Error Management Training and Adaptive Expertise in Learning Computed Tomography Interpretation: A Randomized Clinical Trial.

Importance: Adaptive expertise helps physicians apply their skills to novel clinical cases and reduce preventable errors. Error management training (EMT) has been shown to improve adaptive expertise with procedural skills; however, its application to cognitive skills in medical education is unclear. Objective: To evaluate whether EMT improves adaptive expertise when learning the cognitive skill of head computed tomography (CT) interpretation. Design, Setting, and Participants: This 3-arm randomized clinical trial was conducted from July 8, 2022, to March 30, 2023, in 7 geographically diverse emergency medicine residency programs. Participants were postgraduate year 1 through 4 emergency medicine residents masked to the hypothesis. Interventions: Participants were randomized 1:1:1 to a difficult EMT, easy EMT, or error avoidance training (EAT) control learning strategy for completing an online head CT curriculum. Both EMT cohorts received no didactic instruction before scrolling through head CT cases, whereas the EAT group did. The difficult EMT cohort answered difficult questions about the teaching cases, leading to errors, whereas the easy EMT cohort answered easy questions, leading to fewer errors. All 3 cohorts used the same cases. Main Outcomes and Measures: The primary outcome was a difference in adaptive expertise among the 3 cohorts, as measured using a head CT posttest. Secondary outcomes were (1) differences in routine expertise, (2) whether the quantity of errors during training mediated differences in adaptive expertise, and (3) the interaction between prior residency training and the learning strategies. Results: Among 212 randomized participants (mean [SD] age, 28.8 [2.0] years; 107 men [50.5%]), 70 were allocated to the difficult EMT, 71 to the easy EMT, and 71 to the EAT control cohorts; 150 participants (70.8%) completed the posttest. The difficult EMT cohort outperformed both the easy EMT and EAT cohorts on adaptive expertise cases (60.6% [95% CI, 56.1%-65.1%] vs 45.2% [95% CI, 39.9%-50.6%], vs 40.9% [95% CI, 36.0%-45.7%], respectively; P < .001), with a large effect size (η2 = 0.19). There was no significant difference in routine expertise. The difficult EMT cohort made more errors during training than the easy EMT cohort. Mediation analysis showed that the number of errors during training explained 87.2% of the difficult EMT learning strategy's effect on improving adaptive expertise (P = .01). The difficult EMT learning strategy was more effective in improving adaptive expertise for residents earlier in training, with a large effect size (η2 = 0.25; P = .002). Conclusions and Relevance: In this randomized clinical trial, the findings show that EMT is an effective method to develop physicians' adaptive expertise with cognitive skills. Trial Registration: ClinicalTrials.gov Identifier: NCT05284838.

Factors Associated With Recurrent Pediatric Firearm Injury : A 10-Year Retrospective Cohort Analysis.

BACKGROUND: Firearm injuries are the leading cause of death among children aged 0 to 17 years in the United States. OBJECTIVE: To examine the factors associated with recurrent firearm injury among children who presented with acute (index) nonfatal firearm injury in the St. Louis region. DESIGN: Multicenter, observational, cohort study. SETTING: 2 adult and 2 pediatric level I trauma hospitals in St. Louis, Missouri. PARTICIPANTS: Pediatric patients aged 0 to 17 years presenting with an index firearm injury between 2010 and 2019. MEASUREMENTS: From the St. Louis Region-Wide Hospital-Based Violence Intervention Program Data Repository, we collected data on firearm-injured patient demographics, hospital and diagnostic information, health insurance status, and mortality. The Social Vulnerability Index was used to characterize the social vulnerability of the census tracts of patients' residences. Analysis included descriptive statistics and time-to-event analyses estimating the cumulative incidence of experiencing a recurrent firearm injury. RESULTS: During the 10-year study period, 1340 children presented with an index firearm injury. Most patients were Black (87%), non-Hispanic (99%), male (84%), and between the ages of 15 and 17 years (67%). The estimated risk for firearm reinjury was 6% at 1 year and 14% at 5 years after initial injury. Male children and those seen at an adult hospital were at increased risk for reinjury. LIMITATION: Our data set does not account for injuries occurring outside of the study period and for reinjuries presenting to nonstudy hospitals. CONCLUSION: Children who experience an initial firearm injury are at high risk for experiencing a recurrent firearm injury. Interventions are needed to reduce reinjury and address inequities in the demographic and clinical profiles within this cohort of children. PRIMARY FUNDING SOURCE: National Institutes of Health.

Tau pathology in the dorsal raphe may be a prodromal indicator of Alzheimer's disease.

Protein aggregation in brainstem nuclei is thought to occur in the early stages of Alzheimer's disease (AD), but its specific role in driving prodromal symptoms and disease progression is largely unknown. The dorsal raphe nucleus (DRN) contains a large population of serotonin (5-hydroxytryptamine; 5-HT) neurons that regulate mood, reward-related behavior, and sleep, which are all disrupted in AD. We report here that tau pathology is present in the DRN of individuals 25-80 years old without a known history of dementia, and its prevalence was comparable to the locus coeruleus (LC). By comparison, fewer cases were positive for other pathological proteins including α-synuclein, ß-amyloid, and TDP-43. To evaluate how early tau pathology impacts behavior, we overexpressed human P301L-tau in the DRN of mice and observed depressive-like behaviors and hyperactivity without deficits in spatial memory. Tau pathology was predominantly found in neurons relative to glia and colocalized with a significant proportion of Tph2-expressing neurons in the DRN. 5-HT neurons were also hyperexcitable in P301L-tauDRN mice, and there was an increase in the amplitude of excitatory post-synaptic currents (EPSCs). Moreover, astrocytic density was elevated in the DRN and accompanied by an increase in IL-1α and Frk expression, which suggests increased inflammatory signaling. Additionally, tau pathology was detected in axonal processes in the thalamus, hypothalamus, amygdala, and caudate putamen. A significant proportion of this tau pathology colocalized with the serotonin reuptake transporter (SERT), suggesting that tau may spread in an anterograde manner to regions outside the DRN. Together these results indicate that tau pathology accumulates in the DRN in a subset of individuals over 50 years and may lead to behavioral dysregulation, 5-HT neuronal dysfunction, and activation of local astrocytes which may be prodromal indicators of AD.

Integral Dose or Mean Dose for Predicting Radiosurgery Response in Patients With Trigeminal Neuralgia: A Proposal to Target the Narrowest Part of the Nerve.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) is effective for patients with medically refractory trigeminal neuralgia with a 75%-90% response rate. Consideration of the integral dose (ID) to the target nerve within the 50% isodose line was reported to help select prescription doses to maximize effectiveness and minimize bothersome numbness. The objective of this study was to externally validate the ID as a predictor of outcomes after SRS. METHODS: We reviewed the outcomes and parameters of 94 consecutive patients of type 1 trigeminal neuralgia who had SRS for the first time where nerve ID was calculated. 70% of the prescription doses were 80 Gy, with 28% at 85 Gy, and 2% at 70 Gy. RESULTS: The median follow-up time was 14.4 months. A total of 85 (90%) patients reported significant pain relief (Barrow Neurological Institute I-III) after initial SRS. The median pain recurrence-free survival was 82 months (95% CI 41.1-NA), and estimates at 1, 3, and 5 years were 80.5%, 65.5%, and 55.9%, respectively. The ID was not significantly associated with initial pain relief, or affect the risk of pain recurrence or sensory dysfunction after SRS using the Cox proportional hazards model. A nerve mean dose ≥65 Gy was associated with a reduced risk of pain recurrence on multivariate analysis (hazard ratio 0.408, P = .039). Twenty (21%) patients experienced sensory dysfunction after SRS with 3 (3%) requiring further medications, which was not correlated with the prescription dose or brainstem maximum dose. CONCLUSION: The ID did not predict recurrence-free survival or sensory dysfunction. Our observations suggest improved nerve coverage by the most powerful area of the isocenter, for instance, by targeting a narrower segment if feasible, could result in more durable pain relief. Further studies to validate these findings are needed.

Structure of the MlaC-MlaD complex reveals molecular basis of periplasmic phospholipid transport.

The Maintenance of Lipid Asymmetry (Mla) pathway is a multicomponent system found in all gram-negative bacteria that contributes to virulence, vesicle blebbing and preservation of the outer membrane barrier function. It acts by removing ectopic lipids from the outer leaflet of the outer membrane and returning them to the inner membrane through three proteinaceous assemblies: the MlaA-OmpC complex, situated within the outer membrane; the periplasmic phospholipid shuttle protein, MlaC; and the inner membrane ABC transporter complex, MlaFEDB, proposed to be the founding member of a structurally distinct ABC superfamily. While the function of each component is well established, how phospholipids are exchanged between components remains unknown. This stands as a major roadblock in our understanding of the function of the pathway, and in particular, the role of ATPase activity of MlaFEDB is not clear. Here, we report the structure of E. coli MlaC in complex with the MlaD hexamer in two distinct stoichiometries. Utilising in vivo complementation assays, an in vitro fluorescence-based transport assay, and molecular dynamics simulations, we confirm key residues, identifying the MlaD ß6-ß7 loop as essential for MlaCD function. We also provide evidence that phospholipids pass between the C-terminal helices of the MlaD hexamer to reach the central pore, providing insight into the trajectory of GPL transfer between MlaC and MlaD.

Machine learning classification of new firearm injury encounters in the St Louis region: 2010-2020.

OBJECTIVES: To improve firearm injury encounter classification (new vs follow-up) using machine learning (ML) and compare our ML model to other common approaches. MATERIALS AND METHODS: This retrospective study used data from the St Louis region-wide hospital-based violence intervention program data repository (2010-2020). We randomly selected 500 patients with a firearm injury diagnosis for inclusion, with 808 total firearm injury encounters split (70/30) for training and testing. We trained a least absolute shrinkage and selection operator (LASSO) regression model with the following predictors: admission type, time between firearm injury visits, number of prior firearm injury emergency department (ED) visits, encounter type (ED or other), and diagnostic codes. Our gold standard for new firearm injury encounter classification was manual chart review. We then used our test data to compare the performance of our ML model to other commonly used approaches (proxy measures of ED visits and time between firearm injury encounters, and diagnostic code encounter type designation [initial vs subsequent or sequela]). Performance metrics included area under the curve (AUC), sensitivity, and specificity with 95% confidence intervals (CIs). RESULTS: The ML model had excellent discrimination (0.92, 0.88-0.96) with high sensitivity (0.95, 0.90-0.98) and specificity (0.89, 0.81-0.95). AUC was significantly higher than time-based outcomes, sensitivity was slightly (but not significantly) lower than other approaches, and specificity was higher than all other methods. DISCUSSION: ML successfully delineated new firearm injury encounters, outperforming other approaches in ruling out encounters for follow-up. CONCLUSION: ML can be used to identify new firearm injury encounters and may be particularly useful in studies assessing re-injuries.

Radiation Therapy for Lung Cancer: Imaging Appearances and Pitfalls.

Radiation therapy is part of a multimodality treatment approach to lung cancer. The radiologist must be aware of both the expected and the unexpected imaging findings of the post-radiation therapy patient, including the time course for development of post- radiation therapy pneumonitis and fibrosis. In this review, a brief discussion of radiation therapy techniques and indications is presented, followed by an image-heavy differential diagnostic approach. The review focuses on computed tomography imaging examples to help distinguish normal postradiation pneumonitis and fibrosis from alternative complications, such as infection, local recurrence, or radiation-induced malignancy.

Harnessing the cGAS-STING pathway to potentiate radiation therapy: current approaches and future directions.

In this review, we cover the current understanding of how radiation therapy, which uses ionizing radiation to kill cancer cells, mediates an anti-tumor immune response through the cGAS-STING pathway, and how STING agonists might potentiate this. We examine how cGAS-STING signaling mediates the release of inflammatory cytokines in response to nuclear and mitochondrial DNA entering the cytoplasm. The significance of this in the context of cancer is explored, such as in response to cell-damaging therapies and genomic instability. The contribution of the immune and non-immune cells in the tumor microenvironment is considered. This review also discusses the burgeoning understanding of STING signaling that is independent of inflammatory cytokine release and the various mechanisms by which cancer cells can evade STING signaling. We review the available data on how ionizing radiation stimulates cGAS-STING signaling as well as how STING agonists may potentiate the anti-tumor immune response induced by ionizing radiation. There is also discussion of how novel radiation modalities may affect cGAS-STING signaling. We conclude with a discussion of ongoing and planned clinical trials combining radiation therapy with STING agonists, and provide insights to consider when planning future clinical trials combining these treatments.

Judicious use of corticosteroid injections prior to shoulder arthroplasty does not compromise outcomes at a minimum of 2 years following surgery.

BACKGROUND: The use of total shoulder arthroplasty is continuing to rise with its expanding indications. For patients with chronic conditions, such as glenohumeral arthritis and rotator cuff arthropathy, nonoperative treatment is typically done prior to arthroplasty and often includes corticosteroid injections (CSIs). Recent studies in the shoulder arthroplasty literature as well as applied from the hip and knee literature have focused on the risk of periprosthetic infection. Literature is lacking as to whether the judicious use of corticosteroids in the year prior to arthroplasty influences patient-reported outcomes (PROs). The purpose of this study was to determine if preoperative CSIs prior to shoulder arthroplasty affected 2-year PROs. METHODS: Retrospective review of anatomic and reverse total shoulder arthroplasty (RSA) patients (n = 230) was performed at a single institution including multiple surgeons. Patients were included if they had preoperative and a minimum of 2-year postoperative PROs, including: American Shoulder and Elbow Surgeons (ASES), visual analog scale, Single Assessment Numeric Evaluation, Veteran's RAND 12 Physical Component Score, and Veteran's RAND 12 Mental Component Score. Patients were included in the injection group if they had received an injection, either glenohumeral or subacromial, within 12 months prior to arthroplasty (inject = 134). Subgroup analysis included anatomic (total shoulder arthroplasty [TSA] = 92) and RSA (RSA = 138) as well as those with no injection within 12 months prior to surgery. An analysis of variance was used to compare outcomes between patients who received an injection and those who did not prior to TSA and RSA. RESULTS: There were 230 patients included with 134 patients in the injection group and 96 in the no injection group. Patients who received an injection in the year prior to arthroplasty displayed a significantly higher ASES (82 [16.23 standard deviation] vs. 76 [19.43 standard deviation], P < .01) and Single Assessment Numeric Evaluation (70 [24.49 standard deviation] vs. 63 [29.22 standard deviation], P < .01) scores vs. those who had not received injection. There was no difference when comparing preoperative injection vs. no injection in patients undergoing TSA. Those patients undergoing RSA displayed significantly higher ASES scores (P < .01). There were no significant differences in visual analog scale, Veteran's RAND 12 Physical Component Score, and Veteran's RAND 12 Mental Component Score among any analysis (P > .05), and the minimal clinically important difference in ASES was not different between groups (P.09). CONCLUSION: CSIs within 12 months prior to anatomic and RSA do not compromise PROs during a minimum of 2-year follow-up. Although more complications occurred in the injection group, it did not reach statistical significance and warrants further study in a larger population.

Lasting Impact of the COVID-19 Pandemic on Care and Prevention of Sexually Transmitted Infections in the Midwest.

BACKGROUND: The COVID-19 pandemic reduced the general accessibility of health services. Many sexually transmitted infection (STI) testing and treatment sites modified services (e.g., reduced hours, limited walk-in availability, decreased testing capacity), changes that may result in permanent change in STI service availability. At the same time, systems were driven to innovate in ways that could benefit patients. This study aimed to describe how the COVID-19 pandemic changed STI clinical services, with a focus on long-term impacts. METHODS: In July 2022, a phone survey was designed to assess services for STIs at the 105 STI testing and treatment providers in the St. Louis metropolitan statistical area. Sexually transmitted infection testing providers included STI clinics, primary care clinics that cater to a broad population, and community-based organizations, and excluded emergency departments and urgent care centers. In most cases, the survey was completed by a clinic manager, medical director, or nursing staff member. RESULTS: Of the 75 locations that were interviewed, 12 (16%) had not returned to prepandemic capacity and operations as of July 2022. Five sites had closed completely since the pandemic began, 3 of which are in the northwestern region of the metropolitan statistical area. Most (58.6%) of the open clinics had added telehealth appointments. CONCLUSIONS: Sexually transmitted infection testing sites decreased during the pandemic with lasting impact in one area of the Midwest. Resources to support STI infrastructure should be expanded. Maintaining updated information on STI care providers in the region can aid future assessments.

Predictive Factors Associated With Radiation Myelopathy in Pediatric Patients With Cancer: A PENTEC Comprehensive Review.

PURPOSE: Radiation myelitis (RM) is a rare complication of radiation therapy (RT). The Pediatric Normal Tissue Effects in the Clinic spinal cord task force aimed to identify RT dose effects and assess risk factors for RM in children. Through systematic review, we analyzed RT dose, fraction size, latency between completion of RT and toxicity, chemotherapy use, age when irradiated, and sex. METHODS AND MATERIALS: We conducted literature searches of peer-reviewed manuscripts published from 1964 to June 2017 evaluating RM among children. Normality of variables was assessed with Kolmogorov-Smirnov or Shapiro-Wilk tests. Spearman's rank correlation coefficients were used to test correlations between RT dose/fraction size and latency between RT and development of toxicity. RESULTS: Of 1329 identified and screened reports, 144 reports were fully reviewed and determined to have adequate data for analysis; 16 of these reports had a total of 33 cases of RM with a median age of 13 years (range, 0.2-18) at the time of RT. The most common primary tumor histologies were rhabdomyosarcoma (n = 9), medulloblastoma (n = 5), and Hodgkin lymphoma (n = 2); the most common chemotherapy agents given were vincristine (n = 15), intrathecal methotrexate (n = 12), and intrathecal cytarabine (n = 10). The median RT dose and fraction size were 40 Gy (range, 24-57.4 Gy) and 1.8 Gy (range, 1.3-2.6 Gy), respectively. RT dose resulting in RM in patients who also received chemotherapy was lower than in those not receiving chemotherapy (mean 39.6 vs 49.7 Gy; P = .04). There was no association of age with RT dose. The median latency period was 7 months (range, 1-29). Higher RT dose was correlated with longer latency periods (P = .03) to RM whereas sex, age, fraction size, and chemotherapy use were not. Two of 17 patients with adequate follow-up recovered from RM; unfortunately, it was fatal in 6 of 15 evaluable patients. Complication probability modeling was not possible because of the rarity of events. CONCLUSIONS: This report demonstrates a relatively short latency from RT (with or without chemotherapy) to RM and a wide range of doses (including fraction sizes) associated with RM. No apparent association with age at the time of RT could be discerned. Chemotherapy appears to reduce spinal cord tolerance. Recovery from RM is rare, and it is often fatal.

Personal goals of young survivors of violent injury: implications for practice.

INTRODUCTION: Firearm injuries are the leading cause of death among young people in the USA and disproportionately impact communities of colour and those experiencing socioeconomic distress. Understanding the personal goals of violently injured patients is essential to identifying protective factors and developing interventions that promote them. However, limited research characterising these personal goals exists. OBJECTIVE: The objective of this study was to use qualitative thematic analysis to analyse and describe the personal goals of young people who enrolled in a region-wide hospital-based violence intervention programme after surviving a violent injury. METHODS: A qualitative coding framework was developed, evaluated, and implemented using data from Life Outside of Violence, the St. Louis Area Hospital-Based Violence Intervention Programme. Chart abstraction procedures were used to compile qualitative data on Life Outside of Violence participants' personal goals documented by clinical case managers during individual treatment planning sessions with participants (n=168). Descriptive analyses are reported and implications for practice are discussed. RESULTS: Key findings reveal that (1) violent injury survivors have unmet therapeutic and resource needs, indicating the importance of having service providers with both clinical and case management skills, (2) anger management is a common clinical goal, and (3) employment opportunities are a common resource need. CONCLUSIONS: Findings from this study inform the implementation of the Life Outside of Violence programme and offer a roadmap to other hospital-based violence intervention programmes operating nation-wide. Our results provide insight into participants' needs, desires, and motivations, allowing unique opportunities for improved participant engagement and service delivery.

An octameric PqiC toroid stabilises the outer-membrane interaction of the PqiABC transport system.

The E. coli Paraquat Inducible (Pqi) Pathway is a putative Gram-negative phospholipid transport system. The pathway comprises three components: an integral inner membrane protein (PqiA), a periplasmic spanning MCE family protein (PqiB) and an outer membrane lipoprotein (PqiC). Interactions between all complex components, including stoichiometry, remain uncharacterised; nevertheless, once assembled into their quaternary complex, the trio of Pqi proteins are anticipated to provide a continuous channel between the inner and outer membranes of diderms. Here, we present X-ray structures of both the native and a truncated, soluble construct of the PqiC lipoprotein, providing insight into its biological assembly, and utilise neutron reflectometry to characterise the nature of the PqiB-PqiC-membrane interaction. Finally, we employ phenotypic complementation assays to probe specific PqiC residues, which imply the interaction between PqiB and PqiC is less intimate than previously anticipated.

Long-Term Impact of COVID-19 Related Disruption of National Health Service Elective Services on Emergency Major Lower Limb Amputations.

BACKGROUND: The COVID-19 pandemic has affected the healthcare systems worldwide since the dawn of 2020. In March 2020, the United Kingdom government announced the first national lockdown which severely disturbed all National Health Service (NHS) healthcare elective services. Our aim is to assess the long-term impact of COVID-19 related disruption of NHS elective services on emergency major lower limb amputations (MLLAs). METHODS: Patients' data for emergency MLLA for critical limb-threatening ischemia and diabetic foot infections performed at Aberdeen Royal Infirmary was collected through Trakcare and divided into the control prepandemic group (April 2018-March 2020) and the pandemic group (April 2020-March 2022). The statistical analysis was conducted using the IBM SPSS software (v28.0.1.1 [14]). RESULTS: A total of 358 patients underwent MLLA and 206 (57.5%) of these had diabetes mellitus. There was a 17% increase in the number of urgent referrals and every 1 in 5 of these finally underwent an amputation. There was an increase in the absolute number of Above- and Below-Knee amputations. There was a statistically significant increase by 33% in emergency MLLAs during the pandemic period (P < 0.05). A total of 165 postoperative deaths up to December 2022 were recorded with 30-day mortality rate of 7.26% (n = 26). CONCLUSIONS: NHS vascular management groups should update themselves with evolving technologies to optimize the care provided during future unprecedented times. Furthermore, more effective measures should also be implemented to avoid delayed presentations, which can potentially lead to higher rates of major limb amputations.

Selective Personalized RadioImmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial (SPRINT).

PURPOSE: Standard therapy for locally advanced non-small-cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy followed by adjuvant durvalumab. For biomarker-selected patients with LA-NSCLC, we hypothesized that sequential pembrolizumab and risk-adapted radiotherapy, without chemotherapy, would be well-tolerated and effective. METHODS: Patients with stage III NSCLC or unresectable stage II NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1 were eligible for this trial. Patients with a PD-L1 tumor proportion score (TPS) of ≥50% received three cycles of induction pembrolizumab (200 mg, once every 21 days), followed by a 20-fraction course of risk-adapted thoracic radiotherapy (55 Gy delivered to tumors or lymph nodes with metabolic volume exceeding 20 cc, 48 Gy delivered to smaller lesions), followed by consolidation pembrolizumab to complete a 1-year treatment course. The primary study end point was 1-year progression-free survival (PFS). Secondary end points included response rates after induction pembrolizumab, overall survival (OS), and adverse events. RESULTS: Twenty-five patients with a PD-L1 TPS of ≥50% were enrolled. The median age was 71, most patients (88%) had stage IIIA or IIIB disease, and the median PD-L1 TPS was 75%. Two patients developed disease progression during induction pembrolizumab, and two patients discontinued pembrolizumab after one infusion because of immune-related adverse events. Using RECIST criteria, 12 patients (48%) exhibited a partial or complete response after induction pembrolizumab. Twenty-four patients (96%) received definitive thoracic radiotherapy. The 1-year PFS rate is 76%, satisfying our efficacy objective. One- and 2-year OS rates are 92% and 76%, respectively. The most common grade 3 adverse events were colitis (n = 2, 8%) and esophagitis (n = 2, 8%), and no higher-grade treatment-related adverse events have occurred. CONCLUSION: Pembrolizumab and risk-adapted radiotherapy, without chemotherapy, are a promising treatment approach for patients with LA-NSCLC with a PD-L1 TPS of ≥50%.

Mammalian oocytes store proteins for the early embryo on cytoplasmic lattices.

Mammalian oocytes are filled with poorly understood structures called cytoplasmic lattices. First discovered in the 1960s and speculated to correspond to mammalian yolk, ribosomal arrays, or intermediate filaments, their function has remained enigmatic to date. Here, we show that cytoplasmic lattices are sites where oocytes store essential proteins for early embryonic development. Using super-resolution light microscopy and cryoelectron tomography, we show that cytoplasmic lattices are composed of filaments with a high surface area, which contain PADI6 and subcortical maternal complex proteins. The lattices associate with many proteins critical for embryonic development, including proteins that control epigenetic reprogramming of the preimplantation embryo. Loss of cytoplasmic lattices by knocking out PADI6 or the subcortical maternal complex prevents the accumulation of these proteins and results in early embryonic arrest. Our work suggests that cytoplasmic lattices enrich maternally provided proteins to prevent their premature degradation and cellular activity, thereby enabling early mammalian development.

A polymer network architecture provides superior cushioning and lubrication of soft tissue compared to a linear architecture.

We report the relationships between linear vs. network polymer architecture and biomechanical outcomes including lubrication and cushioning when the polymers are applied to the surface of articulating knee cartilage. Aqueous formulations of the bioinspired polymer poly(2-methacryloyloxylethyl phosphorylcholine) (pMPC) exhibit tuneable rheological properties, with network pMPC exhibiting increased elasticity and viscosity compared to linear pMPC. Application of a polymer network, compared to a linear one, to articulating tissue surfaces reduces friction, lessens tissue strain, minimizes wear, and protects tissue - thereby improving overall tissue performance. Administration of the network pMPC to the middle carpal joint of skeletally mature horses elicits a safe response similar to saline as monitored over a 70 day period.