Engineering a robust and anisotropic cardiac-specific extracellular matrix scaffold for cardiac patch tissue engineering.

Extracellular matrix (ECM) fabricated using human induced pluripotent stem cells (hiPSCs)-derived cardiac fibroblasts (hiPSC-CFs) could serve as a completely biological scaffold for an engineered cardiac patch, leveraging the unlimited source and outstanding reproducibility of hiPSC-CFs. Additionally, hiPSC-CF-derived ECM (hiPSC-CF-ECM) holds the potential to enhance maturation of exogenous cardiomyocytes, such as hiPSC-derived cardiomyocytes (hiPSC-CMs), by providing a microenvironment rich in cardiac-specific biochemical and signaling cues. However, achieving sufficient robustness of hiPSC-CF-ECM is challenging. This study aims to achieve appropriate ECM deposition, scaffold thickness, and mechanical strength of an aligned hiPSC-CF-ECM by optimizing the culture period, ranging from 2 to 10 weeks, of hiPSC-CFs grown on micro-grated substrates, which can direct the alignment of both hiPSC-CFs and their secreted ECM. The hiPSC-CFs demonstrated a production rate of 13.5 µg ECM per day per 20,000 cells seeded. An anisotropic nanofibrous hiPSC-CF-ECM scaffold with a thickness of 20.0 ± 2.1 µm was achieved after 6 weeks of culture, followed by decellularization. Compositional analysis through liquid chromatography-mass spectrometry (LC-MS) revealed the presence of cardiac-specific fibrillar collagens, non-fibrillar collagens, and matricellular proteins. Uniaxial tensile stretching of the hiPSC-CF-ECM scaffold indicated robust tensile resilience. Finally, hiPSCs-CMs cultured on the hiPSC-CF-ECM exhibited alignment following the guidance of ECM nanofibers and demonstrated mature organization of key structural proteins. The culture duration of the anisotropic hiPSC-CF-ECM was successfully refined to achieve a robust scaffold containing structural proteins that resembles cardiac microenvironment. This completely biological, anisotropic, and cardiac-specific ECM holds great potential for cardiac patch engineering.

Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency.

Vitamin B12 is critical for hematopoiesis and myelination. Deficiency can cause neurologic deficits including loss of coordination and cognitive decline. However, diagnosis relies on measurement of vitamin B12 in the blood, which may not accurately reflect the concentration in the brain. Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Anti-CD320 impaired cellular uptake of cobalamin (B12) in vitro by depleting its target from the cell surface. Despite a normal serum concentration, B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic B12 supplementation were associated with increased B12 in the CSF and clinical improvement. Optofluidic screening enabled isolation of a patient-derived monoclonal antibody that impaired B12 transport across an in vitro model of the blood-brain barrier (BBB). Autoantibodies targeting the same epitope of CD320 were identified in seven other patients with neurologic deficits of unknown etiology, 6% of healthy controls, and 21.4% of a cohort of patients with neuropsychiatric lupus. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. However, these individuals did not display any hematologic signs of B12 deficiency despite systemic CD320 impairment. Using a genome-wide CRISPR screen, we found that the low-density lipoprotein receptor serves as an alternative B12 uptake pathway in hematopoietic cells. These findings dissect the tissue specificity of B12 transport and elucidate an autoimmune neurologic condition that may be amenable to immunomodulatory treatment and nutritional supplementation.

Room Temperature Diels-Alder Reactions of 4-Vinylimidazoles.

In the course of studying Diels-Alder reactions of 4-vinylimidazoles with N-phenylmaleimide, it was discovered that they engage in cycloaddition at room temperature to give high yields of the initial cycloadduct as a single stereoisomer. In certain cases, the product precipitated out of the reaction mixture and could be isolated by simple filtration, thereby avoiding issues with aromatization observed during chromatographic purification. Given these results, intramolecular variants using doubly activated dienophiles were also investigated at room temperature. Amides underwent cycloaddition at room temperature in modest yields, but the initial adducts were not isolable with Nimid-benzyl-protected systems. Attempts to extend these results to the corresponding esters and hydroxamate were less successful with these substrates only undergoing cycloaddition at elevated temperatures in lower yields. Density functional theory calculations were performed to evaluate the putative transition states for both the inter- and intramolecular variants to rationalize experimental observations.

BioCloneBot: A versatile, low-cost, and open-source automated liquid handler.

Liquid handler systems can provide significant benefits to researchers by automating laboratory work, however, their unaffordable price provides a steep barrier to entry. Therefore, we provide the BioCloneBot, a versatile, low-cost, and open-source automated liquid handler. This system can be easily built with 3D-printed parts and readily available commercial components. The BioCloneBot is highly adaptive to user needs and facilitates various liquid handling tasks in research and diagnostics. Its user-friendly interface and programmable nature make it suitable for a wide range of applications, from small-scale experiments to larger laboratory setups. By utilizing BioCloneBot, researchers and scientists can streamline their liquid handling processes without the financial constraints posed by traditional systems. In this paper, we detail the design, construction, and validation of BioCloneBot, showcasing its precise control, accuracy, and repeatability in various liquid handling tasks. The open-source nature of the system encourages collaboration and customization, enabling researchers to contribute and adapt the technology to specific experimental requirements.

Effects of long-term voluntary wheel running and selective breeding for wheel running on femoral nutrient canals.

The nutrient artery provides ~50%-70% of the total blood volume to long bones in mammals. Studying the functional characteristics of this artery in vivo can be difficult and expensive, so most researchers have measured the nutrient foramen, an opening on the outer surface of the bone that served as the entry point for the nutrient artery during development and bone ossification. Others have measured the nutrient canal (i.e., the passage which the nutrient artery once occupied), given that the external dimensions of the foramen do not necessarily remain uniform from the periosteal surface to the medullary cavity. The nutrient canal, as an indicator of blood flow to long bones, has been proposed to provide a link to studying organismal activity (e.g., locomotor behavior) from skeletal morphology. However, although external loading from movement and activity causes skeletal remodeling, it is unclear whether it affects the size or configuration of nutrient canals. To investigate whether nutrient canals can exhibit phenotypic plasticity in response to physical activity, we studied a mouse model in which four replicate high runner (HR) lines have been selectively bred for high voluntary wheel-running behavior. The selection criterion is the average number of wheel revolutions on days 5 and 6 of a 6-day period of wheel access as young adults (~6-8 weeks old). An additional four lines are bred without selection to serve as controls (C). For this study, 100 female mice (half HR, half C) from generation 57 were split into an active group housed with wheels and a sedentary group housed without wheels for 12 weeks starting at ~24 days of age. Femurs were collected, soft tissues were removed, and femora were micro-computed tomography scanned at a resolution of 12 µm. We then imported these scans into AMIRA and created 3D models of femoral nutrient canals. We tested for evolved differences in various nutrient canal traits between HR and C mice, plastic changes resulting from chronic exercise, and the selection history-by-exercise interaction. We found few differences between the nutrient canals of HR versus C mice, or between the active and sedentary groups. We did find an interaction between selection history and voluntary exercise for the total number of nutrient canals per femur, in which wheel access increased the number of canals in C mice but decreased it in HR mice. Our results do not match those from an earlier study, conducted at generation 11, which was prior to the HR lines reaching selection limits for wheel running. The previous study found that mice from the HR lines had significantly larger total canal cross-sectional areas compared to those from C lines. However, this discrepancy is consistent with studies of other skeletal traits, which have found differences between HR and C mice to be somewhat inconsistent across generations, including the loss of some apparent adaptations with continued selective breeding after reaching a selection limit for wheel-running behavior.

Novel ß-galactosidase activity and first crystal structure of Glycoside Hydrolase family 154.

Polysaccharide Utilization Loci (PULs) are physically linked gene clusters conserved in the Gram-negative phylum of Bacteroidota and are valuable sources for Carbohydrate Active enZyme (CAZyme) discovery. This study focuses on BD-ß-Gal, an enzyme encoded in a metagenomic PUL and member of the Glycoside Hydrolase family 154 (GH154). BD-ß-Gal showed exo-ß-galactosidase activity with regiopreference for hydrolyzing ß-d-(1,6) glycosidic linkages. Notably, it exhibited a preference for d-glucopyranosyl (d-Glcp) over d-galactopyranosyl (d-Galp) and d-fructofuranosyl (d-Fruf) at the reducing end of the investigated disaccharides. In addition, we determined the high resolution crystal structure of BD-ß-Gal, thus providing the first structural characterization of a GH154 enzyme. Surprisingly, this revealed an (α/α)6 topology, which has not been observed before for ß-galactosidases. BD-ß-Gal displayed low structural homology with characterized CAZymes, but conservation analysis suggested that the active site was located in a central cavity, with conserved E73, R252, and D253 as putative catalytic residues. Interestingly, BD-ß-Gal has a tetrameric structure and a flexible loop from a neighboring protomer may contribute to its reaction specificity. Finally, we showed that the founding member of GH154, BT3677 from Bacteroides thetaiotaomicron, described as ß-glucuronidase, displayed exo-ß-galactosidase activity like BD-ß-Gal but lacked a tetrameric structure.

Notes on [post]human nursing: What It MIGHT Be, What it is Not.

With this paper, we walk out some central ideas about posthumanisms and the ways in which nursing is already deeply entangled with them. At the same time, we point to ways in which nursing might benefit from further entanglement with other ideas emerging from posthumanisms. We first offer up a brief history of posthumanisms, following multiple roots to several points of formation. We then turn to key flavors of posthuman thought to differentiate between them and clarify our collective understanding and use of the terms. This includes considerations of the threads of transhumanism, critical posthumanism, feminist new materialism, and the speculative, affirmative ethics that arise from critical posthumanism and feminist new materialism. These ideas are fruitful for nursing, and already in action in many cases, which is the matter we occupy ourselves with in the final third of the paper. We consider the ways nursing is already posthuman-sometimes even critically so-and the speculative worldbuilding of nursing as praxis. We conclude with visions for a critical posthumanist nursing that attends to humans and other/more/nonhumans, situated and material and embodied and connected, in relation.

Open Fractures in National Football League Athletes: Analyzing Performance and Return to Sport.

INTRODUCTION: Open fractures are potentially devastating injuries for the professional athlete. We sought to compare return to sports (RTS) and performance in National Football League (NFL) athletes sustaining open versus closed fractures. METHODS: NFL athletes with surgically treated open and closed fractures of the forearm, tibial shaft, and ankle from 2009-2018 were identified through publicly available reports and records. Data including demographics, RTS, career duration, and the approximate value performance metric before and after injury were collected. Statistical analyses were performed comparing open to closed injuries. Continuous variables were compared using Mann-Whitney U or two sample t- tests while categorical variables were compared using Fisher's exact test. RESULTS: Ninety-five athletes met inclusion criteria (10 open and 85 closed fractures). Overall, 90% (n = 9) returned to sport after an open injury and 83.5% (n = 71) returned after closed injury with a median time missed of 48.9 (range 35.1 - 117.4) weeks and 43.0 (range 2.4 - 108.0) weeks, respectively. Athletes undergoing forearm surgery were able to return sooner, at around 20.8 weeks, and ankle fractures conferred the lowest return rate at 80% (n = 48). There were no significant differences in career duration and post-injury performance between open or closed fracture cohorts. CONCLUSIONS: Although open fractures are relatively uncommon injuries seen in NFL athletes, our study suggests RTS for these players is high. Athletes undergoing surgical treatment for open fractures had similar RTS rates, performance metrics, and career durations compared to those with comparable closed fractures. This information can provide guidance for providers counseling elite athletes on postoperative expectations.

Coming of age in recovery: The prevalence and correlates of substance use recovery status among adolescents and emerging adults.

BACKGROUND AND AIMS: To date, no epidemiological survey has estimated the prevalence of adolescents identifying as being in recovery. This is necessary for planning and identifying the needs of youth with current and remitted substance use disorders. This study estimated the prevalence of recovery status in a large statewide epidemiological survey administered between January and March 2020. PARTICIPANTS: Participants were high school students in 9th through 12th grades throughout Illinois. MEASUREMENTS: Youth were asked if they were in recovery and if they had resolved problems with substances. Youth who reported recovery and problem resolving dual status (DS), recovery only (RO), and problem resolution only (PRO) were compared to propensity score matched control groups who reported neither status (neither/nor; NN). Outcomes included alcohol use, binge alcohol use, cannabis use, and prescription drug use in the past 30 days. FINDINGS: Prevalence estimates were 884 (1.4%) for DS, 1546 (2.5%) for PRO, and 1,811 (2.9%) for RO. Relative to propensity matched control samples, all three groups had significantly lower odds of prescription drug use. The PRO group had lower odds of past month cannabis use. There were no significant differences for either alcohol outcome. CONCLUSIONS: Prevalence estimates of youth in recovery are slightly lower than those of adults in recovery, and estimates should be replicated. Youth in recovery and those resolving problems have numerous behavioral health needs, and relative to matched controls, have even odds for past 30-day alcohol use. These findings compel us to further define recovery for adolescents and emerging adults to allow for improving treatments and epidemiological research.

Induction Chemotherapy Prior to Endoscopic Resection of Alveolar Rhabdomyosarcoma.

Head and neck rhabdomyosarcoma (HNRMS) is a rare type of soft tissue tumor that affects both adults and children with an overall incidence of 0.041 per 100,000 people. Adults make up approximately 31.2% of all HNRMS diagnoses and have an overall survival rate between 20% and 40%. We present a case of a 46-year-old male who initially presented with nasal congestion and vision changes. Maxillofacial computed tomography and magnetic resonance imaging of the brain showed involvement of the orbital apex, abutment of the planum sphenoidale, and extension to the foramen rotundum (FR). Nasal endoscopy with biopsy confirmed the diagnosis of T2aN0M0 parameningeal HNRMS. The patient underwent induction chemotherapy, followed by endoscopic resection, which resulted in negative intraoperative margins. Subsequently, he underwent adjuvant concurrent chemotherapy and proton beam radiation after positive microscopic positive margins were found on the optic nerve. The patient did not experience any significant complications, and he is currently without radiographic or clinical recurrence 18 months after the treatment. He was able to maintain his vision throughout the treatment. In adults, HNRMS is usually treated with chemoradiotherapy based on pediatric protocols, since there are limited data available for adult treatment protocols and outcomes. Although surgery has been associated with positive outcomes in adult patients, there are no previous reports of its use with either neoadjuvant or adjuvant treatment. This type of treatment protocol has never been described for adult HNRMS. We hope that our report can add more data to the growing body of literature on HNRMS treatment protocols.

Jugular Foramen Syndrome Caused by Varicella Zoster Virus Infection.

Jugular foramen syndrome (JFS) is a lower cranial neuropathy syndrome characterized by dysphonia and dysphagia. The syndrome is caused by dysfunction of the glossopharyngeal, vagus, and spinal accessory nerves at the level of the pars nervosa and pars vascularis within the jugular foramen. There are numerous etiologies for JFS, including malignancy, trauma, vascular, and infection. Here, we present the case of a healthy adult man who developed JFS secondary to an atypical presentation of Varicella Zoster meningitis, and was promptly diagnosed and treated with rapid symptom resolution. We diagnosed the patient using specialized skull-based imaging which detailed the jugular foramen, as well as CSF analysis. This case highlights the clinical value of detailed structural evaluation, consideration for infection in the absence of systemic symptoms, and favorable outcomes following early identification and treatment.

Myelomeningocele repair at pediatric hospitals: association with routine discharge and shorter hospital stay.

OBJECTIVE: Postnatal repair for myelomeningocele (MMC) is a time-sensitive and technically challenging procedure. More experienced hospitals may provide improved outcomes for the complexity of care associated with these patients. No prior study has investigated the impact of MMC treatment at pediatric hospitals. The authors sought to examine the effect of pediatric hospital designation on patients undergoing postnatal MMC repair to identify factors associated with maximizing improved patient outcomes. METHODS: The Nationwide Readmissions Database records from 2010 to 2018 were analyzed retrospectively to determine the effect of hospital designation on patient outcomes after postnatal MMC repair. Univariate and multivariate regression analyses of patient and hospital characteristics were conducted to evaluate if MMC repair at a designated pediatric hospital was independently associated with patient outcomes of perinatal infection rates, discharge disposition, and length of stay. RESULTS: Of the total of 6353 pediatric patients who underwent postnatal MMC repair between 2010 and 2018, 2224 (35.0%) received care at a pediatric hospital. Those with an extreme level of disease burden as defined by the all patient refined diagnosis-related group severity of illness index were more likely to be treated at a pediatric hospital (p = 0.03). Patients undergoing repair at a pediatric hospital were also associated with a decreased likelihood of perinatal infection (OR 0.54, 95% CI 0.35-0.83, p = 0.005); greater likelihood of routine disposition (OR 4.85, 95% CI 2.34-10.06, p < 0.0001); and shorter length of stay (incidence rate ratio 0.88, 95% CI 0.77-0.995, p = 0.04). CONCLUSIONS: Pediatric patients requiring intervention for postnatal repair of MMC may benefit from the multidisciplinary subspeciality care offered at pediatric hospitals. The authors found that postnatal repair of MMC at pediatric hospitals was associated with a greater likelihood of improved patient outcomes.

Using Trauma Video Review to Assess EMS Handoff and Trauma Team Non-Technical Skills.

OBJECTIVE: Handoffs by emergency medical services (EMS) personnel suffer from poor structure, inattention, and interruptions. The relationship between the quality of EMS communication and the non-technical performance of trauma teams remains unknown. METHODS: We analyzed 3 months of trauma resuscitation videos (highest acuity activations or patients with an Injury Severity Score [ISS] of ≥15). Handoffs were scored using the mechanism-injury-signs-treatment (MIST) framework for completeness (0-20), efficiency (category jumps), interruptions, and timeliness. Trauma team non-technical performance was scored using the Trauma Non-Technical Skills (T-NOTECHS) scale (5-15). RESULTS: We analyzed 99 videos. Handoffs lasted a median of 62 seconds [IQR: 43-74], scored 11 [10-13] for completeness, and had 2 [1-3] interruptions. Most interruptions were verbal (85.2%) and caused by the trauma team (64.9%). Most handoffs (92%) were efficient with 2 or fewer jumps. Patient transfer during handoff occurred in 53.5% of the videos; EMS providers giving handoff helped transfer in 69.8% of the Primary surveys began during handoff in 42.4% of the videos. Resuscitation teams who scored in the top-quartile on the T-NOTECHS (>11) had higher MIST scores than teams in lower quartiles (13 [11.25-14.75] vs. 11 [10-13]; p < .01). There were no significant differences in ISS, efficiency, timeliness, or interruptions between top- and lower-quartile groups. CONCLUSIONS: There is a relationship between EMS MIST completeness and high performance of non-technical skill by trauma teams. Trauma video review (TVR) can help identify modifiable behaviors to improve EMS handoff and resuscitation efforts and therefore trauma team performance.

Nursing for the Chthulucene: Abolition, affirmation, antifascism.

Critical posthumanism as a philosophical, antifascist nonhierarchical imagination for nursing offers a liberatory passageway forward amidst environmental collapse, an epic pandemic, global authoritarianism, extreme health and wealth disparities, over-reliance on technology and empirics, and unjust societal systems based in whiteness. Drawing upon philosophical and theoretical works from Black and Indigenous scholars, Haraway's idea of the Chthulucene, Deleuze and Guattari's rhizomatic thought, and Kaba's abolitionist organizing among others, we as activist nurse scholars continue the speculative discussion outlined in prior papers. Here we further imagine how we can engage a radical philosophical mission of care for all beings human and non, walking and working alongside the people and communities nurses accompany, connected as we are on this dystopian celestial orb. Discussion is centred on critical analyses of traditional justice framing in nursing, and on the praxis possibilities found within rhizomatic thought, making kin, and just episteme while knitting filaments of nursing theory and history, humming song lyrics from collective memory, and critically dismantling received wisdoms to stumble toward a more emancipatory present future.

Preoperative Association Between Quantitative Lumbar Muscle Parameters and Spinal Sagittal Alignment in Lumbar Fusion Patients.

STUDY DESIGN: A retrospective cross-sectional study. OBJECTIVE: To assess the association between spinal muscle morphology and spinopelvic parameters in lumbar fusion patients, with a special emphasis on lumbar lordosis (LL). SUMMARY OF BACKGROUND DATA: Maintenance of sagittal alignment relies on muscle forces, but the basic association between spinal muscles and spinopelvic parameters is poorly understood. MATERIALS AND METHODS: Patients operated between 2014 and 2017 who had both lumbar magnetic resonance imaging scan and standing whole-spine radiographs within six months before surgery were included. Muscle measurements were conducted on axial T2-weighted magnetic resonance images at the superior endplate L3-L5 for the psoas and L3-S1 for combined multifidus and erector spinae (paraspinal) muscles. A pixel intensity threshold method was used to calculate the total cross-sectional area (TCSA) and the functional cross-sectional area (FCSA). Spinopelvic parameters were measured on lateral standing whole-spine radiographs and included LL, pelvic incidence (PI), PI-LL mismatch, pelvic tilt, sacral slope, thoracic kyphosis, and sagittal vertical axis. Analyses were stratified by biological sex. Multivariable linear regression analyses with adjustments for age and body mass index (BMI) were performed. RESULTS: A total of 104 patients (62.5% female) were included in the analysis. The patient population was 90.4% White with a median age at surgery of 69 years and a median BMI of 27.8 kg/m 2 . All muscle measurements were significantly smaller in women. PI, pelvic tilt, and thoracic kyphosis were significantly greater in women. PI-LL mismatch was 6.1° (10.6°) in men and 10.2° (13.5°) in women ( P =0.106), and sagittal vertical axis was 45.3 (40.8) mm in men and 35.7 (40.8) mm in women ( P =0.251). After adjusting for age and BMI, paraspinal TCSA at L3-L5, and paraspinal FCSA at L4 showed significant positive associations with LL in women. In men, psoas TCSA at L5 and psoas FCSA at L5 showed significant negative associations with LL, but none of the paraspinal muscle measurements. CONCLUSION: Our findings indicate that psoas and lumbar spine extensor muscles interact differently on LL among men and women, creating a unique mechanical environment. LEVEL OF EVIDENCE: Level 4.

Plasma Lysosphingolipid Biomarker Measurement by Liquid Chromatography Tandem Mass Spectrometry.

Plasma lysosphingolipids are highly elevated in patients with Gaucher, Krabbe, Fabry, and Niemann-Pick diseases and tend to accumulate to a greater extent than their respective primary sphingolipids in the plasma of affected patients. In this chapter, we describe two liquid chromatography tandem mass spectrometry (LC-MS/MS) methods to measure plasma concentrations of four lysosphingolipids species. The first method described measures glucosylsphingosine (lyso-GL1) and galactosylsphingosine (psychosine), biomarkers that accumulate in Gaucher and Krabbe diseases, respectively. The second method measures globotriaosylsphingosine (lyso-Gb3) and sphingosylphosphorylcholine (lyso-SPM), biomarkers for Fabry and Niemann-Pick diseases, respectively. Each method utilizes isotope-labeled internal standards and multipoint calibration curves to quantify the analytes of interest. Briefly, plasma samples are mixed with five volumes of LC-MS grade methanol containing internal standard, and protein is removed via centrifugation. Supernatant is dried and resuspended in initial mobile phase. Samples are separated by liquid chromatography using either a BEH amide column (lyso-GL1 + psychosine) or a C18 column (lyso-Gb3 + lyso-SPM). Protonated analytes are measured by selected reaction monitoring (SRM) in positive electrospray ionization mode. Using these methods, we have observed elevations of these lyso- species in Gaucher, Fabry, and Niemann-Pick and successfully distinguished different subtypes reflecting the disease severity.

Irrigation techniques used in spine surgery for surgical site infection prophylaxis: a systematic review and meta-analysis.

BACKGROUND: The greater likelihood of morbidity, mortality, length of hospital stays and poorer long-term outcomes as a result of surgical site infections secondary to spinal surgery makes prophylactic measures an imperative focus. Therefore, the aim of this review was to evaluate the available research related to the efficacy of different intraoperative irrigation techniques used in spinal surgery for surgical site infection (SSI) prophylaxis. METHODS: We performed a comprehensive search using Ovid Medline, EMBASE, Web of Science and the Cochrane library pertaining to this topic. Our meta-analysis was conducted according to PRISMA guidelines. The inclusion criteria consist of spine surgeries with intraoperative use of any wound irrigation technique, comparison groups with a different intraoperative irrigation technique or no irrigation, SSI identified with bacterial cultures or clinically in the postoperative period, reported SSI rates. Data extracted from eligible studies included, but was not limited to, SSI rates, irrigation technique and control technique. Exclusion criteria consist of articles with no human subjects, reviews, meta-analyses and case control studies and no details about SSI identification or rates. Pooled risk ratios were calculated. A meta-analysis was performed with a forest plot to determine risk estimates' heterogeneity with I2 index, Q-statistic, and p value under a random-effects model. Funnel plot was used to assess publication bias. All databases were last checked on January, 2022. PROBAST tool was used to assess both risk of bias and applicability concerns. RESULTS: After reviewing 1494 titles and abstracts, 18 articles met inclusion criteria. They included three prospective randomized-controlled trials, 13 retrospective cohort studies, two prospective cohort studies. There were 54 (1.8%) cases of SSIs in the povidone-iodine irrigation group (N = 2944) compared to 159 (4.6%) in the control group (N = 3408). Using intraoperative povidone-iodine wound irrigation produced an absolute risk reduction of 2.8%. Overall risk ratio was 0.32 (95% CI 0.20-0.53, p < 0.00001). In a global analysis, study heterogeneity and synthesizing mostly retrospective data were primary limitations. CONCLUSION: The most evidence exists for povidone-iodine and has Level 2 evidence supporting SSI reduction during spinal surgery. Other antiseptic solutions such as dilute chlorhexidine lack published evidence in this patient population which limits the ability to draw conclusions related to its use in spinal surgery. LEVEL OF EVIDENCE: II - Systematic Review with Meta-Analysis.

Self-assembling Peptides with Internal Ionizable Unnatural Amino Acids: A General Approach to pH-responsive Peptide Materials.

Self-assembled peptides are an emerging family of biomaterials that show great promise for a range of biomedical and biotechnological applications. Introducing and tuning the pH-responsiveness of the assembly is highly desirable for improving their biological activities. Inspired by proteins with internal ionizable residues, we report a simple but effective approach to constructing pH-responsive peptide assembly containing unnatural ionic amino acids with an aliphatic tertiary amine side chain. Through a combined experimental and computational investigation, we demonstrate that these residues can be accommodated and stabilized within the internal hydrophobic compartment of the peptide assembly. The hydrophobic microenvironment shifts their pKa significantly from a basic pH typically found for free amines to a more biologically relevant pH in the weakly acidic range. The pH-induced ionization and ionization-dependent self-assembly and disassembly are thoroughly investigated and correlated with the biological activity of the assembly. This new approach has unique advantages in tuning the pH-responsiveness of self-assembled peptides across a large pH range in a complex biological environment. We anticipate the ionizable amino acids developed here can be widely applicable to the synthesis and self-assembly of many amphiphilic peptides with endowed pH-responsive properties to enhance their biological activities toward applications ranging from targeted therapeutic delivery to proton transport.

Chemoprophylactic Anticoagulation 72 Hours After Spinal Fracture Surgical Treatment Decreases Venous Thromboembolic Events Without Increasing Surgical Complications.

Background: Prophylactic anticoagulation is commonly used following operative treatment of spinal fractures to prevent Venous Thromboembolism (VTE) but carries a risk of bleeding complications. The purpose of the study was to compare VTE and bleeding complications for MID (≤72h) versus LATE (>72h) chemoprophylaxis timing after spinal fracture operative intervention. Methods: This is a retrospective review of patients treated for spinal fractures that received anticoagulation chemoprophylaxis between May 2015 and June 2019. Chemoprophylaxis initiation timing (MID vs. LATE) was the primary grouping variable. Patients with traumatic brain injury or evidence of intracranial or intraspinal bleed were excluded. Demographics, injury mechanisms, operative procedures, timing of administration of VTE prophylaxis, Injury Severity Score (ISS) and Spine Abbreviated Injury Scale (AIS), and complications including VTE and bleeding complications were collected. Predictors of VTE were identified using a binary logistic regression. Results: Eighty-eight patients (65M, 23F) met inclusion criteria. The median age was 55 years, and median Injury Severity Score (ISS) was 14. MID had 68 patients and LATE had 20. Nine patients developed VTE (6 LATE, 3 MID, p<0.01). Three patients developed bleeding complications, and all occurred in the LATE group (p=0.01). ISS (p<0.01) and GCS (p<0.01) also correlated with an increased VTE rate. Conclusions: Chemoprophylactic anticoagulation at 72 hours in surgically treated spinal fracture patients demonstrates a lower VTE rate without increasing complications. VTE prophylaxis can be initiated at 72 hours following spine fixation to decrease postinjury morbidity and mortality in this high-risk patient population.