Corticomuscular cross-recurrence analysis reveals between-limb differences in motor control among individuals with ACL reconstruction.

Surgical reconstruction of the anterior cruciate ligament (ACL) and subsequent physical therapy can help athletes return to competition; however, re-injury rates remain disproportionately high due, in part, to lingering biomechanical and neurological factors that are not fully addressed during rehabilitation. Prior reports indicate that individuals exhibit altered electrical activity in both brain and muscle after ACL reconstruction (ACLR). In this investigation, we aimed to extend existing approaches by introducing a novel non-linear analysis of corticomuscular dynamics, which does not assume oscillatory coupling between brain and muscle: Corticomuscular cross-recurrence analysis (CM-cRQA). Our findings indicate that corticomuscular dynamics vary significantly between involved (injured) and uninvolved legs of participants with ACLR during voluntary isometric contractions between the brain and both the vastus medialis and lateralis. This finding points to a potential lingering neural deficit underlying re-injury for athletes after surgical reconstruction, namely the dynamical structure of neuromuscular (brain to quad muscle) coordination, which is significantly asymmetric, between limbs, in those who have ACLR.

Extension request avoidance predicts greater time stress among women.

In nine studies using archival data, surveys, and experiments, we identify a factor that predicts gender differences in time stress and burnout. Across academic and professional settings, women are less likely to ask for more time when working under adjustable deadlines (studies 1 to 4a). Women's discomfort in asking for more time on adjustable deadlines uniquely predicts time stress and burnout, controlling for marital status, industry, tenure, and delegation preferences (study 1). Women are less likely to ask for more time to complete their tasks because they hold stronger beliefs that they will be penalized for these requests and worry more about burdening others (studies 1 to 2d). We find no evidence that women are judged more harshly than men (study 3). We also document a simple organizational intervention: formal processes for requesting deadline extensions reduce gender differences in asking for more time (studies 4a to 5).

Posterior Shoulder Instability, Part I-Diagnosis, Nonoperative Management, and Labral Repair for Posterior Shoulder Instability-An International Expert Delphi Consensus Statement.

PURPOSE: To establish consensus statements on the diagnosis, nonoperative management, and labral repair for posterior shoulder instability. METHODS: A consensus process on the treatment of posterior shoulder instability was conducted, with 71 shoulder/sports surgeons from 12 countries participating on the basis of their level of expertise in the field. Experts were assigned to 1 of 6 working groups defined by specific subtopics within posterior shoulder instability. Consensus was defined as achieving 80% to 89% agreement, whereas strong consensus was defined as 90% to 99% agreement, and unanimous consensus was indicated by 100% agreement with a proposed statement. RESULTS: Unanimous agreement was reached on the indications for nonoperative management and labral repair, which include whether patients had primary or recurrent instability, with symptoms/functional limitations, and whether there was other underlying pathology, or patient's preference to avoid or delay surgery. In addition, there was unanimous agreement that recurrence rates can be diminished by attention to detail, appropriate indication and assessment of risk factors, recognition of abnormalities in glenohumeral morphology, careful capsulolabral debridement and reattachment, small anchors with inferior placement and multiple fixation points that create a bumper with the labrum, treatment of concomitant pathologies, and a well-defined rehabilitation protocol with strict postoperative immobilization. CONCLUSIONS: The study group achieved strong or unanimous consensus on 63% of statements related to the diagnosis, nonoperative treatment, and labrum repair for posterior shoulder instability. The statements that achieved unanimous consensus were the relative indications for nonoperative management, and the relative indications for labral repair, as well as the steps to minimize complications for labral repair. There was no consensus on whether an arthrogram is needed when performing advanced imaging, the role of corticosteroids/orthobiologics in nonoperative management, whether a posteroinferior portal is required. LEVEL OF EVIDENCE: Level V, expert opinion.

Posterior Shoulder Instability Part II - Glenoid Bone-Grafting, Glenoid Osteotomy, and Rehabilitation/Return to Play - An International Expert Delphi Consensus Statement.

PURPOSE: The purpose of this study was to establish consensus statements on glenoid bone-grafting, glenoid osteotomy, rehabilitation, return to play, and follow-up for posterior shoulder instability. METHODS: A consensus process on the treatment of posterior shoulder instability was conducted, with 71 shoulder/sports surgeons from 12 countries participating based on their level of expertise in the field. Experts were assigned to one of 6 working groups defined by specific subtopics within posterior shoulder instability. Consensus was defined as achieving 80-89% agreement, whereas strong consensus was defined as 90-99% agreement, and unanimous consensus was indicated by 100% agreement with a proposed statement. RESULTS: All of the statements relating to rehabilitation, return to play, and follow-up achieved consensus. There was unanimous consensus that the following criteria should be considered: restoration of strength, range of motion, proprioception, and sport-specific skills, with a lack of symptoms. There is no minimum time point required to return to play. Collision athletes and military athletes may take longer to return because of their higher risk for recurrent instability, and more caution should be exercised in clearing them to return to play, with elite athletes potentially having different considerations in returning to play. The relative indications for revision surgery are symptomatic apprehension, multiple recurrent instability episodes, further intra-articular pathologies, hardware failure, and pain. CONCLUSION: The study group achieved strong or unanimous consensus on 59% of statements. Unanimous consensus was reached regarding the criteria for return to play, collision/elite athletes having different considerations in return to play, indications for revision surgery, and imaging only required as routine for those with glenoid bone-grafting/osteotomies at subsequent follow-ups. There was no consensus on optimal fixation method for a glenoid bone-block, the relative indications for glenoid osteotomy, whether fluoroscopy is required or if the labrum should be concomitantly repaired. LEVEL OF EVIDENCE: Level V Expert Opinion.

Infection in Shoulder Arthroplasty: Prevention, Diagnosis, and Treatment.

Prosthetic joint infection is a devastating complication following shoulder arthroplasty that can lead to pain, poor function, and poor quality of life. With the increasing number of shoulder arthroplasties performed annually, recognition of prosthetic infection and treatment is necessary. The skin surrounding the shoulder has a unique microbiome, and Cutibacterium acnes is the most commonly encountered bacteria causing prosthetic joint infection. C acnes is a low-virulence organism that resides in the subcutaneous layer of the skin. As a result, the clinical presentation is typically less obvious than prosthetic infections seen in other joints such as the hip and knee. Therefore, diagnosis is not always straightforward, and optimal treatment strategy is unclear. Guidance on prevention, diagnosis, and treatment of shoulder prosthetic joint infection with special emphasis on the consensus definition established at the 2018 International Consensus Meeting is provided.

Job satisfaction and practice characteristics of shoulder and elbow surgeons: a survey of American Shoulder and Elbow Surgeons society members.

BACKGROUND: The purpose of this study is to assess the current trends in fellowship training, career satisfaction, practice characteristics, and surgical case volume among shoulder and elbow surgeons. METHODS: A web-based, anonymous 25-item survey was sent to the membership of the American Shoulder and Elbow Surgeons (ASES) in October of 2022. Questions posed included respondent demographics, fellowship training, career satisfaction, practice characteristics, and surgical case characteristics. Descriptive statistics were performed to report demographic information, assess job and training satisfaction rates, and evaluate practice characteristics. Chi-squared and independent samples t-tests were performed to analyze satisfaction rates, job applications, and surgical case volume with regard to years in practice and practice setting. RESULTS: Twenty percent (243/1248) of ASES members satisfactorily completed the survey. Of the 243 ASES member respondents, 97% (236/243) stated that they would pursue their fellowship training again. Ninety-eight percent (239/243) of respondents were satisfied with their specialty choice. One-hundred percent (242/243) were satisfied with their training in shoulder. Seventy-two percent (176/243) were satisfied with their training in elbow. Seventy-four percent (179/243) were satisfied with their job availability and 85% (207/243) were satisfied with their job location. The mean total number of orthopedic surgical cases per year was 393 ± 171. The mean total number of shoulder cases per year was 253 ± 149. The mean total number of elbow cases per year was 41 ± 41. Physicians who have been in practice for 11 years or more were comparatively more satisfied (90% vs. 80%) with their job location (P value = .008) and job availability (81% vs. 64%, P value < .001). Additionally, senior surgeons completed more orthopedic (431 vs. 347, P value < .001) and shoulder (279 vs. 220, P value = .002) cases annually than surgeons earlier in their careers. Satisfaction rates, job applications, and surgical case volume did not associate with practice setting. CONCLUSIONS: The majority of ASES member shoulder and elbow surgeons are satisfied with their training, their case volume and complexity, and their specialty choice. Fewer surgeons are satisfied with their elbow training and overall elbow case volume remains low among shoulder and elbow surgeons. Shoulder and elbow surgeons earlier in their careers perform fewer surgical cases, are less satisfied with their job availability and location, and completed more job applications for their first job after fellowship when compared to more senior surgeons.

How to avoid baseplate failure: the effect of compression and reverse shoulder arthroplasty baseplate design on implant stability.

BACKGROUND: Failure to achieve fixation of the glenoid baseplate will lead to clinical failure. The fixation of the baseplate to the scapula must be able to withstand sufficient shear forces to allow bony ingrowth. The importance of compression to neutralize the forces at the baseplate-bone interface has been assumed to be critical in limiting excessive micromotion. The purpose of this study is to determine the effect of compression on implant stability with different baseplate designs. METHODS: Various baseplate designs (1-piece monolithic central screw [1P], 2-piece locking central screw [2PL], and 2-piece nonlocking center screw [2PNL]) were investigated at 3 different compressive forces (high [810 N], medium [640 N], and low [530 N]). Synthetic bone cylinders were instrumented, and peripheral screws were used in all models. The combination of 1 locking and 3 nonlocking peripheral screw fixation was selected as worst-case scenario. Dynamic testing protocol followed the ASTM F2028-17 standard. The baseplate micromotion at high compression was compared to low compression. Additionally, the baseplate micromotion for each design was compared at baseline (first 50 cycles) and at 10,000 cycles for the 3 different compressive forces where motion above 150 µm was defined as failure. RESULTS: Baseplate micromotion was found to negatively correlate with compression (rpb = -0.83, P < .0001). At baseline, all baseplate designs were considered stable, regardless of compression. With high compression, average micromotion at the glenoid baseplate-bone interface remained below the 150-µm threshold for all baseplate designs at 10,000 cycles (1P: 50 ± 10 µm; 2PL: 78 ± 32 µm; 2PNL: 79 ± 8 µm; P = .060). With medium compression, average micromotion at 10,000 cycles for all 3 designs remained below the 150-µm threshold (1P: 88 ± 22 µm; 2PL: 132 ± 26 µm; 2PNL: 107 ± 39 µm). The 2PL design had the highest amount of micromotion (P = .013). With low compression, both 2-piece designs had an average micromotion above the 150-µm threshold whereas the 1-piece design did not (1P: 133 ± 35 µm; 2PL: 183 ± 21 µm; 2PNL: 166 ± 39 µm). The 2PL design had significantly higher micromotion when compared to 1P design (P = .041). DISCUSSION: The stability of a central screw baseplate correlates with the amount of compression obtained and is affected by implant design. For the same amount of compression, more micromotion is observed in a 2-piece design than a 1-piece design.

How Fellowship Training Affects Complication Rate After Shoulder Arthroplasty: A Nationwide Assessment.

BACKGROUND: Total shoulder arthroplasty is performed by orthopedic surgeons with various fellowship training backgrounds. Whether surgeons performing shoulder arthroplasty with different types of fellowship training have differing rates of complications and reoperation remains unknown. METHODS: The PearlDiver Mariner database was retrospectively queried from the years 2010-2022. Patients undergoing shoulder arthroplasty were selected using the CPT code 23472. Those undergoing revision arthroplasty and those with a history of fracture, infection, or malignancy were excluded. Fellowship was determined and verified via online search. Only surgeons who performed a minimum of 10 cases were selected; and PearlDiver was queried using their provider ID codes. Primary outcome measures included 90-day, 1-year, and 5-year rates of complication and reoperation. A Bonferroni correction was utilized in which the significance threshold was set at p≤0.00023 RESULTS: In total, 150,385 patients met the inclusion criteria and were included in the study. Analysis of surgical trends revealed that Sports Medicine and Shoulder and Elbow fellowship- trained surgeons are performing an increasing percentage of all shoulder arthroplasty over time, with each cohort exhibiting am 11.3% and 4.2% increase from 2010 to 2022, respectively. The geographic region with the highest proportion of cases performed by Sports Medicine surgeons was the West, while the Northeast has the highest proportion of cases performed by Shoulder and Elbow surgeons. Shoulder and Elbow surgeons operated on patients that were significantly younger and had fewer comorbidities. Both Shoulder and Elbow and Sports Medicine surgeons had lower rates of postoperative complications at 90 days, 1 year and 5 years in comparison to surgeons who completed another type of fellowship or no fellowship. Across each time point, the rates of individual complications between Sports Medicine and Shoulder and Elbow were comparable, but the pooled complication rate was lowest in the Shoulder and Elbow cohort. CONCLUSION: Surgeons who have completed either a Sports Medicine or Shoulder and Elbow fellowship are performing an increasing proportion of shoulder arthroplasty over time. Sports Medicine and Shoulder and Elbow-trained surgeons have significantly lower complication rates at 90 days, 1 year and 5 years postoperatively. The individual complication rates between Sports Medicine and Shoulder and Elbow are comparable, but Shoulder and Elbow has the lowest pooled complication rates overall.

3-dimensionally printed patient-specific glenoid drill guides vs. standard nonspecific instrumentation: a randomized controlled trial comparing the accuracy of glenoid component placement in anatomic total shoulder arthroplasty.

BACKGROUND: Traditional, commercially sourced patient-specific instrumentation (PSI) systems for shoulder arthroplasty improve glenoid component placement but can involve considerable cost and outsourcing delays. The purpose of this randomized controlled trial was to compare the accuracy of glenoid component positioning in anatomic total shoulder arthroplasty (aTSA) using an in-house, point-of-care, 3-dimensionally (3D) printed patient-specific glenoid drill guide vs. standard nonspecific instrumentation. METHODS: This single-center randomized controlled trial included 36 adult patients undergoing primary aTSA. Patients were blinded and randomized 1:1 to either the PSI or the standard aTSA guide groups. The primary endpoint was the accuracy of glenoid component placement (version and inclination), which was determined using a metal-suppression computed tomography scan taken between 6 weeks and 1 year postoperatively. Deviation from the preoperative 3D templating plan was calculated for each patient. Blinded postoperative computed tomography measurements were performed by a fellowship-trained shoulder surgeon and a musculoskeletal radiologist. RESULTS: Nineteen patients were randomized to the patient-specific glenoid drill guide group, and 17 patients were allocated to the standard instrumentation control group. There were no significant differences between the 2 groups for native version (P = .527) or inclination (P = .415). The version correction was similar between the 2 groups (P = .551), and the PSI group was significantly more accurate when correcting version than the control group (P = .042). The PSI group required a significantly greater inclination correction than the control group (P = .002); however, the 2 groups still had similar accuracy when correcting inclination (P = .851). For the PSI group, there was no correlation between the accuracy of component placement and native version, native inclination, or the Walch classification of glenoid wear (P > .05). For the control group, accuracy when correcting version was inversely correlated with native version (P = .033), but accuracy was not correlated with native inclination or the Walch classification of glenoid wear (P > .05). The intraclass correlation coefficient was 0.703 and 0.848 when measuring version and inclination accuracy, respectively. CONCLUSION: When compared with standard instrumentation, the use of in-house, 3D printed, patient-specific glenoid drill guides during aTSA led to more accurate glenoid component version correction and similarly accurate inclination correction. Additional research should examine the influence of proper component position and use of PSI on clinical outcomes.

Artificial intelligence in shoulder and elbow surgery: overview of current and future applications.

Artificial intelligence (AI) is amongst the most rapidly growing technologies in orthopedic surgery. With the exponential growth in healthcare data, computing power, and complex predictive algorithms, this technology is poised to aid providers in data processing and clinical decision support throughout the continuum of orthopedic care. Understanding the utility and limitations of this technology is vital to practicing orthopedic surgeons, as these applications will become more common place in everyday practice. AI has already demonstrated its utility in shoulder and elbow surgery for imaging-based diagnosis, predictive modeling of clinical outcomes, implant identification, and automated image segmentation. The future integration of AI and robotic surgery represents the largest potential application of AI in shoulder and elbow surgery with the potential for significant clinical and financial impact. This editorial's purpose is to summarize common AI terms, provide a framework to understand and interpret AI model results, and discuss current applications and future directions within shoulder and elbow surgery.

Predictors of dislocations after reverse shoulder arthroplasty: a study by the ASES complications of RSA multicenter research group.

BACKGROUND: Instability after reverse shoulder arthroplasty (RSA) is one of the most frequent complications and remains a clinical challenge. Current evidence is limited by small sample size, single-center, or single-implant methodologies that limit generalizability. We sought to determine the incidence and patient-related risk factors for dislocation after RSA, using a large, multicenter cohort with varying implants. METHODS: A retrospective, multicenter study was performed involving 15 institutions and 24 American Shoulder and Elbow Surgeons members across the United States. Inclusion criteria consisted of patients undergoing primary or revision RSA between January 2013 and June 2019 with minimum 3-month follow-up. All definitions, inclusion criteria, and collected variables were determined using the Delphi method, an iterative survey process involving all primary investigators requiring at least 75% consensus to be considered a final component of the methodology for each study element. Dislocations were defined as complete loss of articulation between the humeral component and the glenosphere and required radiographic confirmation. Binary logistic regression was performed to determine patient predictors of postoperative dislocation after RSA. RESULTS: We identified 6621 patients who met inclusion criteria with a mean follow-up of 19.4 months (range: 3-84 months). The study population was 40% male with an average age of 71.0 years (range: 23-101 years). The rate of dislocation was 2.1% (n = 138) for the whole cohort, 1.6% (n = 99) for primary RSAs, and 6.5% (n = 39) for revision RSAs (P < .001). Dislocations occurred at a median of 7.0 weeks (interquartile range: 3.0-36.0 weeks) after surgery with 23.0% (n = 32) after a trauma. Patients with a primary diagnosis of glenohumeral osteoarthritis with an intact rotator cuff had an overall lower rate of dislocation than patients with other diagnoses (0.8% vs. 2.5%; P < .001). Patient-related factors independently predictive of dislocation, in order of the magnitude of effect, were a history of postoperative subluxations before radiographically confirmed dislocation (odds ratio [OR]: 19.52, P < .001), primary diagnosis of fracture nonunion (OR: 6.53, P < .001), revision arthroplasty (OR: 5.61, P < .001), primary diagnosis of rotator cuff disease (OR: 2.64, P < .001), male sex (OR: 2.21, P < .001), and no subscapularis repair at surgery (OR: 1.95, P = .001). CONCLUSION: The strongest patient-related factors associated with dislocation were a history of postoperative subluxations and having a primary diagnosis of fracture nonunion. Notably, RSAs for osteoarthritis showed lower rates of dislocations than RSAs for rotator cuff disease. These data can be used to optimize patient counseling before RSA, particularly in male patients undergoing revision RSA.

Electrochemical Imaging of Precisely-Defined Redox and Reactive Interfaces.

Understanding the diverse electrochemical reactions occurring at electrode-electrolyte interfaces (EEIs) is a critical challenge to developing more efficient energy conversion and storage technologies. Establishing a predictive molecular-level understanding of solid electrolyte interphases (SEIs) is challenging due to the presence of multiple intertwined chemical and electrochemical processes occurring at battery electrodes. Similarly, chemical conversions in reactive electrochemical systems are often influenced by the heterogeneous distribution of active sites, surface defects, and catalyst particle sizes. In this mini review, we highlight an emerging field of interfacial science that isolates the impact of specific chemical species by preparing precisely-defined EEIs and visualizing the reactivity of their individual components using single-entity characterization techniques. We highlight the broad applicability and versatility of these methods, along with current state-of-the-art instrumentation and future opportunities for these approaches to address key scientific challenges related to batteries, chemical separations, and fuel cells. We establish that controlled preparation of well-defined electrodes combined with single entity characterization will be crucial to filling key knowledge gaps and advancing the theories used to describe and predict chemical and physical processes occurring at EEIs and accelerating new materials discovery for energy applications.

Dimensionality and Modularity of Adaptive Variation: Divergence in Threespine Stickleback from Diverse Environments.

AbstractPopulations are subjected to diverse environmental conditions that affect fitness and induce evolutionary or plastic responses, resulting in phenotypic divergence. Some authors contend that such divergence is concentrated along a single major axis of trait covariance even if that axis does not lead populations directly toward a fitness optimum. Other authors argue that divergence can occur readily along many phenotype axes at the same time. We use populations of threespine stickleback (Gasterosteus aculeatus) from 14 lakes with contrasting ecological conditions to find some resolution along the continuum between these two extremes. Unlike many previous studies, we included several functional suites of traits (defensive, swimming, trophic) potentially subject to different sources of selection. We find that populations exhibit dimensionality of divergence that is high enough to preclude a history of constraint along a single axis-both for divergence in multivariate mean trait values and for the structure of trait covariances. Dimensionality varied among trait suites and were strongly influenced by the inclusion of specific traits, and integration of trait suites varied between populations. We leverage this variation into new insights about the process of divergence and suggest that similar analyses could increase understanding of other adaptive radiations.

Paternal Medications in Inflammatory Bowel Disease and Male Fertility and Reproductive Outcomes: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Studies evaluating reproductive outcomes among male patients with inflammatory bowel disease (IBD) are limited. We evaluated use of IBD medications and association with semen parameters, a proxy of male fertility, and adverse pregnancy outcomes (early pregnancy loss [EPL], preterm birth [PB], congenital malformations [CM]). METHODS: We searched Medline, Embase, Scopus, and Web of Science (PROSPERO CRD42020197098) from inception to April 2022 for studies reporting semen parameters and adverse pregnancy outcomes among male patients exposed to biologics, thiopurine, or methotrexate. Standardized mean difference, prevalence, and odds ratios (ORs) of outcomes were pooled and analyzed using a random effects model. RESULTS: Ten studies reporting semen parameters (268 patients with IBD) and 16 studies reporting adverse pregnancy outcomes (over 25,000 patients with IBD) were included. Biologic, thiopurine, or methotrexate use were not associated with decreased sperm count, motility, or abnormal morphology compared with nonexposed patients. The prevalence of adverse pregnancy outcomes with paternal biologic (5%), thiopurine (6%), or methotrexate (6%) exposure was comparable to nonexposed patients (5%). Biologic use was not associated with risk of EPL (OR, 1.26; I2 = 0%; P = .12), PB (OR, 1.10; I2 = 0%; P = .17), or CM (OR, 1.03; I2 = 0%; P = .69). Thiopurine use was not associated with risk of EPL (OR, 1.31; I2 = 19%; P = .17), PB (OR, 1.05; I2 = 0%; P = .20), or CM (OR, 1.07; I2 = 7%; P = .34). Methotrexate use was not associated with risk of PB (OR, 1.06; I2 = 0%; P = .62) or CM (OR, 1.03; I2 = 0%; P = .81). CONCLUSIONS: Biologic, thiopurine, or methotrexate use among male patients with IBD are not associated with impairments in fertility or with increased odds of adverse pregnancy outcomes.

Gene therapy for hemophilia B using CB 2679d-GT: a novel factor IX variant with higher potency than factor IX Padua.

Sustained expression of therapeutic factor IX (FIX) levels has been achieved after adeno-associated viral (AAV) vector-based gene therapy in patients with hemophilia B. Nevertheless, patients are still at risk of vector dose-limiting toxicity, particularly liver inflammation, justifying the need for more efficient vectors and a lower dosing regimen. A novel increased potency FIX (designated as CB 2679d-GT), containing 3 amino acid substitutions (R318Y, R338E, T343R), significantly outperformed the R338L-Padua variant after gene therapy. CB 2679d-GT demonstrated a statistically significant approximately threefold improvement in clotting activity when compared with R338L-Padua after AAV-based gene therapy in hemophilic mice. Moreover, CB 2679d-GT gene therapy showed significantly reduced bleeding time (approximately fivefold to eightfold) and total blood loss volume (approximately fourfold) compared with mice treated with the R338L-Padua, thus achieving more rapid and robust hemostatic correction. FIX expression was sustained for at least 20 weeks with both CB 2679d-GT and R338L-Padua whereas immunogenicity was not significantly increased. This is a novel gene therapy study demonstrating the superiority of CB 2679d-GT, highlighting its potential to obtain higher FIX activity levels and superior hemostatic efficacy following AAV-directed gene therapy in hemophilia B patients than what is currently achievable with the R338L-Padua variant.

Apomorphine for Parkinson's disease: pharmacologic and clinical considerations.

INTRODUCTION: In Parkinson's disease, dopamine depletion in the basal ganglia leads to symptoms including bradykinesia, gait abnormalities, and cognitive impairment. Even with treatment, the disease course leads to decreases in the amount of dopamine produced and released into the synapse. As dopamine production falls and the treatment course is insufficient to match the metabolic supply and demand, acute 'off' periods develop that cause reemergence of symptoms. Apomorphine is used to reverse these 'off' periods and restore function in patients with Parkinson's. This review will provide clinicians a concise article to read to learn more about apomorphine and its appropriate utilization. AREAS COVERED: The research discussed is focused on the history, pharmacokinetics, and mechanism of action of Apomorphine. Its utilization as a treatment for Parkinson's Disease and its comparison to currently utilized drugs is also discussed in this review. We focused on articles published on PubMed and Google Scholar within the last 10 years, but in some instances had to go as far back as 1951 to include early articles published about apomorphine. EXPERT OPINION: The expert opinion section focuses on the ways in which apomorphine could be administered in the future to better promote utilization and increase tolerability.

Rheology of oligomer melts in the nematic and isotropic states.

Oligomers prepared by chain extension of liquid crystalline monomers are thermotropic. The alignment of liquid crystalline oligomers to shear flow via direct ink write printing is an increasingly popular approach to prepare aligned and 3-D printed liquid crystalline elastomers (LCEs). Here, we are concerned with the contribution of order and thermal history on the rheological properties of liquid crystalline. When the oligomers begin in a polydomain nematic state, the transition to an aligned nematic state occurs gradually over a wide range of shear rates. Conversely, when the oligomers begin in an isotropic state they behave as a Newtonian fluid until a critical shear rate is reached, at which point they align in a critical manner. It is shown that by either decreasing liquid crystalline content or increasing temperature, the viscosity of the oligomer melt decreases while this critical shear rate increases. In addition, the normal stress of oligomers is positive over all shear rates but decreases significantly in magnitude with increasing temperature. By combining the analysis of both temperature and liquid crystalline content, it is demonstrated that the temperature relative to the nematic-isotropic transition temperature is key to the oligomers' unique flow behaviors.

Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthesis.

The ancient UbiB protein kinase-like family is involved in isoprenoid lipid biosynthesis and is implicated in human diseases, but demonstration of UbiB kinase activity has remained elusive for unknown reasons. Here, we quantitatively define UbiB-specific sequence motifs and reveal their positions within the crystal structure of a UbiB protein, ADCK3. We find that multiple UbiB-specific features are poised to inhibit protein kinase activity, including an N-terminal domain that occupies the typical substrate binding pocket and a unique A-rich loop that limits ATP binding by establishing an unusual selectivity for ADP. A single alanine-to-glycine mutation of this loop flips this coenzyme selectivity and enables autophosphorylation but inhibits coenzyme Q biosynthesis in vivo, demonstrating functional relevance for this unique feature. Our work provides mechanistic insight into UbiB enzyme activity and establishes a molecular foundation for further investigation of how UbiB family proteins affect diseases and diverse biological pathways.

Direct functionalization of C-H bonds by electrophilic anions.

Alkanes and [B12X12]2- (X = Cl, Br) are both stable compounds which are difficult to functionalize. Here we demonstrate the formation of a boron-carbon bond between these substances in a two-step process. Fragmentation of [B12X12]2- in the gas phase generates highly reactive [B12X11]- ions which spontaneously react with alkanes. The reaction mechanism was investigated using tandem mass spectrometry and gas-phase vibrational spectroscopy combined with electronic structure calculations. [B12X11]- reacts by an electrophilic substitution of a proton in an alkane resulting in a B-C bond formation. The product is a dianionic [B12X11CnH2n+1]2- species, to which H+ is electrostatically bound. High-flux ion soft landing was performed to codeposit [B12X11]- and complex organic molecules (phthalates) in thin layers on surfaces. Molecular structure analysis of the product films revealed that C-H functionalization by [B12X11]- occurred in the presence of other more reactive functional groups. This observation demonstrates the utility of highly reactive fragment ions for selective bond formation processes and may pave the way for the use of gas-phase ion chemistry for the generation of complex molecular structures in the condensed phase.

Biphasic Interpositional Allograft for Rotator Cuff Repair Augmentation Is Safe in an Ovine Model.

PURPOSE: To perform a preclinical histologic assessment of a biphasic acellular interpositional cancellous allograft in an ovine model of rotator cuff repair (RCR) designed to better understand its safety profile and effects on tendon healing after RCR. METHODS: Thirty skeletally mature sheep with clinically normal shoulders with an artificially created degenerative infraspinatus tendon tear were randomized to control and treatment groups. Animals were euthanized at 3 weeks, 6 weeks, and 12 weeks. After gross dissection, rotator cuff specimens were fixed with formalin and polymerized for sectioning and staining. Blinded histologic scores evaluated inflammatory cell infiltrates, signs of degradation, particulate debris, collagen arrangement, neovascularization, and enthesis qualitative measures. RESULTS: There were no treatment specimens that exhibited histologic signs of a significant infection, inflammatory infiltrate, or foreign body reaction such as granuloma or fibrous capsule formation. Histologic scores in all categories were not significantly different at all time points, including the primary end point mean cumulative inflammatory score (control: 3.66 ± 1.21 vs treated: 4.33 ± 1.51, P = .42), when comparing the treatment and control RCR groups. In general, the degree of tendon healing and host tissue response was essentially equivalent between the 2 groups with observation of low overall levels of inflammation and progressive improvements in collagen organization, reduced tenocyte activity, and fibrocartilaginous enthesis reformation. CONCLUSIONS: This histologic study demonstrated the use of a biphasic interpositional allograft for RCR augmentation in an ovine model does not generate an inflammatory response or foreign body reaction. Use of the biphasic interpositional allograft resulted in a histological profile that was essentially equivalent to that of a standard RCR at 3-, 6-, and 12-week postoperative timepoints. These findings suggest that a biphasic interpositional allograft is safe for further clinical investigation in humans before broader clinical application. CLINICAL RELEVANCE: Patch augmentation of RCR is a popular technique that has shown clinical success in improving the likelihood of a successful repair in patients at elevated risk for retear. Newer augmentation technologies are being developed to address the biology at the interface between the bone and soft tissue where failure typically occurs.