Conversion Rate of Abstracts Presented at Plastic Surgery The Meeting From 2010 to 2019: A 10-Year Analysis of Factors for Success.

BACKGROUND: Presentations are an important means of knowledge generation. Publication of these studies is important for dissemination of findings beyond meeting attendees. We analyzed a 10-year sample of presented abstracts at Plastic Surgery The Meeting and describe factors that improve rate and speed of conversion to peer-reviewed publication. METHODS: Abstracts presented between 2010 and 2019 at Plastic Surgery The Meeting were sourced from the American Society of Plastic Surgery Abstract Archive. A random sample of 100 abstracts from each year was evaluated. Abstract information and demographics were recorded. The title or author and keywords of each abstract were searched using a standardized workflow to find a corresponding published paper on PubMed, Google Scholar, and Google. Data were analyzed for trends and factors affecting conversion rate. RESULTS: A total of 983 presented abstracts were included. The conversion rate was 54.1%. Residents and fellows constituted the largest proportion of presenters (38.4%). There was a significant increase in medical student and research fellow presenters during the study period (P < 0.001). Conversion rate was not affected by the research rank of a presenter's affiliated institution (ß = 1.001, P = 0.89), geographic location (P = 0.60), or subspecialty tract (P = 0.73). US academics had a higher conversion rate (61.8%) than US nonacademics (32.7%) or international presenters (47.1%) (P < 0.001). Medical students had the highest conversion rate (65.6%); attendings had the lowest (45.0%). Research fellows had the lowest average time to publication (11.6 months, P = 0.007). CONCLUSIONS: Lower levels of training, factors associated with increased institution-level support, and research quality affect rate and time to publication. These findings highlight the success of current models featuring medical student and research fellow-led projects with strong resident and faculty mentorship.

Reactive Oxygen Species Modulation in the Current Landscape of Anticancer Therapies.

Significance: Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism, and are tightly controlled through homeostatic mechanisms to maintain intracellular redox, regulating growth and proliferation in healthy cells. However, ROS production is perturbed in cancers where abnormal accumulation of ROS leads to oxidative stress and genomic instability, triggering oncogenic signaling pathways on one hand, while increasing oxidative damage and triggering ROS-dependent death signaling on the other. Recent Advances: Our review illuminates how critical interactions between ROS and oncogenic signaling, the tumor microenvironment, and DNA damage response (DDR) pathways have led to interest in ROS modulation as a means of enhancing existing anticancer strategies and developing new therapeutic opportunities. Critical Issues: ROS equilibrium exists via a delicate balance of pro-oxidant and antioxidant species within cells. "Antioxidant" approaches have been explored mainly in the form of chemoprevention, but there is insufficient evidence to advocate its routine application. More progress has been made via the "pro-oxidant" approach of targeting cancer vulnerabilities and inducing oxidative stress. Various therapeutic modalities have employed this approach, including direct ROS-inducing agents, chemotherapy, targeted therapies, DDR therapies, radiotherapy, and immunotherapy. Finally, emerging delivery systems such as "nanosensitizers" as radiotherapy enhancers are currently in development. Future Directions: While approaches designed to induce ROS have shown considerable promise in selectively targeting cancer cells and dealing with resistance to conventional therapies, most are still in early phases of development and challenges remain. Further research should endeavor to refine treatment strategies, optimize drug combinations, and identify predictive biomarkers of ROS-based cancer therapies.

Programmable RNA-guided DNA endonucleases are widespread in eukaryotes and their viruses.

Programmable RNA-guided DNA nucleases perform numerous roles in prokaryotes, but the extent of their spread outside prokaryotes is unclear. Fanzors, the eukaryotic homolog of prokaryotic TnpB proteins, have been detected in genomes of eukaryotes and large viruses, but their activity and functions in eukaryotes remain unknown. Here, we characterize Fanzors as RNA-programmable DNA endonucleases, using biochemical and cellular evidence. We found diverse Fanzors that frequently associate with various eukaryotic transposases. Reconstruction of Fanzors evolution revealed multiple radiations of RuvC-containing TnpB homologs in eukaryotes. Fanzor genes captured introns and proteins acquired nuclear localization signals, indicating extensive, long-term adaptation to functioning in eukaryotic cells. Fanzor nucleases contain a rearranged catalytic site of the RuvC domain, similar to a distinct subset of TnpBs, and lack collateral cleavage activity. We demonstrate that Fanzors can be harnessed for genome editing in human cells, highlighting the potential of these widespread eukaryotic RNA-guided nucleases for biotechnology applications.

Living Alone, Environmental Hazards, and Falls Among U.S. Older Adults.

Background and Objectives: Physical conditions of living environments can affect the incidence of falls; however, prior work has focused typically on 1 domain at a time-either neighborhood or home, capturing limited environmental boundaries of older adults. We examined how neighborhood together with the home environment affect the incidence of falls over time and whether living arrangement modifies the influence of the environmental risks on falls. Research Design and Methods: Using the 2012-2020 waves of the Health and Retirement Study (HRS; N = 1,893), we fitted logistic regression to estimate the incidence of falls over an 8-year study period. We used the neighborhood and housing data that are collected systematically by trained observers in the HRS to assess environmental hazards. Sidewalk quality, neighborhood disorder, and the presence of green space were measured to capture outdoor environmental hazards. Indoor environmental hazards included the presence of housing decay and poorly maintained stairways. All models were stratified by living arrangement. Results: Neighborhood and housing environment were independently associated with the odds of falls net of demographic characteristics and preexisting health conditions, and effects were significant for people living alone only. The presence of green space and poorly maintained stairways were associated with greater odds of falling, net of covariates during 8 years of follow-up (odds ratios = 2.10 and 2.65, p < .05, respectively). None of the environmental risk factors were significant for those living with others. Discussion and Implications: Falls in old age may be determined in part by a combination of outdoor and indoor risk factors. More research is needed to understand pathways that lead to greater vulnerability among older adults living alone to environmental hazards.

Programmable RNA-guided endonucleases are widespread in eukaryotes and their viruses.

TnpB proteins are RNA-guided nucleases that are broadly associated with IS200/605 family transposons in prokaryotes. TnpB homologs, named Fanzors, have been detected in genomes of some eukaryotes and large viruses, but their activity and functions in eukaryotes remain unknown. We searched genomes of diverse eukaryotes and their viruses for TnpB homologs and identified numerous putative RNA-guided nucleases that are often associated with various transposases, suggesting they are encoded in mobile genetic elements. Reconstruction of the evolution of these nucleases, which we rename Horizontally-transferred Eukaryotic RNA-guided Mobile Element Systems (HERMES), revealed multiple acquisitions of TnpBs by eukaryotes and subsequent diversification. In their adaptation and spread in eukaryotes, HERMES proteins acquired nuclear localization signals, and genes captured introns, indicating extensive, long term adaptation to functioning in eukaryotic cells. Biochemical and cellular evidence show that HERMES employ non-coding RNAs encoded adjacent to the nuclease for RNA-guided cleavage of double-stranded DNA. HERMES nucleases contain a re-arranged catalytic site of the RuvC domain, similar to a distinct subset of TnpBs, and lack collateral cleavage activity. We demonstrate that HERMES can be harnessed for genome editing in human cells, highlighting the potential of these widespread eukaryotic RNA-guided nucleases for biotechnology applications.

Mycobacterium tuberculosis Inhibitors Based on Arylated Quinoline Carboxylic Acid Backbones with Anti-Mtb Gyrase Activity.

New antitubercular agents with either a novel mode of action or novel mode of inhibition are urgently needed to overcome the threat of drug-resistant tuberculosis (TB). The present study profiles new arylated quinoline carboxylic acids (QCAs) having activity against replicating and non-replicating Mycobacterium tuberculosis (Mtb), the causative agent of TB. Thus, the synthesis, characterization, and in vitro screening (MABA and LORA) of 48 QCAs modified with alkyl, aryl, alkoxy, halogens, and nitro groups in the quinoline ring led to the discovery of two QCA derivatives, 7i and 7m, adorned with C-2 2-(naphthalen-2-yl)/C-6 1-butyl and C-2 22-(phenanthren-3-yl)/C-6 isopropyl, respectively, as the best Mtb inhibitors. DNA gyrase inhibition was shown to be exhibited by both, with QCA 7m illustrating better activity up to a 1 µM test concentration. Finally, a docking model for both compounds with Mtb DNA gyrase was developed, and it showed a good correlation with in vitro results.

Arg-tRNA synthetase links inflammatory metabolism to RNA splicing and nuclear trafficking via SRRM2.

Cells respond to perturbations such as inflammation by sensing changes in metabolite levels. Especially prominent is arginine, which has known connections to the inflammatory response. Aminoacyl-tRNA synthetases, enzymes that catalyse the first step of protein synthesis, can also mediate cell signalling. Here we show that depletion of arginine during inflammation decreased levels of nuclear-localized arginyl-tRNA synthetase (ArgRS). Surprisingly, we found that nuclear ArgRS interacts and co-localizes with serine/arginine repetitive matrix protein 2 (SRRM2), a spliceosomal and nuclear speckle protein, and that decreased levels of nuclear ArgRS correlated with changes in condensate-like nuclear trafficking of SRRM2 and splice-site usage in certain genes. These splice-site usage changes cumulated in the synthesis of different protein isoforms that altered cellular metabolism and peptide presentation to immune cells. Our findings uncover a mechanism whereby an aminoacyl-tRNA synthetase cognate to a key amino acid that is metabolically controlled during inflammation modulates the splicing machinery.

Polyphenolic Natural Products Active In Silico Against SARS-CoV-2 Spike Receptor Binding Domains and Non-structural Proteins - A Review.

The ongoing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has been proven to be more severe than the previous coronavirus outbreaks due to the virus' high transmissibility. With the emergence of new variants, this global phenomenon took a more dramatic turn, with many countries recently experiencing higher surges of confirmed cases and deaths. On top of this, the inadequacy of effective treatment options for COVID-19 aggravated the problem. As a way to address the unavailability of target-specific viral therapeutics, computational strategies have been employed to hasten and systematize the search. The objective of this review is to provide initial data highlighting the utility of polyphenols as potential prophylaxis or treatment for COVID-19. In particular, presented here are virtually screened polyphenolic compounds which showed potential as either antagonists to viral entry and host cell recognition through binding with various receptor-binding regions of SARS-CoV-2 spike protein or as inhibitors of viral replication and post-translational modifications through binding with essential SARS-CoV-2 non-structural proteins.

Drag-and-drop genome insertion of large sequences without double-strand DNA cleavage using CRISPR-directed integrases.

Programmable genome integration of large, diverse DNA cargo without DNA repair of exposed DNA double-strand breaks remains an unsolved challenge in genome editing. We present programmable addition via site-specific targeting elements (PASTE), which uses a CRISPR-Cas9 nickase fused to both a reverse transcriptase and serine integrase for targeted genomic recruitment and integration of desired payloads. We demonstrate integration of sequences as large as ~36 kilobases at multiple genomic loci across three human cell lines, primary T cells and non-dividing primary human hepatocytes. To augment PASTE, we discovered 25,614 serine integrases and cognate attachment sites from metagenomes and engineered orthologs with higher activity and shorter recognition sequences for efficient programmable integration. PASTE has editing efficiencies similar to or exceeding those of homology-directed repair and non-homologous end joining-based methods, with activity in non-dividing cells and in vivo with fewer detectable off-target events. PASTE expands the capabilities of genome editing by allowing large, multiplexed gene insertion without reliance on DNA repair pathways.

Piriformis syndrome as a result of intramuscular haematoma mimicking cauda equina effectively treated with piriformis tendon release.

We present a case of piriformis syndrome in a woman in her 30's following low energy trauma, presenting with unilateral lower limb weakness, altered sensation and urinary retention. CT imaging revealed a bulky piriformis muscle which was further clarified on MRI as an intramuscular haematoma within the left piriformis causing compression of the left lumbosacral plexus. Haematoma formation was exacerbated due to use of an antiplatelet medication the patient was taking for Moyamoya disease, which carries an increased risk of cerebrovascular accident. Surgical exploration of the piriformis and sciatic nerve was undertaken and confirmed a haematoma within the piriformis. A full release of the piriformis tendon was undertaken, and the sciatic nerve was inspected, no further abnormality was found. After review in clinic post-discharge, the patient reported normal sensation and normal muscle power in her feet.

Understanding the Pathophysiology of L5-S1 Loss of Lordosis and Retrolisthesis: An EOS Study of Lumbopelvic Movement Between Standing and Slump Sitting Postures.

OBJECTIVE: To understand the pathophysiology of L5-S1 loss of lordosis and retrolisthesis by comparing 2 commonly assumed physiological weight-bearing postures. METHODS: This was a prospective comparative study of whole-body standing and slump sitting EOS radiographs in clinic patients presenting with back pain or lower limb radicular pain. Patients with prior spinal intervention, malignancy, trauma, inflammatory diseases, transitional lumbosacral vertebra, pregnancy, and L5-S1 retrolisthesis or spondylolisthesis from nondegenerative causes were excluded. C7 sagittal vertical axis, global cervical angle, global thoracic angle, global lumbar angle, thoracolumbar angle, T1-slope, pelvic incidence, pelvic tilt, sacral slope, L5-S1 angle, L5-S1 vertebral translation, L5-S1 disc height, and presence of L4-5 vertebral translation were measured. Univariate and multivariate analyses were performed to identify predictors of L5-S1 lordosis loss and retrolisthesis. RESULTS: L5-S1 loss of lumbar lordosis (7.02 ± 9.90°, P < 0.001), retrolisthesis (0.07 ± 0.411 cm, P < 0.001), and loss of disc height (0.10 ± 0.23 cm, P < 0.001) occurred when changing from standing to slump sitting along with other sagittal profile changes (P < 0.001). Taller L5-S1 disc height (odds ratio [OR] 2.57, P = 0.04), larger lumbar range-of-motion change (OR 3.82, P = 0.012), lower sacral slope on sitting (OR 2.50, P = 0.043), and presence of L4-5 spondylolisthesis (OR 2.75, P = 0.032) were predictive of larger L5-S1 lordosis loss (>7°) on multivariate analysis, while larger lumbar range-of-motion change (OR 2.21, P = 0.050) and presence of L4-5 spondylolisthesis (OR 3.08, P = 0.023) were predictive of greater L5-S1 retrolisthesis (>0.07 cm). CONCLUSIONS: Degenerative L5-S1 loss of lordosis and retrolisthesis likely result from long-standing lower lumbar spine bending forces against the posterior ligamentous complex with slump sitting, predisposed by a negatively sloped sacrum and increased lumbar flexibility.

Primary total hip replacement using Burch-Schneider cages for acetabular fractures.

INTRODUCTION: Osteoporotic acetabular fractures are common and pose a difficult technical challenge for the trauma surgeon. Acute total hip arthroplasty (THA) using a Burch-Schneider antiprotrusio cage with immediate postoperative weight-bearing is a method to approach these injuries. This case series reports our outcomes of acute THA using Burch-Schneider cages for acetabular fractures from a UK major trauma centre based on length of stay, radiological outcome, complications and outcome scores. METHODS: Data were collected from all patients who underwent acute THA with a Burch-Schneider cage for acetabular fractures between June 2006 and August 2015. Patients were followed up clinically, radiologically, and using Oxford Hip Scores (OHS). RESULTS: 20 patients with a median age of 73 (range 60-90 years) were identified. All patients were independent walkers at follow-up, and had achieved radiological union. There were no dislocations, subsidence, revision or deep infections. Significant complications include 1 perioperative death as a result of complications arising from pre-existing pulmonary fibrosis; 1 deep vein thrombosis; 1 intraoperative arterial injury to the superior gluteal artery; and 1 leg-length discrepancy. Mean length of stay was 10 days. The mean OHS was 37/48 at a mean follow-up of 26 months. CONCLUSIONS: This case series further validates the use of Burch-Schneider cages with primary THA in acute acetabular fractures.

The Theoretical Framework of the Clinical Pilates Exercise Method in Managing Non-Specific Chronic Low Back Pain: A Narrative Review.

Exercise plays an important role in rehabilitating people with chronic low back pain. Aerobic exercise and resistance training are general exercise strategies to manage chronic low back pain, but these strategies require longer intervention period to achieve clinical outcomes in pain reduction and functional improvements. Directional preference is recognised as an important exercise strategy in managing low back pain. The Clinical Pilates exercise method leverages on the directional preference of an individual to achieve clinical outcomes faster. Clinical Pilates is a hybrid of two of the best exercise interventions for low back pain, which are general Pilates and the McKenzie method. Due to the scarcity of Clinical Pilates literature, a review of its theory and studies was undertaken to provide a structured guide to the technique in managing people with chronic low back pain. Hypothetical algorithms are developed to support translation into clinical practice and future research studies. These algorithms are useful in the management of complex cases involving multiple directional trauma. Although limited, current evidence suggests that the Clinical Pilates exercise method is safe and provides faster functional recovery in the early stage of rehabilitation and similar longer term outcomes as general exercises.

Cattle-Related Trauma: A 5-Year Retrospective Review in a Adult Major Trauma Center.

INTRODUCTION: Bovine injuries are a common and significant cause of trauma, often requiring admission and operative treatment. We review all bovine-related injuries over 5 years, both emergency and general practitioner (GP) referrals at an adult major trauma center in England. METHODS: Retrospective evaluation was undertaken using the keywords through radiology referrals and hospital admissions speciality databases. By searching patient notes, demographics were collected as well as the mechanism and the situation of injury; trauma scores were calculated using: injury severity score (ISS) and probability of survival (Ps19). The results were divided into emergency patients and GP referrals. RESULTS: Sixty-seven patients were identified retrospectively over 5 years, 44 emergency patients (including 23 major traumas), and 23 GP referrals. Combined (emergency and GP) mean age 52 years old; 67% male; and mean ISS 11. Most common combined mechanism of injury, kicked (n = 23). In emergency patients, trampling injuries were the most common. Eighty-six percent of the trampled patients were major traumas and associated with increased ISS (mean 13). Indirect injuries mainly involved farm gates (92%). Seventy-three percent of bull-related injuries were major traumas and had increased ISS scores (mean 17). Orthopaedics was the most common admitting speciality followed by cardiothoracic and neurosurgery. In emergency patients, fractures were the most common primary injury (n = 20), upper limb followed by spine. In GP, soft-tissue injuries were the most common primary injury. Seventy percent of the emergency referrals required admission and 50% operations. Fracture fixation was the most common operative procedure. Only, one GP referral required an operation. There were significant delays in GP patients presenting. Two patients had a Ps19 score <90. There were two mortalities. CONCLUSION: Cattle-related injuries are a significant cause of severe morbidity and mortality. They are under-reported. Patterns of injury are similar to high-velocity road traffic collisions and bull-related injuries or trampling in particular, should alert the clinician to more significant trauma. Farm gates are a frequent cause of trauma associated with cattle. GP referrals with ongoing symptoms for more than 2 weeks seeking medical advice should alert the clinician to a more serious diagnosis.

Genoppi is an open-source software for robust and standardized integration of proteomic and genetic data.

Combining genetic and cell-type-specific proteomic datasets can generate biological insights and therapeutic hypotheses, but a technical and statistical framework for such analyses is lacking. Here, we present an open-source computational tool called Genoppi (lagelab.org/genoppi) that enables robust, standardized, and intuitive integration of quantitative proteomic results with genetic data. We use Genoppi to analyze 16 cell-type-specific protein interaction datasets of four proteins (BCL2, TDP-43, MDM2, PTEN) involved in cancer and neurological disease. Through systematic quality control of the data and integration with published protein interactions, we show a general pattern of both cell-type-independent and cell-type-specific interactions across three cancer cell types and one human iPSC-derived neuronal cell type. Furthermore, through the integration of proteomic and genetic datasets in Genoppi, our results suggest that the neuron-specific interactions of these proteins are mediating their genetic involvement in neurodegenerative diseases. Importantly, our analyses suggest that human iPSC-derived neurons are a relevant model system for studying the involvement of BCL2 and TDP-43 in amyotrophic lateral sclerosis.

The effect of COVID-19 pandemic on the care of fragility hip fracture patients in the United Kingdom. A case control study in a major trauma centre.

INTRODUCTION: Coronavirus disease 2019 is a pandemic that forced a transformation in the services provided by the National Health Service in the United Kingdom. Fragility hip fractures account for over 65,000 cases per year in the elderly population. The study aims to assess the impact of the pandemic on fragility hip fractures. METHODS: A retrospective data gather was performed to identify fragility hip fractures from the 23rd of March 2020 to the 13th of May 2020, and from the 23rd of March 2019 to the 13th of May 19. Two groups were formed and compared over their 30 day follow up. RESULTS: The control group comprised of 97 patients, with a mean age of 82.1 years old (62-102 years) and M:F ratio of 38:59. The case group comprised of 102 patients, with a mean age of 82.3 years old (60-100 years) and a M:F ratio of 16:86. Significant differences between groups were identified for gender (p < 0.001), time to theatre (p = 0.002), length of stay (p < 0.001) and COVID-19 status (p = 0.001). In the Case group, association with mortality was found for male gender (p = 0.041), right side (p = 0.031) and COVID-19 positive test results (p = 0.011). CONCLUSION: Early surgical intervention is advocated wherever possible, and sufficient optimisation, prior to surgery whenever a COVID-19 positive patient is identified. A safe rehabilitation environment is paramount for recovery in this group of patients. Further studies are required to understand the effect of this pandemic on the fragility hip fractures. LEVEL OF EVIDENCE: Level III: Retrospective case-control study.

Pelvic and acetabular fracture management in intravenous drug users.

INTRODUCTION: Pelvic and acetabular fractures are significant injuries associated with high morbidity or mortality. Intravenous drug users (IVDU) represent a challenging group of patients, with an increased risk of complications and infection. To our knowledge there has not been any published literature concerning IVDU and this type of injuries. PATIENTS AND METHODS: A group of 19 patients with a history of IVDU and who had sustained an injury were identified. RESULTS: The mean age at injury was 36 years old; nine had a pelvic fracture and ten had an acetabular fracture. No complications were observed in the pelvic group. In the acetabular group, the infection risk was 50% and the risk of femoral head avascular necrosis was 33%. The mean follow up was 43.1 months from injury. CONCLUSION: We advise emphasis in the high infection and avascular necrosis rates, when consenting the patient for an operation. Furthermore, non-operative treatment should be considered, where possible. LEVEL OF EVIDENCE: Level III. Retrospective cohort study. Prognostic-investigating the effect of a patient characteristic on the outcome of the disease.

Can locking plate fixation of symphyseal disruptions allow early weight bearing?

INTRODUCTION: Anterior pubic symphyseal plate fixation is the recommended treatment for disruption of pubic symphysis in an unstable pelvic ring injury. The rigid construct offered by locking symphyseal plate has the theoretical advantage of allowing patients to weight bear early. However, there are concerns of catastrophic failure about the locked plate construct. The purpose of the study was to establish if locking plate fixation for pubic symphysis disruption was effective to allow patients to mobilise weight bearing immediately after surgery. PATIENT AND METHODS: Retrospective analysis of a prospectively collected database from a single centre was performed. The study period was from 2008 to 2017. Radiographic evidence of fixation failure, revision surgery, removal of metalwork and follow up duration was noted. RESULTS: We identified 46 patients (F:M 8:38) with a mean age of 46 years (range 14 to 74 years). Based on the mechanism of injury patients were classified into Antero-posterior compression (28), Vertical shear [10], lateral compression [4] and combined mechanism [4]. Either a 4-hole or 6-hole locking plate was used in all patients, depending on fracture extension. Posterior fixation was required in 28 (61%) patients. All patients were allowed to fully or partial weight bear. The mean radiological follow-up period was 31 weeks with 13 (28%) patients having evidence of radiological failure. Revision was performed in 1 (2%) patient, in whom the screws had pulled out of the bone. The most common mode of failure was either the screw backing out from the plate or broken screw. Among the 4 (8%) patients who had their metalwork removed, 1 (2%) had delayed onset of infection, 2 (4%) had symptoms related to backed out screw and 1 (2%) opted electively to have metalwork removed. CONCLUSIONS: With our series of patients, we have found that using locking plate for pubic symphyseal diastasis is safe and effective in allowing patients to weight bear early. A low complication rate and need for re-operation is demonstrated.