Modern multiligament knee injury surgical reconstruction techniques can achieve excellent knee function and patient satisfaction, with low complication rates.

PURPOSE: To report on the recovery of strength and functional capacity symmetry following multiligament knee surgical reconstruction (MLKR), as well as the capacity of athletes to return to sport. METHODS: This prospective cohort study recruited 47 patients undergoing MLKR between February 2018 and July 2021. Forty patients had full outcome assessment postoperatively at 6, 12 and 24 months and were included in the analysis, 75% were knee dislocation one injuries and 60% were injured playing sport. Patient-reported outcome measures (PROMs) assessed included the International Knee Documentation Committee score, the Knee Outcome Survey, the Lysholm Knee Score and the Tegner Activity Scale (TAS). Patient satisfaction was also assessed. Objective assessment included assessment of active knee flexion and extension range of motion (ROM), the single (single horizontal hop for distance [SHD]) and triple (triple horizontal hop for distance [THD]) hop tests for distance and peak isokinetic knee flexor/extensor torque. RESULTS: All PROMs significantly improved (p < 0.001) from presurgery to 24 months postsurgery. At 24 months, 70% of patients were satisfied with their sports participation. Active knee flexion (p < 0.0001) and extension (p < 0.0001) ROM significantly improved over time, as did the limb symmetry indices (LSIs) for the SHD (p < 0.0001), THD (p < 0.0001), peak knee extensor (p < 0.0001) and flexor (p = 0.012) torque. While LSIs for the SHD, THD and knee flexor strength tended to plateau by 12 months, knee extensor strength continued to improve from 12 to 24 months. CONCLUSIONS: The majority of patients undergoing modern MLKR surgical techniques and rehabilitation can achieve excellent knee function, with low complication rates. LEVEL OF EVIDENCE: Level IV.

Fluid inertia controls mineral precipitation and clogging in pore to network-scale flows.

Mineral precipitation caused by fluid mixing presents complex control and predictability challenges in a variety of natural and engineering processes, including carbon mineralization, geothermal energy, and microfluidics. Precipitation dynamics, particularly under the influence of fluid flow, remain poorly understood. Combining microfluidic experiments and three-dimensional reactive transport simulations, we demonstrate that fluid inertia controls mineral precipitation and clogging at flow intersections, even in laminar flows. We observe distinct precipitation regimes as a function of Reynolds number (Re). At low Reynolds numbers (Re < 10), precipitates form a thin, dense layer along the mixing interface, which shuts precipitation off, while at high Reynolds numbers (Re > 50), strong three-dimensional flows significantly enhance precipitation over the entire intersection, resulting in rapid clogging. When injection rates from two inlets are uneven, flow symmetry-breaking leads to unexpected flow bifurcation phenomena, which result in enhanced concurrent precipitation in both downstream channels. Finally, we extend our findings to rough channel networks and demonstrate that the identified inertial effects on precipitation at the intersection scale are also present and even more dramatic at the network scale. This study sheds light on the fundamental mechanisms underlying mixing-induced mineral precipitation and provides a framework for designing and optimizing processes involving mineral precipitation.

Increasing aggregate size reduces single-cell organic carbon incorporation by hydrogel-embedded wetland microbes.

Microbial degradation of organic carbon in sediments is impacted by the availability of oxygen and substrates for growth. To better understand how particle size and redox zonation impact microbial organic carbon incorporation, techniques that maintain spatial information are necessary to quantify elemental cycling at the microscale. In this study, we produced hydrogel microspheres of various diameters (100, 250, and 500 µm) and inoculated them with an aerobic heterotrophic bacterium isolated from a freshwater wetland (Flavobacterium sp.), and in a second experiment with a microbial community from an urban lacustrine wetland. The hydrogel-embedded microbial populations were incubated with 13C-labeled substrates to quantify organic carbon incorporation into biomass via nanoSIMS. Additionally, luminescent nanosensors enabled spatially explicit measurements of oxygen concentrations inside the microspheres. The experimental data were then incorporated into a reactive-transport model to project long-term steady-state conditions. Smaller (100 µm) particles exhibited the highest microbial cell-specific growth per volume, but also showed higher absolute activity near the surface compared to the larger particles (250 and 500 µm). The experimental results and computational models demonstrate that organic carbon availability was not high enough to allow steep oxygen gradients and as a result, all particle sizes remained well-oxygenated. Our study provides a foundational framework for future studies investigating spatially dependent microbial activity in aggregates using isotopically labeled substrates to quantify growth.

Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease.

Five-Year Incidence of Progression to Osteoarthritis and Total Joint Arthroplasty in Patients Prescribed Glucagon-Like Peptide 1 Receptor Agonists.

BACKGROUND: Research has suggested that glucagon-like peptide-1 receptor agonists (GLP-1-RAs) may have therapeutic effects on osteoarthritis of the hip and knee, in addition to managing diabetes and obesity. However, there is a lack of understanding regarding the association between GLP-1-RA use and the diagnosis of osteoarthritis (OA) of the hip and knee. METHODS: A collaborative network analytics platform was queried for obese diabetic (n = 1,094,198), obese nondiabetic (n = 916,235), and nonobese diabetic (n = 157,305) patients who had an index visit between 2015 and 2017. Patients who had pre-existing hip and/or knee OA were excluded. A 1:1 propensity score matching was used to balance GLP-1-RA use in stratified cohorts for age, sex, race, body mass index, and hemoglobin A1c. The primary outcomes were rates of progression to hip OA, knee OA, major joint injections, total hip arthroplasty, and total knee arthroplasty. Cox proportional hazards models determined hazard ratios (HRs) between cohorts prescribed and not prescribed GLP-1-RAs. RESULTS: All patients had a five-year follow-up. Rates of progression to hip and knee OA were higher among the GLP-1-RA users in both obese diabetic (hip HR: 1.63, 95% confidence interval [CI]: 1.46 to 1.82; knee HR: 1.52, CI: 1.41 to 1.64) and nonobese diabetic (hip HR: 1.78, CI: 1.50 to 2.10; knee HR: 1.58, CI: 1.39 to 1.80) cohorts. These diabetic cohorts received higher rates of major joint injections, though there was no difference in rates of total hip arthroplasty or total knee arthroplasty. No differences in five-year outcomes were seen when comparing obese, nondiabetic patients who were prescribed GLP-1-RAs with obese, nondiabetic patients not exposed to GLP-1-RAs. CONCLUSIONS: This five-year analysis found a greater risk of progression to hip and knee OA among obese and non-obese diabetic GLP-1-RA users. Further studies should explore GLP-1-RA effects upon glucose management, weight loss, and lower extremity arthritis development. LEVEL OF EVIDENCE: III, retrospective cohort study.

JWST detection of a supernova associated with GRB 221009A without an r-process signature.

Identifying the sites of r-process nucleosynthesis, a primary mechanism of heavy element production, is a key goal of astrophysics. The discovery of the brightest gamma-ray burst (GRB) to date, GRB 221009A, presented an opportunity to spectroscopically test the idea that r-process elements are produced following the collapse of rapidly rotating massive stars. Here we present James Webb Space Telescope observations of GRB 221009A obtained +168 and +170 rest-frame days after the gamma-ray trigger, and demonstrate that they are well described by a SN 1998bw-like supernova (SN) and power-law afterglow, with no evidence for a component from r-process emission. The SN, with a nickel mass of approximately 0.09 M ⊙, is only slightly fainter than the brightness of SN 1998bw at this phase, which indicates that the SN is not an unusual GRB-SN. This demonstrates that the GRB and SN mechanisms are decoupled and that highly energetic GRBs are not likely to produce significant quantities of r-process material, which leaves open the question of whether explosions of massive stars are key sources of r-process elements. Moreover, the host galaxy of GRB 221009A has a very low metallicity of approximately 0.12 Z ⊙ and strong H2 emission at the explosion site, which is consistent with recent star formation, hinting that environmental factors are responsible for its extreme energetics.

Zinc mediates control of nitrogen fixation via transcription factor filamentation.

Plants adapt to fluctuating environmental conditions by adjusting their metabolism and gene expression to maintain fitness1. In legumes, nitrogen homeostasis is maintained by balancing nitrogen acquired from soil resources with nitrogen fixation by symbiotic bacteria in root nodules2-8. Here we show that zinc, an essential plant micronutrient, acts as an intracellular second messenger that connects environmental changes to transcription factor control of metabolic activity in root nodules. We identify a transcriptional regulator, FIXATION UNDER NITRATE (FUN), which acts as a sensor, with zinc controlling the transition between an inactive filamentous megastructure and an active transcriptional regulator. Lower zinc concentrations in the nodule, which we show occur in response to higher levels of soil nitrate, dissociates the filament and activates FUN. FUN then directly targets multiple pathways to initiate breakdown of the nodule. The zinc-dependent filamentation mechanism thus establishes a concentration readout to adapt nodule function to the environmental nitrogen conditions. In a wider perspective, these results have implications for understanding the roles of metal ions in integration of environmental signals with plant development and optimizing delivery of fixed nitrogen in legume crops.

Factors associated with immune responses to SARS-CoV-2 vaccination in individuals with autoimmune diseases.

Patients with autoimmune diseases are at higher risk for severe infection due to their underlying disease and immunosuppressive treatments. In this real-world observational study of 463 patients with autoimmune diseases, we examined risk factors for poor B and T cell responses to SARS-CoV-2 vaccination. We show a high frequency of inadequate anti-spike IgG responses to vaccination and boosting in the autoimmune population but minimal suppression of T cell responses. Low IgG responses in B cell-depleted patients with multiple sclerosis (MS) were associated with higher CD8 T cell responses. By contrast, patients taking mycophenolate mofetil (MMF) exhibited concordant suppression of B and T cell responses. Treatments with highest risk for low anti-spike IgG response included B cell depletion within the last year, fingolimod, and combination treatment with MMF and belimumab. Our data show that the mRNA-1273 (Moderna) vaccine is the most effective vaccine in the autoimmune population. There was minimal induction of either disease flares or autoantibodies by vaccination and no significant effect of preexisting anti-type I IFN antibodies on either vaccine response or breakthrough infections. The low frequency of breakthrough infections and lack of SARS-CoV-2-related deaths suggest that T cell immunity contributes to protection in autoimmune disease.

Anterior-Posterior Laxity in Midflexion After Posterior-Stabilized TKA Is Sensitive to MCL Tension in Passive Flexion: An in Vitro Biomechanical Study.

BACKGROUND: Knee instability in midflexion may contribute to patient dissatisfaction following total knee arthroplasty (TKA). Midflexion instability involves abnormal motions and tissue loading in multiple planes. Therefore, we quantified and compared the tensions carried by the medial and lateral collateral ligaments (MCL and LCL) following posterior-stabilized (PS) TKA through knee flexion, and then compared these tensions with those carried by the native knee. Finally, we examined the relationships between collateral ligament tensions and anterior tibial translation (ATT). METHODS: Eight cadaveric knees (from 5 male and 3 female donors with a mean age of 62.6 years and standard deviation of 10.9 years) underwent PS TKA. Each specimen was mounted to a robotic manipulator and flexed to 90°. ATT was quantified by applying 30 N of anterior force to the tibia. Tensions carried by the collateral ligaments were determined via serial sectioning. Robotic testing was also conducted on a cohort of 15 healthy native cadaveric knees (from 9 male and 6 female donors with a mean age of 36 years and standard deviation of 11 years). Relationships between collateral ligament tensions during passive flexion and ATT were assessed via linear and nonlinear regressions. RESULTS: MCL tensions were greater following PS TKA than in the native knee at 15° and 30° of passive flexion, by a median of ≥27 N (p = 0.002), while the LCL tensions did not differ. Median tensions following PS TKA were greater in the MCL than in the LCL at 15°, 30°, and 90° of flexion, by ≥4 N (p ≤ 0.02). Median tensions in the MCL of the native knee were small (≤11 N) and did not exceed those in the LCL (p ≥ 0.25). A logarithmic relationship was identified between MCL tension and ATT following TKA. CONCLUSIONS: MCL tensions were greater following PS TKA with this typical nonconforming PS implant than in the native knee. Anterior laxity at 30° of flexion was highly sensitive to MCL tension during passive flexion following PS TKA but not in the native knee. CLINICAL RELEVANCE: Surgeons face competing objectives when performing PS TKA: they can either impart supraphysiological MCL tension to reduce anterior-posterior laxity or maintain native MCL tensions that lead to heightened anterior-posterior laxity, as shown in this study.

Factors associated with skeletal-related events in patients with bone metastatic melanoma: A retrospective study of 481 patients.

OBJECTIVES: Metastatic bone disease is estimated to develop in up to 17% of patients with melanoma, compromising skeleton integrity resulting in skeletal-related events (SREs), which impair quality of life and reduce survival. The objective of the study was to investigate (1) the proportion of melanoma patients developing SREs following diagnosis of bone metastasis and (2) the predictors for SREs in this patient cohort. METHODS: Four hundred and eighty-one patients with bone metastatic melanoma from two tertiary centers in the United States from 2008 to 2018 were included. The primary outcome was 90-day and 1-year occurrence of a SRE, including pathological fractures of bones, cord compression, hypercalcemia, radiotherapy, and surgery. Fine-Gray regression analysis was performed for overall SREs and pathological fracture, with death as a competing risk. RESULTS: By 1-year, 52% (258/481) of patients experienced SREs, and 28% (137/481) had a pathological fracture. At 90-day, lytic lesions, bone pain, elevated calcium and absolute lymphocyte, and decreased albumin and hemoglobin were associated with higher SRE risk. The same factors, except for decreased hemoglobin, were shown to predict development of SREs at 1-year. CONCLUSION: The high incidence of SREs and pathological fractures warrants vigilance using the identified factors in this study and preventative measures during clinical oncological care.

Motivations to Enhance One's Facial Hair: Affiliation, Rivalry, and Stress.

Facial hair is a sexually dimorphic trait with potential evolutionary and sociocultural functions. Bearded men are perceived as dominant, aggressive, and masculine, but also as having better parenting skills. Men may intentionally manage the amount and shape of their facial hair as a part of their self-promotion strategy; however, facial hair management entails costs in terms of time, effort, and money. We explored psychological factors associated with facial hair enhancement motivation among men. A total of 414 men (aged 18-40 years) reported the current amount of their facial hair along with their facial hair enhancement motivations, gender role stress, intrasexual competitiveness, and fundamental social motives. Willingness to care for facial hair was associated with the amount of facial hair men claimed to have and correlated with the fundamental social motives of affiliation and social status, intrasexual competition, and gender role stress. Therefore, facial hair enhancement may be regarded as a self-presentation strategy aimed at acquiring a beneficial position in social networks.

Trends in Initial Anticoagulation Among US Patients Hospitalized With Acute Pulmonary Embolism 2011-2020.

STUDY OBJECTIVE: Guidelines recommend low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs) rather than unfractionated heparin (UFH) for treatment of acute pulmonary embolism (PE) given their efficacy and reduced risk of bleeding. Using data from a large consortium of US hospitals, we examined trends in initial anticoagulation among hospitalized patients diagnosed with acute PE. METHODS: We conducted a retrospective study of inpatient and observation cases between January 1, 2011, and December 31, 2020, among individuals aged more than or equal to 18 years treated at acute care hospitals contributing data to the Premier Healthcare Database. Included cases received a diagnosis of acute PE, underwent imaging for PE, and received anticoagulation at the time of admission. The primary outcome was the initial anticoagulant selected for treatment. RESULTS: Among 299,016 cases at 1,045 hospitals, similar proportions received initial treatment with UFH (47.4%) and LMWH (47.9%). Between 2011 and 2020, the proportion of patients initially treated with UFH increased from 41.9% to 56.3%. Over this period, use of LMWH as the initial anticoagulant was reduced from 58.1% in 2011 to 37.3% in 2020. The proportion of cases admitted to the ICU, treated with mechanical ventilation or vasopressors, and inpatient mortality were stable. Factors most strongly associated with receipt of UFH were admission to the ICU (odds ratio [OR] 6.90; 95% confidence interval [CI] 6.31 to 7.54) or step-down unit (OR 2.30; 95% CI 2.16 to 2.45), receipt of thrombolysis (OR 4.25; 95% CI 3.09 to 5.84) or vasopressors (OR 1.83; 95% CI 1.32 to 2.54), and chronic renal disease (OR 1.67; 95% CI 1.54 to 1.81). CONCLUSIONS: Despite recommendations that LMWH and DOACs be considered first-line for most patients with acute PE, use of UFH is common and increasing. Further research is needed to elucidate factors associated with persistent use of UFH and opportunities for deimplementation of low-value care.

Understanding the Role of Female Genital Tract Microbiome in Recurrent Implantation Failure.

The realization of the role of the microbiome of the female reproductive tract in health and disease has opened numerous possibilities for the scientific examination of the intertwining role between the human host and its microbiota. The imbalance in the composition of the microbial communities of the vagina and uterus is now recognized as a risk factor for many complications in pregnancy and according to the data from numerous studies, it is possible for this imbalance to play a crucial role in creating a hostile endometrial environment, and therefore, contributing to the etiology of recurrent implantation failure. Nevertheless, our current understanding of these complicated biological phenomena is far from complete, and in the future, there needs to be a systematic and thorough investigation of the diagnosis and therapy of this condition. This will enable scientists who engage in the field of assisted reproduction technologies to accurately identify and cure women in whom dysbiosis hinders the achievement of a healthy pregnancy.

An Extended Trochanteric Osteotomy is Necessary for the Removal of Broken Modular Metaphyseal Engaging Femoral Stems.

INTRODUCTION: Modular metaphyseal engaging (MME) femoral components in total hip arthroplasty (THA) allow optimized femoral length, offset, and anteversion and are useful in patients with unusual proximal femoral anatomy. Fretting, corrosion, and stem fractures above the modular sleeve are complications associated with these implants. The purpose of this study was to identify failure mechanisms of retrieved MME femoral components at our institution, identify all broken stem cases, and evaluate how often an extended trochanteric osteotomy (ETO) was required for removal. METHODS: All consecutively retrieved MME femoral components from September 2002 to May 2023 were reviewed. Patient demographics, procedure information, component specifications, indications for removal, and requirements for further revision surgery were reviewed. Descriptive statistics were calculated for the variables of interest. RESULTS: There were 131 retrieved MME components. The mean age at surgery was 59 years (range, 28 to 75), 49% were women, the mean body mass index (BMI) was 29.4 (range, 20.7 to 33.3), and the mean American Society of Anesthesiologists (ASA) score was 2.4 ± 0.5. There were 102 (78%) stems of one design (Stem A), and the remaining 29 (22%) were of a different design (Stem B). Of the 131 components, ten (7.6%) failed secondary to a stem fracture proximal to the modular sleeve. Regarding each MME stem design, 4 of 102 (4%) of Stem A and 6 of 29 (21% of Stem B) fractured. All broken stems required additional intervention for removal during revision THA, using an extended trochanteric osteotomy (N = 9) or cortical window (N = 1) in which an intraoperative proximal femoral fracture occurred. CONCLUSIONS: Broken MME stems present a challenge for orthopaedic surgeons during revision THA. When a stem fracture occurs above the ingrown sleeve, the distal splines may also have osseous interdigitation into the clothespin. Thus, when revising a broken MME stem, an ETO should be performed, and the segment should be long enough to allow distal access.

Health Insurance Type and Outpatient Specialist Care Among Children With Asthma.

Importance: Although children with asthma are often successfully treated by primary care clinicians, outpatient specialist care is recommended for those with poorly controlled disease. Little is known about differences in specialist use for asthma among children with Medicaid vs private insurance. Objective: To examine differences among children with asthma regarding receipt of asthma specialist care by insurance type. Design, Setting, and Participants: In this cross-sectional study using data from the Massachusetts All Payer Claims Database (APCD) between 2014 to 2020, children with asthma were identified and differences in receipt of outpatient specialist care by whether their insurance was public (Medicaid and the Children's Health Insurance Program) or private were examined. Eligible participants included children with asthma in 2015 to 2020 aged 2 to 17 years. Data analysis was conducted from January 2023 to April 2024. Exposure: Medicaid vs private insurance. Main Outcomes and Measures: The primary outcome was receipt of specialist care (any outpatient visit with a pulmonology, allergy and immunology, or otolaryngology physician). Multivariable logistic regression models estimated differences in receipt of specialist care by insurance type accounting for child and area characteristics including demographics, health status, persistent asthma, calendar year, and zip code characteristics. Additional analyses examined if the associations of specialist care with insurance type varied by asthma persistence and severity, and whether associations varied over time. Results: Among 198 101 unique children, there were 432 455 child-year observations (186 296 female [43.1%] and 246 159 male [56.9%]; 211 269 aged 5 to 11 years [48.9%]; 82 108 [19.0%] with persistent asthma) including 286 408 (66.2%) that were Medicaid insured and 146 047 (33.8%) that were privately insured. Although persistent asthma was more common among child-year observations with Medicaid vs private insurance (57 381 [20.0%] vs 24 727 [16.9%]), children with Medicaid were less likely to receive specialist care. Overall, 64 239 child-year observations (14.9%) received specialist care, with substantially lower rates for children with Medicaid vs private insurance (34 093 child-year observations [11.9%] vs 30 146 child-year observations [20.6%]). Regression-based estimates confirmed these disparities; children with Medicaid had 55% lower odds of receiving specialist care (adjusted odds ratio, 0.45; 95% CI, 0.43 to 0.47) and a regression-adjusted 9.7 percentage point (95% CI, -10.4 percentage points to -9.1 percentage points) lower rate of receipt of specialist care. Compared with children with private insurance, there was an additional 3.2 percentage point (95% CI, 2.0 percentage points to 4.4 percentage points) deficit for children with Medicaid with persistent asthma. Conclusions and Relevance: In this cross-sectional study, children with Medicaid were less likely to receive specialist care, with the largest gaps among those with persistent asthma. These findings suggest that closing this care gap may be one approach to addressing ongoing disparities in asthma outcomes.

Development and utility of a SARS-CoV-2 pseudovirus assay for compound screening and antibody neutralization assays.

Background: The highly infectious nature of SARS-CoV-2 necessitates using bio-containment facilities to study viral pathogenesis and identify potent antivirals. However, the lack of high-level bio-containment laboratories across the world has limited research efforts into SARS-CoV-2 pathogenesis and the discovery of drug candidates. Previous research has reported that non-replicating SARS-CoV-2 Spike-pseudotyped viral particles are effective tools to screen for and identify entry inhibitors and neutralizing antibodies. Methods: To generate SARS-CoV-2 pseudovirus, a lentiviral packaging plasmid p8.91, a luciferase expression plasmid pCSFLW, and SARS-CoV-2 Spike expression plasmids (Wild-type (D614G) or Delta strain) were co-transfected into HEK293 cells to produce a luciferase-expressing non-replicating pseudovirus which expresses SARS-CoV-2 spike protein on the surface. For relative quantitation, HEK293 cells expressing ACE2 (ACE2-HEK293) were infected with the pseudovirus, after which luciferase activity in the cells was measured as a relative luminescence unit. The ACE2-HEK293/Pseudovirus infection system was used to assess the antiviral effects of some compounds and plasma from COVID-19 patients to demonstrate the utility of this assay for drug discovery and neutralizing antibody screening. Results: We successfully produced lentiviral-based SARS-CoV2 pseudoviruses and ACE2-expressing HEK293 cells. The system was used to screen compounds for SARS-CoV-2 entry inhibitors and identified two compounds with potent activity against SARS-CoV-2 pseudovirus entry into cells. The assay was also employed to screen patient plasma for neutralizing antibodies against SARS-CoV-2, as a precursor to live virus screening, using successful hits. Significance: This assay is scalable and can perform medium-to high-throughput screening of antiviral compounds with neither severe biohazard risks nor the need for higher-level containment facilities. Now fully deployed in our resource-limited laboratory, this system can be applied to other highly infectious viruses by swapping out the envelope proteins in the plasmids used in pseudovirus production.

Functional remodeling of presynaptic voltage-gated calcium channels in superficial layers of the dorsal horn during neuropathic pain.

N- and P/Q-type voltage-gated Ca2+ channels are critical for synaptic transmission. While their expression is increased in the dorsal root ganglion (DRG) neuron cell bodies during neuropathic pain conditions, less is known about their synaptic remodeling. Here, we combined genetic tools with 2-photon Ca2+ imaging to explore the functional remodeling that occurs in central presynaptic terminals of DRG neurons during neuropathic pain. We imaged GCaMP6s fluorescence responses in an ex vivo spinal cord preparation from mice expressing GCaMP6s in Trpv1-Cre lineage nociceptors. We show that Ca2+ transient amplitude is increased in central terminals of these neurons after spared nerve injury, and that this increase is mediated by both N- and P/Q-type channels. We found that GABA-B receptor-dependent inhibition of Ca2+ transients was potentiated in the superficial layer of the dorsal horn. Our results provide direct evidence toward nerve injury-induced functional remodeling of presynaptic Ca2+ channels in Trpv1-lineage nociceptor terminals.

Public Perception of Scrub Color and Style in Plastic Surgery.

Background: Scrubs have become widespread office attire for plastic surgeons. The purpose of this study is to evaluate the public perception of scrub color and style for plastic surgeons. Methods: A crowdsourced survey was performed via MTurk. Respondents were asked to rate images of a surgeon dressed in black, navy, blue, and green scrubs as well as traditional or fitted scrubs. Qualities including representativeness, skill, trustworthiness, knowledge, and compassion were rated on a Likert scale across all images. Analysis of variance and one-sided t test were used to analyze differences in means. Results: In total, 562 responses were collected. For female plastic surgeons, navy and blue scrubs were perceived to be superior to those wearing black for skill, representativeness, trustworthiness, and compassion (P < 0.05). For male plastic surgeons, navy and blue scrubs were superior to black for knowledge, skill, representativeness, trustworthiness, and compassion (P < 0.05). For skill and representativeness, navy was superior to green (P < 0.05). For representativeness, blue was superior to green (P < 0.05). For trustworthiness and compassion, green was superior to black (P < 0.05). Fitted scrubs were significantly preferred (P < 0.05) across all characteristics with the exception of representativeness in the subgroup of male plastic surgeons. Conclusions: Black scrubs are associated with more negative characteristics than navy or blue scrubs, which were found to be the most positively perceived. Fitted scrubs were associated with positive characteristics for both male and female surgeons. The purchase of fitted scrubs may be a worthwhile purchase to maximize the patient-physician relationship.

A unique case report of a revision extensor mechanism reconstruction using Marlex mesh in the setting of proximal tibial bone deficiency: The tantalum clamshell technique.

Extensor mechanism (EM) disruption is a rare but severe complication of total knee arthroplasty (TKA) that can greatly impair function. Treatment options for chronic patella tendon ruptures include primary repair, autograft augmentation, and reconstruction with allograft or synthetic material. Despite various techniques, failures can occur, and options for reconstruction after a failed allograft or mesh are limited, especially if the tibial component is well-fixed and cannot be easily removed, and if there is proximal tibial deficiency from a previous failed EM allograft. This case report presents a novel solution for revision EM reconstruction in a 72y.o. female patient with a history of multiple EM failures using an off-label Trabecular Metal Cone-Mesh-Cone (TM CMC) clamshell construct. The surgical procedure involved the removal of a non-viable allograft from the knee joint and the creation of a custom trabecular metal (TM) clamshell construct with a Marlex mesh graft in between the two TM implants. The customized TM cone was designed to cover the deficient anterior tibia and wrap around the ingrown TM cone. The Marlex mesh was cemented between the existing implant and the customized TM cone, and the construct was secured in place with two cancellous screws. The mesh was tunneled between soft tissue to prevent contact with the implant and rotated scar tissue was interposed to prevent abrasion of the mesh on the implant surfaces. The patient tolerated the procedure well and no complications were noted postoperatively. At a follow-up 12 months after the operation the patient remains satisfied with the result.