The Relationship of Cup Inclination and Anteversion in the Coronal Plane with Ante-Inclination in the Sagittal Plane: Exposing the Fallacy of Cup Safe Zones.

Background: This study aimed to establish an equation for calculating cup ante-inclination (AI) from radiographic cup inclination and anteversion, to validate this equation in a total hip arthroplasty (THA) cohort, and to test whether achieving previously described radiographic cup inclination and anteversion targets would also satisfy sagittal cup AI targets. Methods: A mathematical equation linking cup AI, radiographic inclination (RI), and anteversion (RA) was determined: tan(AI) = tan(RA)/cos(RI). Supine and standing anteroposterior and lateral radiographs of 440 consecutive THAs were assessed to measure cup RI and RA and spinopelvic parameters, including cup AI, using a validated software tool. Whether orientation within previously defined RI and RA targets was associated with achieving the AI target and satisfying the sagittal component orientation (combined sagittal index, 205° to 245°) was tested. Results: The cups in the THA cohort had a measured mean inclination (and standard deviation) of 43° ± 7°, anteversion of 26° ± 9°, and AI of 34° ± 10°. The calculated cup AI was 34° ± 12°. A strong correlation existed between measured and calculated AI (r = 0.75; p < 0.001), with a mean error of 0° ± 8°. The inclination and anteversion targets were both satisfied in 194 (44.1%) to 330 (75.0%) of the cases, depending on the safe zone targets that were used, and 311 cases (70.7%) satisfied the AI target. Only 125 (28.4%) to 233 (53.0%) of the cases satisfied the AI target as well as the inclination and anteversion targets. Satisfying inclination and anteversion targets was not associated with increased chances of satisfying the AI target. Conclusions: Achieving optimal cup inclination and anteversion does not ensure optimal orientation in the sagittal plane. The equation and nomograms provided can be used to determine and visualize how the 2 planes used for evaluating the cup orientation and the pertinent angles relate, potentially aiding in preoperative planning.

Rising incidence of acute total hip arthroplasty for primary and adjunctive treatment of acetabular fracture in older and middle-aged adults.

BACKGROUND: Acute total hip arthroplasty (THA) may be an alternative or an adjuvant to internal fixation for surgical treatment of acetabular fractures. We investigate recent trends in the operative management of acetabular fractures. We hypothesize that the incidence of acute THA for acetabular fractures has increased over time. METHODS: 4569 middle-aged (45-64 years) and older adults (≥ 65 years) who received acute operative management of an acetabular fracture within 3 weeks of admission between 2010 and 2020 were identified from the United States Nationwide Inpatient Sample database. Treatment was classified as open reduction internal fixation (ORIF), THA, or combined ORIF and THA (ORIF + THA). Patients were stratified by age ≥ 65 years old. Associations between demographic factors and the incidence of each procedure over the study period were modeled using linear regression. RESULTS: The relative incidence of treatments was 80.9% ORIF, 12.1% THA, and 7.0% ORIF + THA. Among patients aged 45-64 years old, THA increased 4.8% [R2 = 0.62; ß1 = 0.6% (95% Confidence Interval (CI) 0.2-0.9%)] and ORIF + THA increased 2.6% [R2 = 0.73; ß1 = 0.3% (95% CI 0.2-0.4%)], while the use of ORIF decreased 7.4% [R2 = 0.75; ß1 = -0.9% (95% CI -1.2 to -0.5%)]. Among patients ≥ 65 years old, THA increased 16.5% [R2 = 0.87; ß1 = 1.7% (95% CI 1.2-2.2%)] and ORIF + THA increased 5.0% [R2 = 0.38, ß1 = 0.6% (95% CI 0.0-1.3%)], while ORIF decreased 21.5% [R2 = 0.75; ß1 = -2.4% (95% CI -3.45 to -1.3%)]. CONCLUSION: The treatment of acetabular fractures with acute THA has increased in the last decade, particularly among older adults.

Accuracy of digital templating in uncemented primary total hip arthroplasty: which factors are associated with accuracy of preoperative planning?

BACKGROUND: Preoperative planning is a fundamental step for successful total hip arthroplasty (THA). Studies have highlighted the accuracy of preoperative digital templating for estimating acetabular cup and stem size. Stem design such as single-wedge metadiaphyseal (Type 1 stem) versus mid-short stem (microplasty) and surgical approach (anterior, direct lateral or posterior) have not been well investigated as predictors of THA templating accuracy. METHODS: 204 patients (220 hips) who had undergone elective THA between November 2016 and December 2019 and presented a saved preoperative template were retrospectively reviewed. Templates from 5 different surgeons were involved in the analysis. 3 different approaches were used: direct lateral (DL), posterior (PA), direct anterior (DAA). 2 different stem designs were used: single-wedge metadiaphyseal and single-wedge mid-short (Biomet Taperloc Microplasty), while the acetabular component remained the same. Bivariate and multivariate regression analyses were performed to determine predictors of accuracy. RESULTS: Femoral component size templating accuracy was significantly improved when using the single-wedge mid-short stem (Taperloc Microplasty) design when performing bivariate analysis. Although accuracy of cup sizing was not affected by approach, precision was significantly better in the PA group (p < 0.05). Accuracy of templating was found to be independent of BMI and gender but dependent on presence of calibration marker and stem design (p < 0.05). CONCLUSIONS: When striving for improved templating accuracy, acetabular and femoral component accuracy were best achieved using a calibration marker and a metaphyseal short femoral stem design.

Open Reduction Internal Fixation Versus Distal Femoral Replacement (DFR) for Treatment of OTA/AO 33C Fractures in the Elderly: A Review of Functional Outcomes and Cost Analysis.

OBJECTIVES: To determine the economic cost associated with the treatment of OTA/AO 33C fractures in patients older than 65 years of age using open reduction internal fixation (ORIF) or DFR and to assess the perioperative outcomes of elderly patients treated surgically following OTA/AO 33C fractures. DESIGN: Retrospective cohort over a 10-year period. SETTING: A single level-1 trauma center. PARTICIPANTS AND INTERVENTION: Thirty-nine patients 65 or older with OTA/AO 33C fractures who underwent treatment with ORIF (n = 27) or DFR (n = 12) were included. MAIN OUTCOME MEASUREMENTS: Direct cost associated with surgical treatment along with LOS, functional outcomes, patient-reported outcomes, and all-cause reoperation. RESULTS: Index procedure costs were as follows: DFR: $ 61,259 vs. ORIF: $44,490 (P = 0.056). Five (20%) ORIF patients required revision versus one (8%) in the DFR group. Total cost when including reoperation resulted in DFR being $14,805 more costly, which was not significant. Hospital LOS was similar between groups; however, convalescent LOS was longer in ORIF patients (43.2 vs. 23.1 days, P = 0.02). CONCLUSION: This study demonstrates that there is no significant difference in overall cost between ORIF and DFR when all costs are considered. A larger portion of DFR patients were able to mobilize postoperatively, with subacute length of stay being longer in ORIF patients. A multicenter trial is warranted to determine optimal treatment for this complex problem. LEVEL OF EVIDENCE: Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Computing the Differences between Asn-X and Gln-X Deamidation and Their Impact on Pharmaceutical and Physiological Proteins: A Theoretical Investigation Using Model Dipeptides.

Protein deamidation is a degradation mechanism that significantly impacts both pharmaceutical and physiological proteins. Deamidation impacts two amino acids, Asn and Gln, where the net neutral residues are converted into their acidic forms. While there are multiple similarities between the reaction mechanisms of the two residues, the impact of Gln deamidation has been noted to be most significant on physiological proteins while Asn deamidation has been linked to both pharmaceutical and physiological proteins. For this purpose, we sought to analyze the thermochemical and kinetic properties of the different reactions of Gln deamidation relative to Asn deamidation. In this study, we mapped the deamidation of Gln-X dipeptides into Glu-X dipeptides using density functional theory (DFT). Full network mapping facilitated the prediction of reaction selectivity between the two primary pathways, as well as between the two products of Gln-X deamidation as a function of solvent dielectric. To achieve this analysis, we studied a total of 77 dipeptide reactions per solvent dielectric (308 total reactions). Modeled at a neutral pH and using quantum chemical and statistical thermodynamic methods, we computed the following values: enthalpy of reaction (ΔHRXN), entropy (ΔSRXN), Gibbs free energy of reaction (ΔGRXN), activation energy (EA), and the Arrhenius preexponential factor (log(A)) for each dipeptide. Additionally, using chemical reaction principles, we generated a database of computed rate coefficients for all possible N-terminus Gln-X deamidation reactions at a neutral pH, predicted the most likely deamidation reaction mechanism for each dipeptide reaction, analyzed our results against our prior study on Asn-X deamidation, and matched our results against qualitative trends previously noted by experimental literature.

Fentanyl Assay Derived from Intermolecular Interaction-Enabled Small Molecule Recognition (iMSR) with Differential Impedance Analysis for Point-of-Care Testing.

Rapid and effective differentiation and quantification of a small molecule drug, such as fentanyl, in bodily fluids are major challenges for diagnosis and personal medication. However, the current toxicology methods used to measure drug concentration and metabolites require laboratory-based testing, which is not an efficient or cost-effective way to treat patients in a timely manner. Here, we show an assay for monitoring fentanyl levels by combining the intermolecular interaction-enabled small molecule recognition (iMSR) with differential impedance analysis of conjugated polymers. The differential interactions with the designed anchor interface were transduced through the perturbance of the electric status of the flexible conducting polymer. This assay showed excellent fentanyl selectivity against common interferences, as well as in variable body fluids through either testing strips or skin patches. Directly using the patient blood, the sensor provided 1%-5% of the average deviation compared to the "gold" standard method LC-MS results in the medically relevant fentanyl range of 20-90 nM. The superior sensing properties, in conjunction with mechanical flexibility and compatibility, enabled point-of-care detection and provided a promising avenue for applications beyond the scope of biomarker detection.

Electronic structure of the ground and excited states of neutral and charged silicon hydrides, SiHx0/+/-, x = 1-4.

The ground and excited electronic states of the titled species are investigated with multi-reference configuration interaction and diffuse basis sets. We found that in addition to the valence orbitals, the inclusion of the 4s, 4p, and especially 3d orbitals (although with minimal population) of silicon in the active space of the reference complete active space self-consistent field wavefunction are necessary for the proper convergence of the calculations. We also demonstrate that the aug-cc-pVTZ basis set provides quite accurate results compared to both larger basis sets and basis set limit results at a lower computational cost. The excited states involve excitations within the 3s and 3p orbitals of silicon (especially for the mono- and di-hydrides), followed by excitations from the Si-H bonding orbitals to either silicon valence or Rydberg (4s, 4p) orbitals. The number of electronic states per energy unit decrease as we add hydrogen atoms, and the first excited state of SiH4 is at 9.0 eV and leads to SiH3 + H. All species have stable ground state structures with all hydrogen atoms bound to silicon, except for SiH4+ and SiH4-. The former dissociates to SiH2+ + H2, while the latter loses an electron or can dissociate forming H2 as well.

Competitive Hydrogen Migration in Silicon Nitride Nanoclusters: Reaction Kinetics Generalized from Supervised Machine Learning.

The rate coefficients for 52 hydrogen shift reactions for silicon nitrides containing up to 6 atoms of silicon and nitrogen have been calculated using the G3//B3LYP composite method and statistical thermodynamics. The overall reaction of substituted acyclic and cyclic silylenes to their respective silene and imine species by a 1,2-hydrogen shift reaction was sorted by three different types of H shift reactions using overall reaction thermodynamics: (1) endothermic H shift between N and Si:, (2) endothermic H shift between Si and Si:, and (3) exothermic H shift between Si and Si:. Endothermic H shift reactions between Si atoms have one dominant activation barrier where the exothermic H shift reaction between Si atoms has two barriers and a stable intermediate. The rate-determining step was determined to be from the intermediate to the substituted silene, and then kinetic parameters for the overall reaction were calculated for the two-step pathway. The single event pre-exponential factors, Ã, and activation energies, Ea, for the three different classes of hydrogen shift reactions of silicon nitrides were computed. The hydrogen shift reaction was explored for acyclic and cyclic monofunctional silicon nitrides, and the type of hydrogen shift reaction gives the most significant influence on the kinetic parameters. Using a supervised machine learning approach, the models for predicting the energy barrier of three different hydrogen shift reactions were generalized and suggested based on selected descriptors.

The SLIM Study: Economic, Energy, and Waste Savings Through Lowering of Instrumentation Mass in Total Hip Arthroplasty.

BACKGROUND: Nearly 700,000 total hip arthroplasties (THAs) are annually performed in North America, costing the healthcare system >$15 billion and creating over 5 million tons of waste. This study aims to (1) assess satisfaction of current THA setup; (2) determine economic cost, energy cost, and waste cost of current setup and apply lean methodology to improve efficiency; and (3) design and test "Savings through Lowering of Instrumentation Mass (SLIM) setup" based on lean principles and its ability to be safely implemented into practice. METHODS: A Needs Assessment Survey was performed. After review and surgeon input, the "SLIM" set was designed, significantly reducing redundancy. Eighty patients were randomized to either Standard or SLIM setup. Operating room time, blood loss, perioperative adverse events and complications, cost/case, instrument weight (kg/case), total waste (kg/case), case setup time, and number of times and number of extra trays required were compared between groups. RESULTS: The SLIM setup was associated with the following savings: Cost = -$408.19/case; Energy = -7.16 kWh/case; Waste = -1.61 kg/case; Trays = -6 (758 kg/case). No differences in operating room time, blood loss, and complication rate were detected (P > .05) between groups. Setup time was significantly shorter with SLIM (P < .05) and extra instrumentation was opened in <5% of cases. CONCLUSION: A more "minimalist approach" to THA can be safely implemented. The SLIM setup is efficient and has been openly accepted by our allied staff. Such setup can lead to 1,610 kg reduction in waste, 7,160 kWh, and $408,190 in savings per 1,000 THAs performed.

Outcome After Open Reduction Internal Fixation of Acetabular Fractures in the Elderly.

OBJECTIVES: (1) Assess outcomes of acetabular open reduction and internal fixation (ORIF) in the elderly, (2) investigate factors influencing outcome, and (3) compare outcomes after low-energy and high-energy mechanisms of injury. DESIGN: Retrospective case series. SETTING: Level 1 trauma center. PATIENTS: Seventy-eight patients older than 60 years (age: 70.1 ± 7.4; 73.1% males). INTERVENTION: ORIF for acetabular fractures. MAIN OUTCOME MEASUREMENTS: Complications, reoperation rates, Oxford Hip Score (OHS), and joint preservation and development of symptomatic osteoarthritis. Cases with osteoarthritis, OHS < 34, and those who required subsequent total hip arthroplasty were considered as poor outcome. RESULTS: At a mean follow-up of 4.3 ± 3.7 years, 11 cases post-ORIF required a total hip arthroplasty. The 7-year joint survival post-ORIF was 80.7 ± 5.7%. Considering poor outcome as failure, the 7-year joint survival was 67.0 ± 8.9%. The grade of reduction was the most significant factor associated with outcome post-ORIF. Female sex (P = 0.03), pre-existing osteoporosis (P = 0.03), low-energy trauma (P = 0.04), and Matta grade (P = 0.002) were associated with poor outcome. Patients with associated both-column fractures were more likely to have nonanatomic reduction (P = 0.008). After low-energy trauma, joint survivorship was 36.6 ± 13.5% at 7 years compared with 75.4 ± 7.4% in the high-energy group when considering poor outcome as an end point (log rank P = 0.006). The cohort's mean OHS was 37.9 ± 9.3 (17-48). CONCLUSIONS: We recommend ORIF whenever an anatomic reduction is feasible. However, achievement and maintenance of anatomic reduction are a challenge in the elderly, specifically in those with low-energy fractures involving both columns, prompting consideration for alternative management strategies. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Minimizing misclassification bias with a model to identify acetabular fractures using health administrative data: A cohort study.

ABSTRACT: Acetabular fractures (AFs) are relatively uncommon thereby limiting their study. Analyses using population-based health administrative data can return erroneous results if case identification is inaccurate ('misclassification bias'). This study measured the impact of an AF prediction model based exclusively on administrative data upon misclassification bias.We applied text analytical methods to all radiology reports over 11 years at a large, tertiary care teaching hospital to identify all AFs. Using clinically-based variable selection techniques, a logistic regression model was created.We identified 728 AFs in 438,098 hospitalizations (15.1 cases/10,000 admissions). The International Classification of Disease, 10th revision (ICD-10) code for AF (S32.4) missed almost half of cases and misclassified more than a quarter (sensitivity 51.2%, positive predictive value 73.0%). The AF model was very accurate (optimism adjusted R2 0.618, c-statistic 0.988, calibration slope 1.06). When model-based expected probabilities were used to determine AF status using bootstrap imputation methods, misclassification bias for AF prevalence and its association with other variables was much lower than with International Classification of Disease, 10th revision S32.4 (median [range] relative difference 1.0% [0%-9.0%] vs 18.0% [5.4%-75.0%]).Lone administrative database diagnostic codes are inadequate to create AF cohorts. The probability of AF can be accurately determined using health administrative data. This probability can be used in bootstrap imputation methods to importantly reduce misclassification bias.

Isolating key reaction energetics and thermodynamic properties during hardwood model lignin pyrolysis.

Computational studies on the pyrolysis of lignin using electronic structure methods have been largely limited to dimeric or trimeric models. In the current work we have modeled a lignin oligomer consisting of 10 syringyl units linked through 9 ß-O-4' bonds. A lignin model of this size is potentially more representative of the polymer in angiosperms; therefore, we used this representative model to examine the behavior of hardwood lignin during the initial steps of pyrolysis. Using this oligomer, the present work aims to determine if and how the reaction enthalpies of bond cleavage vary with positions within the chain. To accomplish this, we utilized a composite method using molecular mechanics based conformational sampling and quantum mechanically based density functional theory (DFT) calculations. Our key results show marked differences in bond dissociation enthalpies (BDE) with the position. In addition, we calculated standard thermodynamic properties, including enthalpy of formation, heat capacity, entropy, and Gibbs free energy for a wide range of temperatures from 25 K to 1000 K. The prediction of these thermodynamic properties and the reaction enthalpies will benefit further computational studies and cross-validation with pyrolysis experiments. Overall, the results demonstrate the utility of a better understanding of lignin pyrolysis for its effective valorization.

Towards thermoneutral hydrogen evolution reaction using noble metal free molybdenum ditelluride/graphene nanocomposites.

The development of efficient electrocatalysts for hydrogen generation is an essential task to meet future energy demand. In recent years, molybdenum ditelluride (MoTe2) has triggered incredible research interests due to intrinsic nontrivial band gap with promising semi-metallic behaviors. In this work, 2D MoTe2 nanosheets have been synthesized uniformly on graphene substrate through ultra-fast microwave-initiated approach, that shows a superior hydrogen evolution in acidic medium with low overpotential (~150 mV), low activation energy (8.4362 ± 1.5413 kJ mol-1), along with a Tafel slope of 94.5 mV/decade. Interestingly, MoTe2/graphene exhibits the enhanced electrocatalytic stability during the long cycling test, resulting an increase in specific surface area of catalyst materials. Moreover, the results from periodic plane-wave density functional theory (DFT) indicate that, the best active sites are the corner of a Mo-atom and a critical bifunctional site comprised of adjacent Mo and Te edge atoms. Furthermore, the corresponding volcano plot reveals the near thermoneutral catalytic activity of MoTe2/graphene for hydrogen generation.

Data-Driven Investigation of Monosilane and Ammonia Co-Pyrolysis to Silicon-Nitride-Based Ceramic Nanomaterials.

With its high strength, high thermal stability, low density, and high electrical resistance, silicon-nitride-based ceramics have been widely used as gate insulating layers, oxidation masks, and passivation layers. Employing SiN nanomaterials in anode applications also improves rate performances and cycling stability of the lithium-ion batteries. However, a fundamental understanding of the SiN synthetic process remains elusive. SiN gas-phase synthesis can be tailored with a comprehensive understanding of the underlying thermodynamics. In comparison to the characterization data available for solid-state SiN materials, high-level theoretical studies on gas-phase materials possessing Si-N bonds and comprehensive investigation of the SiN chemistry, particularly for nanoclusters, are very uncommon. Thus, we performed a theoretical study of Si and SiN alloy acyclic hydrides and polycyclic clusters to predict electronic structures and thermochemistry using quantum chemical calculation and statistical thermodynamics. Electronic properties by way of highest and lowest occupied molecular orbital energy gap and natural bonding orbitals analysis were calculated to explore the influence of elemental composition and geometry on the stability. Our studies provide characteristic data of SiN species for a data-driven approach to map the design space for discovery of novel silicon-nitride-based ceramic materials for advanced electronic and coating applications.

Managing bone loss in open fractures.

Segmental bone loss continues to pose substantial clinical and technical challenges to orthopaedic surgeons. While several surgical options exist for the treatment of these complex patients, there is not a clear consensus or specific guidelines on the optimal management of these injuries as a whole. Many factors must be taken into consideration when planning surgery for these individuals. In order for these techniques to yield optimal results, each injury must be approached in a step-wise and multidisciplinary fashion to ensure that care is taken in bone and wound bed preparation, that soft tissues are healthy and free of contaminants, and that the patient's medical condition has been optimized. Through this article, we will answer relevant questions and discuss common obstacles and challenges encountered with these complex injuries. We will also review the many treatment options available or in development to address this problem.

Tuning Hydrogenated Silicon, Germanium, and SiGe Nanocluster Properties Using Theoretical Calculations and a Machine Learning Approach.

There are limited studies available that predict the properties of hydrogenated silicon-germanium (SiGe) clusters. For this purpose, we conducted a computational study of 46 hydrogenated SiGe clusters (Si xGe yH z, 1 < X + Y ≤ 6) to predict the structural, thermochemical, and electronic properties. The optimized geometries of the Si xGe yH z clusters were investigated using quantum chemical calculations and statistical thermodynamics. The clusters contained 6 to 9 fused Si-Si, Ge-Ge, or Si-Ge bonds, i.e., bonds participating in more than one 3- to 4-membered rings, and different degrees of hydrogenation, i.e., the ratio of hydrogen to Si/Ge atoms varied depending on cluster size and degree of multifunctionality. Our studies have established trends in standard enthalpy of formation, standard entropy, and constant pressure heat capacity as a function of cluster composition and structure. A novel bond additivity correction model for SiGe chemistry was regressed from experimental data on seven acyclic Si/Ge/SiGe species to improve the accuracy of the standard enthalpy of formation predictions. Electronic properties were investigated by analysis of the HOMO-LUMO energy gap to study the effect of elemental composition on the electronic stability of Si xGe yH z clusters. These properties will be discussed in the context of tailored nanomaterials design and generalized using a machine learning approach.

Patient-specific anatomical and functional parameters provide new insights into the pathomechanism of cam FAI.

BACKGROUND: Femoroacetabular impingement (FAI) represents a constellation of anatomical and clinical features, but definitive diagnosis is often difficult. The high prevalence of cam deformity of the femoral head in the asymptomatic population as well as clinical factors leading to the onset of symptoms raises questions as to what other factors increase the risk of cartilage damage and hip pain. QUESTIONS/PURPOSES: The purpose was to identify any differences in anatomical parameters and squat kinematics among symptomatic, asymptomatic, and control individuals and if these parameters can determine individuals at risk of developing symptoms of cam FAI. METHODS: Forty-three participants (n = 43) were recruited and divided into three groups: symptomatic (12), asymptomatic (17), and control (14). Symptomatic participants presented a cam deformity (identified by an elevated alpha angle on CT images), pain symptoms, clinical signs, and were scheduled for surgery. The other recruited volunteers were blinded and unaware whether they had a cam deformity. After the CT data were assessed for an elevated alpha angle, participants with a cam deformity but who did not demonstrate any clinical signs or symptoms were considered asymptomatic, whereas participants without a cam deformity and without clinical signs or symptoms were considered healthy control subjects. For each participant, anatomical CT parameters (axial alpha angle, radial alpha angle, femoral head-neck offset, femoral neck-shaft angle, medial proximal femoral angle, femoral torsion, acetabular version) were evaluated. Functional squat parameters (maximal squat depth, pelvic range of motion) were determined using a motion capture system. A stepwise discriminant function analysis was used to determine which of the parameters were most suitable to classify each participant with their respective subgroup. RESULTS: The symptomatic group showed elevated alpha angles and lower femoral neck-shaft angles, whereas the asymptomatic group showed elevated alpha angles in comparison with the control group. The best discriminating parameters to determine symptoms were radial alpha angle, femoral neck-shaft angle, and pelvic range of motion (p < 0.001). CONCLUSIONS: In the presence of a cam deformity, indications of a decreased femoral neck-shaft angle and reduced pelvic range of motion can identify those at risk of symptomatic FAI.

Distinct patterns of constitutive phosphodiesterase activity in mouse sinoatrial node and atrial myocardium.

Phosphodiesterases (PDEs) are critical regulators of cyclic nucleotides in the heart. In ventricular myocytes, the L-type Ca(2+) current (I(Ca,L)) is a major target of regulation by PDEs, particularly members of the PDE2, PDE3 and PDE4 families. Conversely, much less is known about the roles of PDE2, PDE3 and PDE4 in the regulation of action potential (AP) properties and I(Ca,L) in the sinoatrial node (SAN) and the atrial myocardium, especially in mice. Thus, the purpose of our study was to measure the effects of global PDE inhibition with Isobutyl-1-methylxanthine (IBMX) and selective inhibitors of PDE2, PDE3 and PDE4 on AP properties in isolated mouse SAN and right atrial myocytes. We also measured the effects of these inhibitors on I(Ca,L) in SAN and atrial myocytes in comparison to ventricular myocytes. Our data demonstrate that IBMX markedly increases spontaneous AP frequency in SAN myocytes and AP duration in atrial myocytes. Spontaneous AP firing in SAN myocytes was also increased by the PDE2 inhibitor erythro-9-[2-hydroxy-3-nonyl] adenine (EHNA), the PDE3 inhibitor milrinone (Mil) and the PDE4 inhibitor rolipram (Rol). In contrast, atrial AP duration was increased by EHNA and Rol, but not by Mil. IBMX also potently, and similarly, increased I(Ca,L) in SAN, atrial and ventricular myocytes; however, important differences emerged in terms of which inhibitors could modulate I(Ca,L) in each myocyte type. Consistent with our AP measurements, EHNA, Mil and Rol each increased I(Ca,L) in SAN myocytes. Also, EHNA and Rol, but not Mil, increased atrial I(Ca,L). In complete contrast, no selective PDE inhibitors increased I(Ca,L) in ventricular myocytes when given alone. Thus, our data show that the effects of selective PDE2, PDE3 and PDE4 inhibitors are distinct in the different regions of the myocardium indicating important differences in how each PDE family constitutively regulates ion channel function in the SAN, atrial and ventricular myocardium.

The natriuretic peptides BNP and CNP increase heart rate and electrical conduction by stimulating ionic currents in the sinoatrial node and atrial myocardium following activation of guanylyl cyclase-linked natriuretic peptide receptors.

Natriuretic peptides (NPs) are best known for their ability to regulate blood vessel tone and kidney function whereas their electrophysiological effects on the heart are less clear. Here, we measured the effects of BNP and CNP on sinoatrial node (SAN) and atrial electrophysiology in isolated hearts as well as isolated SAN and right atrial myocytes from mice. BNP and CNP dose-dependently increased heart rate and conduction through the heart as indicated by reductions in R-R interval, P wave duration and P-R interval on ECGs. In conjunction with these ECG changes BNP and CNP (100 nM) increased spontaneous action potential frequency in isolated SAN myocytes by increasing L-type Ca(2+) current (I(Ca,L)) and the hyperpolarization-activated current (I(f)). BNP had no effect on right atrial myocyte APs in basal conditions; however, in the presence of isoproterenol (10nM), BNP increased atrial AP duration and I(Ca,L). Quantitative gene expression and immunocytochemistry data show that all three NP receptors (NPR-A, NPR-B and NPR-C) are expressed in the SAN and atrium. The effects of BNP and CNP on SAN and right atrial myocytes were maintained in mutant mice lacking functional NPR-C receptors and blocked by the NPR-A antagonist A71915 indicating that BNP and CNP function through their guanylyl cyclase-linked receptors. Our data also show that the effects of BNP and CNP are completely absent in the presence of the phosphodiesterase 3 inhibitor milrinone. Based on these data we conclude that NPs can increase heart rate and electrical conduction by activating the guanylyl cyclase-linked NPR-A and NPR-B receptors and inhibiting PDE3 activity.