and a time-moving perspective in which future events are perceived as approaching the self. While previous research has found that processing spatial information in one's environment can preferentially activate either an ego-moving or time-moving temporal perspective, potential downstream impacts on everyday decision-making have received less empirical attention. Based on the idea people may feel closer to positive events they see themselves as actively approaching rather than passively waiting for, in this pre-registered study we tested the hypothesis that spatial primes corresponding to an ego-moving (vs. time-moving) perspective would attenuate temporal discounting by making future rewards feel more proximal. 599 participants were randomly assigned to one of three spatial prime conditions (ego-moving, time-moving, control) resembling map-based tasks people may engage with on digital devices, before completing measures of temporal perspective, perceived wait time, perceived control over time, and temporal discounting. Partly consistent with previous research, the results indicated that the time-moving prime successfully activated the intended temporal perspective-though the ego-moving prime did not. Contrary to our primary hypotheses, the spatial primes had no effect on either perceived wait time or temporal discounting. Processing spatial information in a map-based task therefore appears to influence how people conceptualise the passage of time, but there was no evidence for downstream effects on intertemporal preferences. Additionally, exploratory analysis indicated that greater perceived control over time was associated with lower temporal discounting, mediated by a reduction in perceived wait time, suggesting a possible area for future research into individual differences and interventions in intertemporal decision-making.

Application of an NMR/Crystallography Fragment Screening Platform for the Assessment and Rapid Discovery of New HIV-CA Binding Fragments.

Identification and assessment of novel targets is essential to combat drug resistance in the treatment of HIV/AIDS. HIV Capsid (HIV-CA), the protein playing a major role in both the early and late stages of the viral life cycle, has emerged as an important target. We have applied an NMR fragment screening platform and identified molecules that bind to the N-terminal domain (NTD) of HIV-CA at a site close to the interface with the C-terminal domain (CTD). Using X-ray crystallography, we have been able to obtain crystal structures to identify the binding mode of these compounds. This allowed for rapid progression of the initial, weak binding, fragment starting points to compounds 37 and 38, which have 19F-pKi values of 5.3 and 5.4 respectively.

Electrodiagnostic Severity Does Not Predict Short to Mid-term Outcomes of Cubital Tunnel Release Surgery.

HYPOTHESIS: This study aimed to explore the prognostic value of electrodiagnostic studies (EDS) to clarify their utility in clinical practice prior to cubital tunnel release surgery as well as identify patient factors associated with patient-reported functional improvement after surgery. Our hypothesis is that patients with severe preoperative findings on EDS will tend to experience less functional improvement after surgery given the extent of ulnar nerve compressive injury. METHODS: Patients with cubital tunnel syndrome and preoperative electrodiagnostic data treated from 2012-2022 with cubital tunnel release were assessed regarding demographic information, preoperative physical exam findings, EDS findings, postoperative complications, and patient-reported outcomes. Short to mid-term qDASH scores were collected for all patients for further evaluation of preoperative EDS data. Patients were grouped into those who had met the MCID in delta qDASH at short to mid-term follow-up and those that did not. EDS data included sensory nerve onset latency, peak latency, amplitude, conduction velocity as well as motor nerve latency, velocity, and amplitude. Electromyogram (EMG) studies were also reviewed which included data pertaining to fibrillations, presence of abnormal fasciculation, positive sharp waves, variation in insertional activity, motor unit activity, duration of activity, and presence of increasing polymorphisms. RESULTS: Of the 257 patients included, 160 (62.0%) were found to meet the MCID for short to mid-term qDASH scores. There were no significant differences between patients who did or did not meet the MCID regarding baseline demographics, comorbidities, preoperative exam findings, and operative technique. Patients who met MCID tended to have lower complication (3.80% vs 7.20%; p=0.248) and revision (0.60% vs 4.10%; p=0.069) rates but these findings were not statistically significant. The cubital tunnel severity as determined by the EDS was similar between cohorts (14.1% vs. 14.3%, p=0.498). Analysis of EMG testing showed there were no significant differences in preoperative, short to mid-term qDASH, or delta short to mid-term qDASH scores for patients with or without abnormal EMG findings. Multivariate regression suggested that only age (p=0.003) was associated with larger delta qDASH scores (Table 7). CONCLUSION: Patient-reported preoperative disease severity may predict the expected postoperative change in ulnar nerve functional improvement and EDS may not have prognostic value for patients undergoing cubital tunnel decompression. Therefore, physicians may suggest surgical treatment without positive EDS findings and still expect postoperative improvement in functional outcomes.

Triceps Tendon Reattachment Using Mini Plates and Screws After Failure of Olecranon Avulsion Fracture Fixation in Osteoporotic Bone: A Case Report.

This is a case report of an 85-year-old woman with osteopenia who underwent olecranon avulsion fracture repair with supplemental triceps tendon repair following a fall on an outstretched arm. The initial procedure failed due to osteoporotic bone quality and an atraumatic disruption of the olecranon fracture fixation. The patient subsequently underwent further surgical intervention with an olecranon avulsion fracture excision and a novel triceps tendon repair technique using plate augmentation and fiber tape. Surgeons may consider this novel approach as an initial treatment for elderly patients with osteopenia or osteoporosis undergoing olecranon avulsion fracture fixation, to prevent the failure and consequent revision surgery.

Pickleball- and Paddleball-Related Injuries in the Lower Extremity: Description, Treatment Options, and Return to Play.

Background Pickleball and paddleball are the fastest-growing sports in the United States. However, there are limited studies on the types of lower extremity injuries and treatment options in an outpatient clinic setting. Hypothesis/purpose This study reports the incidence rate, treatments, and return-to-play (RTP) outcomes for patients presenting to a single orthopedic outpatient center with pickleball- and paddleball-related lower extremity injuries. Study design This study is a retrospective case series, with level IV evidence. Methods A database search of our multispecialty electronic medical record (EMR) system from 2015 to 2023 identified 166 patients with outpatient pickleball- and paddleball-related lower extremity injuries. The retrospective data were reviewed for patient demographics, injury type, mechanism of injury, surgical or non-surgical treatment, and return-to-play recommendations. Results We observed that the majority of the patients with pickleball- and paddleball-related injuries in the lower extremities were over 60 years of age, with more males. Additionally, most injuries encountered were ankle sprain/strain from a twisting mechanism, which was treated non-surgically. Additionally, a significant number of patients suffered an Achilles tendon rupture (12.0%), which was treated surgically with an Achilles tendon repair (88.1%), accounting for the most common surgical treatment performed in this study. Of the 166 patients who were seen and treated, 68 (40.9%) returned to play, and 93 (56.3%) were lost to follow-up. Conclusion Most of these injuries were seen in the older population and caused by a sprain or strain due to sudden changes in direction, which were treated non-surgically. The most common surgical treatment was an Achilles tendon repair due to an Achilles tendon rupture. Although a relatively good number of patients were cleared to return to play, some patients were lost to follow-up. Meanwhile, some patients were advised to stop playing pickleball or paddleball due to the severity of their injuries. As this sport continues to rise in popularity and with the incidence rate of lower extremity injuries increasing over time, orthopedic surgeons should be aware of the types of injuries, treatment options, and outcomes, as well as ways to advise patients on prevention. Therefore, further research on the standard treatments and outcomes of pickleball- and paddleball-related injuries in the lower extremities is encouraged.

Identification of biomarkers for the early detection of non-small cell lung cancer: a systematic review and meta-analysis.

Lung cancer (LC) causes few symptoms in the earliest stages, leading to one of the highest mortality rates among cancers. Low-dose computerised tomography (LDCT) is used to screen high-risk individuals, reducing the mortality rate by 20%. However, LDCT results in a high number of false positives and is associated with unnecessary follow-up and cost. Biomarkers with high sensitivities and specificities could assist in the early detection of LC, especially in patients with high-risk features. Carcinoembryonic antigen (CEA), cytokeratin 19 fragments and cancer antigen 125 have been found to be highly expressed during the later stages of LC but have low sensitivity in the earliest stages. We determined the best biomarkers for the early diagnosis of LC, using a systematic review of eight databases. We identified 98 articles that focussed on the identification and assessment of diagnostic biomarkers and achieved a pooled area under curve of 0.85 (95% CI 0.82-0.088), indicating that the diagnostic performance of these biomarkers when combined was excellent. Of the studies, 30 focussed on single/antigen panels, 22 on autoantibodies, 31 on miRNA and RNA panels, and 15 suggested the use of circulating DNA combined with CEA or neuron-specific enolase (NSE) for early LC detection. Verification of blood biomarkers with high sensitivities (Ciz1, exoGCC2, ITGA2B), high specificities (CYFR21-1, antiHE4, OPNV) or both (HSP90α, CEA) along with miR-15b and miR-27b/miR-21 from sputum may improve early LC detection. Further assessment is needed using appropriate sample sizes, control groups that include patients with non-malignant conditions, and standardised cut-off levels for each biomarker.

A Nine-Year Follow-Up of Stage II Preiser's Disease Treated With a Temporary Dorsal Wrist-Spanning Plate: A Case Report.

Preiser's disease, also known as avascular necrosis of the scaphoid, is a rare condition that is incompletely understood in regard to pathophysiology, diagnosis, and management. There have been numerous case reports and case series evaluating a variety of conservative and operative interventions, but optimal treatment has not been well established. We describe the case of a 20-year-old female with stage II Preiser's disease that was managed with a vascularized bone graft from the 1,2 intercompartmental supraretinacular artery, in addition to temporary dorsal wrist-spanning bridge plate fixation. At the nine-year follow-up, the patient had near full wrist range of motion, no pain, and radiographs showing preserved carpal alignment and a scapholunate angle within normal range. Our findings suggest that this surgical technique is a viable option for restoring scaphoid vascularity, preserving carpal alignment, and halting disease progression.

Clinical Outcomes Following Open Olecranon Bursa Excision for Septic and Aseptic Olecranon Bursitis: An Observational Study.

Background and objective Olecranon bursitis (aseptic or septic) is caused by inflammation in the bursal tissue. While it is typically managed with conservative measures, refractory cases may indicate surgical intervention. There is currently limited research about outcomes following bursal excision for both septic and aseptic etiologies. In light of this, the purpose of this study was to determine if patients experienced improvement following surgical olecranon bursa excision and to compare outcomes between septic and aseptic forms. Materials and methods A retrospective review was performed involving patients who underwent olecranon bursa excision from 2014 to 2021. Demographic data, patient characteristics, surgical data, and outcome-related data were collected from the medical records. Patients were classified into subgroups based on the type of olecranon bursitis (septic or aseptic). Preoperative and one-year postoperative 12-item short-form survey (SF-12) results and range of motion (ROM) outcomes were evaluated for the entire cohort as well as the subgroups. Results We included 61 patients in our study and found significant improvement in the Physical Component Scale 12 (PCS-12) score for all patients (42.0 vs. 45.5, p=0.010) following surgery. However, based on subgroup analysis, the aseptic group improved in PCS-12 following surgery (41.5 vs. 46.8, p<0.001), but the septic group did not (43.6 vs. 40.5, p=0.277). No improvements were found in the Mental Component Scale 12 (MCS-12) scores following surgery in either group. Eighteen of the 61 patients experienced postoperative complications (29.5%), but only 6.5% required a second surgical procedure. Specifically, 14 of the 18 complications occurred in the aseptic group while two septic and two aseptic patients required additional surgeries. Elbow ROM did not change significantly after surgery but more patients were found to have full ROM postoperatively (83.0% to 91.8%, p=0.228). Conclusion Our findings suggest that patients with refractory olecranon bursitis, particularly if aseptic, tend to gain significant physical health benefits from open bursectomy.

Statistical Effective Diffusivity Estimation in Porous Media Using an Integrated On-site Imaging Workflow for Synchrotron Users.

Transport in porous media plays an essential role for many physical, engineering, biological and environmental processes. Novel synchrotron imaging techniques and image-based models have enabled more robust quantification of geometric structures that influence transport through the pore space. However, image-based modelling is computationally expensive, and end users often require, while conducting imaging campaign, fast and agile bulk-scale effective parameter estimates that account for the pore-scale details. In this manuscript we enhance a pre-existing image-based model solver known as OpenImpala to estimate bulk-scale effective transport parameters. In particular, the boundary conditions and equations in OpenImpala were modified in order to estimate the effective diffusivity in an imaged system/geometry via a formal multi-scale homogenisation expansion. Estimates of effective pore space diffusivity were generated for a range of elementary volume sizes to estimate when the effective diffusivity values begin to converge to a single value. Results from OpenImpala were validated against a commercial finite element method package COMSOL Multiphysics (abbreviated as COMSOL). Results showed that the effective diffusivity values determined with OpenImpala were similar to those estimated by COMSOL. Tests on larger domains comparing a full image-based model to a homogenised (geometrically uniform) domain that used the effective diffusivity parameters showed differences below 2 % error, thus verifying the accuracy of the effective diffusivity estimates. Finally, we compared OpenImpala's parallel computing speeds to COMSOL. OpenImpala consistently ran simulations within fractions of minutes, which was two orders of magnitude faster than COMSOL providing identical supercomputing specifications. In conclusion, we demonstrated OpenImpala's utility as part of an on-site tomography processing pipeline allowing for fast and agile assessment of porous media processes and to guide imaging campaigns while they are happening at synchrotron beamlines. Supplementary Information: The online version contains supplementary material available at 10.1007/s11242-023-01993-7.

Arthroscopic Treatment of Shoulder Stiffness With Rotator Cuff Repair Yields Similar Outcomes to Isolated Rotator Cuff Repair.

Purpose: To compare patient-reported and surgical outcome measures in patients with and without secondary shoulder stiffness (SSS) undergoing rotator cuff repair (RCR). Methods: Patients undergoing rotator cuff repair from 2014 to 2020 with complete patient-reported outcome measures (PROMs) by the short-form 12 survey (SF-12) were retrospectively reviewed to identify if operative intervention for SSS was performed alongside the RCR. Those patients with operative intervention for SSS were propensity matched to a group without prior intervention for stiffness by age, sex, laterality, body mass index, diabetes mellitus status, and the presence of a thyroid disorder. The groups were compared by rotator cuff tear (RCT) size, surgical outcomes, further surgical intervention, rotator cuff retear rate, postoperative range of motion (ROM), and SF-12 results at 1 year after surgery. Delta values were calculated for component scores of the SF-12 and ROM values by subtracting the preoperative result from the postoperative result. Results: A total of 89 patients with SSS were compared to 156 patients in the control group at final analysis. The patients in the SSS group experienced a significant improvement in the delta mental health component score (MCS-12) of the SF-12 survey that was not seen in the control group (P = .005 to P = .539). Both groups experienced significant improvement by the delta physical health component score (PCS-12) of the SF-12 survey (SSS: 7.68; P < .001; control: 6.95; P < .001). The SSS group also experienced greater improvement of their forward flexion (25.8° vs 12.9°; P = .005) and external rotation (7.13° vs 1.65°; P = .031) ROM than the control group. Conclusions: Operative intervention of SSS at the time of RCR has equivalent postoperative SF-12 survey outcome scores when compared to patients undergoing RCR without preoperative stiffness despite those patients having lower preoperative scores. Level of Evidence: Level III retrospective comparative study.

Pickleball- and Paddleball-Related Injuries to the Upper Extremity.

Introduction While pickleball and paddleball are rapidly growing as popular sports in the United States, research on the incidence of hand and upper extremity injuries and treatments in outpatient clinics are lacking. This study evaluates the incidence rates and treatment options, both surgically and nonsurgically, for patients presenting with pickleball/paddleball-related injuries. Methods A retrospective database search of our multispecialty, multilocation electronic medical record (EMR) system from 2015 to 2022 identified 204 patients with outpatient pickleball- and paddleball-related injuries. The data from these patients' charts were reviewed for injury incidences, treatment trends, and demographics. Results  The majority of patients suffered wrist fractures due to a fall/dive and were treated nonsurgically. The most common surgical treatment, when required, was open reduction and internal fixation of the distal radius. We found that pickleball and paddleball players who sustained wrist fractures required surgery at a higher rate than the general population if above the age of 65. Conclusion As pickleball and paddleball continue to gain popularity, hand surgeons should be aware of the types of injuries that can occur and, when possible, counsel patients accordingly to try to prevent them. Additionally, hand surgeons should recognize the common treatments and outcomes that arise from pickleball/paddleball-related injuries.

A Direct Comparison, and Prioritisation, of the Immunotherapeutic Targets Expressed by Adult and Paediatric Acute Myeloid Leukaemia Cells: A Systematic Review and Meta-Analysis.

Acute myeloid leukaemia (AML) is characterized by impaired myeloid differentiation resulting in an accumulation of immature blasts in the bone marrow and peripheral blood. Although AML can occur at any age, the incidence peaks at age 65. The pathobiology of AML also varies with age with associated differences in incidence, as well as the frequency of cytogenetic change and somatic mutations. In addition, 5-year survival rates in paediatrics are 60-75% but fall to 5-15% in older AML patients. This systematic review aimed to determine whether the altered genes in AML affect the same molecular pathways, indifferent of patient age, and, therefore, whether patients could benefit from the repurposing drugs or the use of the same immunotherapeutic strategies across age boundaries to prevent relapse. Using a PICO framework and PRISMA-P checklist, relevant publications were identified using five literature databases and assessed against an inclusion criteria, leaving 36 articles, and 71 targets for therapy, for further analysis. QUADAS-2 was used to determine the risk of bias and perform a quality control step. We then priority-ranked the list of cancer antigens based on predefined and pre-weighted objective criteria as part of an analytical hierarchy process used for dealing with complex decisions. This organized the antigens according to their potential to act as targets for the immunotherapy of AML, a treatment that offers an opportunity to remove residual leukaemia cells at first remission and improve survival rates. It was found that 80% of the top 20 antigens identified in paediatric AML were also within the 20 highest scoring immunotherapy targets in adult AML. To analyse the relationships between the targets and their link to different molecular pathways, PANTHER and STRING analyses were performed on the 20 highest scoring immunotherapy targets for both adult and paediatric AML. There were many similarities in the PANTHER and STRING results, including the most prominent pathways being angiogenesis and inflammation mediated by chemokine and cytokine signalling pathways. The coincidence of targets suggests that the repurposing of immunotherapy drugs across age boundaries could benefit AML patients, especially when used in combination with conventional therapies. However, due to cost implications, we would recommend that efforts are focused on ways to target the highest scoring antigens, such as WT1, NRAS, IDH1 and TP53, although in the future other candidates may prove successful.

Engineered molecular sensors for quantifying cell surface crowding.

Cells mediate interactions with the extracellular environment through a crowded assembly of transmembrane proteins, glycoproteins and glycolipids on their plasma membrane. The extent to which surface crowding modulates the biophysical interactions of ligands, receptors, and other macromolecules is poorly understood due to the lack of methods to quantify surface crowding on native cell membranes. In this work, we demonstrate that physical crowding on reconstituted membranes and live cell surfaces attenuates the effective binding affinity of macromolecules such as IgG antibodies in a surface crowding-dependent manner. We combine experiment and simulation to design a crowding sensor based on this principle that provides a quantitative readout of cell surface crowding. Our measurements reveal that surface crowding decreases IgG antibody binding by 2 to 20 fold in live cells compared to a bare membrane surface. Our sensors show that sialic acid, a negatively charged monosaccharide, contributes disproportionately to red blood cell surface crowding via electrostatic repulsion, despite occupying only ~1% of the total cell membrane by mass. We also observe significant differences in surface crowding for different cell types and find that expression of single oncogenes can both increase and decrease crowding, suggesting that surface crowding may be an indicator of both cell type and state. Our high-throughput, single-cell measurement of cell surface crowding may be combined with functional assays to enable further biophysical dissection of the cell surfaceome.

Measurement of Molecular Height Using Cell Surface Optical Profilometry (CSOP).

The plasma membrane of cells is covered by proteins, glycoproteins, and glycolipids with molecular heights ranging from just a few nanometers to hundreds of nanometers. Formation of cell-cell contacts and signal transduction by individual receptors can be dependent on both the average height of a cell's glycocalyx and the specific height of individual receptors, sometimes with nanometer-scale sensitivity. While super-resolution imaging techniques allow molecular distances to be measured with the sub-diffraction limited resolution, typically 10 nm in the lateral direction and 100 nm in the axial direction, measurements of molecular heights at the single nanometer scale on native cell membranes have been difficult to obtain. Cell surface optical profilometry (CSOP) is a simple and rapid method that achieves nanometer height resolution by localizing fluorophores at the tip and base of cell surface molecules and determining their separation with high precision by radially averaging across many molecules. Here we describe how to make CSOP measurements of multi-domain proteins on model membrane surfaces as well as native cell surfaces.

Distal Radioulnar Joint Osteoarthritis: An Update on Treatment Options.

The distal radioulnar joint (DRUJ), the articulation between the sigmoid notch of the radius and the distal ulna, plays a pivotal role in stability and load bearing and allows for pronation and supination of the forearm. Osteoarthritis (OA) of the DRUJ commonly occurs due to distal radius trauma but may also be the result of conditions such as joint instability, septic arthritis, or primary OA. It is initially managed with conservative therapy, but surgery is often considered when nonoperative methods fail. The surgical approaches available to treat this pathology have grown over the years. The procedures have generally favorable outcomes, each with their own unique complications and considerations. This paper comprises a review of the outcomes and complications for the different procedures commonly used to surgically treat DRUJ OA.