Search

In this study, we present a detailed surgical technique for treating chronic osteomyelitis (COM) of the intramedullary canal with injectable tobramycin and vancomycin-loaded calcium sulfate (CS).Chronic osteomyelitis of the long bones has been treated using antibiotic-impregnated polymethyl methacrylate (PMMA), which typically requires a second procedure for removal.Removal of the infected intramedullary nail (if any), copious irrigation, canal reaming, and intramedullary canal injection of vancomycin- and tobramycin-loaded calcium sulfate as a single-stage procedure for the treatment of COM of long bones.Intramedullary injection of vancomycin- and tobramycin-loaded CS can be used as a single-stage procedure for the treatment of long bone intramedullary COM. Further studies are necessary to compare the long-term outcomes of antibiotic-coated CS vs other antibiotic carriers for infection eradication.The authors have endeavored to explain the best surgical technique to eradicate long bones COM with injectable tobramycin and vancomycin-loaded CS.Elhessy AH, Rivera JC, Shu HT

Adult T-cell /lymphomaleukemia (ATLL) is caused by human T-cell lymphotropic virus type 1 (HTLV-1). Approximately 80% of ATLL patients develop humoral hypercalcemia of malignancy (HHM), a life-threatening complication leading to a poor prognosis. Parathyroid hormone–related protein (PTHrP) and macrophage inflammatory protein-1α (MIP-1α) are important factors in the pathogenesis of HHM in ATLL and the expression of PTHrP can be activated by nuclear factor κB (NF-κB). NF-κB is constitutively activated in ATLL cells and is essential for leukemogenesis including transformation of lymphocytes infected by HTLV-1. Our goal was to evaluate the effects of NF-κB disruption by a proteasomal inhibitor (PS-341) and osteoclastic inhibition by zoledronic acid (Zol) on the development of ATLL and HHM using a novel bioluminescent mouse model. We found that PS-341 decreased cell viability, increased apoptosis, and down-regulated PTHrP expression in ATLL cells in vitro. To investigate the in vivo efficacy, nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice were xenografted with ATLL cells and treated with vehicle control, PS-341, Zol, or a combination of PS-341 and Zol. Bioluminescent imaging and tumor cell count showed a significant reduction in tumor burden in mice from all treatment groups. All treatments also significantly reduced the plasma calcium concentrations. Zol treatment increased trabecular bone volume and decreased osteoclast parameters. PS-341 reduced PTHrP and MIP-1α expression in tumor cells in vivo. Our results indicate that both PS-341 and Zol are effective treatments for ATLL and HHM, which are refractory to conventional therapy. [Cancer Res 2007;67(24):11859–66]

Supplementary Table 1 from A Novel Bioluminescent Mouse Model and Effective Therapy for Adult T-Cell Leukemia/Lymphoma

To (1) characterize hamstring injury (HSI) recurrence rates across the 2009-2010 to 2019-2020 NFL seasons and (2) to identify HSI recurrence risk factors among positions and determine the weekly return to play (RTP) recurrence risk. We hypothesized that older players, skill position players, and players returning to play faster were most at risk.Public data from the 2009-2010 to 2019-2020 seasons were reviewed to identify HSIs. Player characteristics were collected before and two seasons following injury. A week-by-week analysis of recurrence risk was evaluated with linear and logarithmic trendlines of the best fit.A total of 2075 HSI were identified with a mean age of 26.2 years (20.0-43.0), BMI of 29.6 (22.7-43.5), and 3.4 seasons of experience (0-17), with 1826 strains (88.0%), 236 partial tears (11.3%), and 13 complete tears (0.63%). Of the 2075 injuries, 796 (38.4%) were recurrent, with 247 (11.9%) being a same-season reinjury. Logistic regression found that fewer weeks before RTP, in-game injury, and lower BMI were risk factors for same-season recurrence. For any recurrence, logistic regression identified more recent year of injury, lower BMI, and longer playing experience as significant risk factors. Wide receivers were found to be at risk for same-season recurrence. For any-season recurrence, defensive backs, linebackers, running backs, tight ends, and wide receivers were at risk. Week-by-week recurrence analysis determined the greatest risk to be when players returned within 2 weeks (13.4%).There is a high rate of HSI recurrence in the NFL. Risk factors for same-season injury include shorter time to RTP, in-game injury, lower BMI, and playing wide receiver. Risk factors for any-season recurrence were more recent year of injury, lower BMI, longer playing experience, and playing defensive back, linebacker, running back, tight end, or wide receiver. The greatest risk factor for HSI recurrence was RTP within 2 weeks.

Purpose The purpose of this study was to determine return-to-play (RTP), performance and career survivorship for National Football League (NFL) athletes sustaining pectoralis major (PM) injuries with comparison among grades of injury and between nonoperative and operative management. Methods Publicly available data from the 1998–2020 NFL seasons were reviewed to identify athletes with PM injuries. Athlete characteristics were collected 1 season before and 2 seasons after injury. Percent of total games played in a season, player efficiency rating (PER), and Pro Football Focus (PFF) grades were compared for the preinjury season and 2 postinjury seasons. Kaplan-Meier survivorship plots were computed for RTP and postinjury career length, whereas a log-rank test was used to compare survivorship differences. Results In total, 258 PM injuries were reported at a mean age of 27.1 ± 3.3 years. A total of 126 surgical repairs occurred in 48.8% (n = 126) of injuries, with athletes undergoing repair possessing a lower RTP rate and longer time to RTP compared to athletes treated conservatively (P < .001). Survival analysis revealed shorter career length for athletes sustaining PM tears compared to strains (P < .001), although no difference in career length was appreciated on the basis of injury management (P = .980). Defensive linemen and wide receivers had lower PER during their second postinjury seasons (P = .019 and .030, respectively), whereas defensive linemen had lower PFF grades during their second post-injury seasons (P = .044). Conclusion NFL athletes requiring PM repair may experience a lower likelihood of RTP, and longer RTP timing, likely because of higher-grade injuries. Defensive linemen and wide receivers experiencing PM injuries are at risk for diminished performance post-injury. Career length does not appear to be affected based on injury management. Level of Evidence Level III, cohort study.

Purpose To evaluate clinical outcomes and patient-reported outcomes of patients who underwent primary anterior cruciate ligament (ACL) repair using suture tape augmentation. Methods Patients with a proximal tear of the ACL who underwent primary ACL repair with a minimum 2-year follow-up were included. The exclusion criteria included multiligamentous knee injuries, midsubstance tears, tibial avulsion fractures, and distal tears. Demographic characteristics, injury pattern, concomitant injury pattern, and patient-reported outcome measures were recorded. Patients were evaluated at a minimum 2-year follow-up for clinical success, defined as stability not requiring revision ACL reconstruction, and for patient-reported outcome measurements. Failure was defined as the need for revision surgery. Results The mean follow-up period was 2.8 ± 0.9 years. Thirty-five patients met the inclusion criteria, with an average age of 32.2 ± 7.2 years, and 2-year follow-up was obtained for 29 of these patients. Revision surgery was required in 2 of the 29 patients (6.9%); successful treatment was achieved in the remaining 93.1%. The Single Assessment Numeric Evaluation score and Knee Injury and Osteoarthritis Outcome Score for the 27 successfully treated patients were recorded, with 70.4% having Single Assessment Numeric Evaluation scores of 80 or greater. Conclusions This case series shows that primary surgical repair of proximal ACL tears using suture tape augmentation results in a low rate of revision surgery. Level of Evidence Level IV, prospective case series.

炎症反应是心血管疾病重要的病理生理过程，嗜酸性粒细胞（EOS）作为炎症反应的效应细胞，可分泌多种促炎因子、趋化因子以及毒性颗粒蛋白，并可与多种细胞相互作用。早期研究认为EOS主要参与寄生虫感染和过敏性疾病，近年来发现EOS与心血管疾病发生发展具有相关性，但现有研究有限，EOS在心血管疾病中的具体作用机制尚不清楚。该文对EOS在心血管疾病中的损伤/保护作用及研究中存在的争议进行了综述，以期进一步明确EOS在心血管疾病中的作用机制，为临床诊疗提供新思路。.

OBJECTIVE: To evaluate the effects of silicone ankle sleeves (SASs) and lace-up ankle braces (LABs) on neuromuscular control, net joint torques, and cutting agility in healthy, active individuals. DESIGN: Markerless motion-capture technology tracked subjects fitted with SASs, LABs, or no brace while they performed the movements: Y-excursion, left cutting, right cutting, single-leg drop vertical jump (SLDVJ), 45-degree bound, and single-leg squat (SLS). SETTING: University Laboratory. PARTICIPANTS: Ten healthy, active individuals (5 males and 5 females, mean ± SD 23.60 ± 1.43 years of age). MAIN OUTCOME MEASURES: Degrees of joint range of motion (ROM), Newton-meters of joint torque, time to perform a cutting maneuver. RESULTS: SASs and LABs resulted in significantly different knee and ankle ROM and hip internal rotation in the SLDVJ, SLS, Y-excursion, cutting maneuver, and 45-degree bound when compared to control (p

The HIV-1 virulence factor Nef promotes high-titer viral replication, immune escape, and pathogenicity. Nef interacts with interleukin-2-inducible T-cell kinase (Itk) and Bruton's tyrosine kinase (Btk), two Tec-family kinases expressed in HIV-1 target cells (CD4 T cells and macrophages, respectively). Using a cell-based bimolecular fluorescence complementation assay, here we demonstrate that Nef recruits both Itk and Btk to the cell membrane and induces constitutive kinase activation in transfected 293T cells. Nef homodimerization-defective mutants retained their interaction with both kinases but failed to induce activation, supporting a role for Nef homodimer formation in the activation mechanism. HIV-1 infection up-regulates endogenous Itk activity in SupT1 T cells and donor-derived peripheral blood mononuclear cells. However, HIV-1 strains expressing Nef variants with mutations in the dimerization interface replicated poorly and were significantly attenuated in Itk activation. We conclude that direct activation of Itk and Btk by Nef at the membrane in HIV-infected cells may override normal immune receptor control of Tec-family kinase activity to enhance the viral life cycle.

PURPOSE: This study sought to compare the risk of subtrochanteric stress-riser fractures and biomechanical stability of the Femoral Neck System (FNS) versus multiple screw fixation (MSF). METHODS: Eight paired cadaveric femurs were randomly assigned to FNS or MSF. Physiologic load mimicking single leg stance at the subtrochanteric region was applied to the constructs. RESULTS: No constructs failed in the subtrochanteric region during loading. There was no significant difference in force (P = 0.364) or loading cycles (P = 0.348) between groups. CONCLUSION: FNS constructs were not associated with an increased incidence of iatrogenic subtrochanteric fractures or biomechanical stability versus MSF.

Environmental exposures to endocrine disrupting compounds (EDCs) such as the organochlorines have been linked with various diseases including neurodevelopmental disorders. Autism spectrum disorder (ASD) is a highly complex neurodevelopmental disorder that is considered strongly genetic in origin due to its high heritability. However, the rapidly rising prevalence of ASD suggests that environmental factors may also influence risk for ASD. In the present study, whole genome bisulfite sequencing was used to identify genome-wide differentially methylated regions (DMRs) in a total of 52 sperm samples from a cohort of men from the Faroe Islands (Denmark) who were equally divided into high and low exposure groups based on their serum levels of the long-lived organochlorine 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), a primary breakdown product of the now banned insecticide dichlorodiphenyltrichloroethane (DDT). Aside from being considered a genetic isolate, inhabitants of the Faroe Islands have a native diet that potentially exposes them to a wide range of seafood neurotoxicants in the form of persistent organic pollutants (POPs). The DMRs were mapped to the human genome using Bismark, a 3-letter aligner used for methyl-seq analyses. Gene ontology, functional, and pathway analyses of the DMR-associated genes showed significant enrichment for genes involved in neurological functions and neurodevelopmental processes frequently impacted by ASD. Notably, these genes also significantly overlap with autism risk genes as well as those previously identified in sperm from fathers of children with ASD in comparison to that of fathers of neurotypical children. These results collectively suggest a possible mechanism involving altered methylation of a significant number of neurologically relevant ASD risk genes for introducing epigenetic changes associated with environmental exposures into the sperm methylome. Such changes may provide the potential for transgenerational inheritance of ASD as well as other disorders.

Purpose The purpose of this study is to determine whether tranexamic acid (TXA) use was associated with lower rates of blood transfusion in patients undergoing pelvic and/or acetabular fracture surgery. Methods Four studies were included, 3 of which were included in the pooled data analysis for a total of 308 patients. Results The transfusion rate was significantly lower in the TXA group (44%) compared with the non-TXA group (57%) (P = 0.02). Conclusion TXA use was associated with a significantly lower transfusion rate in patients who underwent pelvic and/or acetabular fracture surgery. Level of evidence Level 3. Systematic review of retrospective cohort studies and prospective randomized controlled trials.

Objectives: The purpose of this case series is to describe the orthopedic management of pubic symphysis osteomyelitis with an emphasis on the key principles of treating bony infection. Furthermore, we sought to identify whether debridement of the pubic symphysis without subsequent internal fixation would result in pelvic instability. Methods: A retrospective chart review was performed to identify all cases of pubic symphysis osteomyelitis treated at both institutions from 2011 to 2020. Objective outcomes collected included infection recurrence, change in pubic symphysis diastasis, sacroiliac (SI) joint diastasis, and ambulatory status. Subjective outcome measures collected included the numeric pain rating scale (NPRS) and the 36-Item Short Form Survey (SF-36). Pubic symphysis diastasis was measured as the distance between the two superior tips of the pubis on a standard anterior–posterior (AP) view of the pelvis. SI joint diastasis was measured bilaterally as the joint space between the ileum and sacrum approximately at the level of the sacral promontory on the inlet view of the pelvis. A paired t test was utilized to compare the differences in outcome measures. An α value of 0.05 was utilized. Results: Six patients were identified, of which five were males and one was female (16.7 %), with a mean ± standard deviation (SD) follow-up of 19 ± 12 months (range 6–37 months). Mean ± SD age was 76.2 ± 9.6 years (range 61.0–88.0 years) and body mass index (BMI) was 28.0 ± 2.9 kg/m2 (range 23.0–30.8 kg/m2). When postoperative radiographs were compared to final follow-up radiographs, there were no significant differences in pubic symphysis diastasis (P = 0.221) or SI joint diastasis (right, P = 0.529 and left, P = 0.186). All patients were ambulatory without infection recurrence at final follow-up. Mean improvement for NPRS was 5.6 ± 3.4 (P = 0.020) and mean improvement for SF-36 physical functioning was 53.0 ± 36.8 (P = 0.032). Conclusion: This case series highlights our treatment strategy for pubic symphysis osteomyelitis of aggressive local debridement with local antibiotic therapy. Additionally, debridement of the pubic symphysis without subsequent internal fixation did not result in pelvic instability, as determined by pelvic radiographs and ability to fully weight bear postoperatively.

The Autism-Spectrum Quotient-Adult (AQ-Adult) is a screening tool for adults with autism spectrum disorder (ASD). The present study examined the psychometric properties of the Chinese self- and parent-report versions of the AQ-Adult in Hong Kong (AQ-Adult-HK). Participants included adults with ASD (n = 27) and community controls (n = 345). Parents of a subset of adults with ASD (n = 21) and controls (n = 87) also participated as informants. The parent-report version showed significantly stronger psychometric properties, including a larger area under receiver operating characteristic curve (AUC) and higher sensitivity/specificity, than those of the self-report version. The stronger psychometric properties of the former were related to its significantly higher ratings of ASD symptoms in the ASD adults.

Parathyroid hormone-related protein (PTHrP) and macrophage inflammatory protein-1α (MIP-1α) are important factors that increase bone resorption and hypercalcemia in Adult T-cell Leukemia (ATL). We investigated the role of PTHrP and MIP-1α in the development of local osteolytic lesions in T-cell leukemia through overexpression in Jurkat T-cells. Injections of Jurkat-PTHrP and Jurkat-MIP-1α into the tibia and the left ventricle of NSG mice were performed to evaluate tumor growth and metastasis in vivo. Jurkat-pcDNA tibial neoplasms grew at a significantly greater rate and total tibial tumor burden was significantly greater than Jurkat-PTHrP neoplasms. Despite the lower tibial tumor burden, Jurkat-PTHrP bone neoplasms had significantly greater osteolysis than Jurkat-pcDNA and Jurkat-MIP-1α neoplasms. Jurkat-PTHrP and Jurkat-pcDNA cells preferentially metastasized to bone following intracardiac injection, though the overall metastatic burden was lower in Jurkat-PTHrP mice. These findings demonstrate that PTHrP induced pathologic osteolysis in T-cell leukemia but did not increase the incidence of skeletal metastasis.

To evaluate the effects of neoprene sleeves (NSs) and prophylactic knee braces (PKBs) on neuromuscular control and cutting agility.Markerless motion-capture technology tracked subjects (1) without a brace as a control (2) with NSs and (3) with PKBs during single-leg drop vertical jump (SLDVJ), single-leg squat (SLS), Y-excursion, and cutting movements. Movements were recorded five times per bracing condition in three different sessions.University laboratory.Ten healthy, active subjects (5 male, 5 female; age range, 22-26 years).Degrees of motion and time to completion.Use of NSs and PKBs reduced subjects' hip internal rotation in the loading phase of SLDVJ (p = 0.026, 0.02) and SLS (p = 0.005,0.001), reduced knee flexion in the loading phase of SLDVJ (p = 0.038,0.001), and reduced knee frontal plane abduction (FPA) with SLS (p = 0.015, 0.024) and Y-excursion (p = 0.002, 0.005) compared to control. Use of PKBs decreased subjects' hip internal rotation in the Y-excursion (p = 0.024) and reduced knee FPA in the SLDVJ loading phase (p = 0.014) compared to control. There was no difference in cutting agility for either group (p = 0.145, 0.347).Both NSs and PKBs positively impacted neuromuscular control without impacting cutting agility.

1. The slow skeletal muscle troponin I (TNNI1) gene has been found to be specifically expressed in slow muscle fibres and plays an important role in muscle development. The aim of this study was to determine the active control area of duck TNNI1 and identify the potential cis-regulatory elements in the promoter. 2. In this study, the TNNI1 promoter was first cloned by genome walking and the sequences were analysed using bioinformatics software. Firefly luciferase reporter gene vectors, driven by a series of constructs with progressive deletions, were used to identify the core transcriptional regulatory region of the duck TNNI1 gene. The methylation status of the CpG island in the TNNI1 promoter was detected in skeletal muscle on embryonic days 21 and 27, by bisulphite sequencing PCR (BSP). 3. The results showed two CpG islands presented in the promoter region, with one of the CpG islands located in the core transcriptional regulatory region (−2078/−885 bp). The total methylation levels of the 14 CpG sites were not altered between breast and leg muscles on embryonic days 21 and 27. However, four CpG sites (loci of positions 4, 11, 13, and 14) showed dramatically different methylation levels between breast and leg muscles at embryonic days 21 and 27. Analysis showed that multiple CpG sites had a significant correlation between the methylation levels of the CpG sites and mRNA expressions in skeletal muscle. Multiple transcription factor binding sites including Sp1, c-Myc, Oct-1 and NF-kB motifs were identified and might be responsible for transcriptional regulation of the TNNI1 gene. 4. These findings contribute to further understanding of the fundamental mechanism for transcriptional regulation of the TNNI1 gene in ducks.

It is unclear which pharmacological agents, and at what dosage and timing, are most effective for venous thromboembolism (VTE) prophylaxis in patients with pelvic/acetabular fractures.We searched the Cochrane Database of Systematic Reviews, Embase, Web of Science, EBSCO, and PubMed on October 3, 2020, for English-language studies of VTE prophylaxis in patients with pelvic/acetabular fractures. We applied no date limits. We included studies that compared efficacy of pharmacological agents for VTE prophylaxis, timing of administration of such agents, and/or dosage of such agents. We recorded interventions, sample sizes, and VTE incidence, including deep vein thrombosis (DVT) and pulmonary embolism.Two studies (3604 patients) compared pharmacological agents, reporting that patients who received direct oral anticoagulants (DOACs) were less likely to develop DVT than those who received low molecular weight heparin (LMWH) (p0.01). Compared with unfractionated heparin (UH), LMWH was associated with lower odds of VTE (odds ratio [OR] = 0.37, 95% confidence interval [CI]: 0.22-0.63) and death (OR = 0.27, 95% CI: 0.10-0.72). Three studies (3107 patients) compared timing of VTE prophylaxis, reporting that late prophylaxis was associated with higher odds of VTE (OR = 1.9, 95% CI: 1.2-3.2) and death (OR = 4.0, 95% CI: 1.5-11) and higher rates of symptomatic DVT (9.2% vs. 2.5%, p = 0.03; and 22% vs. 3.1%, p = 0.01). One study (31 patients) investigated dosage of VTE prophylaxis, reporting that a higher proportion of patients with acetabular fractures were underdosed (23% of patients below range of anti-Factor Xa [aFXa] had acetabular fractures vs. 4.8% of patients within adequate range of aFXa, p0.01).Early VTE chemoprophylaxis (within 24 or 48 h after injury) was better than late administration in terms of VTE and death. Many patients with acetabular fractures are underdosed with LMWH, with inadequate aFXa levels. Compared with UH, LMWH was associated with lower odds of VTE and death. DOACs were associated with lower risk of DVT compared with LMWH.III, systematic review of retrospective cohort studies.

Purpose The purpose of this study is to evaluate the reliability of magnetic resonance imaging (MRI) in predicting the location of ACL tears in preoperative planning for anterior cruciate ligament (ACL) repair. Methods Thirty-four patients who underwent ACL repair were retrospectively analyzed to compare intraoperative arthroscopic findings with preoperative MRIs. Results For identifying type I tears, the sensitivity of MRI was 9.0% and the accuracy of MRI was 8.8%. There was moderate interrater agreement between MRI findings for tear location and tear degree. Conclusion MRI alone may not necessarily be accurate in identifying which ACL tears are amenable to repair. Study design Retrospective case series; Level of Evidence: IV

Background: Although autism spectrum disorder (ASD) is among the most heritable of neurodevelopmental disorders, the rapidly rising prevalence of ASD suggests that environmental factors may contribute to epigenetic modifications that can influence risk for ASD. Endocrine disrupting compounds (EDCs), such as the long-lived organochlorines, are of particular interest with respect to risk for autism because of their ability to interfere with sex hormones that have been implicated in ASD. Methods: Whole genome bisulfite sequencing was used to identify genome-wide differentially methylated regions (DMRs) in a total of 52 sperm samples from a cohort of Faroese men who were equally divided into high and low exposure groups based on their serum levels of the long-lived organochlorine 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE). Inhabitants of the Faroe Islands, who as a group are considered a genetic isolate, may be exposed to higher than average levels of such persistent EDCs because of their native diet that is enriched in pilot whale meat and blubber. Gene ontology and pathway analyses were used to determine enrichment in ASD-relevant pathways and functions among the DMR-associated genes. Results: DMRs were enriched in autism risk genes and could also discriminate between samples in high and low exposure groups. Functional and pathway analyses of these DMR-associated genes show significant enrichment for neurodevelopmental processes frequently impacted by ASD. Of note, the DMR-associated genes significantly overlap with those previously identified in sperm from fathers of children with ASD versus fathers of neurotypical children, thus suggesting a potential environmental mechanism for introducing ASD-associated epigenetic changes in the sperm methylome. Limitations: A limitation of this study is the relatively low number of samples, although this is somewhat offset by the use of a genetic isolate which reduces the genetic heterogeneity that is often a major challenge in epigenetic studies. Another limitation is the lack of a completely unexposed set of samples for comparisons since persistent EDCs can be detected in a majority of individuals. Conclusion: Results of this study show that elevated exposure to certain organochlorines is associated with genome-wide DNA methylation patterns in sperm affecting genes involved in neurological functions and developmental disorders, including ASD.

Standard multimodal pain management for anterior cruciate ligament reconstruction typically includes a combination of local anesthetics, nonsteroidal anti-inflammatory drugs, and opioids. Opioids present a substantial risk, and there is a rising number of prescription opioid-related overdoses in the United States. The goal of this study was to evaluate the quantity of opioids prescribed to patients who received liposomal bupivacaine as a component of their multi-modal pain regimen. The electronic medical records of patients who underwent anterior cruciate ligament reconstruction by a single surgeon at an urban hospital during a 2-year period were evaluated. Patients in the case group received liposomal bupivacaine and those in the control group did not. Statistical analysis of the number of pills prescribed and numeric pain rating scale scores was performed with a 2-tailed unequal variance t test. Statistical analysis of opioid prescription refills was performed with a chi-square test. A total of 67 patients were included. The mean number of 5-mg oxycodone tablets prescribed to the case group (9.29±10.29 tablets) was significantly lower ( P P P =.09). Patients who received liposomal bupivacaine as part of multimodal pain management had significantly fewer opioid prescriptions. Despite the reduction in opioids prescribed, patients in the case group only showed a trend toward a reduction in pain at 2-week follow-up. [ Orthopedics . 2021;44(2):e229–e235.]

We apply the gradient flow on a color-electric two-point function that encodes the heavy quark momentum diffusion coefficient. The simulations are done on fine isotropic lattices in the quenched approximation at $1.5\,T_c$. The continuum extrapolation is performed at fixed flow time followed by a second extrapolation to zero flow time. Perturbative calculations of this correlation function under Wilson flow are used to enhance the extrapolations of the non-perturbative lattice correlator. The final estimate for the continuum correlator at zero flow time largely agrees with one obtained from a previous study using the multi-level algorithm. We perform a spectral reconstruction based on perturbative model fits to estimate the heavy quark momentum diffusion coefficient. The approach we present here yields high-precision data for the correlator and is also applicable for actions with dynamical fermions., Published version, 14 pages, 15 figures

We present two cases of posterior cruciate ligament (PCL) repair with suture augmentation (SA) in the setting of multiligamentous knee injury (MLKI). Excellent clinical outcomes were obtained at two-year follow-up with both patients returning to sport following injury. Both patients demonstrated improvements in Knee Injury and Osteoarthritis Outcome Score (KOOS) that exceeded the minimal clinically important difference (MCID) as reported in the literature for ligamentous knee injuries. One patient developed arthrofibrosis, which was successfully treated with manipulation under anesthesia and arthroscopic lysis of adhesions two months postoperatively. Both patients had full knee range of motion (ROM) by a one-year follow-up. One patient returned to full preinjury level of sport at six months postoperatively while the other patient returned to 50% of preinjury intensity at two-year follow-up. This series of two cases of PCL repair with SA in MLKIs demonstrates that PCL repair with SA is a viable procedure that can result in excellent short-term outcomes and restore knee stability.

We present continuum extrapolated results of charmonium and bottomonium correlators in the vector channel at several temperatures below and above $T_c$. The continuum extrapolation jointly performed with the interpolations to have physical values of $J/\psi$ and $\Upsilon$ masses in the confined phase is based on calculations on several large quenched isotropic lattices using clover-improved Wilson valence fermions carrying different quark masses. The extrapolated lattice correlators are confronted with perturbation theory results incorporating resummed thermal effects around the threshold from pNRQCD and vacuum asymptotics above the threshold. An additional transport peak is modelled below the threshold allowing for an estimate of the diffusion coefficients for charm and bottom quarks. We find that charmonium correlators in the vector channel can be well reproduced by perturbative spectral functions above $T_c$ where no resonance peaks for $J/\psi$ are needed at and above 1.1 $T_c$, while for bottomonium correlators a resonance peak for $\Upsilon$ is still needed up to 1.5 $T_c$. By analyzing the transport contribution to the correlators we find that the drag coefficient of a charm quark is larger than that of a bottom quark., Comment: published version

Purpose To examine trends in the incidence of pectoralis major (PM) injuries over the last 22 National Football League (NFL) seasons and identify risk factors for injuries requiring operative management. Methods Publicly available data from the 1998-1999 through 2019-2020 NFL seasons were reviewed to identify PM injuries, demographics, injury mechanisms, and management. Injury incidence was calculated using linear regression per 10,000 athlete-exposures, while risk factors for operative management were identified through multivariate logistic regression. Results There were 258 PM injuries. Mean athlete age at the time of injury was 27.1 years (range: 21-37) with a mean body mass index of 32.6 (range: 24.8-43.1). Overall incidence was 0.603 per 10,000 athlete-exposures, which was found to significantly increase with time by 0.039 per athlete-exposures per year (R2 = .787, P < .001). Defensive athletes accounted for 64.7% of PM injuries. Repair was performed in 48.8% of athletes, with defensive linemen (odds ratio [OR] 3.78, CI 1.42-10.60, P = .009), defensive backs (OR 12.20, CI 2.13-76.60, P = .006), linebackers (OR 8.98, CI 2.58-33.60, P < .001), more recent time of injury (OR 1.11, CI 1.05-1.17, P < .001), and shorter NFL experience (OR .77 for older athletes, CI .59-.99), P = .047) at significant risk for operative treatment. Conclusion A total of 258 PM injuries were identified over 22 NFL seasons, with an overall incidence of 0.603 per 10,000 athlete-exposures, which was found to increase by 0.039 injuries per 10,000 athlete-exposures per year. Repair was performed in 48.8% of athletes, with more recent time of injury, shorter NFL experience, defensive linemen, defensive backs and linebackers at significantly higher risk for operative treatment. Study Design Cohort study; Level of evidence, 3.

Non-receptor protein-tyrosine kinases regulate cellular responses to many external signals and are important drug discovery targets for cancer and infectious diseases. While many assays exist for the assessment of kinase activity in vitro, methods that report changes in tyrosine kinase activity in single cells have the potential to provide information about kinase responses at the cell population level. In this protocol, we combined bimolecular fluorescence complementation (BiFC), an established method for the assessment of protein-protein interactions, and immunofluorescence staining with phosphospecific antibodies to characterize changes in host cell tyrosine kinase activity in the presence of an HIV-1 virulence factor, Nef. Specifically, two Tec family kinases (Itk and Btk) as well as Nef were fused to complementary, non-fluorescent fragments of the Venus variant of YFP. Each kinase was expressed in 293T cells in the presence or absence of Nef and immunostained for protein expression and activity with anti-phosphotyrosine (pTyr) antibodies. Multi-color confocal microscopy revealed the interaction of Nef with each kinase (BiFC), kinase activity, and kinase protein expression. Strong BiFC signals were observed when Nef was co-expressed with both Itk and Btk, indicative of interaction, and a strong anti-pTyr immunoreactivity was also seen. The BiFC, pTyr, and kinase expression signals co-localized to the plasma membrane, consistent with Nef-mediated kinase activation in this subcellular compartment. Image analysis allowed calculation of pTyr-to-kinase protein ratios, which showed a range of responses in individual cells across the population that shifted upward in the presence of Nef and back down in the presence of a kinase inhibitor. This method has the potential to reveal changes in steady-state non-receptor tyrosine kinase activity and subcellular localization in a cell population in response to other protein-kinase interactions, information that is not attainable from immunoblotting or other in vitro methods.

Antiretroviral therapy has revolutionized the treatment of AIDS, turning a deadly disease into a manageable chronic condition. Life-long treatment is required because existing drugs do not eradicate HIV-infected cells. The emergence of drug-resistant viral strains and uncertain vaccine prospects highlight the pressing need for new therapeutic approaches with the potential to clear the virus. The HIV-1 accessory protein Nef is essential for viral pathogenesis, making it a promising target for antiretroviral drug discovery. Nef enhances viral replication and promotes immune escape of HIV-infected cells but lacks intrinsic enzymatic activity. Instead, Nef works through diverse interactions with host cell proteins primarily related to kinase signaling pathways and endosomal trafficking. This review emphasizes the structure, function, and biological relevance of Nef interactions with host cell protein-tyrosine kinases in the broader context of Nef functions related to enhancement of the viral life cycle and immune escape. Drug discovery targeting Nef-mediated kinase activation has allowed identification of promising inhibitors of multiple Nef functions. Pharmacological inhibitors of Nef-induced MHC-I down-regulation restore the adaptive immune response to HIV-infected cells in vitro and have the potential to enhance immune recognition of latent viral reservoirs as part of a strategy for HIV clearance.

CASE We report the case of a 44-year-old woman with previous anterior cruciate ligament (ACL) reconstruction 25 years ago in the right knee, who sustained a bucket-handle medial meniscus tear after pain and instability while pivoting during tennis. Magnetic resonance imaging demonstrated an intact but vertical and anterior ACL graft. A novel ACL retensioning procedure with suture augmentation (SA) was performed as the revision procedure. Excellent clinical outcomes and knee stability were obtained at both 17 and 36 months postoperatively. CONCLUSIONS In certain cases, ACL retensioning with SA may be performed as the revision procedure for unsuccessful primary ACL reconstruction.

Background The frequencies of systemic antibiotics and oral corticosteroids taken for chronic rhinosinusitis (CRS) indicate poor CRS disease control. We sought to determine the validity and responsiveness of these metrics as reflections of CRS disease burden. Methodology One hundred and eighty-seven patients undergoing medical management for CRS were recruited. Participants were assessed at two time points: enrollment and a follow-up appointment three to nine months later. At each time point, CRS related antibiotic and oral corticosteroid usage in the previous three months was measured, while general and disease-specific quality of life (QOL) was measured using the visual analog scale of the 5-dimension EuroQol questionnaire (EQ-5D VAS) and the 22-item Sinonasal Outcome Test (SNOT-22), respectively. Results The frequency of CRS-related antibiotics and oral corticosteroids use was cross-sectionally correlated with EQ-5D VAS and SNOT-22 at the corresponding time points. For participants reporting usage of these medications at enrollment, there was a decrease of 1 course per 3 months for both CRS-related antibiotics and oral corticosteroids. Change in CRS-related antibiotics from enrollment to follow-up was correlated with change in both EQ-5D and SNOT-22 over the same timeframe. The change in CRSrelated oral corticosteroids was correlated with change in both EQ-5D VAS and SNOT-22). These correlations were stronger in the subset of patients who had a change in these metrics over the study period. Conclusions The frequencies of CRS-related antibiotic use and oral corticosteroid use are valid and responsive measures of CRS disease burden.

In this paper, the development and capabilities of the 2020 World Gas Model (WGM) are presented and exemplified through the analysis of two important case studies currently facing the natural gas market, a key component of the global energy sector. The goal of the United States - China Trade War case study is to analyze the potential short- and long-term effects of a prolonged trade war under several different, possible scenarios. Results from the study indicate that while increased tariffs on LNG trade from the U.S. to China greatly reduce the amount of trade volume between the two countries; however, the overall economic effect is negligible. The U.S. Coast Guard (USCG) LNG inspection workforce planning case study utilizes the WGM to provide future workforce demand for USCG personnel based on the growth of the U.S. LNG industry. The results from the study indicate that in order to avoid restriction on the U.S. LNG industry, the USCG must increase its LNG inspection workforce at a rate between 10% to 15% per annum. The U.S. - China Trade War effects on the USCG LNG inspection workforce were found to negligible as U.S. trade levels remain heightened and ever-growing despite increasing tariffs or Chinese domestic gas production.

Arthrofibrosis can be a devastating complication after ligamentous knee reconstruction. Beyond early range of motion (ROM), manipulation under anesthesia (MUA) and arthroscopic lysis of adhesions (LOAs) are the most frequently employed interventions for the condition. There is a paucity of data regarding predictive factors of arthrofibrosis requiring MUA and LOA, and even less data regarding changes in validated patient-reported outcome measures following the procedure. A retrospective case–control study was performed at an academic, urban Level I trauma center of patients that developed arthrofibrosis requiring MUA and LOA following ligamentous reconstruction. The indication for LOA was failure to achieve a 90° arc of ROM by 6 weeks. Seventeen cases and 141 controls were identified. Follow-up for cases was 26.9 ± 17.1 months (mean ± standard deviation). Time from initial reconstruction to LOA was 75.2 ± 27.9 days. Cases had higher body mass indices by a mean of 2.9 (p = 0.024). The most significant risk factors for stiffness were concomitant anterior cruciate ligament, posterior cruciate ligament, and posterolateral corner/lateral collateral ligament injury (odds ratio [OR], 17.08), knee dislocation (OR, 12.84), and use of an external fixator (OR, 12.81, 95% confidence interval [CI], 3.03–54.20) (all p

Acute myelogenous leukemia (AML) is the most common hematologic malignancy in adults, and is often associated with constitutive tyrosine kinase signaling. These pathways involve the non-receptor tyrosine kinases Fes, Syk and the three Src-family kinases expressed in myeloid cells (Fgr, Hck, and Lyn). In this study, we report remarkable anti-AML efficacy of an N-phenylbenzamide kinase inhibitor, TL02–59. This compound potently suppressed the proliferation of bone marrow samples from twenty of twenty-six AML patients, with a striking correlation between inhibitor sensitivity and expression levels of the myeloid Src family kinases Fgr, Hck, and Lyn. No correlation was observed with Flt3 expression or mutational status, with the four most sensitive patient samples wild-type for Flt3. Kinome-wide target specificity profiling coupled with in vitro kinase assays demonstrated a narrow overall target specificity profile for TL02–59, with picomolar potency against the myeloid Src-family member Fgr. In a mouse xenograft model of AML, oral administration of TL02–59 for three weeks at 10 mg/kg completely eliminated leukemic cells from the spleen and peripheral blood while significantly reducing bone marrow engraftment. These results identify Fgr as a previously unrecognized kinase inhibitor target in AML, and TL02–59 as a possible lead compound for clinical development in AML cases that overexpress this kinase independent of Flt3 mutations.