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Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia carries high mortality with limited treatment options. Studies over the last decade support glycolipopeptide and beta-lactam combination therapy with daptomycin (DAP) and ceftaroline (CFT) combination gaining prominence. While data supports de-escalation to monotherapy after bacteremia clearance it does not guide the choice of agent. With barriers including accessibility, cost, and tolerability of these agents, data is needed to optimize treatment. This study aims to evaluate de-escalation options after combination DAP/CFT therapy for persistent MRSA bacteremia. Methods A single-center, retrospective review of cases of persistent MRSA bacteremia (defined as greater than 72 hours on appropriate therapy) requiring escalation to DAP/CFT between 2014 and 2021 was performed. Details of bacteremia, source of infection, and comorbidities were assessed, and outcomes including recurrence of infection, infection-associated mortality, and tolerability were compared using exact Chi-square testing and univariant analysis. Results Sixty-six cases were identified of which 7 were de-escalated to vancomycin (VAN), 48 to DAP, 4 to CFT, and 7 continued DAP/CFT combination. Demographics and details of bacteremia such as prior anti-MRSA therapy, duration prior to DAP/CFT therapy, and source identification were similar between groups. Differences included higher rates of hemodialysis patients in the VAN group, higher rates of immunocompromised hosts in the DAP group, higher average Pitt bacteremia score in the DAP/CFT group, and lower rates of source control in the VAN group. Recurrence of infection (29% VAN, 13% DAP, 25% CFT) and infection-related mortality (14% VAN, 8% DAP) were higher in the VAN group (p=0.0452). In the DAP group 23% required change in therapy during their course. Univariant analysis assessing for confounding from comorbidities and source control yielded no significant associations. Conclusion This study is limited by small, uneven sample sizes but the results identify a trend of increased recurrence rates and mortality with de-escalation to VAN but tolerability concerns with DAP. More study is needed to guide clinical care and this data provides framework for future research. Disclosures All Authors: No reported disclosures.

Background With advances in genomics, microbiologists can accurately rename existing bacteria which may cause confusion among clinicians familiar with prior names. Limited investigation is available on the clinical impact of these name changes. University of Alabama at Birmingham Hospital microbiology updated Klebsiella aerogenes in the electronic medical record (EMR) to "Klebsiella (Enterobacter) aerogenes" to reflect change in nomenclature. Therapy selection differs between Klebsiella pneumoniae and Enterobacter spp. due to differences in Ambler Class C (AmpC) beta-lactamase production. Our Antimicrobial Stewardship Program previously implemented selective and cascaded susceptibility reporting for E. aerogenes to guide antibiotic selection which remained after nomenclature change. The goal of this study is to determine if the change led to inappropriate antibiotic use. Methods We reviewed blood culture data from May 2016-2020 which grew Enterobacter aerogenes or Klebsiella "Enterobacter" aerogenes. We excluded polymicrobial blood cultures, patients aged 18 and under, and patients who died within 48 hours of drawing blood cultures. Appropriate therapy was defined as an antibiotic with reported susceptibility with consideration of AmpC induction for a duration appropriate to clinical syndrome with minimum of 7 days. We recorded patient demographics, nature of therapy, and clinical outcomes. We performed comparative analysis with descriptive statistics to compare the two groups. Results There were 38 patients with K. aerogenes bacteremia, 21 patients prior to name change and 17 afterwards. None were ESBL. Cefepime was most often used directed inpatient therapy while oral ciprofloxacin was the most common outpatient regimen with no use of ceftriaxone. Prior to name change, there was one case (4.76%) that did not receive targeted AmpC therapy while there were two afterwards (11.8%), one of which decided by the ID consult team. Table 1 Demographics (Data presented as No. (%)) Table 2 Microbiology and Outcomes (Data presented as No. (%)) Table 3 Antimicrobial Selection. One patient that received 72 hours of appropriate therapy but died prior to completion of therapy. This was labeled labelled as appropriate therapy. Conclusion Care must be taken when taxonomic changes of clinically relevant bacteria may potentially affect optimization of antibiotics. As the ID consultants, we must be aware of these name changes and provide up to date recommendations. Cascade reporting and documentation in the EMR may be helpful to reduce morbidity related to changes in nomenclature. Disclosures Sixto M. Leal, Jr., MD, PhD, GenMark Dx: Grant/Research Support|GenMark Dx: Honoraria.

The scope of antimicrobial stewardship programs has expanded beyond the acute hospital setting. The need to optimize antimicrobial use in emergency departments, urgent, primary, and specialty care clinics, nursing homes, and long-term care facilities prompted the development of core elements of stewardship programs in these settings. Identifying the most innovative and well-designed stewardship literature in these novel stewardship areas can be challenging. The Southeastern Research Group Endeavor (SERGE-45) network evaluated antimicrobial stewardship–related, peer-reviewed literature published in 2021 that detailed actionable interventions specific to the nonhospital setting. The top 13 publications were summarized following identification using a modified Delphi technique. This article highlights the selected interventions and may serve as a key resource for expansion of antimicrobial stewardship programs beyond the acute hospital setting.

Objective:We observed an overall increase in the use of third- and fourth-generation cephalosporins after fluoroquinolone preauthorization was implemented. We examined the change in specific third- and fourth-generation cephalosporin use, and we sought to determine whether there was a consequent change in non-susceptibility of select Gram-negative bacterial isolates to these antibiotics.Design:Retrospective quasi-experimental study.Setting:Academic hospital.Intervention:Fluoroquinolone preauthorization was implemented in the hospital in October 2005. We used interrupted time series (ITS) Poisson regression models to examine trends in monthly rates of ceftriaxone, ceftazidime, and cefepime use and trends in yearly rates of nonsusceptible isolates (NSIs) of select Gram-negative bacteria before (1998–2004) and after (2006–2016) fluoroquinolone preauthorization was implemented.Results:Rates of use of ceftriaxone and cefepime increased after fluoroquinolone preauthorization was implemented (ceftriaxone RR, 1.002; 95% CI, 1.002–1.003; P < .0001; cefepime RR, 1.003; 95% CI, 1.001–1.004; P = .0006), but ceftazidime use continued to decline (RR, 0.991, 95% CI, 0.990–0.992; P < .0001). Rates of ceftazidime and cefepime NSIs of Pseudomonas aeruginosa (ceftazidime RR, 0.937; 95% CI, 0.910–0.965, P < .0001; cefepime RR, 0.937; 95% CI, 0.912–0.963; P < .0001) declined after fluoroquinolone preauthorization was implemented. Rates of ceftazidime and cefepime NSIs of Enterobacter cloacae (ceftazidime RR, 1.116; 95% CI, 1.078–1.154; P < .0001; cefepime RR, 1.198; 95% CI, 1.112–1.291; P < .0001) and cefepime NSI of Acinetobacter baumannii (RR, 1.169; 95% CI, 1.081–1.263; P < .0001) were increasing before fluoroquinolone preauthorization was implemented but became stable thereafter: E. cloacae (ceftazidime RR, 0.987; 95% CI, 0.948–1.028; P = .531; cefepime RR, 0.990; 95% CI, 0.962–1.018; P = .461) and A. baumannii (cefepime RR, 0.972; 95% CI, 0.939–1.006; P = .100).Conclusions:Fluoroquinolone preauthorization may increase use of unrestricted third- and fourth-generation cephalosporins; however, we did not observe increased antimicrobial resistance to these agents, especially among clinically important Gram-negative bacteria known for hospital-acquired infections.

Background: Despite the high success rate of total hip arthroplasty (THA), new implant technologies continue to be developed. Although potentially useful, such novel developments may result in unintended consequences, leading to revision surgery, often prematurely. In several instances, new technology that appeared promising was later found to be inferior to existing technology and resulting in early revision surgery. Additionally, technical surgical errors may also lead to early revisions. Some have argued that revisions related to such phenomena are potentially avoidable. The present analysis investigates to what extent the contribution of “failed new technology” and “technical errors” contributes to the revision burden and to the need for premature revision arthroplasty. Methods: We retrospectively analysed 432 revision THAs and categorised them as either “late revisions” based on survivorship of 10 years or “premature revisions”. Among both cohorts, we determined what percentage of revisions were potentially avoidable and due to failed novel technologies and technical errors, and what percent were “unavoidable”. Results: Of the 432 revisions, 267 (62%) were considered premature and 38% were considered late. Of the premature revisions, 108 were considered potentially avoidable (81 failed novel technologies, 27 technical errors). Conclusions: Our data demonstrates that new technology and surgical techniques can result in premature failure of THA. Surgeons should take caution when incorporating new implant technology or surgical techniques into their practice.

The solvothermal synthesis and characterization of a three-dimensional, interpenetrated uranyl dicyanoaurate coordination polymer, K2(UO2)2(UO2)2(Au(CN)2)2(O)2(NO3)4, from UO2(NO3)2·6H2O and KAu(CN)2 is described. The structure contains a three-dimensional (3D) lattice of planar tetranuclear uranyl–oxo–nitrate clusters connected by dicyanoaurate linkers, with the rotation of the clusters providing the increased dimensionality. The material undergoes a reversible single-crystal to single-crystal transformation on exposure to water vapour, which is taken up in the channels of the 3D system. A second uranyl dicyanoaurate coordination polymer of the form [UO2(DMSO)3(H2O)(Au(CN)2)][Au(CN)2] was structurally characterized as a linear chain of dicyanoaurate units connected by gold–gold bonds with pendant uranyl–water–DMSO adducts that are hydrogen bonded into a two-dimensional sheet. Both materials exhibit emission arising from both the uranyl moiety and the gold(I) centre and represent the first multidimensional uranyl–dicyanoaurate coordination polymers.

Introduction Historically, hip precautions have been prescribed after total hip arthroplasty (THA) to limit certain motions felt to place the arthroplasty construct in a position at increased risk for dislocation. This study aimed to determine whether relaxed hip precautions after primary THA done via a posterolateral approach resulted in a higher early dislocation rate compared with standard hip precautions. Methods The hip precaution protocol was changed from standard to relaxed at our institution for all patients with THA in December 2016. One cohort had THA in the 18 months before the protocol change and had standard hip precautions, and the second cohort had THA in the 18 months after the protocol change and had relaxed precautions. We determined the early dislocation rate (within 3 months postoperatively) for both cohorts and controlled for selected demographic and surgical details. Results The standard precaution group included 597 primary THAs and the relaxed precaution group included 692 hips. No notable differences were found between the groups in terms of age at surgery, body mass index, sex, laterality, or diagnosis. Early dislocation occurred in seven hips (1.2%) in the standard precaution cohort and in nine hips (1.4%) in the relaxed precaution cohort. This difference was not statistically significant (P = 0.77). Discussion The results of our study suggest that well-trained, high-volume surgeons may potentially relax hip precautions prescribed to the patients after primary THA done via a posterolateral approach without subjecting patients to a markedly higher incidence of dislocation. However, unlike previous studies, this study controlled for femoral head size, which is a well-known confounder for dislocation risk.

Background:The cause of osteochondritis dissecans (OCD) is unknown.Purpose:To determine if mechanical axis deviation correlates with OCD lesion location in the knee, if degree of mechanical axis deviation correlates with size of OCD lesion, and if the deformity was primarily in the distal femur or proximal tibia.Study Design:Cross-sectional study; Level of evidence, 3.Methods:We identified 61 knees that underwent osteochondral allograft (OCA) transplantation for femoral condyle OCD lesions and used preoperative lower extremity alignment radiographs to measure lower extremity mechanical axis, mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), and hip-knee-ankle angle. Lesion location and area were retrieved from operative records.Results:The location of the OCD lesion was the medial femoral condyle (MFC) for 37 knees and lateral femoral condyle (LFC) for 24 knees. Among knees with MFC lesions, alignment was varus in 25 (68%). Conversely, knees with LFC lesions had valgus alignment in 16 (67%). The mLFDA was significantly more valgus in the LFC group. mMPTA was not different between MFC and LFC groups. There was no significant correlation between degree of mechanical axis deviation and lesion size.Conclusion:In this cohort, two-thirds of patients with symptomatic OCD lesions had associated mechanical axis deviation. Lesion location correlated with mechanical axis deviation (LFC lesions were associated with a deformity in the distal femur). Degree of deformity was not correlated with lesion size. Mechanical axis deviation may play a role in OCD pathogenesis. These data do not allow analysis of the role of mechanical axis deviation in causation or prognosis of OCD lesions, but surgeons treating OCD should be aware of this common association.

The impact of fluidic pockets with different dimensions and geometries on the quality factor, resonant frequency and phase shift of SIW cavities is reported. A symmetrically tapered fluidic pocket configuration implemented using discrete circular pockets with increasing radius yields a wide resonant frequency range while minimizing quality factor degradation as fluid is added to the pockets. The fluidically reconfigurable cavities are used to synthesize a frequency-reconfigurable third-order Chebyshev BPF on a Rogers 3010 substrate (ϵ r = 10.2, tan δ = 0.0035, h = 1.27 mm). Experiments using acetone (ϵ r = 20.7, tan δ = 0.05 at 2.4 GHz) as the dielectric fluid show that the filter's center frequency can be shifted over a range of 170 MHz using only 13 mL of liquid per cavity. Additionally, a SIW phase shifter using acetone is presented, demonstrating a maximum phase shift of 44±6° using only 56 mL of fluid.

Although the vast majority of arthroplasty surgeons allow patients to return to participation in golf following total knee arthroplasty (TKA) and total hip arthroplasty (THA), there is relatively little published data regarding how TKA or THA affects a patient's golfing ability. The purpose of this study was to determine how golfers' handicaps change following TKA and THA. We mailed a questionnaire to patients who had underwent primary TKA or THA at our institution and asked whether they played golf and for their golf handicap information network (GHIN) number. We then obtained handicap data for each patient that provided a GHIN number. Handicap increased 0.9 strokes 1 year following THA; however, this difference was not statistically significant (p = 0.20). Handicap increased 0.3 strokes 1 year following TKA; however, this difference was not statistically significant (p = 0.29). Our study demonstrates that despite improved implants, surgical techniques, and rehabilitation protocols that golf handicap does not change significantly following lower extremity total joint arthroplasty (TJA). (Journal of Surgical Orthopaedic Advances 29(4):216-218, 2020).

A fluidically-tuned substrate integrated waveguide (SIW) quasi-elliptic bandpass filter using reconfigurable TE 101 mode cavity resonators is presented. A quadruplet filter with a pair of finite transmission zeros is presented using cross-coupled cavities to achieve a highly selective passband. The four SIW cavities have vias near their corners that are selectively filled with eutectic gallium indium (EGaIn) to tune the resonant frequency of the cavities. A symmetric via placement is implemented to maintain the par of finite transmission zeros equally spaced on either side of the passband. Measured results indicate that the filter’s center frequency can be discretely tuned between 7.96 GHz, 8.12 GHz, 8.24 GHz and 8.39 GHz, indicating a 400 MHz tuning range while maintaining a symmetric and sharp roll-off. The filter was designed and fabricated on a 1.54 mm thick Rogers 4003 substrate (ϵ r = 3.55, tan δ = 0.0027).

Purpose This study aims to compare the performance of alternative weight-based vancomycin dosing strategies to traditional dosing in obese patients using area under the curve (AUC) monitoring. Methods This retrospective study compared target attainment of an AUC between 400–600mcg*H/mL using alternative vancomycin dosing strategies. All patients received allometrically dosed vancomycin, with patient-specific AUCs calculated using 2 post-infusion steady-state vancomycin serum concentrations using the trapezoidal rule. Predicted AUCs were calculated using the following: 15 mg/kg total body weight (TBW), 15 mg/kg corrected body weight (CBW), and 12.5 mg/kg TBW. Predicted AUCs from the traditional 15 mg/kg TBW dosing were then compared to alternative dosing strategies using the predicted AUCs from 12.5 mg/kg TBW, 15 mg/kg CBW, and the actual AUCs calculated using allometrically scaled vancomycin dosing. The primary outcome was attainment of initial AUC within the target range of 400–600mcg*H/mL for each dosing method. Results Eighty-four patients were included. When AUCs were compared to traditional 15 mg/kg dosing strategy, the CBW, 12.5 mg/kg, and allometric dosing strategies were significantly more likely to result in initial attainment of an AUC within a target range of 400–600 mcg*H/mL (P = 0.0003, 0.0135, and 0.0088, respectively). No significant differences were seen between each of the alternative dosing methods (P = 0.73). Conclusion The 3 alternative vancomycin dosing strategies examined were all significantly more likely to achieve an initial AUC within the target range compared to traditional vancomycin dosing in obese patients. Clinicians should strongly consider one of these alternative dosing strategies for obese patients as opposed to traditional vancomycin dosing.

Understanding the conformational ensemble of an intrinsically disordered protein (IDP) is of great interest due to its relevance to critical intracellular functions and diseases. It is now well established that the polymer scaling behavior can provide a great deal of information about the conformational properties as well as liquid-liquid phase separation of an IDP. It is, therefore, extremely desirable to be able to predict an IDP’s scaling behavior from the protein sequence itself. The work in this direction so far has focused on highly charged proteins and how charge patterning can perturb their structural properties. As naturally occurring IDPs are composed of a significant fraction of uncharged amino acids, the rules based on charge content and patterning are only partially helpful in solving the problem. Here, we propose a new order parameter, sequence hydropathy decoration (SHD), which can provide a near quantitative understanding of scaling and structural properties of IDPs devoid of charged residues. We combine this with a charge patterning parameter, sequence charge decoration (SCD), to obtain a general equation, parameterized from extensive coarse-grained simulation data, for predicting protein dimensions from the sequence. We finally test this equation against available experimental data and find a semi-quantitative match in predicting the scaling behavior. We also provide guidance on how to extend this approach to experimental data, which should be feasible in the near future.Graphical TOC Entry

Genetic ablation of cyclooxygenase-2 (COX-2) in mice is known to impair fracture healing. To determine if teriparatide (human PTH1-34) can promote healing of Cox-2-deficient fractures, we performed detailed in vivo analyses using a murine stabilized tibia fracture model. Periosteal progenitor cell proliferation as well as bony callus formation was markedly reduced in Cox-2-/- mice at day 10 post-fracture. Remarkably, intermittent PTH1-34 administration increased proliferation of periosteal progenitor cells, restored callus formation on day 7, and enhanced bone formation on days 10, 14 and 21 in Cox-2-deficient mice. PTH1-34 also increased biomechanical torsional properties at days 10 or 14 in all genotypes, consistent with enhanced bony callus formation by radiologic examinations. To determine the effects of intermittent PTH1-34 for callus remodeling, TRAP staining was performed. Intermittent PTH1-34 treatment increased the number of TRAP positive cells per total callus area on day 21 in Cox-2-/- fractures. Taken together, the present findings indicate that intermittent PTH1-34 treatment could compensate for COX-2 deficiency and improve impaired fracture healing in Cox-2-deficient mice.

A branchline coupler is presented that uses 12 microfluidic channels (3 per branch) to tune its center frequency. A lumped-element equivalent circuit model (ECM) is extracted for the fluidic channels and is used to predict the response of the coupler prior to fabrication. The circuit is realized on a 1.524-mm-thick Rogers 4003C substrate with $\epsilon _{r} = 3.55$ . The microfluidic channels are milled through the ground backplane and are filled with ethyl acetate $(\mathrm {C_{4}H_{8}O_{2}})$ , for which $\epsilon _{r}=6.00$ . Experiments with the coupler show that starting with empty (i.e., air-filled) channels and progressively filling them with the fluid, the center frequency of the coupler can be tuned from 2.19 to 1.80 GHz, yielding a tuning range of 19.5%. A comparison between the modeled and measured results shows that the ECM predicted the coupler tuning range with an error below 2.8%.

Background Periprosthetic joint infection (PJI) represents a devastating complication of total hip arthroplasty (THA) or total knee arthroplasty (TKA). Modifiable patient risk factors as well as various intraoperative and postoperative variables have been associated with risk of PJI. In 2011, our institution formulated a "bundle" to optimize patient outcomes after THA and TKA. The purpose of this report is to describe the "bundle" protocol we implemented for primary THA and TKA patients and to analyze its impact on rates of PJI and readmission. Methods Our bundle protocol for primary THA and TKA patients is conceptually organized about 3 chronological periods of patient care: preoperative, intraoperative, and postoperative. The institutional total joint database and electronic medical record were reviewed to identify all primary THAs and TKAs performed in the 2 years before and following implementation of the bundle. Rates of PJI and readmission were then calculated. Results Thirteen of 908 (1.43%) TKAs performed before the bundle became infected compared to only 1 of 890 (0.11%) TKAs performed after bundle implementation ( P = .0016). Ten of 641 (1.56%) THAs performed before the bundle became infected, which was not statistically different from the 4 of 675 (0.59%) THAs performed after the bundle that became infected ( P = .09). Conclusion The bundle protocol we describe significantly reduced PJIs at our institution, which we attribute to patient selection, optimization of modifiable risk factors, and our perioperative protocol. We believe the bundle concept represents a systematic way to improve patient outcomes and increase value in total joint arthroplasty.

Significant debate persists about posterior cruciate-retaining (CR) versus posterior cruciate-substituting (PS) implant design for total knee arthroplasty (TKA). This study sought to test the hypothesis that CR TKA will facilitate improved early functional outcomes in gait compared with PS TKA. Patients were randomized to either the CR or PS implant. Various patient-reported and surgeon-reported outcomes as well as gait analyses were obtained pre- and postoperatively. Patients undergoing PS TKA had higher University of California, Los Angeles activity scores at 12 months. No significant difference in spatiotemporal, kinematic, or kinetic parameters between groups was detected, but there was a trend toward quadriceps overuse gait pattern in the CR group. Patients undergoing TKA with a PS implant were more willing to engage in regular higher level physical activity. The CR implant may be a risk factor for quadriceps overuse gait pattern, while the PS implant may be protective against quadriceps overuse. (Journal of Surgical Orthopaedic Advances 28(3):215-223, 2019).

A method of 3D printing complex or challenging structures by breaking them into parts with connectors, printing each part separately, and then assembling the structure post-printing has been developed. This has advantages such as multicoloured printing, framework optimization and reduction, print time reduction, and can be used to bypass print tray size limits. This method is particularly applicable to extended structures such as coordination polymers, metal-organic frameworks, and hydrogen bonding networks, but examples where it can be used to simplify the printing of small molecules are also shown.

Introduction15%-20% of patients presenting for total hip arthroplasty (THA) have bilateral disease. While simultaneous bilateral THA is of interest to patients and surgeons, debate persists regarding its merits. The majority of previous reports on simultaneous bilateral THA involve patients in the lateral decubitus position, which require repositioning, prepping and draping, and exposure of a fresh wound to pressure and manipulation for the contralateral THA. The purpose of this study was to compare complications, component position, and financial parameters for simultaneous versus staged bilateral THAs using the direct anterior approach (DAA).MethodsMedical records were reviewed for patient demographics, medical history, operative time, estimated blood loss (EBL), change in hemoglobin, transfusion, tranexamic acid (TXA) use, length of stay (LOS), discharge disposition, leg length discrepancy, acetabular cup position, and perioperative complications. Cost and reimbursement data were analysed.Results44 patients were included in the sequential group and fifteen patients in the simultaneous group. Operative time, EBL, hemoglobin drop, transfusion rate, and LOS were significantly increased for simultaneous group. There was no significant difference in component position, complications, or readmissions between groups. Profit per hip was significantly higher for the simultaneous group.DiscussionWhile simultaneous DAA THA presents challenges, our results suggest that simultaneous DAA THA may add value to the healthcare system without resulting in increased complications compared to sequential hip arthroplasty.

Range of motion (ROM) is important for functional outcome after total knee arthroplasty (TKA); however, some patients hesitate to maximize their ROM postoperatively. The Tampa Scale of Kinesiophobia (TSK) measures patients' fear of movement. The primary purpose of this investigation was to determine whether TSK scores correlated with decreased ROM after primary TKA. A secondary purpose was to determine whether biofeedback could increase ROM after TKA.Patients were recruited from the senior author's practice between June 2011 and March 2013. A clinical photograph was taken of each patient's knee in maximum passive flexion in the operating room immediately following closure. Patients were randomized to the control or photograph group before incision. A linear mixed model was implemented to determine whether the TSK score and viewing the photo correlated to ROM.Seventy-nine patients were analyzed for correlation between the TSK score and the knee ROM. Sixty patients were analyzed for correlation between viewing the clinical photograph and the knee ROM. The linear mixed model demonstrated a significant negative correlation between the TSK score and both active (β = -0.47, P.01) and passive (β = -0.66, P.001) knee flexions. There was a trend toward decreased knee flexion among patients shown their clinical photograph.The TSK was developed as a tool to identify patients at risk for maladaptive responses to painful stimuli. Our data suggest that the TSK may help arthroplasty surgeons identify patients at risk for decreased ROM after TKA. Showing patients a clinical photograph failed to increase ROM after TKA.

[PdCl{P(OC6H4NMe)2}{P(OC6H4NMe)OC6H4NHMe}] was prepared by the reaction of LiP(OC6H4N(CH3))2 with [PdCl2{P(OC6H4N(CH3))(OC6H4NH(CH3))}]. The expected four diastereomers of the complex are observed in the 31P{1H} and 1H NMR at −20 °C, however at room temperature there is fast exchange between pairs of diastereomers. The energetics of three possible mechanisms by which the diastereomers may be interconverting, are considered by DFT studies: displacement of the coordinated amine, followed by inversion at the nitrogen atom; displacement of the coordinated phosphoramidite, followed by inversion at the phosphorus atom; Berry pseudorotation at the coordinated phosphoranide. The inversion of a dissociated amine appears to be the most likely mechanism.

A lumped-element equivalent circuit model (ECM) for a short length of microstrip transmission line incorporating a microfluidic channel filled with dielectric fluid is proposed. With this model, advanced microstrip circuits containing microfluidic channels can be designed in a fast and accurate manner. For verification, an ECM is extracted for a l-mm length of $50\,\Omega $ transmission line on a 1.5-mm thick substrate with $\epsilon _{r}=3.55$ that has a 0.5-mm long $\times\,0.5$-mm tall $\times\,6.9$-mm wide microfluidic channel underneath it filled with a dielectric fluid of $\epsilon _{r} = 81.$ The model parameter values are extracted using the structure’s two-port S-parameter response obtained through full-wave 3D electromagnetic simulation. The extracted ECM is then used to design a fluidic phase shifter.

Background: Microscopic parasite detection during the course of treatment or follow-up suggests that a proportion of ACT treated children in Kenya do not completely clear Plasmodium falciparum parasitemia. Plasmodium falciparum mutation in chloroquine resistance transporter gene (Pfcrt76), multidrug resistance gene1 (Pfmdr1), deubiquitinating enzyme gene (Pfcubp-1) and clathrin vesicle associated adapter 2, u subunit encoding gene (Pfap2mu) and multidrug resistant protein 1 gene (Pfmrp1) have been associated with subsequent patent recrudescence after ACT treatment. As there are no validated markers of ACT resistance in Africa to-date, surveillance of changes in these polymorphisms during the course of treatment is useful in establishing their role in ACT treatment outcome. Methods: 118 P. falciparum 2013 to 2015 samples from ACT clinical efficacy studies were genotyped for frequency of drug resistance polymorphisms using sequence analyzers. Each sample was screened at least three to four-time points namely; day zero before start of treatment then days 2 and 3 after initiation of treatment plus the day of subsequent parasitemia by microscopy prior to day 42 for some of the subjects. Sequence analyzers were used to genotype for frequency of drug resistance polymorphisms, Pfmdr1 gene copy number and genetic diversity typing of the 12 microsatellite loci. Genetic diversity of parasite populations across four time-points was determined by analysis of 12 microsatellite loci. Worldwide Antimalarial Resistance Network’s parasite clearance estimator (PCE) was used to determine parasite clearance rates. Results: The new genes Pfap2mu and Pfubp had S145C and E1528D being most polymorphic with prevalence’s of 18% and 19%, respectively Pfmdr1 86,184 and 1246 had significant increase in wild type alleles between day zero and time-points 3 and 4. Microsatellite profile analysis show that the mean number of alleles in all the loci across the 8 populations ranged from 9.250 to 1.000. Poly α was the most polymorphic with 35 alleles. The mean unbiased HE was 0.672 while Shannon diversity index for the 8 populations was ranging between 0.182-0.000, none of the parasite analyzed had matching haplotypes. The mean parasite clearance half-life was 2.63 h (95% confidence interval [CI]) and the median clearance half-life was 2.24 h. The parasite clearance half-life ranged from 1.14-5.05 h. Conclusion: Increased wild-type Pfmdr1 86,184 and 1246 as well as polymorphisms in Pfap2mu and Pfcubp-1 in post day zero suggest that these genes could be responding to ACT dosing and therefore require continued monitoring. Samples with multiple copies of the Pfmdr1 did not indicate show effect on parasite clearance rate. Though there was no correlation between these profiles and clearance rates, further evaluations are needed to determine the potential public health implications of these observations and the utility of these loci as markers of artemisinin sensitivity in populations of P. falciparum worldwide.

The purpose of this study was to test the hypothesis that overstuffing the patellofemoral joint during total knee arthroplasty (TKA) would decrease passive knee flexion and alter patellar kinematics during knee flexion. Ten cadaveric knees were implanted with cruciate-retaining TKAs, and the patellofemoral joint was overstuffed in 2-mm increments with custom-augmented patellar prostheses (+2 mm through +8 mm). Changes to knee flexion, patellar shift, tilt and rotation were measured with an imageless optical-tracking computer navigation system. Knee flexion decreased an average 1.2° with each additional 2 mm of patellar thickness. Compared with control TKA (+0 mm), no significant decrease in knee flexion was detected until the patellofemoral joint was overstuffed with the +8-mm patellar prosthesis. Kinematic tracking data showed significantly greater lateral shift of patella with the +6- and +8-mm prostheses and significantly greater lateral tilt with the +8-mm prosthesis. Overstuffing had no appreciable effect on patellar rotation. Passive knee flexion after TKA is significantly reduced when overstuffing the patellofemoral joint by +8 mm, and patellofemoral kinematics are altered when overstuffing the joint by +6 mm. These results demonstrate the relatively modest effects of patellofemoral overstuffing on knee flexion and patellar tracking kinematics after TKA.

A description of how to use the Mercury software from the CCDC to print 3-dimensional crystal structures that depict the anisotropic displacement parameters, matching the commonly used ellipsoidal depiction used in scientific papers. Details on how to convert a cif file into a 3D printing data file is included in the main paper, and details on the preparation of that data file for printing on a number of different 3D printers is included in the ESI.

Purpose Results of a study comparing the performance of allometric versus consensus guideline–recommended vancomycin dosing in achieving initial trough concentrations within the desired range are reported. Methods A retrospective study was conducted to compare selected outcomes with 2 vancomycin dosing methods: (1) dosing by total body weight, as recommended in current consensus guidelines, and (2) a new empirical vancomycin dosing strategy grounded in allometry (the study of the relationship between body size and physiology). The primary outcome was attainment of an initial vancomycin trough concentration within the target range (10–20 mg/L). Rates of nephrotoxicity associated with the 2 dosing methods were compared. Results Allometric dosing resulted in 77% of the evaluated patient sample ( n = 81) achieving vancomycin trough concentration targets at the initial measurement, as compared with a target attainment rate of 57% ( n = 81) with guideline-recommended dosing ( p = 0.0121); the rate of target attainment in obese patients was also improved with allometric dosing (73% versus 46%, p = 0.0327). Nephrotoxicity rates did not differ significantly between the 2 groups, but a lower rate was observed with allometric versus guideline-based dosing (1.2% versus 7.4%, p = 0.0584). Conclusion In hospitalized adults, allometric vancomycin dosing achieved a higher frequency of initial vancomycin trough concentrations within the target range of 10–20 mg/L, compared with dosing as recommended by consensus guidelines. The difference between methods in the percentage of troughs within the target range was most pronounced in obese patients.

The CH2Cl2/MeOH (1:1) extract of the aerial parts of Tephrosia subtriflora afforded a new flavanonol, named subtriflavanonol (1), along with the known flavanone spinoflavanone B, and the known flavanonols MS-II (2) and mundulinol. The structures were elucidated by the use of NMR spectroscopy and mass spectrometry. The absolute configuration of the flavanonols was determined based on quantum chemical ECD calculations. In the antiplasmodial assay, compound 2 showed the highest activity against chloroquine-sensitive Plasmodium falciparum reference clones (D6 and 3D7), artemisinin-sensitive isolate (F32-TEM) as well as field isolate (KSM 009) with IC50 values 1.4–4.6 μM without significant cytotoxicity against Vero and HEp2 cell lines (IC50 > 100 μM). The new compound (1) showed weak antiplasmodial activity, IC50 12.5–24.2 μM, but also showed selective anticancer activity against HEp2 cell line (CC50 16.9 μM).

Rust of soybean, caused by Phakopsora pachyrhizi, was first reported in the southeastern US in 2004 where it quickly became established. Yield losses ranged from 35% to more than 80%. The mycophilic fungus Simplicillium lanosoniveum was previously shown to colonize rust pustules on soybean leaves and prevent germination of urediniospores. The number of pustules on soybean leaves also was significantly reduced when S. lanosoniveum colonized leaves. This study examined the antagonistic interactions between P. pachyrhizi and S. lanosoniveum using confocal, transmission (TEM) and scanning electron microscopy (SEM) in order to determine if S. lanosoniveum was mycoparasitic. Co-inoculated detached soybean leaves were examined using TEM and SEM to examine changes in urediniospores colonized by S. lanosoniveum. An isolate of S. lanosoniveum, previously shown to be an antagonist of P. pachyrhizi, was transformed with the green fluorescent protein (GFP) gene and used to document the infection process using confocal microscopy. S. lanosoniveum colonized pustules and coiled around urediniospores before infection. The mycoparasite penetrated urediniospores through germ pores within 24 h after inoculation, at which time organelles showed signs of degradation. By 2 days after inoculation, there was extensive colonization of urediniospores by hyphae of S. lanosoniveum. Hyphae of the mycoparasite erupted from the colonized urediniospores at 7 days after inoculation, and there was extensive sporulation on the surface of urediniospores. Over 90% of urediniospores were colonized within 5 days after inoculation with the mycoparasite. We showed in previous studies that S. lanosoniveum is an antagonist of P. pachyrhizi as well as an effective biocontrol agent, but we were unable to document its mode of action. We now present microscopic evidence that S. lanosoniveum is a mycoparasite.

The synthesis and characterisation of a series of new actinide(IV) complexes supported by the mixed-donor amido–amino–siloxo framework [RN(Li)SiMe2N(R)SiMe2OLi] ([RNNO]Li2; R = 2,4,6-Me3Ph, 2,6-iPr2Ph) are presented. The reaction of 1 equiv. of [RNNO]Li2 with ThCl4·2DME (DME = 1,2-dimethoxyethane) in DME generated {Li·nDME}{[RNNO]2Th2Cl5} (1: R = 2,4,6-Me3Ph, n = 2; 2: R = 2,6-iPr2Ph, n = 3) in high yield, and the addition of [NNO]Li2 to UCl4 in tetrahydrofuran (THF) resulted in the formation of {[NNO]UCl3Li·THF}2 (3). The structures of 1–3 indicate that they retain LiCl as “ate” complexes. The addition of 2 equiv. of [NNO]Li2 to ThCl4·2DME and UCl4 gives the bis-ligated complexes [NNO]2ThClLi (4) and [NNO]2U (5), respectively. In 1–5, the [RNNO]2– ligands all coordinate through the amido and siloxo donors as well as the ipso carbon atom of the phenyl group of the amido ligand but not through the central amino group. Complex 3 can be alkylated through the addition of 2 equiv. of LiCH2SiMe3 to give [NNO]U(CH2SiMe3)2 (6) or NaCp (Cp = cyclopentadienyl) to give [NNO]UCp2 (7); the latter has been structurally characterised.

Background Patients who undergo allogeneic hematopoietic stem cell transplantation (alloHSCT) are at increased risk for invasive fungal infections with associated high morbidity and mortality that necessitates the use of prophylactic antifungals. Voriconazole is commonly used for prophylaxis, but there are no recommendations for therapeutic drug monitoring. The purpose of this study was to characterize voriconazole therapeutic drug monitoring and associated outcomes in this patient population. Methods AlloHSCT patients receiving voriconazole prophylaxis at the University of Alabama at Birmingham Hospital between March 2015 and March 2018 were included in the analysis. Serum voriconazole levels (SVL) were evaluated to determine what percentage of patients achieved prophylactic or therapeutic concentrations. Incidence of invasive fungal infections (IFI) and voriconazole discontinuation was also assessed. Results Voriconazole prophylaxis was used in 151 of 162 alloHSCT patients, and 120 patients (79%) had SVL drawn correctly (≥4 days after initiation of course). We found that 35 (29%) patients achieved a subtherapeutic level ( Conclusion Even though approximately one-third of patients achieved a subtherapeutic SVL, there was no correlation with breakthrough IFI. There was also no linear correlation between SVL and risk of adverse effects requiring discontinuation. Our observational data do not support a need for therapeutic drug monitoring in alloHSCT patients receiving prophylactic voriconazole. Disclosures All authors: No reported disclosures.

The new N,C-chelate boron compounds B(2-phenylazolyl)Mes2 [Mes = mesityl; azolyl = benzothiazolyl (1a), 4-methylthiazolyl (2a), benzoxazolyl (3a), benzimidazolyl (4a)] undergo an unprecedented multistructural transformation upon light irradiation or heating, sequentially producing isomers b, c, d, and e. The dark isomers b generated by photoisomerization of a undergo a rare thermal intramolecular H-atom transfer (HAT), reducing the azole ring and generating new isomers c, which are further transformed into isomers d. Remarkably, isomers d can be converted to their diastereomers e quantitatively by heating, and e can be converted back to d by irradiation at 300 nm. The structures of isomers 1d and 1e were established by X-ray diffraction. The unusual HAT reactivity can be attributed to the geometry of the highly energetic isomers b and the relatively low aromaticity of the azole rings. The boryl unit plays a key role in the reversible interconversion of d and e, as shown by mechanistic pathways established through DFT and TD-DFT calculations.

Stiffness and loss of motion following total knee arthroplasty (TKA) is a complex and multifactorial complication that may require manipulation under anesthesia (MUA). However, patient and surgical factors that potentially influence the development of knee stiffness following TKA are not fully understood. The purpose of this study was to identify patient and surgical factors that may influence range of motion loss following TKA by assessing a cohort of patients that underwent MUA and comparing them to a matched cohort of patients without complications.The joints registry was searched for patients who underwent MUA following primary TKA between 2004 and 2013. Demographic and surgical information was obtained from the electronic medical record including range of motion (ROM), comorbidities and timing of MUA. Patients who underwent MUA were then double-matched by baseline (prior to primary TKA) knee ROM to patients who underwent primary TKA with normal postoperative range of motion recovery during the same time period.Fifty-two patients (fifty-six knees) (66% female, mean BMI 32.4 kg/m2) underwent MUA after TKA during the study period. MUA was performed a mean of 13.6 weeks after primary TKA. Study patients were double-matched by baseline flexion (mean 107º±2º) to 111 patients (112 knees) with a similar mean baseline flexion (104º±2º, p=0.138). Patients requiring MUA were younger (mean age 56 vs. 64 years, p0.001), had more comorbidities (5 vs. 3, p0.001), and a higher number of previous knee surgeries (56% vs. 21%, p0.001) compared with controls. The risk for requiring MUA following primary TKA was significantly higher (2.4, p0.001) in patients with previous knee surgery (arthroscopy for meniscal pathology, ACL reconstruction, osteotomies). Tourniquet time, length of stay, number of physical therapy sessions, blood loss50 mL, and any complication during the hospital stay were not found to be associated with an increased risk of requiring MUA.Younger patients with more comorbidities and a history of previous knee surgery were found to have significantly higher risk for developing stiffness and loss of motion requiring MUA after primary TKA in the current study. Patients with this risk profile need to be counseled regarding the risk for postoperative knee stiffness and range of motion loss possibly requiring MUA after primary TKA.

Pentagonal bipyramidal uranyl complexes of salen ligands, N,N’-bis(3-tert-butyl-(5R)-salicylidene)-1,2-phenylenediamine, in which R = tBu (1a), OMe (1b), and NMe2 (1c), were prepared and the electronic structure of the one-electron oxidized species [1a-c]+ were investigated in solution. The solid-state structures of 1a and 1b were solved by X-ray crystallography, and in the case of 1b an asymmetric UO22+ unit was found due to an intermolecular hydrogen bonding interaction. Electrochemical investigation of 1a-c by cyclic voltammetry showed that each complex exhibited at least one quasi-reversible redox process assigned to the oxidation of the phenolate moieties to phenoxyl radicals. The trend in redox potentials matches the electron-donating ability of the para-phenolate substituents. The electron paramagnetic resonance spectra of cations [1a-c]+ exhibited gav values of 1.997, 1.999, and 1.995, respectively, reflecting the ligand radical character of the oxidized forms, and in addition, spin-orbit coupling to the uranium centre. Chemical oxidation as monitored by ultraviolet-visible-near-infrared (UV-vis-NIR) spectroscopy afforded the one-electron oxidized species. Weak low energy intra-ligand charge transfer (CT) transitions were observed for [1a-c]+ indicating localization of the ligand radical to form a phenolate / phenoxyl radical species. Further analysis using density functional theory (DFT) calculations predicted a localized phenoxyl radical for [1a-c]+ with a small but significant contribution of the phenylenediamine unit to the spin density. Time-dependent DFT (TD-DFT) calculations provided further insight into the nature of the low energy transitions, predicting both phenolate to phenoxyl intervalence charge transfer (IVCT) and phenylenediamine to phenoxyl CT character. Overall, [1a-c]+ are determined to be relatively localized ligand radical complexes, in which localization is enhanced as the electron donating ability of the para-phenolate substituents is increased (NMe2 > OMe > tBu).

Our first generation CRTH2 and DP dual antagonists, represented by AMG 009, are more potent toward the CRTH2 receptor than to the DP receptor. Here we report our efforts in the discovery of CRTH2 and DP dual antagonists with more balanced potencies to both receptors, such as compound 15.