Racial and ethnic disparities in prostate cancer screening following the 2018 US Preventive Services Task Force recommendation statement.

OBJECTIVE: In 2018, the United States Preventive Services Task Force promoted shared decision making between healthcare provider and patient for men aged 55 to 69. This study aimed to analyze rates of prostate-specific antigen (PSA) testing across racial and ethnic groups following this new recommendation. METHODS: A secondary analysis was conducted of the 2020-2021 Behavioral Risk Factor Surveillance System database to assess men aged 55 or older without a history of prostate cancer. We defined four race-ethnicity groups: non-Hispanic Whites (NHWs), non-Hispanic Blacks (NHBs), Hispanics, and Other. The primary outcome was the most recent PSA test (MRT), defined as the respondent's most recent PSA test occurring pre-2018 or post-2018 guidelines. Logistic regression adjusted for covariates including age, socioeconomic status factors, marital status, smoking history, and healthcare access factors. RESULTS: In the age 55 to 69 study sample, NHW men had the greatest proportion of MRT post-2018 guidelines (n = 15,864, 72.5%). NHB men had the lowest percentage of MRT post-2018 guidelines (n = 965, 66.6%). With NHW as referent, the crude odds of the MRT post-2018 guidelines was 0.68 (95% confidence interval (CI) = 0.53-0.90) for NHB. The maximally adjusted odds ratio was 0.78 (0.59-1.02). CONCLUSIONS: We found that NHB aged 55 to 69 reported decreased rates of PSA testing after 2018 when compared to NHW. This was demonstrated on crude analysis but not after adjustment. Such findings suggest the influence of social determinants of health on preventative screening for at-risk populations.

Demographics and Career Trends of Urology Fellowship Directors in the United States.

INTRODUCTION: Fellowship directors (FDs) hold significant leadership roles within the academic urology community. We sought to characterize common trends in training and academic productivity among urology FDs. Moreover, we aimed to characterize gender differences across subspecialties to better inform gender-based inclusion efforts and contemporary leadership pathways. METHODS: FDs were studied across 6 urologic subspecialties. Society and institutional websites were queried for demographics, education/training institutions, timelines of career milestones, and academic productivity. χ2, Mann-Whitney U, and Kruskal-Wallis tests and Kendall tau rank correlation were employed with an alpha cutoff of .05. RESULTS: There were 219 FDs included, representing 208 fellowship programs at 93 institutions. FDs were 176 (80%) males and 43 (20%) females. There was a significant association between gender and subspecialty. The median age for all FDs was 52 years old. Significant differences in age were demonstrated across subspecialties. For all FDs, females were younger than males, at 49 and 53 years, respectively (P = .001). The median H-index for all FDs was 23.5. H-index was significantly different between genders and subspecialities. There was a strong, positive correlation between age vs H-index for all FDs. Half of FDs had completed fellowship training at one of 14 institutions. CONCLUSIONS: We describe the landscape of leadership in urology subspecialty training. There are an increasing number of female FDs. Composition of leadership varies by subspecialty; however, the careers of all current urology FDs are marked by lifelong achievements in academic productivity. Moreover, a small group of institutions produce a substantial number of FDs.

Resection of Traumatic Triradiate Bar Led To Restored Triradiate Growth: A Case Report.

CASE: A 2-year-old boy suffered an injury to the acetabular physis resulting in the formation of an osseus bar across all 3 limbs of the triradiate, growth arrest, and secondary hip dysplasia. This condition was treated with bony bar resection using an anterior intrapelvic approach. Over a follow-up period of more than 3 years, there was notable restoration of triradiate cartilage growth. CONCLUSION: Our case demonstrates that resection of a triradiate bar can be an effective treatment of premature traumatic triradiate closure. Early recognition and intervention are preferable before secondary changes in the acetabulum have fully developed.

Propensity score matched survival analysis of octogenarians with muscle-invasive bladder cancer: chemoradiation compared to radical cystectomy.

INTRODUCTION: Radical cystectomy (RC) is an effective curative treatment option for muscle-invasive bladder cancer (MIBC). However, chemoradiation (CRT) is an evolving bladder preservation protocol alternative to RC. With the increase in life expectancy, it is essential to understand the survival outcomes among octogenarians treated with RC and CRT. In this study, we use the National Cancer Database (NCDB) to compare the survival outcomes between RC and CRT in octogenarians. MATERIALS AND METHODS: We collected the data of patients treated for bladder cancer between 2004 to 2018 from the NCDB. Our primary analytic cohort included patients with MIBC (cT2-T4N0M0). We identified the octogenarians and categorized them into RC and CRT arms. The RC arm included those who received RC. The CRT arm included those who received chemotherapy within 90 days of curative radiation therapy. After 1:1 propensity score matching, overall survival (OS) outcomes were compared between both arms. RESULTS: Among the octogenarians, the median OS for patients treated with RC was 26.1 months (95% CI, 23.9-28.2), and CRT was 28.7 months (95% CI, 26.8-30.6). Our covariate analyses showed that academic institutions performed more RC (49% RC and 29.7% CRT) and community programs served more CRT (45.7% CRT and 24.2% RC). A multivariate Cox regression analysis showed that the mortality risk increased as the Charlson-Deyo comorbidity score and T stage increased. CONCLUSION: Octogenarians treated with RC and CRT had similar OS. As life expectancy increases, it is essential to individualize the treatment strategy based on risk assessment and its potential benefits.

The Impact of COVID-19 on Trends of Violence-Related Offences in Australia.

OBJECTIVE: To investigate the medium-term impacts of the COVID-19 pandemic on violence-related offences in Australia, and whether there was evidence of a 'dual pandemic' of family violence in addition to COVID-19. METHODS: Autoregressive Integrated Moving Average time series were conducted to analyse publicly available violent crime statistics data from January 2017 to November 2021. Population rates of homicide, sexual, domestic and non-domestic assault were assessed across each Australian state and territory, with the effects of COVID-19 being modelled using the average monthly World Health Organization COVID-19 stringency rating for each jurisdiction. FINDINGS: All jurisdictions in Australia showed increasing or stable domestic assault trends over the past decade, which were not significantly impacted by COVID-19, nor by the subsequent lockdowns. Non-domestic assaults demonstrated a significant, negative relationship with the stringency index for each jurisdiction, except Western Australia. There was no significant change in the rates of homicide or sexual assault across Australia in relation to COVID-19. CONCLUSION: Overall, there was no evidence of a 'dual pandemic' in Australia, and whilst domestic assaults continue to increase across the country, non-domestic assaults showed a notable but brief decline. However, these have returned to levels at least as high as pre-COVID-19 and some states show a continuing upward trend. The findings also suggest that alcohol availability may have played a role in continuing high violence numbers. Given the ongoing increasing and high levels of family violence in Australia, revised conceptual frameworks and interventions are indicated.

Trends in Leadership Among Neurosurgical Oncology Fellowships.

OBJECTIVE: To examine current neurosurgical oncology leadership trends and provide a guide for those interested in obtaining fellowship directorship, we investigated fellowship director (FD) demographic, educational, and leadership characteristics. METHODS: The American Association of Neurological Surgeons Academic Fellowship Directory and Committee on Advanced Subspecialty Training websites were reviewed for current U.S. program FDs for which data were collected using online resources and surveys. RESULTS: In total, 23 FDs (20 male and 3 female) were represented whose mean age was 52.4 years (standard deviation = 8.7). Our analysis found 65% of current neurosurgical oncology FDs to be singularly trained in neurosurgical oncology, with 8.7% possessing multiple fellowships and 34.8% possessing additional degrees. Fellowship programs producing the most FDs were University of Texas MD Anderson (4), Memorial Sloan Kettering (3), and University of Miami (2). FDs possessed an average of 148 publications, 6423 citations, and an h-index of 33.9. H-index had a high-positive correlation with age and time from residency graduation but not duration of FD appointment. Among survey respondents, 91.7% reported membership and 75% reported leadership positions among national academic societies, whereas 66.7% reported holding journal-editorial positions. The mean age of FD appointment was 46.8 years, with a mean time from fellowship completion to FD appointment of 10.0 years. CONCLUSIONS: Through the characterization of current leaders in the field, we provide valuable information with regards to training location trends, research productivity goals, career timelines, and target journal/national academic society involvement worth consideration among young trainees when making career decisions and plans.

Molecular encoding of stimulus features in a single sensory neuron type enables neuronal and behavioral plasticity.

Neurons modify their transcriptomes in response to an animal's experience. How specific experiences are transduced to modulate gene expression and precisely tune neuronal functions are not fully defined. Here, we describe the molecular profile of a thermosensory neuron pair in C. elegans experiencing different temperature stimuli. We find that distinct salient features of the temperature stimulus, including its duration, magnitude of change, and absolute value, are encoded in the gene expression program in this single neuron type, and we identify a novel transmembrane protein and a transcription factor whose specific transcriptional dynamics are essential to drive neuronal, behavioral, and developmental plasticity. Expression changes are driven by broadly expressed activity-dependent transcription factors and corresponding cis-regulatory elements that nevertheless direct neuron- and stimulus-specific gene expression programs. Our results indicate that coupling of defined stimulus characteristics to the gene regulatory logic in individual specialized neuron types can customize neuronal properties to drive precise behavioral adaptation.

Molecular encoding of stimulus features in a single sensory neuron type enables neuronal and behavioral plasticity.

Neurons modify their transcriptomes in response to an animal’s experience. How specific experiences are transduced to modulate gene expression and precisely tune neuronal functions are not fully defined. Here, we describe the molecular profile of a thermosensory neuron pair in C. elegans experiencing different temperature stimuli. We find that distinct salient features of the temperature stimulus including its duration, magnitude of change, and absolute value are encoded in the gene expression program in this single neuron, and identify a novel transmembrane protein and a transcription factor whose specific transcriptional dynamics are essential to drive neuronal, behavioral, and developmental plasticity. Expression changes are driven by broadly expressed activity-dependent transcription factors and corresponding cis -regulatory elements that nevertheless direct neuron- and stimulus-specific gene expression programs. Our results indicate that coupling of defined stimulus characteristics to the gene regulatory logic in individual specialized neuron types can customize neuronal properties to drive precise behavioral adaptation.

Volar Lunate Facet Fractures of the Distal Radius: Fracture Mapping Using 3D CT Scans.

Background Fractures of the distal radius involving the lunate facet at the volar articular surface are unstable injuries and are usually managed operatively. Management of these fractures is challenging as our understanding of the exact fracture characteristics and associated injuries to the carpus is poor. Purpose This study aims to define the anatomy and associated injuries of lunate facet fractures using three-dimensional computed tomography (CT) scans and fracture mapping techniques. Methods A consecutive series of CT wrists was analyzed to identify intra-articular fractures involving the lunate facet at the volar distal radius. Fractures were mapped onto standardized templates of the distal radius using previously described fracture mapping techniques. We also identified instabilities of the carpus including volar carpal translation, ulnar translocation, scapholunate diastasis, and distal radioulnar joint (DRUJ) instability. Results We present 23 lunate facet fractures of the distal radius. The lunate facet fragment displaces in a volar and proximal direction and the lunate always articulates with the displaced fragment. The smaller fragments displace a greater amount, in a volar direction, with pronation. The fracture tends to occur between the origin of the short and long radiolunate ligaments. Conclusion Lunate facet fractures are frequently comprised of osteoligamentous units of the distal radius involving the short and long radiolunate ligaments and the radioscaphocapitate ligament. Assessment and management of volar carpal subluxation, scapholunate instability, ulnar translocation, and DRUJ instability should be considered. Clinical relevance Our mapping of these fractures contributes to our understanding of the anatomy and associated instabilities and will aid in surgical planning and decision making.

P300 promotes tumor recurrence by regulating radiation-induced conversion of glioma stem cells to vascular-like cells.

Glioma stem cells (GSC) exhibit plasticity in response to environmental and therapeutic stress leading to tumor recurrence, but the underlying mechanisms remain largely unknown. Here, we employ single-cell and whole transcriptomic analyses to uncover that radiation induces a dynamic shift in functional states of glioma cells allowing for acquisition of vascular endothelial-like and pericyte-like cell phenotypes. These vascular-like cells provide trophic support to promote proliferation of tumor cells, and their selective depletion results in reduced tumor growth post-treatment in vivo. Mechanistically, the acquisition of vascular-like phenotype is driven by increased chromatin accessibility and H3K27 acetylation in specific vascular genes allowing for their increased expression post-treatment. Blocking P300 histone acetyltransferase activity reverses the epigenetic changes induced by radiation and inhibits the adaptive conversion of GSC into vascular-like cells and tumor growth. Our findings highlight a role for P300 in radiation-induced stress response, suggesting a therapeutic approach to prevent glioma recurrence.

Neuronal temperature perception induces specific defenses that enable C. elegans to cope with the enhanced reactivity of hydrogen peroxide at high temperature.

Hydrogen peroxide is the most common reactive chemical that organisms face on the microbial battlefield. The rate with which hydrogen peroxide damages biomolecules required for life increases with temperature, yet little is known about how organisms cope with this temperature-dependent threat. Here, we show that Caenorhabditis elegans nematodes use temperature information perceived by sensory neurons to cope with the temperature-dependent threat of hydrogen peroxide produced by the pathogenic bacterium Enterococcus faecium. These nematodes preemptively induce the expression of specific hydrogen peroxide defenses in response to perception of high temperature by a pair of sensory neurons. These neurons communicate temperature information to target tissues expressing those defenses via an insulin/IGF1 hormone. This is the first example of a multicellular organism inducing their defenses to a chemical when they sense an inherent enhancer of the reactivity of that chemical.

The Earth's environment is full of reactive chemicals that can cause harm to organisms. One of the most common is hydrogen peroxide, which is produced by several bacteria in concentrations high enough to kill small animals, such as the roundworm Caenorhabditis elegans. Forced to live in close proximity to such perils, C. elegans have evolved defenses to ensure their survival, such as producing enzymes that can break down hydrogen peroxide. However, this battle is compounded by other factors. For instance, rising temperatures can increase the rate at which the hydrogen peroxide produced by bacteria reacts with the molecules and proteins of C. elegans. In 2020, a group of researchers found that roundworms sense these temperature changes through special cells called sensory neurons and use this information to control the generation of enzymes that break down hydrogen peroxide. This suggests that C. elegans may pre-emptively prepare their defenses against hydrogen peroxide in response to higher temperatures so they are better equipped to shield themselves from this harmful chemical. To test this theory, Servello et al. ­ including some of the authors involved in the 2020 study ­ exposed C. elegans to a species of bacteria that produces hydrogen peroxide. This revealed that the roundworms were better at dealing with the threat of hydrogen peroxide when growing in warmer temperatures. Experiments done in C. elegans lacking a class of sensory cells, the AFD neurons, showed that these neurons increased the roundworms' resistance to the chemical when temperatures increase. They do this by repressing the activity of INS-39, a hormone that stops C. elegans from switching on their defense mechanism against peroxides. This is the first example of a multicellular organism preparing its defenses to a chemical after sensing something (such as temperature) that enhances its reactivity. It is possible that other animals may also use this 'enhancer sensing' strategy to anticipate and shield themselves from hydrogen peroxide and potentially other external threats.

A snapshot of contemporary leadership at pediatric neurosurgery fellowships.

OBJECTIVE: Many pathways to positions of leadership exist within pediatric neurological surgery. The authors sought to investigate common trends in leadership among pediatric neurosurgery fellowship directors (FDs) and describe how formalized pediatric neurosurgical training arrived at its current state. METHODS: Fellowship programs were identified using the Accreditation Council for Pediatric Neurosurgery Fellowships website. Demographic, training, membership, and research information was collected via email, telephone, curricula vitae, and online searches. RESULTS: The authors' survey was sent to all 35 identified FDs, and 21 responses were received. Response data were supplemented with curricula vitae and online data prior to analysis. FDs were predominantly male, self-identified predominantly as Caucasian, and had a mean age of 53 years. The mean duration from residency graduation until FD appointment was 13.4 years. The top training programs to produce future FDs were New York University and Washington University in St. Louis (residency) and Washington University in St. Louis (fellowship). CONCLUSIONS: This study characterizes the current state of pediatric neurosurgery fellowship program leadership. The data serve as an important point of reference to compare with future leadership as well as contrast with neurosurgery and other surgical disciplines in general.

Demographics and Academic Productivity of Cardiothoracic Imaging Fellowship Program Directors in the United States: A Cross-Sectional Review.

Background In this study, we aimed to assess current demographics, measures of academic productivity, and other objective leadership characteristics among United States cardiothoracic imaging fellowship directors (FDs). Methodology A survey was sent to active members listed in the Society of Thoracic Radiology Cardiothoracic Imaging Fellowship Directory. Demographic, post-graduate training, and scholarly activity data were collected, including, but not limited to, age, sex, residency and fellowship training institutions, time since training completion until FD, length of time as FD, and Hirsch-index (h-index) to measure research activity. Results We identified 53 FDs from 50 cardiothoracic imaging fellowship programs. Of these, 31 (58.5%) were male and 22 (41.5%) were female with an average age of 48.5 years (standard deviation (SD) = 8.4, range = 35-67). There was no statistically significant difference between the mean age of male and female FDs (47.5 vs 50.2 years, p = 0.2811). The mean age of appointment to the FD role was 41.8 years. On average, FDs graduated from residency in 2005 and 2007 for fellowships. Most attended allopathic medical schools (52/53, 98.1%). The average Scopus h-index was 15.7 (SD = 17.4). Gender-wise comparison of mean h-indices revealed 16.2 for males and 15 for females, with no statistically significant difference between the two groups (p = 0.81). Ten (18.9%) FDs and 20 (37.7%) FDs were at the same location they completed residency and fellowship training, respectively. Conclusions This cross-sectional study shows the present demographics within the cardiothoracic radiology FD position. This field of radiology is observed to have FDs with research productivity that is comparable with other medical specialties. Some radiology residency and fellowship programs were shown to produce more FDs than others; however, we were not able to identify causality. Program directors appear to be selected from a familiar pool of applicants, and ultimately FDs are being replaced by individuals with similar distinctions. Overall, this research into cardiothoracic radiology FDs demographics and research productivity can add to the current body of literature on FDs in various medical specialties. It is important to continue to reflect on medical leadership as the field continues to advance.

Volar Marginal Rim Fractures of the Distal Radius Have a Higher Rate of Associated Carpal Injuries-A Comparative Cohort Study.

Background Volar marginal rim distal radius fractures can be challenging due to volar instability of the carpus. The associated carpal injuries, however, have not previously been reported. Purpose The aim of this study was to compare volar marginal rim fractures to other distal radius fractures to determine if there is any association with other carpal injuries. If so, do these injuries lead to further instability and fixation failure? Materials and Methods A retrospective radiological review of 25 volar marginal rim fractures was conducted. This was compared with a comparison cohort of 25 consecutive intra-articular distal radius fractures not involving the volar marginal rim. All radiographs were reviewed for associated carpal injuries, including carpal and ulnar styloid fractures, scapholunate instability, and carpal translocation. Results Volar marginal rim fractures had a significantly higher incidence of associated carpal injuries per patient (2.52 vs. 1.64), scapholunate diastasis (36 vs. 12%), and carpal dislocation (80 vs. 48%). The fixation chosen was more likely to involve a volar rim-specific plate (44 vs. 0%). Following surgical fixation, the volar marginal rim fractures had a significantly higher incidence of carpal instability (56 vs. 24%), failure of fixation (24 vs. 0%), and revision surgery (12 vs. 0%). Conclusions Volar marginal rim fractures have significantly more carpal injuries, scapholunate instability, and volar carpal instability, compared with other distal radius fractures. Despite the use of volar rim-specific plating, volar marginal rim fractures have a significantly higher incidence of persistent carpal instability, including scapholunate instability, ulnar translocation, volar subluxation, failure of fixation, and revision surgery. Level of Evidence This is a level III, retrospective review.

Anatomical and Clinical Concepts in Distal Radius Volar Ulnar Corner fractures.

Background Volar ulnar corner fractures are a subset of distal radius fractures that can have disastrous complications if not appreciated, recognized, and appropriately managed. The volar ulnar corner of the distal radius is the "critical corner" between the radial calcar, distal ulna, and carpus and is responsible for maintaining stability while transferring force from the carpus. Description Force transmitted from the carpus to the radial diaphysis is via the radial calcar. A breach in this area of thickened cortex may result in the collapse of the critical corner. The watershed ridge (line) is clinically important in these injuries and must be appreciated during planning and fixation. Fractures distal to the watershed ridge create an added level of complexity and associated injuries must be managed. An osteoligamentous unit comprises bone-ligament-bone construct. Volar ulnar corner fractures represent a spectrum of osteoligamentous injuries each with their own associated injuries and management techniques. The force from the initial volar ulnar corner fracture can propagate along the volar rim resulting in an occult volar ligament injury, which is a larger zone of injury than appreciated on radiographs and computerized tomography scan. These lesions are often underestimated at the time of fixation, and for this reason, we refer to them as sleeper lesions. Unfortunately, they may become unmasked once the wrist is mobilized or loaded. Conclusions Management requires careful planning due to a relatively high rate of complications after fixation. A systematic approach to plate positioning, utilizing several fixation techniques beyond the standard volar rim plate, and utilizing fluoroscopy and/or arthroscopy is the key strategy to assist with management. In this article, we take a different view of the volar ulnar corner anatomy, applied anatomy of the region, associated injuries, and management options.

Feeding state functionally reconfigures a sensory circuit to drive thermosensory behavioral plasticity.

Internal state alters sensory behaviors to optimize survival strategies. The neuronal mechanisms underlying hunger-dependent behavioral plasticity are not fully characterized. Here we show that feeding state alters C. elegans thermotaxis behavior by engaging a modulatory circuit whose activity gates the output of the core thermotaxis network. Feeding state does not alter the activity of the core thermotaxis circuit comprised of AFD thermosensory and AIY interneurons. Instead, prolonged food deprivation potentiates temperature responses in the AWC sensory neurons, which inhibit the postsynaptic AIA interneurons to override and disrupt AFD-driven thermotaxis behavior. Acute inhibition and activation of AWC and AIA, respectively, restores negative thermotaxis in starved animals. We find that state-dependent modulation of AWC-AIA temperature responses requires INS-1 insulin-like peptide signaling from the gut and DAF-16/FOXO function in AWC. Our results describe a mechanism by which functional reconfiguration of a sensory network via gut-brain signaling drives state-dependent behavioral flexibility.

Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing Progression during Ketogenic Diet Therapy.

Glioblastoma (GBM) metabolism has traditionally been characterized by a primary dependence on aerobic glycolysis, prompting the use of the ketogenic diet (KD) as a potential therapy. In this study we evaluated the effectiveness of the KD in GBM and assessed the role of fatty acid oxidation (FAO) in promoting GBM propagation. In vitro assays revealed FA utilization throughout the GBM metabolome and growth inhibition in nearly every cell line in a broad spectrum of patient-derived glioma cells treated with FAO inhibitors. In vivo assessments revealed that knockdown of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme for FAO, reduced the rate of tumor growth and increased survival. However, the unrestricted ketogenic diet did not reduce tumor growth and for some models significantly reduced survival. Altogether, these data highlight important roles for FA and ketone body metabolism that could serve to improve targeted therapies in GBM.

Neanderthal-Denisovan ancestors interbred with a distantly related hominin.

Previous research has shown that modern Eurasians interbred with their Neanderthal and Denisovan predecessors. We show here that hundreds of thousands of years earlier, the ancestors of Neanderthals and Denisovans interbred with their own Eurasian predecessors-members of a "superarchaic" population that separated from other humans about 2 million years ago. The superarchaic population was large, with an effective size between 20 and 50 thousand individuals. We confirm previous findings that (i) Denisovans also interbred with superarchaics, (ii) Neanderthals and Denisovans separated early in the middle Pleistocene, (iii) their ancestors endured a bottleneck of population size, and (iv) the Neanderthal population was large at first but then declined in size. We provide qualified support for the view that (v) Neanderthals interbred with the ancestors of modern humans.

Reduced Aseptic Loosening With Fully Cemented Short-Stemmed Tibial Components in Primary Cemented Total Knee Arthroplasty.

BACKGROUND: Recently, the use of short tibial stems in the obese population undergoing total knee arthroplasty (TKA) has been proposed. Thus, we designed a study to assess tibial component survivorship after primary TKA using a single implant both with and without a fully cemented stem extension performed by a single surgeon. METHODS: A search of our institutional research database was performed. A minimum 2-year follow-up was selected. Cohorts were created according to patient body mass index (BMI; >40 kg/m2 and <40 kg/m2) and the presence (stemmed tibia [ST]) or absence (non-stemmed tibia [NST]) of a short tibial stem extension. Kaplan-Meier survival analyses for aseptic loosening and log-rank tests were performed. RESULTS: A total of 236 patients were identified (ST = 162, NST = 74). Baseline patient characteristics were statistically similar between cohorts with the exception of BMI which was greater in the ST cohort (32.9 kg/m2, 30.6 kg/m2; P = .01). Kaplan-Meier survival analysis at 5 years was superior for the BMI < 40 kg/m2 cohort (98.9%, 93.1%; P = .045), the ST cohort (100%, 94.5%; P = .006), and the BMI > 40 kg/m2 with ST cohort at 4 years (71.4%, 100%; P = .008). CONCLUSION: Morbid obesity and a short native tibial stem design appear to be associated with aseptic loosening in primary TKA. This appears to be mitigated through the use of an ST. As such, the use of ST may be considered in at-risk patients. Alternatively, implants with longer native stem designs can be employed. Modern short-stemmed tibial components may need to be redesigned.

Epigenetic Signaling in Glia Controls Presynaptic Homeostatic Plasticity.

Epigenetic gene regulation shapes neuronal fate in the embryonic nervous system. Post-embryonically, epigenetic signaling within neurons has been associated with impaired learning, autism, ataxia, and schizophrenia. Epigenetic factors are also enriched in glial cells. However, little is known about epigenetic signaling in glia and nothing is known about the intersection of glial epigenetic signaling and presynaptic homeostatic plasticity. During a screen for genes involved in presynaptic homeostatic synaptic plasticity, we identified an essential role for the histone acetyltransferase and deubiquitinase SAGA complex in peripheral glia. We present evidence that the SAGA complex is necessary for homeostatic plasticity, demonstrating involvement of four new genes in homeostatic plasticity. This is also evidence that glia participate in presynaptic homeostatic plasticity, invoking previously unexplored intercellular, homeostatic signaling at a tripartite synapse. We show, mechanistically, SAGA signaling regulates the composition of and signaling from the extracellular matrix during homeostatic plasticity.