Biomechanical Comparison of Anterior Cervical Plate Fixation Versus Integrated Fixation Cage for Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Cadaveric, biomechanic study. OBJECTIVE: To compare the range of motion profiles of the cervical spine following one-level anterior cervical discectomy and fusion (ACDF) constructs instrumented with either an interbody cage and anterior plate or integrated fixation cage in a cadaveric model. SUMMARY OF BACKGROUND DATA: While anterior plates with interbody cages are the most common construct of fixation in ACDF, newer integrated cage-plate devices seek to provide similar stability with a decreased implant profile. However, differences in postoperative cervical range of motion between the 2 constructs remain unclear. METHODS: Six cadaveric spines were segmented into 2 functional spine units (FSUs): C2-C5 and C6-T2. Each FSU was nondestructively bent in flexion-extension (FE), right-left lateral bending (LB), and right-left axial rotation (AR) at a rate of 0.5°/s under a constant axial load until a limit of 2-Nm was reached to evaluate baseline range of motion (ROM). Matched pairs were then randomly assigned to undergo instrumentation with either the standard anterior cage and plate (CP) or the integrated fixation cage (IF). Following instrumentation, ROM was then remeasured as previously described. RESULTS: For CP fixation, ROM increased by 61.2±31.7% for FE, 36.3±20.4% for LB, and 31.7±19.1% for AR. For IF fixation, ROM increased by 64.2±15.5% for FE, 56.7±39.8% for LB, and 94.5±65.1% for AR. There was no significant difference in motion between each group across FE, LB, and AR. CONCLUSION: This biomechanical study demonstrated increased motion in both the CP and IF groups relative to the intact, un-instrumented state. However, our model showed no differences in ROM between CP and IF constructs in any direction of motion. These results suggest that either method of instrumentation is a suitable option for ACDF with respect to constructing stiffness at time zero.

Cerebral Cavernous Malformations Patient Perception Analysis via Social Media.

BACKGROUND: The rise of social media has allowed for individuals and patients to connect with each other and influence patient behavior. This study aimed to improve our understanding of the patients' experience with cerebral cavernous malformations (CCM) via social media. METHODS: Instagram and Twitter were searched using terms of ("cavernoma," "cavernous malformations," "cavernous angioma," or "cav mal"). Public Instagram posts tagged with "#cavernoma" and "@cavernoma" identified 327 posts that directly included a patient's own experience. Twitter posts that included "#cavernoma" and "@cavernoma" were searched, yielding 75 after eliminating those that did not pertain to the patient's own experience. The posts and tweets were coded for relevant themes related to their experience with the disease. RESULTS: Overall, more patients are using Instagram (n = 327) over Twitter (n = 84) to share their personal experience with CCM with a trend for male patients to use Twitter more compared to females with a female predominance in Instagram. A total of 277 of 327 (84.7%) Instagram posts and 67 of 84 (89.3%) Twitter posts were made after the patient's surgery. The most common theme on Instagram was focused on the postoperative rehabilitation process and mobility support (52.0 and 24.5%, respectively). Other common themes present on Twitter and Instagram were recounting symptoms and complications and life satisfaction (26.0 and 24.2%, respectively). Cavernoma patients prior to surgery were more likely to discuss on Instagram their symptoms (p = 0.001), fear of bleeding (p < 0.001), and mental health (p = 0.014). Postoperatively, cavernoma patients were more likely to discuss disability than they were preoperatively (p = 0.001). CONCLUSION: Social media platforms offer a communication tool for patients with CCM patients to share their experience with other patients and the general public and portrays their personal experience with CCM. These platforms allow for physicians to better understand the patient experience following cavernoma surgery.

Patient perception of spinal cord injury through social media: An analysis of 703 Instagram and 117 Twitter posts.

Introduction: Social media has developed exponentially over the last decade as a means for individuals and patients to connect to others and has provided a unique opportunity for physicians to provide broader information to the general public to attempt to positively modify health behavior. The purpose of this study was to assess the patient's perception of spinal cord injury (SCI) on social media. Methods: Instagram and Twitter social media platforms were analyzed to determine posts written by patients with SCI. The initial search for Instagram posts tagged with "#spinalcordinjury" yielded over 270,000 posts in April 2021. Posts pertaining to the patient's experience were retrospectively collected from January 2020 to April 2021. Twitter posts that included "#spinalcordinjury," "@spinalcordinjury," and "spinal cord injury" were retrospectively collected in April 2021. One hundred seventeen tweets were found that were directly from a patient with SCI. Themes associated with patients' experiences living with SCI were coded. Results: The most common theme on Instagram was spreading positivity and on Twitter was the appearance of the wheelchair (75.8% and 37.3%, respectively). Other common themes on Instagram were the appearance of a wheelchair (71.8%), recovery or rehabilitation (29.9%), and life satisfaction (29.0%). Prevalent themes on Twitter included spreading positivity (23.2%) and recovery or rehabilitation (21.3%). Conclusion: The prevalence of themes of positivity and awareness may indicate the utilization of social media as a support mechanism for patients living with SCI. Identification of prevalent themes is important for the holistic treatment of SCI survivors.

Patient sentiment regarding stroke: Analysis of 2,992 social media posts.

INTRODUCTION: Social media reflects personalized sentiment toward disease and increasingly impacts perceptions of treatment options. This study aims to assess patients experience with and perception of stroke through an analysis of social media posts. METHODS: A variety of terms ("stroke", "stroke survivor", "stroke rehab", "stroke recovery") were used to search for possible qualified posts on Twitter and Instagram. Twitter posts containing "#stroke" and "@stroke" were identified, yielding 2,506 Twitter posts relating to the patient's own experience. Four hundred sixty-eight public Instagram posts marked under "#stroke" and "@stroke," including direct references to the patient's own experience, were analyzed. First vs. recurrent stroke was identified when possible. The posts were coded for themes relating to patient experience with the disease. RESULTS: The most common Twitter theme was raising stroke awareness (23.4 %), while spreading positivity was the most common Instagram theme (66.7 %). Most Twitter posts (93.9 %) were from patients experiencing their first stroke, with only 6.1 % of the posts being about recurrent strokes. Women created the majority of Instagram (75.7 %) and Twitter (77.3 %) posts. Men were more likely to discuss mobility/functional outcomes (p = 0.001) and survival/death (p = 0.014), while women were more likely to recount symptoms (p = 0.014), depression (p = 0.002), fear (p<0.001), and mental health (p = 0.006). CONCLUSION: Stroke patients most often describe their quality of life and discuss raising awareness via social media. Men and women differ in the most commonly shared aspects of their stroke experience. Gauging social media sentiment may guide physicians toward better counseling and psychosocial management of stroke patients.

Viral-specific T cells for Cytomegalovirus retinitis following hematopoietic stem cell transplantation: A success story.

Cytomegalovirus retinitis (CMVR) following hematopoietic stem cell transplantation (HCT) for a primary immunodeficiency is a rare but highly morbid condition with potential irreversible consequences despite optimal antiviral pharmacotherapy. Viral-specific T cells (VSTs) pose a promising and safe approach eradicating intractable viral disease. We describe the case of a 21-month-old male with Wiskott-Aldrich syndrome (WAS) and CMVR post HCT with sustained long-term virologic and clinical response after CMV-specific T-cell therapy. This case highlights the need to consider VST as an adjunct upfront strategy in refractory CMVR and for routine ophthalmologic screening and surveillance in high-risk patients post HCT.

Evaluation of correlation between Diopsys® NOVA™ fixed-luminance flicker ERG and Diagnosys® Espion 2™ flicker ERG parameters.

PURPOSE: Diopsys® NOVA™ is a novel full-field electroretinography (ffERG) device that can make rapid measurements of retinal electrophysiologic function. Diagnosys® Espion 2™ is a clinical gold-standard ERG device. This study aimed to investigate whether light-adapted Diopsys® NOVA™ fixed-luminance flicker ffERG magnitude and implicit time (converted from phase) measurements correlate with light-adapted Diagnosys® Espion 2™ flicker ffERG amplitude and implicit time measurements, respectively. METHODS: Twelve patients (22 eyes) with various retinal and uveitic diseases underwent light-adapted Diagnosys® Espion 2™ and Diopsys® NOVA™ fixed-luminance flicker testing. Diopsys® magnitude and implicit time (converted from phase) measurements were compared to Diagnosys® amplitude and implicit time measurements, and a Pearson correlation was used to evaluate any existing correlation. Groups were also compared using generalized estimating equations. Bland-Altman plots were utilized to determine agreement between the comparison groups. RESULTS: Age of patients ranged from 14 to 87 years. 58% (n = 7/12) of patients were female. A significant, positive correlation (r = 0.880, P < 0.001) was observed between magnitude (Diopsys®) and amplitude (Diagnosys®) measurements. Amplitude increases by 6.69 µV for each 1 µV increase in Magnitude (p-value < 0.001). A statistically significant, strong positive correlation was observed between Diopsys® implicit time measurements (converted from phase) and Diagnosys® implicit time measurements (r = 0.814, p-value < 0.001). For each 1 ms increase in Diopsys® implicit time, Diagnosys® implicit time increases by 1.13 ms (p-value < 0.001). CONCLUSIONS: There is a statistically significant positive correlation between light-adapted Diopsys® NOVA™ fixed-luminance flicker amplitude and Diagnosys® flicker magnitude values. Additionally, there is a statistically significant positive correlation between Diopsys® NOVA™ fixed-luminance flicker implicit time (converted from phase) and Diagnosys® flicker implicit time values. These results imply that the Diopsys® NOVA™ module, which utilizes the nonstandard shortened International Society for Clinical Electrophysiology of Vision (ISCEV) ERG protocol, can produce reliable light-adapted flicker ffERG measurements.

p-Chloropropynyl Phenylalanine, a Versatile Non-Canonical Amino Acid for Co-Translational Peptide Macrocyclization and Side Chain Diversification.

Macrocyclization has proven to be a beneficial strategy to improve upon some of the disadvantages of peptides as therapeutics. Nevertheless, many peptide cyclization strategies are not compatible with in vitro display technologies like mRNA display. Here we describe the novel amino acid p-chloropropynyl phenylalanine (pCPF). pCPF is a substrate for a mutant phenylalanyl-tRNA synthetase and its introduction into peptides via in vitro translation leads to spontaneous peptide macrocyclization in the presence of peptides containing cysteine. Macrocyclization occurs efficiently with a wide variety of ring sizes. Moreover, pCPF can be reacted with thiols after charging onto tRNA, enabling the testing of diverse ncAAs in translation. The versatility of pCPF should facilitate downstream studies of translation and enable the creation of novel macrocyclic peptide libraries.

What matters most to cerebral aneurysms patients: A digital analysis of 1127 social media posts.

INTRODUCTION: Social media serves as a way for patients to post about their condition online, as well as for healthcare providers to disseminate information. Intrinsic bias exists exist when patients are given surveys by physicians or healthcare providers. We aim to investigate patient-centered social media posts regarding cerebral aneurysms on Instagram, Twitter, and TikTok. METHODS: Posts that included "brain aneurysm", "#brainaneurysm", "#brainaneurysmsurvivor", and "#aneurysmsurvivor" were queried on Instagram, Twitter, and TikTok. Any posts unrelated to the patient experience were excluded. Five hundred and fourteen Instagram posts, fourty tweets, and five hundred seventy three TikTok posts about the patient experience were identified. Posts were coded for the relevant themes related to their experience with the disease. RESULTS: Most posts made online were by women (892, 82.1%). Patients made the post most of the time (776, 67.5%), while other individuals posted less often (420, 36.5%). The most common themes on Instagram were survival (475, 87.3%), spreading positivity (385, 70.77%), and recovery/rehabilitation (329, 60.5%). TikTok users most often referred to survival (573, 97.1%), raising awareness (464. 78.6%), and spreading positivity (414, 70.2%). Patients were more likely to discuss pre-operative pain (p = 0.0382), postoperative pain (p < 0.0001), invisible illness (p = 0.0130), humor (p = 0.0028), recovery (p < 0.0001), angiograms (p < 0.0001), and resiliency (p < 0.0001) when compared to other individuals posting about a patients' experience. CONCLUSION: Patients often focus on different aspects of their care than do other individuals. This may be useful for physicians discussing treatment plans and prognoses with the patient and their families.

Subcortical Backup Tibial Fixation in Anterior Cruciate Ligament Reconstruction Has Similar Maximal Strength to Current Techniques.

Purpose: To evaluate the biomechanical profile of subcortical backup fixation (subcortical button [SB]) in anterior cruciate ligament (ACL) reconstruction as compared with a bicortical post and washer (BP) and suture anchor (SA) when used with interference screw (IS) primary fixation and to evaluate the utility of backup fixation for tibial fixation with extramedullary cortical button primary fixation. Methods: Fifty composite tibias with polyester webbing-simulated graft were used to test constructs across 10 methods. Specimens were separated into the following groups (n = 5): 9-mm IS only, BP (with and without graft and IS), SB (with and without graft and IS), SA (with and without graft and IS), extramedullary suture button (with and without graft and IS), and extramedullary suture button with BP as backup fixation. Specimens were tested under cyclic loading and then loaded to failure. Maximal load at failure, displacement, and stiffness were compared. Results: Without a graft, the SB and BP had similar maximal loads (802.46 ± 185.18 N vs 785.67 ± 100.96 N, P = .560), and both were stronger than the SA (368.13 ± 77.26 N, P < .001). With graft and an IS, there was no significant difference in maximal load between the BP (1,461.27 ± 173.75 N), SB (1,362.46 ± 80.47 N), and SA (1,334.52 ± 195.80 N). All backup fixation groups were stronger than the control group with IS fixation only (932.91 ± 99.86 N, P < .001). There was no significant difference in outcome measures between the extramedullary suture button groups with and without the BP (failure loads of 721.39 ± 103.32 N and 718.15 ± 108.61 N, respectively). Conclusions: Subcortical backup fixation in ACL reconstruction has similar biomechanical properties to current methods and is a viable backup fixation alternative. Backup fixation methods work synergistically with IS primary fixation to strengthen the construct. There is no advantage to adding backup fixation to extramedullary button (all-inside) primary fixation when all suture strands are secured to the extramedullary button. Clinical Relevance: This study provides evidence that subcortical backup fixation is a viable alternative for surgeons during ACL reconstruction.

Development of a Cyclic, Cell Penetrating Peptide Compatible with In Vitro Selection Strategies.

A key limitation for the development of peptides as therapeutics is their lack of cell permeability. Recent work has shown that short, arginine-rich macrocyclic peptides containing hydrophobic amino acids are able to penetrate cells and reach the cytosol. Here, we have developed a new strategy for developing cyclic cell penetrating peptides (CPPs) that shifts some of the hydrophobic character to the peptide cyclization linker, allowing us to do a linker screen to find cyclic CPPs with improved cellular uptake. We demonstrate that both hydrophobicity and position of the alkylation points on the linker affect uptake of macrocyclic cell penetrating peptides (CPPs). Our best peptide, 4i, is on par with or better than prototypical CPPs Arg9 (R9) and CPP12 under assays measuring total cellular uptake and cytosolic delivery. 4i was also able to carry a peptide previously discovered from an in vitro selection, 8.6, and a cytotoxic peptide into the cytosol. A bicyclic variant of 4i showed even better cytosolic entry than 4i, highlighting the plasticity of this class of peptides toward modifications. Since our CPPs are cyclized via their side chains (as opposed to head-to-tail cyclization), they are compatible with powerful technologies for peptide ligand discovery including phage display and mRNA display. Access to diverse libraries with inherent cell permeability will afford the ability to find cell permeable hits to many challenging intracellular targets.

Hooks Versus Pedicle Screws at the Upper Instrumented Level: An In Vitro Biomechanical Comparison.

STUDY DESIGN: Controlled laboratory study. OBJECTIVE: The aim was to compare motions at the upper instrumented vertebra (UIV) and supra-adjacent level (UIV+1) between two fixation techniques in thoracic posterior spinal fusion constructs. We hypothesized there would be greater motion at UIV+1 after cyclic loading across all constructs and bilateral pedicle screws (BPSs) with posterior ligamentous compromise would demonstrate the greatest UIV+1 range of motion. SUMMARY OF BACKGROUND DATA: Proximal junctional kyphosis is a well-recognized complication following long thoracolumbar posterior spinal fusion, however, its mechanism is poorly understood. MATERIALS AND METHODS: Twenty-seven thoracic functional spine units were randomly divided into three UIV fixation groups (n=9): (1) BPS, (2) bilateral transverse process hooks (TPHs), and (3) BPS with compromise of the posterior elements between UIV and UIV+1 (BPS-C). Specimens were tested on a servohydraulic materials testing system in native state, following instrumentation, and after cyclic loading. functional spine units were loaded in flexion-extension (FE), lateral bending, and axial rotation. RESULTS: After cyclic testing, the TPH group had a mean 29.4% increase in FE range of motion at UIV+1 versus 76.6% in the BPS group ( P <0.05). The BPS-C group showed an increased FE of 49.9% and 62.19% with sectioning of the facet joints and interspinous ligament respectively prior to cyclic testing. CONCLUSION: BPSs at the UIV led to greater motion at UIV+1 compared to bilateral TPH after cyclic loading. This is likely due to the increased rigidity of BPS compared to TPH leading to a "softer" transition between the TPH construct and native anatomy at the supra-adjacent level. Facet capsule compromise led to a 49.9% increase in UIV+1 motion, underscoring the importance of preserving the posterior ligamentous complex. Clinical studies that account for fusion rates are warranted to determine if constructs with a "soft transition" result in less proximal junctional kyphosis in vivo .

Biomechanical Analysis of Multilevel Posterior Cervical Spinal Fusion Constructs.

STUDY DESIGN: Controlled Laboratory Study. OBJECTIVE: To compare multilevel posterior cervical fusion (PCF) constructs stopping at C7, T1, and T2 under cyclic load to determine the range of motion (ROM) between the lowest instrumented level and lowest instrumented-adjacent level (LIV-1). SUMMARY OF BACKGROUND DATA: PCF is a mainstay of treatment for various cervical spine conditions. The transition between the flexible cervical spine and rigid thoracic spine can lead to construct failure at the cervicothoracic junction. There is little evidence to determine the most appropriate level at which to stop a multilevel PCF. METHODS: Fifteen human cadaveric cervicothoracic spines were randomly assigned to 1 of 3 treatment groups: PCF stopping at C7, T1, or T2. Specimens were tested in their native state, following a simulated PCF, and after cyclic loading. Specimens were loaded in flexion-extension), lateral bending, and axial rotation. Three-dimensional kinematics were recorded to evaluate ROM. RESULTS: The C7 group had greater flexion-extension motion than the T1 and T2 groups following instrumentation (10.17±0.83 degree vs. 2.77±1.66 degree and 1.06±0.55 degree, P <0.001), and after cyclic loading (10.42±2.30 degree vs. 2.47±0.64 degree and 1.99±1.23 degree, P <0.001). There was no significant difference between the T1 and T2 groups. The C7 group had greater lateral bending ROM than both thoracic groups after instrumentation (8.81±3.44 degree vs. 3.51±2.52 degree, P =0.013 and 1.99±1.99 degree, P =0.003) and after cyclic loading. The C7 group had greater axial rotation motion than the thoracic groups (4.46±2.27 degree vs. 1.26±0.69 degree, P =0.010; and 0.73±0.74 degree, P =0.003) following cyclic loading. CONCLUSION: Motion at the cervicothoracic junction is significantly greater when a multilevel PCF stops at C7 rather than T1 or T2. This is likely attributable to the transition from a flexible cervical spine to a rigid thoracic spine. Although this does not account for in vivo fusion, surgeons should consider extending multilevel PCF constructs to T1 when feasible. LEVEL OF EVIDENCE: Not applicable.

Validation of a targeted metabolomics panel for improved second-tier newborn screening.

Improved second-tier assays are needed to reduce the number of false positives in newborn screening (NBS) for inherited metabolic disorders including those on the Recommended Uniform Screening Panel (RUSP). We developed an expanded metabolite panel for second-tier testing of dried blood spot (DBS) samples from screen-positive cases reported by the California NBS program, consisting of true- and false-positives from four disorders: glutaric acidemia type I (GA1), methylmalonic acidemia (MMA), ornithine transcarbamylase deficiency (OTCD), and very long-chain acyl-CoA dehydrogenase deficiency (VLCADD). This panel was assembled from known disease markers and new features discovered by untargeted metabolomics and applied to second-tier analysis of single DBS punches using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in a 3-min run. Additionally, we trained a Random Forest (RF) machine learning classifier to improve separation of true- and false positive cases. Targeted metabolomic analysis of 121 analytes from DBS extracts in combination with RF classification at a sensitivity of 100% reduced false positives for GA1 by 83%, MMA by 84%, OTCD by 100%, and VLCADD by 51%. This performance was driven by a combination of known disease markers (3-hydroxyglutaric acid, methylmalonic acid, citrulline, and C14:1), other amino acids and acylcarnitines, and novel metabolites identified to be isobaric to several long-chain acylcarnitine and hydroxy-acylcarnitine species. These findings establish the effectiveness of this second-tier test to improve screening for these four conditions and demonstrate the utility of supervised machine learning in reducing false-positives for conditions lacking clearly discriminating markers, with future studies aimed at optimizing and expanding the panel to additional disease targets.

Optimizing a therapy for opiate use disorders: Characterizing ondansetron pharmacokinetics in blood and brain.

Administration of a widely used 5-hydroxytryptamine receptor (5HT3A R) antagonist (ondansetron) potently inhibited the development of experimentally induced opioid dependence and withdrawal responses in mice and humans. However, in several studies examining withdrawal symptoms in subjects with chronic opioid use disorders (OUDs), ondansetron exhibited reduced or absent efficacy. Because attenuation of opioid withdrawal symptomatology is mediated within the brain, this study examined single-dose ondansetron pharmacokinetics in the blood and brain of mice. We demonstrate that ondansetron concentrations in the brain (Cbrain ng/mg) are 1000-fold lower than the blood concentrations (Cblood ng/ml) and decrease rapidly after ondansetron administration; and that a large percentage of brain ondansetron remains in the ventricular fluid. These results indicate that the ondansetron dose, and the time window between ondansetron and opioid administration, and when withdrawal is assessed are critical considerations for clinical studies involving subjects with chronic OUD. The pharmacokinetic results and the dosing considerations discussed here can be used to improve the design of subsequent clinical trials, which will test whether a more prolonged period of ondansetron administration can provide a desperately needed therapy that can prevent the development of neonatal opioid withdrawal syndrome in babies born to mothers with chronic OUD.

All-Suture Suspensory Button Has Similar Biomechanical Performance to Metal Suspensory Button for Onlay Subpectoral Biceps Tenodesis.

Purpose: To evaluate the maximal load at failure, cyclic displacement, and stiffness of onlay subpectoral biceps tenodesis (BT) with an intramedullary unicortical metal button (MB) versus a unicortical all-suture button (ASB). Methods: Eighteen matched paired human cadaveric proximal humeri were randomly allocated for subpectoral BT with either ASB or MB using a high-strength suture. Specimens were tested on a servohydraulic mechanical testing apparatus under cyclic load for 1,000 cycles and then loaded to failure. The clamp was then adjusted to isolate the suture-anchor point interface and loaded to failure. Maximal load to failure, displacement, and stiffness were compared. Results: There was no significant difference between groups in stiffness, displacement, or yield load. The maximal load to failure for the MB was greater than the ASB (347.6 ± 74.1N vs 266.5 ± 69.3N, P = .047). Eight specimens in each group failed by suture pull-through on the tendon. When the suture-anchor point interface was isolated, there was no significant difference in maximal load at failure (MB 586.5 ± 215.8N vs ASB 579.6 ± 255.9N, P = .957). Conclusions: This study demonstrates that the MB and ASB have similar biomechanical performance when used in subpectoral BT. Although the MB showed statistically significant greater maximal load to failure, there was no difference between the MB and ASB when the suture-tendon interface was eliminated. Suture pull-through was the most common mode of failure for both implants, underscoring the importance of the suture-tendon interface. Clinical Relevance: Fixation techniques for the treatment of long head of the biceps brachii tenodesis continue to evolve. The use of an all-suture suspensory button has advantages, but it is important to understand if this implant is a biomechanically suitable alternative to a metal suspensory button.

Natural variation in the maternal and zygotic mRNA complements of the early embryo in Drosophila melanogaster.

BACKGROUND: Maternal gene products supplied to the egg during oogenesis drive the earliest events of development in all metazoans. After the initial stages of embryogenesis, maternal transcripts are degraded as zygotic transcription is activated; this is known as the maternal to zygotic transition (MZT). Recently, it has been shown that the expression of maternal and zygotic transcripts have evolved in the Drosophila genus over the course of 50 million years. However, the extent of natural variation of maternal and zygotic transcripts within a species has yet to be determined. We asked how the maternal and zygotic pools of mRNA vary within and between populations of D. melanogaster. In order to maximize sampling of genetic diversity, African lines of D. melanogaster originating from Zambia as well as DGRP lines originating from North America were chosen for transcriptomic analysis. RESULTS: Generally, we find that maternal transcripts are more highly conserved, and zygotic transcripts evolve at a higher rate. We find that there is more within-population variation in transcript abundance than between populations and that expression variation is highest post- MZT between African lines. CONCLUSIONS: Determining the natural variation of gene expression surrounding the MZT in natural populations of D. melanogaster gives insight into the extent of how a tightly regulated process may vary within a species, the extent of developmental constraint at both stages and on both the maternal and zygotic genomes, and reveals expression changes allowing this species to adapt as it spread across the world.

Intramedullary Unicortical Button and All-Suture Anchors Provide Similar Maximum Strength for Onlay Distal Biceps Tendon Repair.

PURPOSE: To evaluate the biomechanical profile of onlay distal biceps repair with an intramedullary unicortical button versus all-suture anchors under cyclic loading and maximal load to failure. METHODS: Twenty paired fresh-frozen human cadaveric elbows were randomized to onlay distal biceps repair with either a single intramedullary button or with two 1.35-mm all-suture anchors. A 1.3-mm high tensile strength tape was used in a Krackow stitch to suture the tendons in both groups. Specimens and repair constructs were loaded for 3,000 cycles and then loaded to failure. Maximum load to failure, mode of failure, and construct elongation were recorded. RESULTS: Mean (± standard deviation) maximum load to failure for the unicortical intramedullary button and all-suture anchor repairs were 503.23 ± 141.77 N and 537.33 ± 262.13 N (P = .696), respectively. Mean maximum displacement after 3,000 cycles (± standard deviation) was 4.17 ± 2.05 mm in the button group and 2.06 ± 1.05 mm in the suture anchor group (P = .014). Mode of failure in the button group was suture tape rupture in 7 specimens, failure at the tendon-suture interface in 2 specimens, and button pullout in 1 specimen. Anchor pullout was the mode of failure in all suture anchor specimens. There were no tendon ruptures or radial tuberosity fractures in either group. CONCLUSIONS: This study demonstrates that onlay distal biceps repair with 2 all-suture anchors has similar maximum strength to repair with an intramedullary button and that both are viable options for fixation. CLINICAL RELEVANCE: All-suture anchors and unicortical intramedullary button have similar maximum strength at time zero. Both constructs provide suitable fixation for onlay distal biceps repair.

Biomechanical Comparison of Anatomic Restoration of the Ulnar Footprint vs Traditional Ulnar Tunnels in Ulnar Collateral Ligament Reconstruction.

BACKGROUND: Current techniques for ulnar collateral ligament (UCL) reconstruction do not reproduce the anatomic ulnar footprint of the UCL. The purpose of this study was to describe a novel UCL reconstruction technique that utilizes proximal-to-distal ulnar bone tunnels to better re-create the anatomy of the UCL and to compare the biomechanical profile at time zero among this technique, the native UCL, and the traditional docking technique. HYPOTHESIS: The biomechanical profile of the anatomic technique is similar to the native UCL and traditional docking technique. STUDY DESIGN: Controlled laboratory study. METHODS: Ten matched cadaveric elbows were potted with the forearm in neutral rotation. The palmaris longus tendon graft was harvested, and bones were sectioned 14 cm proximal and distal to the elbow joint. Specimen testing included (1) native UCL testing performed at 90° of flexion with 0.5 N·m of valgus moment preload, (2) cyclic loading from 0.5 to 5 N·m of valgus moment for 1000 cycles at 1 Hz, and (3) load to failure at 0.2 mm/s. Elbows then underwent UCL reconstruction with 1 elbow of each pair receiving the classic docking technique using either anatomic (proximal to distal) or traditional (anterior to posterior) tunnel locations. Specimen testing was then repeated as described. RESULTS: There were no differences in maximum load at failure between the anatomic and traditional tunnel location techniques (mean ± SD, 34.90 ± 10.65 vs 37.28 ± 14.26 N·m; P = .644) or when including the native UCL (45.83 ± 17.03 N·m; P = .099). Additionally, there were no differences in valgus angle after 1000 cycles across the anatomic technique (4.58°± 1.47°), traditional technique (4.08°± 1.28°), and native UCL (4.07°± 1.99°). The anatomic group and the native UCL had similar valgus angles at failure (24.13°± 5.86° vs 20.13°± 5.70°; P = .083), while the traditional group had a higher valgus angle at failure when compared with the native UCL (24.88°± 6.18° vs 19.44°± 5.86°; P = .015). CONCLUSION: In this cadaveric model, UCL reconstruction with the docking technique utilizing proximal-to-distal ulnar tunnels better restored the ulnar footprint while providing valgus stability comparable with reconstruction with the docking technique using traditional anterior-to-posterior ulnar tunnel locations. These results suggest that utilization of the anatomic tunnel location in UCL reconstruction has similar biomechanical properties to the traditional method at the time of initial fixation (ie, not accounting for healing after reconstruction in vivo) while keeping the ulnar tunnels farther from the ulnar nerve. Further studies are warranted to determine if an anatomically based UCL reconstruction results in differing outcomes than traditional reconstruction techniques. CLINICAL RELEVANCE: Current UCL reconstruction techniques do not accurately re-create the ulnar UCL footprint. The UCL is a dynamic constraint to valgus loads at the elbow, and a more anatomic reconstruction may afford more natural joint kinematics. This more anatomic technique performs similarly to the traditional docking technique at time zero, and the results of this study may offer a starting point for future in vivo studies.

Targeted plasma metabolomics combined with machine learning for the diagnosis of severe acute respiratory syndrome virus type 2.

Introduction: The routine clinical diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely restricted to real-time reverse transcription quantitative PCR (RT-qPCR), and tests that detect SARS-CoV-2 nucleocapsid antigen. Given the diagnostic delay and suboptimal sensitivity associated with these respective methods, alternative diagnostic strategies are needed for acute infection. Methods: We studied the use of a clinically validated liquid chromatography triple quadrupole method (LC/MS-MS) for detection of amino acids from plasma specimens. We applied machine learning models to distinguish between SARS-CoV-2-positive and negative samples and analyzed amino acid feature importance. Results: A total of 200 samples were tested, including 70 from individuals with COVID-19, and 130 from negative controls. The top performing model overall allowed discrimination between SARS-CoV-2-positive and negative control samples with an area under the receiver operating characteristic curve (AUC) of 0.96 (95%CI 0.91, 1.00), overall sensitivity of 0.99 (95%CI 0.92, 1.00), and specificity of 0.92 (95%CI 0.85, 0.95). Discussion: This approach holds potential as an alternative to existing methods for the rapid and accurate diagnosis of acute SARS-CoV-2 infection.

Meta-Analysis of Neoadjuvant Immunotherapy for Patients with Resectable Non-Small Cell Lung Cancer.

PURPOSE: Immunotherapy has created a paradigm shift in the treatment of metastatic non-small cell lung cancer (NSCLC), overcoming the therapeutic plateau previously achieved by systemic chemotherapy. There is growing interest in the utility of immunotherapy for patients with resectable NSCLC in the neoadjuvant setting. The present systematic review and meta-analysis aim to provide an overview of the existing evidence, with a focus on pathological and radiological response, perioperative clinical outcomes, and long-term survival. METHODS: A systematic review was conducted using electronic databases from their dates of inception to August 2021. Pooled data on pathological response, radiological response, and perioperative outcomes were meta-analyzed where possible. RESULTS: Eighteen publications from sixteen studies were identified, involving 548 enrolled patients who underwent neoadjuvant immunotherapy, of whom 507 underwent surgery. Pathologically, 52% achieved a major pathological response, 24% a complete pathological response, and 20% reported a complete pathological response of both the primary lesion as well as the sampled lymph nodes. Radiologically, 84% of patients had stable disease or partial response. Mortality within 30 days was 0.6%, and morbidities were reported according to grade and frequency. CONCLUSION: The present meta-analysis demonstrated that neoadjuvant immunotherapy was feasible and safe based on perioperative clinical data and completion rates of surgery within their intended timeframe. The pathological response after neoadjuvant immunotherapy was superior to historical data for patients who were treated with neoadjuvant chemotherapy alone, whilst surgical and treatment-related adverse events were comparable. The limitations of the study included the heterogenous treatment regimens, lack of long-term follow-up, variations in the reporting of potential prognostic factors, and potential publication bias.