Complex molecule synthesis by electrocatalytic decarboxylative cross-coupling.

Modern retrosynthetic analysis in organic chemistry is based on the principle of polar relationships between functional groups to guide the design of synthetic routes1. This method, termed polar retrosynthetic analysis, assigns partial positive (electrophilic) or negative (nucleophilic) charges to constituent functional groups in complex molecules followed by disconnecting bonds between opposing charges2-4. Although this approach forms the basis of undergraduate curriculum in organic chemistry5 and strategic applications of most synthetic methods6, the implementation often requires a long list of ancillary considerations to mitigate chemoselectivity and oxidation state issues involving protecting groups and precise reaction choreography3,4,7. Here we report a radical-based Ni/Ag-electrocatalytic cross-coupling of substituted carboxylic acids, thereby enabling an intuitive and modular approach to accessing complex molecular architectures. This new method relies on a key silver additive that forms an active Ag nanoparticle-coated electrode surface8,9 in situ along with carefully chosen ligands that modulate the reactivity of Ni. Through judicious choice of conditions and ligands, the cross-couplings can be rendered highly diastereoselective. To demonstrate the simplifying power of these reactions, concise syntheses of 14 natural products and two medicinally relevant molecules were completed.

Co-chaperone BAG3 enters autophagic pathway via its interaction with microtubule associated protein 1 light chain 3 beta.

The co-chaperone BAG3 is a hub for a variety of cellular pathways via its multiple domains and its interaction with chaperones of the HSP70 family or small HSPs. During aging and under cellular stress conditions in particular, BAG3, together with molecular chaperones, ensures the sequestration of aggregated or aggregation-prone ubiquitinated proteins to the autophagic-lysosomal system via ubiquitin receptors. Accumulating evidence for BAG3-mediated selective autophagy independent of cargo ubiquitination led to analyses predicting a direct interaction of BAG3 with LC3 proteins. Phylogenetically, BAG3 comprises several highly conserved potential LIRs, LC3-interacting regions, which might allow for the direct targeting of BAG3 including its cargo to autophagosomes and drive their autophagic degradation. Based on pull-down experiments, peptide arrays and proximity ligation assays, our results provide evidence of an interaction of BAG3 with LC3B. In addition, we could demonstrate that disabling all predicted LIRs abolished the inducibility of a colocalization of BAG3 with LC3B-positive structures and resulted in a substantial decrease of BAG3 levels within purified native autophagic vesicles compared with wild-type BAG3. These results suggest an autophagic targeting of BAG3 via interaction with LC3B. Therefore, we conclude that, in addition to being a key co-chaperone to HSP70, BAG3 may also act as a cargo receptor for client proteins, which would significantly extend the role of BAG3 in selective macroautophagy and protein quality control.

A correlative study of the genomic underpinning of virulence traits and drug tolerance of Candida auris.

Candida auris is an opportunistic fungal pathogen with high mortality rates which presents a clear threat to public health. The risk of C. auris infection is high because it can colonize the body, resist antifungal treatment, and evade the immune system. The genetic mechanisms for these traits are not well known. Identifying them could lead to new targets for new treatments. To this end, we present an analysis of the genetics and gene expression patterns of C. auris carbon metabolism, drug resistance, and macrophage interaction. We chose to study two C. auris isolates simultaneously, one drug sensitive (B11220 from Clade II) and one drug resistant (B11221 from Clade III). Comparing the genomes, we confirm the previously reported finding that B11220 was missing a 12.8 kb region on chromosome VI. This region contains a gene cluster encoding proteins related to alternative sugar utilization. We show that B11221, which has the gene cluster, readily assimilates and utilizes D-galactose and L-rhamnose as compared to B11220, which harbors the deletion. B11221 exhibits increased adherence and drug resistance compared to B11220 when grown in these sugars. Transcriptomic analysis of both isolates grown on glucose or galactose showed that the gene cluster was upregulated when grown on D-galactose. These findings reinforce growing evidence of a link between metabolism and drug tolerance. B11221 resists phagocytosis by macrophages and exhibits decreased ß-1,3-glucan exposure, a key determinant that allows Candida to evade the host immune system, as compared to B11220. In a transcriptomic analysis of both isolates co-cultured with macrophages, we find upregulation of genes associated with transport and transcription factors in B11221. Our studies show a positive correlation between membrane composition and immune evasion, alternate sugar utilization, and drug tolerance in C. auris.

Lipid and protein content profiling of isolated native autophagic vesicles.

Autophagy is responsible for clearance of an extensive portfolio of cargoes, which are sequestered into vesicles, called autophagosomes, and are delivered to lysosomes for degradation. The pathway is highly dynamic and responsive to several stress conditions. However, the phospholipid composition and protein contents of human autophagosomes under changing autophagy rates are elusive so far. Here, we introduce an antibody-based FACS-mediated approach for the isolation of native autophagic vesicles and ensured the quality of the preparations. Employing quantitative lipidomics, we analyze phospholipids present within human autophagic vesicles purified upon basal autophagy, starvation, and proteasome inhibition. Importantly, besides phosphoglycerides, we identify sphingomyelin within autophagic vesicles and show that the phospholipid composition is unaffected by the different conditions. Employing quantitative proteomics, we obtain cargo profiles of autophagic vesicles isolated upon the different treatment paradigms. Interestingly, starvation shows only subtle effects, while proteasome inhibition results in the enhanced presence of ubiquitin-proteasome pathway factors within autophagic vesicles. Thus, here we present a powerful method for the isolation of native autophagic vesicles, which enabled profound phospholipid and cargo analyses.

The Association Between Mental Health, Substance Use Disorder, and Outcomes After Total Joint Arthroplasty.

BACKGROUND: Prior studies suggest that distressed patients or those who have poor mental health have inferior postoperative outcomes when compared to nondistressed patients. However, these studies typically do not account for substance use or other comorbidities often found in this population, which can independently contribute to postoperative complications. This study sought to control for these factors and assess if a diagnosis of a mental health condition is directly associated with worse outcomes after total joint arthroplasty. METHODS: A retrospective chart review was performed for 3,182 patients who underwent a total hip arthroplasty and 4,430 patients who underwent a total knee arthroplasty. Diagnosis of the mental health disorders included depression, anxiety disorder, adjustment disorder, bipolar disorder, trauma, stressor-related disorder, and schizophrenia or schizoaffective disorder. Multivariable analyses were performed to control for alcohol use, drug use, tobacco use, body mass index, and a comorbidity index. RESULTS: When controlling for body mass index and Charlson comorbidity index, no statistically significant associations were found between a diagnosis of any mental health condition or a specific diagnosis of depression or anxiety, and 90-day readmission, reoperation, or 1 year mortality for patients undergoing total knee arthroplasty or total hip arthroplasty. CONCLUSIONS: When accounting for confounding factors, there does not appear to be a direct association between diagnosis of any of the psychiatric conditions we studied and outcomes after primary total joint arthroplasty. While prior studies suggest addressing the mental health condition may improve outcomes, this study suggests that preoperative medical optimization and potentially addressing substance use may be more effective strategies.

Risk Factors for Trochanteric Bursitis Following Total Hip Arthroplasty: A Radiographic Analysis.

BACKGROUND: Trochanteric bursitis (TB) is a prevalent complication following total hip arthroplasty (THA), with increased offset hypothesized as a potential risk factor. This study investigated potential TB predictors in THA patients, including radiographic measurements of offset and leg length, comorbidities, and patient characteristics. METHODS: In this retrospective cohort study, all THA patients from a single academic tertiary care center between 2005 and 2021 were reviewed. Exclusion criteria included less than one-year follow-up, osteonecrosis, or fracture. Manual radiographic measurements of offset (acetabular, femoral, and total) and leg length from preoperative and postoperative AP (antero-posterior) pelvis X-rays were taken, with scaling using femoral cortical diameter. Univariable and multivariable Cox proportional hazard models were employed to estimate TB risk. RESULTS: Of 1,094 patients, 103 (9.4%) developed trochanteric bursitis, with a median (Q1, Q3) time to presentation of 41.8 weeks (25.5, 66.9). In univariable models, only sex was associated with increased TB risk, with women exhibiting a 1.79 times increased risk (HR [hazard ratio]: 1.79 (1.16, 2.76), P = 0.009). Changes in acetabular offset, femoral offset, total offset, and leg length between preoperative and postoperative radiographs were not associated with an increased risk of developing TB in the univariate or multivariate models. Furthermore, various offset thresholds were evaluated, with no amount of increased offset showing increased TB risk. CONCLUSION: This study found no relationship between femoral, acetabular, or total offset and trochanteric bursitis following THA. These findings suggest that surgeons may consider adding offset for increased prosthetic stability in high-risk cases. However, given that this is a retrospective study, the authors are not advocating for the routine use of increased offset. The study identified women as a risk factor with a 1.79 times higher TB risk, highlighting the importance of counseling women patients on this heightened risk.

Morbidity and Mortality Following Total Hip and Knee Arthroplasty With Spinal Versus General Anesthesia: A Retrospective Analysis.

BACKGROUND: The optimal anesthetic mode in total joint arthroplasty (TJA) has yet to be clearly identified. Patients undergoing TJA may recieve spinal anesthesia (SA) or general anesthesia (GA). While arthroplasty literature indicates differences in postoperative morbidity, hip fracture literature does not show clear superiority of SA or GA. The purpose of this study was to further investigate this relationship and determine if there is a significant difference in morbidity and mortality between GA and SA in patients undergoing primary total joint arthroplasty. METHODS: Patients undergoing primary THA or TKA from February 2007 to February 2021 were retrospectively reviewed, creating four cohorts: THA/GA (n = 1,266), THA/SA (n = 1,084), TKA/GA (n = 882), and THA/SA (n = 2,067). Readmission within 90 days, mortality within 365 days, and thromboembolic events within 30 days postoperatively were compared using logistic regression, controlling for age, body mass index, and Charlson Comorbidity Index. RESULTS: The odds of experiencing a deep venous thrombosis within 30 days postoperatively were elevated in the analysis of both the THA/GA (odds ratio (OR) = 3.1; 95% confidence interval (CI): 1.5 to 7.0; P = .004) and the TKA/GA (OR = 1.9; 95% CI: 1.2 to 3.0; P = .005) groups. Similarly, the risk of pulmonary embolism as higher in the THA/GA cohort (OR = 3.9; 95% CI: 1.2 to 17.3; P = .04). There were also higher odds of mortality within 365 days postoperatively in THA/GA patients (OR = 4.3; 95% CI: 1.7 to 13.0; P = .004). No other differences existed among TKA patients. CONCLUSIONS: Based upon these data, both SA and GA are reasonable options for primary TKA with similar risk profiles. However, GA may be associated with higher rates of deep venous thrombosis in TJA and pulmonary embolism in THA. General anesthesia (GA) was also loosely associated with increased mortality within 1 year of THA, but this result should be considered with caution.

Fourier Analysis of the Vertical Ground Reaction Force During Walking: Applications for Quantifying Differences in Gait Strategies.

Time series biomechanical data inform our understanding of normal gait mechanics and pathomechanics. This study examines the utility of different quantitative methods to distinguish vertical ground reaction forces (VGRFs) from experimentally distinct gait strategies. The goals of this study are to compare measures of VGRF data-using the shape factor method and a Fourier series-based analysis-to (1) describe how these methods reflect and distinguish gait patterns and (2) determine which Fourier series coefficients discriminate normal walking, with a relatively stiff-legged gait, from compliant walking, using deep knee flexion and limited vertical oscillation. This study includes a reanalysis of previously presented VGRF data. We applied the shape factor method and fit 3- to 8-term Fourier series to zero-padded VGRF data. We compared VGRF renderings using Euclidean L2 distances and correlations stratified by gait strategy. Euclidean L2 distances improved with additional harmonics, with limited improvement after the seventh term. Euclidean L2 distances were greater in shape factor versus Fourier series renderings. In the 8 harmonic model, amplitudes of 9 Fourier coefficients-which contribute to VGRF features including peak and local minimum amplitudes and limb loading rates-were different between normal and compliant walking. The results suggest that Fourier series-based methods distinguish between gait strategies.

Jumping performance in tree squirrels: Insights into primate evolution.

Morphological traits suggesting powerful jumping abilities are characteristic of early crown primate fossils. Because tree squirrels lack certain 'primatelike' grasping features but frequently travel on the narrow terminal branches of trees, they make a viable extant model for an early stage of primate evolution. Here, we explore biomechanical determinants of jumping performance in the arboreal Eastern gray squirrel (Sciurus carolinensis, n = 3) as a greater understanding of the biomechanical strategies that squirrels use to modulate jumping performance could inform theories of selection for increased jumping ability during early primate evolution. We assessed vertical jumping performance by using instrumented force platforms upon which were mounted launching supports of various sizes, allowing us to test the influence of substrate diameter on jumping kinetics and performance. We used standard ergometric methods to quantify jumping parameters (e.g., takeoff velocity, total displacement, peak mechanical power) from force platform data during push-off. We found that tree squirrels display divergent mechanical strategies according to the type of substrate, prioritizing force production on flat ground versus center of mass displacement on narrower poles. As jumping represents a significant part of the locomotor behavior of most primates, we suggest that jumping from small arboreal substrates may have acted as a potential driver of the selection for elongated hindlimb segments in primates, allowing the center of mass to be accelerated over a longer distance-and thereby reducing the need for high substrate reaction forces.

Prevention Techniques Have Had Minimal Impact on the Population Rate of Prosthetic Joint Infection for Primary Total Hip and Knee Arthroplasty: A National Database Study.

BACKGROUND: Several studies over the years have offered modalities that may greatly decrease the rate of periprosthetic joint infection when implemented. As a result, one would expect a drastic decrease in infection rate among the implementing population with its widespread use. The purpose of this study was to assess whether there exists a decrease in infection rate over time, after accounting for available confounding variables, within a large national database. METHODS: A large national database from 2005 to 2019 was queried for primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). In total, 221,416 THAs and 354,049 TKAs were performed over the study period. Differences in 30-day infection rate were assessed with time and available preoperative risk factors using multinominal logistic regressions. RESULTS: Rate of infection overall trended downward for both THA and TKA. After accounting for confounding variables, odds of THA infection marginally decreased over time (odds ratio 0.968 [0.952-0.985], P < .0001), while the odds of a TKA infection marginally increased with time (odds ratio 1.037 [1.020-1.054], P < .0001). CONCLUSION: Individual peer-reviewed publications have presented infection control modalities demonstrating dramatic decreases in infection rate while analysis at a population level shows almost no changes in infection rate over a 15-year time period. This study supports continued investigation for influential modalities in preventing periprosthetic joint infection and care in patient selection for primary hip and knee arthroplasty.

Artificial Intelligence Autonomously Measures Cup Orientation, Corrects for Pelvis Orientation, and Identifies Retroversion From Antero-Posterior Pelvis Radiographs.

BACKGROUND: Measuring cup orientation is time consuming and inaccurate, but orientation influences the risk of impingement and dislocation following total hip arthroplasty (THA). This study designed an artificial intelligence (AI) program to autonomously determine cup orientation, correct for pelvis orientation, and identify cup retroversion from an antero-posterior pelvic radiographs. METHODS: There were 2,945 patients between 2012 and 2019 identified to have 504 computed tomographic (CT) scans of their THA. A 3-dimensional (3D) reconstruction was performed on all CTs, where cup orientation was measured relative to the anterior pelvic plane. Patients were randomly allocated to training (4,000 x-rays), validation (511 x-rays), and testing (690 x-rays) groups. Data augmentation was applied to the training set (n = 4,000,000) to increase model robustness. Statistical analyses were performed only on the test group in their accuracy with CT measurements. RESULTS: AI predictions averaged 0.22 ± 0.03 seconds to run on a given radiograph. Pearson correlation coefficient was 0.976 and 0.984 for AI measurements with CT, while hand measurements were 0.650 and 0.687 for anteversion and inclination, respectively. The AI measurements more closely represented CT scans when compared to hand measurements (P < .001). Measurements averaged 0.04 ± 2.21°, 0.14 ± 1.66°, -0.31 ± 8.35°, and 6.48° ± 7.43° from CT measurements for AI anteversion, AI inclination, hand anteversion, and hand inclination, respectively. AI predictions identified 17 radiographs as retroverted with 100.0% accuracy (total retroverted, n = 45). CONCLUSION: The AI algorithms may correct for pelvis orientation when measuring cup orientation on radiographs, outperform hand measurements, and may be implemented in a timely fashion. This is the first method to identify a retroverted cup from a single AP radiograph.

Identification of parallel medicinal chemistry protocols to expand branched amine design space.

α-Branched heteroaryl amines are prevalent motifs in drugs and are typically prepared through C-N bond formation. In contrast, C-C bond-forming approaches to branched amines may dramatically expand available chemical space but are rarely pursued in parallel format due to a lack of established library protocols. Methods for the synthesis of α-branched heteroaryl amines via aldimine addition have been evaluated for compatibility with parallel synthesis. In situ activation of aliphatic carboxylic acids as redox-active esters enables Zn-mediated decarboxylative radical imine addition to access aliphatic-branched heterobenzylic amines. In situ activation of (hetero)aryl bromides via Li-halogen exchange enables heteroaryl-lithium addition to imines to access (hetero)benzhydryl amines. Condensation of heteroaryl amines with heteroaryl aldehydes provides aldimines which may be intercepted with aryl Grignard reagents to provide modular access to (hetero)benzhydryl amines. These protocols minimize synthetic step count and maximize accessible design space, enhancing access to α-branched heteroaryl amines for medicinal chemistry.

Targeting glycogen synthase kinase 3 for therapeutic benefit in lymphoma.

Targeting the B-cell receptor and phosphatidylinositol 3-kinase/mTOR signaling pathways has shown meaningful, but incomplete, antitumor activity in lymphoma. Glycogen synthase kinase 3 (GSK3) α and ß are 2 homologous and functionally overlapping serine/threonine kinases that phosphorylate multiple protein substrates in several key signaling pathways. To date, no agent targeting GSK3 has been approved for lymphoma therapy. We show that lymphoma cells abundantly express GSK3α and GSK3ß compared with normal B and T lymphocytes at the messenger RNA and protein levels. Utilizing a new GSK3 inhibitor 9-ING-41 and by genetic deletion of GSK3α and GSK3ß genes using CRISPR/CAS9 knockout, GSK3 was demonstrated to be functionally important to lymphoma cell growth and proliferation. GSK3ß binds to centrosomes and microtubules, and lymphoma cells treated with 9-ING-41 become arrested in mitotic prophase, supporting the notion that GSK3ß is necessary for the progression of mitosis. By analyzing recently published RNA sequencing data on 234 diffuse large B-cell lymphoma patients, we found that higher expression of GSK3α or GSK3ß correlates well with shorter overall survival. These data provide rationale for testing GSK3 inhibitors in lymphoma patient trials.

Effects of human variation on foot and ankle pain in rural Madagascar.

OBJECTIVES: Foot and ankle dysfunction in barefoot/minimally shod populations remains understudied. Although factors affecting musculoskeletal pain in Western populations are well-studied, little is known about how types of work, gender, and body shape influence bone and joint health in non-Western and minimally shod communities. This study examines the effect of human variation on locomotor disability in an agrarian community in Madagascar. MATERIALS AND METHODS: Foot measurements were collected along with height, weight, age, and self-report data on daily activity and foot and ankle pain from 41 male and 48 female adults. A short form revised foot function index (FFI-R), that measures functional disability related to foot pain, was calculated. Raw and normalized foot measurements were compared by gender and used in a multiple linear regression model to determine predictors of FFI-R. RESULTS: Compared to men, women reported higher FFI-R scores (p = 0.014), spent more time on their feet (p = 0.019), and had higher BMIs (p = 0.0001). For their weight, women had significantly smaller and narrower feet than men. Bimalleolar breadth (p = 0.0005) and foot length (p = 0.0223) standardized by height, time spent on feet (p = 0.0102), ankle circumference standardized by weight (p = 0.0316), and age (p = 0.0090) were significant predictors of FFI-R score. DISCUSSION: Our findings suggest that human variation in anatomical and behavioral patterns serve as significant explanations for increased foot and ankle pain in women in this non-Western rural population. Foot and ankle pain were prevalent at similar levels to those in industrialized populations, indicating that research should continue to examine its effect on similar barefoot/minimally shod communities.

Improving Emergency Cricothyroidotomies: Simulation-Based Training for Critical Care Providers.

This article discusses skill proficiency of providers related to emergency cricothyroidotomies. Various techniques to improve procedural skills were studied. Accurate identification of the cricothyroid membrane via palpation remained consistently inadequate. High-fidelity simulation including the use of human cadavers may be the preferred method of skill training for crisis management. The authors emphasize that additional research is needed regarding a method for rapid cricothyroid membrane identification as well as needle cricothyroidotomy versus surgical airway on cadavers. More consistent training will enable emergency care providers to perform this rare but lifesaving skill.

Mechanics of heel-strike plantigrady in African apes.

The initiation of a walking step with a heel strike is a defining characteristic of humans and great apes but is rarely found in other mammals. Despite the considerable importance of heel strike to an understanding of human locomotor evolution, no one has explicitly tested the fundamental mechanical question of why great apes use a heel strike. In this report, we test two hypotheses (1) that heel strike is a function of hip protraction and/or knee extension and (2) that short-legged apes with a midfoot that dorsiflexes at heel lift and long digits for whom digitigrady is not an option use heel-strike plantigrady. This strategy increases hip translation while potentially moderating the cost of redirecting the center of mass ('collisional costs') during stance via rollover along the full foot from the heel to toes. We quantified hind limb kinematics and relative hip translation in ten species of primates, including lemurs, terrestrial and arboreal monkeys, chimpanzees, and gorillas. Chimpanzees and gorillas walked with relatively extended knees but only with moderately protracted hips or hind limbs, partially rejecting the first hypothesis. Nonetheless, chimpanzees attained relative hip translations comparable with those of digitigrade primates. Heel-strike plantigrady may be a natural result of a need for increased hip translations when forelimbs are relatively long and digitigrady is morphologically restricted. In addition, foot rollover from the heel to toe in large, short-legged apes may reduce energetic costs of redirecting the center of mass at the step-to-step transition as it appears to do in humans. Heel strike appears to have been an important mechanism for increasing hip translation, and possibly reducing energetic costs, in early hominins and was fundamental to the evolution of the modern human foot and human bipedalism.

Impact of Perioperative Urinary Tract Infection on Surgical Site Infection in Patients Undergoing Primary Hip and Knee Arthroplasty.

BACKGROUND: The literature lacks clear consensus regarding the association between postoperative urinary tract infection (UTI) and surgical site infection (SSI). Additionally, in contrast to preoperative asymptomatic bacteriuria, SSI risk in patients with preoperative UTI has been incompletely studied. Therefore, our goal was to determine the effect of perioperative UTI on SSI in patients undergoing primary hip and knee arthroplasty. METHODS: Using the National Surgical Quality Improvement Program database, all patients undergoing primary hip and knee arthroplasty were identified. Univariate and multivariate regressions, as well as propensity matching, were used to determine the independent risk of preoperative and postoperative UTI on SSI, reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Postoperative UTI significantly increased the risk for superficial wound infection (OR 2.147, 95% CI 1.622-2.842), deep periprosthetic joint infection (PJI) (OR 2.288, 95% CI 1.579-3.316), and all SSIs (superficial and deep) (OR 2.193, 95% CI 1.741-2.763) (all P < .001). Preoperative UTI was not associated with a significantly increased risk of superficial infection (P = .636), PJI (P = .330), or all SSIs (P = .284). Further analysis of UTI present at the time of surgery using propensity matching showed no increased risk of superficial infection (P = 1.000), PJI (P = .624), or SSI (P = .546). CONCLUSION: Postoperative UTI was associated with SSI, reinforcing the need to minimize factors which predispose patients to the risk of UTI after surgery. The lack of association between preoperative UTI and SSI suggests that hip and knee arthroplasty can proceed without delay, although initiating antibiotic treatment is prudent and future prospective investigations are warranted.

Ankle fusion in patients with chronic hepatitis C.

BACKGROUND: It appears that both the incidence and survival of patients infected with hepatitis C have recently demonstrated a significant increase. The goal of this investigation was to determine the associated perioperative risks associated with ankle arthrodesis in this growing population. METHODS: The Healthcare Cost and Utilization Project State Inpatient Databases identified patients with chronic hepatitis C infection who underwent ankle arthrodesis between January 2009 and December 2013. International Classification of Diseases, Ninth Revision, codes were used to define the primary composite outcome of death or postoperative complication. Logistic models with frequency weights were used to compare propensity matched groups. RESULTS: 7339 patients met inclusion criteria. Of these, 157 patients had a history of chronic Hepatitis C infection. After performing a propensity score match, the final analytic cohort was 157 in the Hepatitis C group and 386 in the non-Hepatitis C group. There was no statistically significant differences in complications between patients with chronic Hepatitis C undergoing ankle fusion and those without Hepatitis C at any post-operative time point (inpatient, 30 days, or 90 days). DISCUSSION: Patients with chronic hepatitis C infection undergoing ankle arthrodesis are not at an elevated risk of inpatient, thirty, and ninety day postoperative complications compared to patients without chronic HCV infections. Patients with chronic hepatitis C did not have an increased risk of surgical site infection or mortality at any time point. LEVEL OF EVIDENCE: Prognostic Level III.

A Radical Approach to Anionic Chemistry: Synthesis of Ketones, Alcohols, and Amines.

Historically accessed through two-electron, anionic chemistry, ketones, alcohols, and amines are of foundational importance to the practice of organic synthesis. After placing this work in proper historical context, this Article reports the development, full scope, and a mechanistic picture for a strikingly different way of forging such functional groups. Thus, carboxylic acids, once converted to redox-active esters (RAEs), can be utilized as formally nucleophilic coupling partners with other carboxylic derivatives (to produce ketones), imines (to produce benzylic amines), or aldehydes (to produce alcohols). The reactions are uniformly mild, operationally simple, and, in the case of ketone synthesis, broad in scope (including several applications to the simplification of synthetic problems and to parallel synthesis). Finally, an extensive mechanistic study of the ketone synthesis is performed to trace the elementary steps of the catalytic cycle and provide the end-user with a clear and understandable rationale for the selectivity, role of additives, and underlying driving forces involved.

The mechanical origins of arm-swinging.

Arm-swinging is a locomotor mode observed only in primates, in which the hindlimbs no longer have a weight bearing function and the forelimbs must propel the body forward and support the entirety of the animal's mass. It has been suggested that the evolution of arm-swinging was preceded by a shift to inverted quadrupedal walking for purposes of feeding and balance, yet little is known about the mechanics of limb use during inverted quadrupedal walking. In this study, we test whether the mechanics of inverted quadrupedal walking make sense as precursors to arm-swinging and whether there are fundamental differences in inverted quadrupedal walking in primates compared to non-primate mammals that would explain the evolution of arm-swinging in primates only. Based on kinetic limb-loading data collected during inverted quadrupedal walking in primates (seven species) and non-primate mammals (three species), we observe that in primates the forelimb serves as the primary propulsive and weight bearing limb. Additionally, heavier individuals tend to support a greater distribution of body weight on their forelimbs than lighter ones. These kinetic patterns are not observed in non-primate mammals. Based on these findings, we propose that the ability to adopt arm-swinging is fairly simple for relatively large-bodied primates and merely requires the animal to release its grasping foot from the substrate. This study fills an important gap concerning the origins of arm-swinging and illuminates previously unknown patterns of primate locomotor evolution.