High-throughput screen identifies non inflammatory small molecule inducers of trained immunity.

Trained immunity is characterized by epigenetic and metabolic reprogramming in response to specific stimuli. This rewiring can result in increased cytokine and effector responses to pathogenic challenges, providing nonspecific protection against disease. It may also improve immune responses to established immunotherapeutics and vaccines. Despite its promise for next-generation therapeutic design, most current understanding and experimentation is conducted with complex and heterogeneous biologically derived molecules, such as ß-glucan or the Bacillus Calmette-Guérin (BCG) vaccine. This limited collection of training compounds also limits the study of the genes most involved in training responses as each molecule has both training and nontraining effects. Small molecules with tunable pharmacokinetics and delivery modalities would both assist in the study of trained immunity and its future applications. To identify small molecule inducers of trained immunity, we screened a library of 2,000 drugs and drug-like compounds. Identification of well-defined compounds can improve our understanding of innate immune memory and broaden the scope of its clinical applications. We identified over two dozen small molecules in several chemical classes that induce a training phenotype in the absence of initial immune activation-a current limitation of reported inducers of training. A surprising result was the identification of glucocorticoids, traditionally considered immunosuppressive, providing an unprecedented link between glucocorticoids and trained innate immunity. We chose seven of these top candidates to characterize and establish training activity in vivo. In this work, we expand the number of compounds known to induce trained immunity, creating alternative avenues for studying and applying innate immune training.

Stress-activated friction in sheared suspensions probed with piezoelectric nanoparticles.

A hallmark of concentrated suspensions is non-Newtonian behavior, whereby the viscosity increases dramatically once a characteristic shear rate or stress is exceeded. Such strong shear thickening is thought to originate from a network of frictional particle-particle contact forces, which forms under sufficiently large stress, evolves dynamically, and adapts to changing loads. While there is much evidence from simulations for the emergence of this network during shear thickening, experimental confirmation has been difficult. Here, we use suspensions of piezoelectric nanoparticles and exploit the strong local stress focusing within the network to activate charge generation. This charging can then be detected in the measured ac conductance and serve as a signature of frictional contact formation. The direct link between stress-activated frictional particle interactions and piezoelectric suspension response is further demonstrated by tracking the emergence of structural memory in the contact network under oscillatory shear and by showing how stress-activated friction can drive mechano-transduction of chemical reactions with nonlinear reaction kinetics. Taken together, this makes the ac conductance of piezoelectric suspensions a sensitive in-situ reporter of the micromechanics associated with frictional interactions.

Heat Shock Protein 90's Mechanistic Role in Contact Hypersensitivity.

Despite the known dangers of contact allergens and their long-lasting use as models in immunology, their molecular mode of action largely remains unknown. In this study, we report that a contact allergen, 1-chloro-2,4-dinitrobenzene (DNCB), elicits contact hypersensitivity through binding the protein we identify. Starting from an unbiased sampling of proteomics, we found nine candidate proteins with unique DNCB-modified peptide fragments. More than half of these fragments belonged to heat shock protein 90 (HSP90), a common stress-response protein and a damage-associated molecular pattern, and showed the highest probability of incidence. Inhibition and short hairpin RNA knockdown of HSP90 in human monocyte cell line THP-1 suppressed the potency of DNCB by >80%. Next, we successfully reduced DNCB-induced contact hypersensitivity in HSP90-knockout mice, which confirmed our findings. Finally, we hypothesized that DNCB-modified HSP90 activates the immune cells through HSP90's receptor, CD91. Pretreatment of CD91 in THP-1 cell lines and BALB/c mice attenuated the potency of DNCB, consistent with the result of HSP90-knockout mice. Altogether, our data show that DNCB-HSP90 binding plays a role in mediating DNCB-induced contact hypersensitivity, and the activation of CD91 by DNCB-modified HSP90 proteins could mediate this process.

Symptom resolution following a repeat concussion within the same athlete.

INTRODUCTION: Repeat sport-related concussion (SRC) is anecdotally associated with prolonged recovery. Few studies have examined repeat concussion within the same athlete. We sought to explore differences in symptom burden and recovery outcomes in an individual athlete's initial and repeat SRC. METHODS: A retrospective within-subject cohort study of athletes aged 12-23 years diagnosed with two separate SRCs from 11/2017-10/2020 was conducted. Primary outcomes were initial symptom severity and time-to-symptom-resolution. Secondary outcomes included return-to-learn (RTL) and return-to-play (RTP) duration. RESULTS: Of 868 athletes seen, 47 athletes presented with repeat concussions. Median time between concussions was 244 days (IQR 136-395). Comparing initial to repeat concussion, no differences were observed in time-to-clinic (4.3 ± 7.3vs.3.7 ± 4.6 days, p = 0.56) or initial PCSS (26.2 ± 25.3 vs. 30.5 ± 24.1, p = 0.32). While a difference was observed in time-to-symptom resolution between initial/repeat concussion (21.2 ± 16.3 vs. 41.7 ± 86.0 days, p = 0.30), this did not reach statistical significance. No significant differences were observed in time-to-RTL (17.8 ± 60.6 vs. 6.0 ± 8.3 days, p = 0.26) and RTP (33.2 ± 44.1 vs. 29.4 ± 39.1 days, p = 0.75). Repeat concussion was not associated with symptom resolution on univariate (HR 1.64, 95% CI 0.96-2.78, p = 0.07) and multivariable (HR 0.85, 95% CI 0.49-1.46, p = 0.55) Cox regression. CONCLUSION: No significant differences in symptom duration and RTP/RTL were seen between initial/repeat concussion.

Risk of Two Sport-Related Concussions in the Same Year: Is the Second Concussion Worse?

OBJECTIVES: 1) Evaluate the frequency of same-year, repeat concussions; (2) assess predictors of sustaining a repeat concussion; and (3) compare outcomes of athletes with repeat concussions with athletes with single concussion. DESIGN: A retrospective, case-control study. SETTING: Regional sports concussion center. PATIENTS: Adolescents sustaining a sport-related concussions (SRC) from November 2017 to October 2020. INDEPENDENT VARIABLES: Participants were dichotomized into 2 groups: (1) athletes with a single concussion; and (2) athletes with repeat concussions. MAIN OUTCOME MEASURES: Between group and within group analyses were completed to look for differences in demographics, personal and family history, concussion history, and recovery metrics between the 2 groups. RESULTS: Of 834 athletes with an SRC, 56 (6.7%) sustained a repeat concussion and 778 (93.3%) had a single concussion. Between group: Personal history of migraines (19.6% vs 9.5%, χ 2 = 5.795, P = 0.02), family history of migraines (37.5% vs 24.5%, χ 2 = 4.621, P = 0.03), and family history of psychiatric disorders (25% vs 13.1%, χ 2 = 6.224, P = 0.01) were significant predictors of sustaining a repeat concussion. Within group: Among those with a repeat concussion, initial symptom severity was greater (Z = -2.422; P = 0.02) during the repeat concussion and amnesia was more common (χ 2 = 4.775, P = 0.03) after the initial concussion. CONCLUSIONS: In a single-center study of 834 athletes, 6.7% suffered a same-year, repeat concussion. Risk factors included personal/family migraine history and family psychiatric history. For athletes with repeat concussions, initial symptom score was higher after the second concussion, yet amnesia was more common after the initial concussion.

Treatment of hydrocephalus following posterior fossa tumor resection: a multicenter collaboration from the Hydrocephalus Clinical Research Network.

OBJECTIVE: Persistent hydrocephalus following posterior fossa brain tumor (PFBT) resection is a common cause of morbidity in pediatric brain tumor patients, for which the optimal treatment is debated. The purpose of this study was to compare treatment outcomes between VPS and ETV in patients with persistent hydrocephalus following surgical resection of a PFBT. METHODS: A post-hoc analysis was performed of the Hydrocephalus Clinical Research Network (HCRN) prospective observational study evaluating VPS and ETV for pediatric patients. Children who experienced hydrocephalus secondary to PFBT from 2008 to 2021 were included. Primary outcomes were VPS/ETV treatment failure and time-to-failure (TTF). RESULTS: Among 241 patients, the VPS (183) and ETV (58) groups were similar in age, extent of tumor resection, and preoperative ETV Success Score. There was no difference in overall treatment failure between VPS and ETV (33.9% vs 31.0%, p = 0.751). However, mean TTF was shorter for ETV than VPS (0.45 years vs 1.30 years, p = 0.001). While major complication profiles were similar, compared to VPS, ETV patients had relatively higher incidence of minor CSF leak (10.3% vs. 1.1%, p = 0.003) and pseudomeningocele (12.1% vs 3.3%, p = 0.02). No ETV failures were identified beyond 3 years, while shunt failures occurred beyond 5 years. Shunt infections occurred in 5.5% of the VPS cohort. CONCLUSIONS: ETV and VPS offer similar overall success rates for PFBT-related postoperative hydrocephalus. ETV failure occurs earlier, while susceptibility to VPS failure persists beyond 5 years. Tumor histology and grade may be considered when selecting the optimal means of CSF diversion.

Group Differences in Postconcussion Cognitive, Physical, Sleep-Arousal, and Affective Symptom Subscales in High School and Collegiate Athletes by Race, Gender, and Competitive Level.

OBJECTIVE: Prior psychometric research has identified symptom subscales for the Post-Concussion Symptom Scale (PCSS) based on confirmatory factor analysis (CFA), including cognitive, physical, sleep-arousal, and affective symptom factors. Study objectives included: (1) replicate the 4-factor PCSS model in a diverse sample of athletes with concussion, (2) test the model for invariance across race, gender, and competitive level, and (3) compare symptom subscale and total symptom scores across concussed groups with established invariance. SETTING: Three regional concussion care centers. PARTICIPANTS: A total of 400 athletes who completed the PCSS within 21 days of concussion (64% boys/men, 35% Black, and 69.5% collegiate athletes). DESIGN: Cross-sectional. MAIN MEASURES: A CFA tested the 4-factor model and measurement invariance testing was performed across racial, competitive level, and gender groups. Symptom subscales and total symptom severity scores were compared based on demographic groupings with established invariance. RESULTS: The 4-factor model fit well and strong invariance was established across all demographic categories, indicating symptom subscales could be meaningfully compared across groups. Black and White athletes differed on total symptoms (U = 15 714.5, P = .021, r = 0.12), sleep-arousal symptoms (U = 15 953.5, P = .026, r = 0.11), and physical symptoms (U = 16 140, P = .051, r = 0.10), with Black athletes reporting slightly more symptoms. Collegiate athletes reported greater total symptom severity (U = 10 748.5, P < .001, r = 0.30), with greater symptom reporting on the cognitive (U = 12 985, P < .001, r = 0.21), sleep-arousal (U = 12 594, P < .001, r = 0.22), physical (U = 10 959, P < .001, r = 0.29), and emotional (U = 14 727.5, P = .005, r = 0.14) symptom subscales. There were no significant differences by gender in the total symptom score or subscale scores. After controlling for time since injury, no racial differences persisted, but a significant difference by competitive level in physical symptom reporting (F = 7.39, P = .00, η2 = 0.02) and total symptom reporting (F = 9.16, P = .003, η2 = 0.02) remained. CONCLUSION: These results provide external validation for the PCSS 4-factor model and demonstrate that symptom subscale measurements are comparable across race, genders, and competitive levels. These findings support the continued use of the PCSS and 4-factor model for assessing a diverse population of concussed athletes.

Angiographic factors leading to hemorrhage in AVMs: A systematic review and meta-analysis.

For patients with unruptured intracranial arteriovenous malformations (AVMs), the risk of a hemorrhagic event is approximately 2% to 4% annually. These events have an associated 20-50% morbidity and 10% mortality rate. An understanding of risk factors that predispose these lesions to rupture is important for optimal management. We aimed to pool a large cohort of both ruptured and unruptured AVMs from the literature with the goal of identifying angiographic risk factors that contribute to rupture. A systematic review of the literature was conducted in accordance with the PRISMA guidelines using Pubmed, Embase, Scopus, and Web of Science databases. Studies that presented patient-level data from ruptured AVMs from January 1990 to January 2022 were considered for inclusion. The initial screening of 8,304 papers resulted in a quantitative analysis of 25 papers, which identified six angiographic risk factors for AVM rupture. Characteristics that significantly increase the odds of rupture include the presence of aneurysm (OR = 1.45 [1.19, 1.77], p < 0.001, deep location (OR = 3.08 [2.56, 3.70], p < 0.001), infratentorial location (OR = 2.79 [2.08, 3.75], p < 0.001), exclusive deep venous drainage (OR = 2.50 [1.73, 3.61], p < 0.001), single venous drainage (OR = 2.97 [1.93, 4.56], p < 0.001), and nidus size less than 3 cm (OR = 2.54 [1.41, 4.57], p = 0.002). Although previous literature has provided insight into AVM rupture risk factors, obscurity still exists regarding which risk factors pose the greatest risk. We have identified six major angiographic risk factors (presence of an aneurysm, deep location, infratentorial location, exclusive deep venous drainage, single venous drainage, and nidus size less than 3 cm) that, when identified by a clinician, may help to tailor patient-specific approaches and guide clinical decisions.

Bio-inspired mechanically adaptive materials through vibration-induced crosslinking.

In nature, bone adapts to mechanical forces it experiences, strengthening itself to match the conditions placed upon it. Here we report a composite material that adapts to the mechanical environment it experiences-varying its modulus as a function of force, time and the frequency of mechanical agitation. Adaptation in the material is managed by mechanically responsive ZnO, which controls a crosslinking reaction between a thiol and an alkene within a polymer composite gel, resulting in a mechanically driven ×66 increase in modulus. As the amount of chemical energy is a function of the mechanical energy input, the material senses and adapts its modulus along the distribution of stress, resembling the bone remodelling behaviour that materials can adapt accordingly to the loading location. Such material design might find use in a wide range of applications, from adhesives to materials that interface with biological systems.

Decision Support Tool to Judiciously Assign High-Frequency Neurologic Examinations in Traumatic Brain Injury.

INTRODUCTION: Traumatic brain injury (TBI) management includes serial neurologic examinations to assess for changes dictating neurosurgical interventions. We hypothesized hourly examinations are overassigned. We conducted a decision tree analysis to determine an algorithm to judiciously assign hourly examinations. METHODS: A retrospective cohort study of 1022 patients with TBI admitted to a Level 1 trauma center from January 1, 2019, to December 31, 2019, was conducted. Patients with penetrating TBI or immediate or planned interventions and those with nonsurvivable injuries were excluded. Patients were stratified by whether they underwent an unplanned intervention (e.g., craniotomy or invasive intracranial monitoring). Univariate analysis identified factors for inclusion in chi-square automatic interaction detection technique, classifying those at risk for unplanned procedures. RESULTS: A total of 830 patients were included, 287 (35%) were assigned hourly (Q1) examinations, and 17 (2%) had unplanned procedures, with 16 of 17 (94%) on Q1 examinations. Patients requiring unplanned procedures were more likely to have mixed intracranial hemorrhage pattern (82% versus 39%; P = 0.001), midline shift (35% versus 14%; P = 0.023), an initial poor neurologic examination (Glasgow Comas Scale ≤8, 77% versus 14%; P < 0.001), and be intubated (88% versus 17%; P < 0.001). Using chi-square automatic interaction detection, the decision tree demonstrated low-risk (2% misclassification) and excellent discrimination (area under the curve = 0.915, 95% confidence interval 0.844-0.986; P < 0.001) of patients at risk of an unplanned procedure. By following the algorithm, 167 fewer patients could have been assigned Q1 examinations, resulting in an estimated 6012 fewer examinations. CONCLUSIONS: Using a 4-factor algorithm can optimize the assignment of neuro examinations and substantially reduce neuro examination burden without sacrificing patient safety.

Tuning Subunit Vaccines with Novel TLR Triagonist Adjuvants to Generate Protective Immune Responses against Coxiella burnetii.

Coxiella burnetii is an obligate intracellular bacterium and the causative agent of Q fever. C. burnetii is considered a potential bioterrorism agent because of its low infectious dose; resistance to heat, drying, and common disinfectants; and lack of prophylactic therapies. Q-Vax, a formalin-inactivated whole-bacteria vaccine, is currently the only prophylactic measure that is protective against C. burnetii infections but is not U.S. Food and Drug Administration approved. To overcome the safety concerns associated with the whole-bacteria vaccine, we sought to generate and evaluate recombinant protein subunit vaccines against C. burnetii To accomplish this, we formulated C. burnetii Ags with a novel TLR triagonist adjuvant platform, which used combinatorial chemistry to link three different TLR agonists together to form one adjuvanting complex. We evaluated the immunomodulatory activity of a panel of TLR triagonist adjuvants and found that they elicited unique Ag-specific immune responses both in vitro and in vivo. We evaluated our top candidates in a live C. burnetii aerosol challenge model in C56BL/6 mice and found that several of our novel vaccine formulations conferred varying levels of protection to the challenged animals compared with sham immunized mice, although none of our candidates were as protective as the commercial vaccine across all protection criteria that were analyzed. Our findings characterize a novel adjuvant platform and offer an alternative approach to generating protective and effective vaccines against C. burnetii.

Association of Preinjury Medical Diagnoses With Pediatric Persistent Postconcussion Symptoms in Electronic Health Records.

OBJECTIVE: To identify risk factors and generate hypotheses for pediatric persistent postconcussion symptoms (PPCS). SETTING: A regional healthcare system in the Southeastern United States. PARTICIPANTS: An electronic health record-based algorithm was developed and validated to identify PPCS cases and controls from an institutional database of more than 2.8 million patients. PPCS cases (n = 274) were patients aged 5 to 18 years with PPCS-related diagnostic codes or with PPCS key words identified by natural language processing of clinical notes. Age, sex, and year of index event-matched controls (n = 1096) were patients with mild traumatic brain injury codes only. Patients with moderate or severe traumatic brain injury were excluded. All patients used our healthcare system at least 3 times 180 days before their injury. DESIGN: Case-control study. MAIN MEASURES: The outcome was algorithmic classification of PPCS. Exposures were all preinjury medical diagnoses assigned at least 180 days before the injury. RESULTS: Cases and controls both had a mean of more than 9 years of healthcare system use preinjury. Of 221 preinjury medical diagnoses, headache disorder was associated with PPCS after accounting for multiple testing (odds ratio [OR] = 2.9; 95% confidence interval [CI]: 1.6-5.0; P = 2.1e-4). Six diagnoses were associated with PPCS at a suggestive threshold for statistical significance (false discovery rate P < .10): gastritis/duodenitis (OR = 2.8; 95% CI: 1.6-5.1; P = 5.0e-4), sleep disorders (OR = 2.3; 95% CI: 1.4-3.7; P = 7.4e-4), abdominal pain (OR = 1.6; 95% CI: 1.2-2.2; P = 9.2e-4), chronic sinusitis (OR = 2.8; 95% CI: 1.5-5.2; P = 1.3e-3), congenital anomalies of the skin (OR = 2.9; 95% CI: 1.5-5.5; P = 1.9e-3), and chronic pharyngitis/nasopharyngitis (OR = 2.4; 95% CI: 1.4-4.3; P = 2.5e-3). CONCLUSIONS: These results support the strong association of preinjury headache disorders with PPCS. An association of PPCS with prior gastritis/duodenitis, sinusitis, and pharyngitis/nasopharyngitis suggests a role for chronic inflammation in PPCS pathophysiology and risk, although results could equally be attributable to a higher likelihood of somatization among PPCS cases. Identified risk factors should be investigated further and potentially considered during the management of pediatric mild traumatic brain injury cases.

Conditional Vasospasm-Free Survival Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Following aneurysmal subarachnoid hemorrhage (SAH), patients are monitored closely for vasospasm in the intensive care unit. Conditional vasospasm-free survival describes the risk of future vasospasm as a function of time elapsed without vasospasm. Conditional survival has not been applied to this clinical scenario but could improve patient counseling and intensive care unit use. The objective of this study was to characterize conditional vasospasm-free survival following SAH. METHODS: This was a single institution, retrospective cohort study of patients treated for aneurysmal SAH between 1/1/2000-6/1/2020. The primary outcome was the development of vasospasm defined by the first instance of either radiographic vasospasm on computed tomography angiography, Lindegaard Index > 3.0 by transcranial doppler ultrasonography, or vasospasm-specific intraarterial therapy. Multivariable Cox regression was performed, and conditional vasospasm-free survival curves were constructed. RESULTS: A total of 528 patients were treated for aneurysmal SAH and 309 (58.5%) developed vasospasm. Conditional survival curves suggest patients who survive to postbleed day 10 without vasospasm have a nearly 90% chance of being discharged without vasospasm. The median onset of vasospasm was postbleed day 6. Age more than 50 years was associated with a lower risk (hazard ratio [HR] = .76; 95% confidence interval [CI] 0.64-0.91; p < 0.001). Higher initial systolic blood pressure (HR = 1.18; 95% CI 1.046-1.350; p = .008), Hunt-Hess grades 4 or 5 (HR = 1.304; 95% CI 1.014-1.676), and modified Fisher scale score of 4 (HR = 1.808; 95% CI 1.198-2.728) were associated with higher vasospasm than the respective lower grades. CONCLUSION: Conditional survival provides a useful framework for counseling patients and making decisions around vasospasm risk for patients with aneurysmal SAH, while risk factor-stratified plots facilitate a patient-centric, evidence-based approach to these conversations and decisions.

Factors Associated With Additional Clinic Visits in the Treatment of Sports-Related Concussion.

OBJECTIVE: To evaluate the variables associated with additional concussion clinic visits before discharge to athletic trainer (AT). DESIGN: Retrospective cohort study. SETTING: Multidisciplinary Sports Concussion Center. PATIENTS: Patients ages 12 to 23 years presenting with a sport-related concussion between January 11, 2017, and January 10, 2020, and were discharged to an AT. METHODOLOGY: Our main outcome variable was being discharged to AT after the initial clinic visit versus those who attended additional clinic visits before AT discharge. We examined the influence of age, sex, initial visit symptom score, family and personal history of psychiatric disorders and migraines, history of prior concussions, and other variables on this outcome. RESULTS: Of 524 patients, 236 were discharged to AT after the initial clinic visit, while 288 patients required additional clinic visits. The additional visit group had higher initial visit symptom scores ( P = 0.002), head imaging performed more frequently ( P < 0.02), a family history of psychiatric disorders and/or migraines ( P < 0.001, P < 0.001), more often reported a prior concussion ( P = 0.02), and was younger ( P = 0.014) compared with the one visit group. In a multiple variable model, the family history of psychiatric disorders [odds ratio (OR), 3.12 (95% CI, 1.531-6.343), P = 0.002], prior concussions [OR, 1.39 (95% CI, 1.020-1.892), P = 0.037], greater initial symptom score [OR, 1.05 (95% CI, 1.031-1.058), P < 0.001], and younger age [OR, 0.87 (95% CI, 0.773-0.979), P = 0.021] were strongly associated with additional visits. CONCLUSIONS: Among athletes treated at a regional sports concussion center, family history of psychiatric disorders, increased symptom score at initial visit, prior concussions, and younger age were each uniquely associated with needing additional clinic visits at the time of initial assessment. Understanding these variables may guide treatment protocols for optimal care.

Controllable Frontal Polymerization and Spontaneous Patterning Enabled by Phase-Changing Particles.

Frontal polymerization provides a rapid, economic, and environmentally friendly methodology to manufacture thermoset polymers and composites. Despite its efficiency and reduced environmental impact, the manufacturing method is underutilized due to the limited fundamental understanding of its dynamic control. This work reports the control and patterning of the front propagation in a dicyclopentadiene resin by immersion of phase-changing polycaprolactone particles. Predictive and designed patterning is enabled by multiphysical numerical analyses, which reveal that the interplay between endothermic phase transition, exothermic chemical reaction, and heat exchange govern the temperature, velocity, and propagation path of the front via two different interaction regimes. To pattern the front, one can vary the size and spacing between the particles and increase the number of propagating fronts, resulting in tunable physical patterns formed due to front separation and merging near the particles. Both single- and double-frontal polymerization experiments in an open mold are performed. The results confirm the front-particle interaction mechanisms and the shapes of the patterns explored numerically. The present study offers a fundamental understanding of frontal polymerization in the presence of heat-absorbing second-phase materials and proposes a potential one-step manufacturing method for precisely patterned polymeric and composite materials without masks, molds, or printers.

Tumor-related hydrocephalus in infants: a narrative review.

Primary brain tumors diagnosed during infancy present several challenges for the pediatric neurosurgeon including the management of tumor-related hydrocephalus. Infant tumor-related hydrocephalus (iTRH) is present in over 70% of new diagnoses overall and in over 90% of infants with infratentorial neoplasms. iTRH may be related to direct obstruction of cerebrospinal fluid (CSF) pathways, shedding of protein and/or cells leading to dysfunctional subarachnoid, tumor-related CSF production, or, most frequently, a combination of these mechanisms. Treatment plans must consider the acuity of presentation, the mechanism of iTRH, and the additional neoadjuvant or adjuvant therapies required to treat the neoplasm. This narrative review provides a broad reference on the epidemiology, pathophysiology, and treatment of iTRH.

Sport participation and related head injuries following craniosynostosis correction: a survey study.

OBJECTIVE: Craniosynostosis (CS) affects about 1 in 2500 infants and is predominantly treated by surgical intervention in infancy. Later in childhood, many of these children wish to participate in sports. However, the safety of participation is largely anecdotal and based on surgeon experience. The objective of this survey study was to describe sport participation and sport-related head injury in CS patients. METHODS: A 16-question survey related to child/parent demographics, CS surgery history, sport history, and sport-induced head injury history was made available to patients/parents in the United States through a series of synostosis organization listservs, as well as synostosis-focused Facebook groups, between October 2019 and June 2020. Sports were categorized based on the American Academy of Pediatrics groupings. Pearson's chi-square test, Fisher's exact test, and the independent-samples t-test were used in the analysis. RESULTS: Overall, 187 CS patients were described as 63% male, 89% White, and 88% non-Hispanic, and 89% underwent surgery at 1 year or younger. The majority (74%) had participated in sports starting at an average age of 5 years (SD 2.2). Of those participating in sports, contact/collision sport participation was most common (77%), and 71% participated in multiple sports. Those that played sports were less frequently Hispanic (2.2% vs 22.9%, p < 0.001) and more frequently had undergone a second surgery (44% vs 25%, p = 0.021). Only 9 of 139 (6.5%) sport-participating CS patients suffered head injuries; 6 (67%) were concussions and the remaining 3 were nondescript but did not mention any surgical needs. CONCLUSIONS: In this nationwide survey of postsurgical CS patients and parents, sport participation was exceedingly common, with contact sports being the most common sport category. Few head injuries (mostly concussions) were reported as related to sport participation. Although this is a selective sample of CS patients, the initial data suggest that sport participation, even in contact sports, and typically beginning a few years after CS correction, is safe and commonplace.

Chronic traumatic encephalopathy research viewed in the public domain: What makes headlines?

Objective: To determine chronic traumatic encephalopathy (CTE)-related publication characteristics associated with higher Altmetric scores.Methods: A systematic review of the CTE literature was conducted using PubMed. Publications were coded for: journal impact factor (JIF); publication type (primary versus non-primary data collection); discussion of American football; contact sport-CTE association conclusion (yes versus no/neutral); and Altmetric score. Multivariable ordinal logistic regression identified predictors of higher Altmetric scores.Results: Most of the 270 CTE-related publications did not include primary data collection (60%). The median Altmetric score was 12 (range = 0-3745). Higher Altmetric scores were associated with primary data collection [Odds ratio (OR)Adjusted = 2.29; 95% confidence interval (CI) = 1.35-3.89] and discussing American football (ORAdjusted = 2.11; 95%CI = 1.24-3.59). Among publications concluding contact sport-CTE associations, higher Altmetric scores were associated with higher JIF (3-point-JIF-increase ORAdjusted = 2.11; 95%CI = 1.24-3.59); however, the association of higher Altmetric scores with higher JIF was not found among neutral publications or those concluding no contact sport-CTE associations (3-point-JIF-increase ORAdjusted = 1.07; 95%CI = 0.94-1.22).Conclusions: Most CTE-related publications (60%) did not involve primary data collection. Publication characteristics such as higher JIF and concluding contact sport-CTE associations were associated with higher Altmetric scores. It is important for the academic community to consider strategies to counter publication and promotion bias in the presentation of CTE literature.

Sway Balance Mobile Application: Reliability, Acclimation, and Baseline Administration.

OBJECTIVES: To describe historic baseline session administration practices, to assess the utility of a practice trial (an acclimation trial) before the official balance session, and to examine the within-session reliability of the Sway Balance Mobile Application (SBMA). DESIGN: Retrospective observational study. SETTING: Middle schools, high schools, and colleges across the United States. PARTICIPANTS: More than 17 000 student-athletes were included in the Sway Medical database with 7968 individuals meeting this study's inclusion criteria. INDEPENDENT VARIABLES: The Sway Medical database included the following subject characteristics for each student-athlete: age, sex, weight, and height. MAIN OUTCOME MEASURES: Balance assessment score generated by the SBMA. RESULTS: Variable administration practices with significant differences between baseline session averages across methods were found. Individuals who performed an acclimation trial had a significantly higher baseline session average than those who did not. Within-session reliability estimates were in the low to adequate range (r = 0.53-0.78), with higher estimates found for 2 consecutive baseline tests (r = 0.75-0.78). CONCLUSIONS: For maximum clinical utility, a standardized protocol for postural control baseline acquisition is necessary. Acclimation trial should be administered before a baseline session to minimize variability, especially with only 1 to 2 baseline tests. The highest reliability was observed across 2 consecutive baseline tests within the same baseline session. We suggest obtaining baseline balance measurements with an acclimation trial followed by a baseline session with 2 baseline tests. Prospective studies are required for validation.

From Glucose to Polymers: A Continuous Chemoenzymatic Process.

Efforts to synthesize degradable polymers from renewable resources are deterred by technical and economic challenges; especially, the conversion of natural building blocks into polymerizable monomers is inefficient, requiring multistep synthesis and chromatographic purification. Herein we report a chemoenzymatic process to address these challenges. An enzymatic reaction system was designed that allows for regioselective functional group transformation, efficiently converting glucose into a polymerizable monomer in quantitative yield, thus removing the need for chromatographic purification. With this key success, we further designed a continuous, three-step process, which enabled the synthesis of a sugar polymer, sugar poly(orthoester), directly from glucose in high yield (73 % from glucose). This work may provide a proof-of-concept in developing technically and economically viable approaches to address the many issues associated with current petroleum-based polymers.