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Epilepsy is characterized by spontaneous non-provoked seizures, yet the mechanisms that trigger a seizure and allow its evolution remain underexplored. To dissect out phases implicated in the development of a seizure, we evoked hypersynchronous activity with optogenetic stimulation. Focal optogenetic activation of putative excitatory neurons in the mouse hippocampal CA1 reliably evoked convulsive seizures in awake mice. A novel time-vs-time “pulsogram” plot characterized the evolution of the EEG pulse response from a light evoked response to induced seizure activity. Our results depict ictogenesis as a stepwiseprocess comprised of three distinctive phases demarcated by two transition points. The induction phase undergoes the first transition to reverberant phase activity, followed by the second transition into the paroxysmal phase or a seizure. Non-seizure responses are confined to either induction or reverberant phases, suggesting ictogenesis can be stopped at these stages, thus offering novel therapeutic perspectives to abort a seizure before it develops.

Drilling through hard rock to explore for underground oil and gas is especially complicated in geographic areas where the sub-layer is full of dense and impenetrable rock. Charlie Scent, an Engineering Professor working at a university, undertook research to solve this dilemma and developed a solution after approximately 20 years of effort. To commercialize the technology, Scent collaborated with one of his PhD students and formed a company. Through the commercialization process, friction developed among the participants—Scent, the graduate student, and the university. This discord brought to light several important questions regarding intellectual property that is created in a university setting. This case is about who owns intellectual property and decreasing the probability that there will be friction between the individuals who are at the heart of an invention.

Meloidogyne enterolobii (syn. mayaguensis) is an emergent species of root-knot nematode that has become a serious threat to sweet potato (Ipomoea batatas) production in the southeastern United States. The most popular sweet potato cultivars grown in this region are highly susceptible to M. enterolobii. As a result, this pest has spread across most of the sweet potato growing counties in the Carolinas, threatening the industry as well as other crops in the region. The development and release of new sweet potato cultivars with resistance to M. enterolobii would help to manage and slow the spread of this pest. To support sweet potato resistance breeding efforts, 93 accessions selected from the U.S. Department of Agriculture germplasm collection and breeding programs in the United States were screened to identify 19 lines with strong resistance to M. enterolobii. The resistance in these accessions was tested against two M. enterolobii isolates that were collected from sweet potato production fields in the Carolinas. These isolates were found to have distinct pathotypes, with galling and nematode reproduction differences observed on cotton as well as sweet potato. This study is the first report of intraspecific pathotypic variation in M. enterolobii, and it identifies sweet potato germplasm with resistance against both pathogenic variants of this nematode.

The use of antibiotics directly correlates with the increase in antimicrobial resistance (AMR). Targeting novel antibiotics to patients with multidrug-resistant (MDR) pathogens should enhance their durability and slow development of resistance. The discovery, development, and clinical adoption of pathogen-targeted antibiotics have been hampered by technical and regulatory challenges. Growing insights into bacterial physiology and mechanisms of resistance, innovative clinical trial designs, streamlined regulatory approval pathways, and availability of rapid bacterial diagnostics are recent developments that can help address those challenges. Pathogen-targeted antibiotics provide an opportunity to treat patients with the right drug at the right time, leading to improved patient outcomes and better antimicrobial stewardship. Patient-centered pricing and reimbursement reform is needed to incentivize innovation.

Neck injuries in football are attributed to helmet-to-helmet contact with youth players being at greatest risk. In 2014, the National Federation of State High School Associations (NFHS) implemented rules defining illegal contact against a defenseless player above the shoulders to reduce head and neck injuries in football players. This study evaluates whether rule implementation decreased rates of high school football neck injuries presenting to the emergency department (ED) pre-rule implementation (2009-2013) to post-rule implementation (2015-2019).Data were queried from the National Electronic Injury Surveillance System for high school football players 14 to 18 years old diagnosed with a neck injury from 1 January 2009 to 31 December 2019. Narratives in the data were reviewed for mechanism of injury, setting, loss of consciousness (LOC), and type of injury.Between 2009 and 2019, an estimated 47,577 high school football neck injuries were diagnosed in EDs across the United States. 52.0% of neck injuries were sustained during competition compared to 48.0% during practice. A statistically significant (This study is the first to identify a decrease in overall and helmet-to-helmet related neck injuries diagnosed in the ED following the 2014 NFHS targeting rule implementation. These findings add to the growing literature regarding the importance and efficacy of rule implementation in reducing sports-related neck injuries.

Background This study directly compares the recurrence rates of dorsal wrist ganglion cysts in patients treated via open surgical excision versus arthroscopic surgical excision. We hypothesized that there would be no difference between recurrence rates with these 2 surgical options. Methods We retrospectively reviewed the charts of all patients with a dorsal ganglion cyst undergoing either open or arthroscopic surgical excision at a single academic center with 3 fellowship-trained attending hand surgeons from 2012 to 2017. Charts were identified using Current Procedural Terminology codes and were reviewed using postoperative office notes for preoperative and postoperative symptoms, episodes of recurrence, time at which recurrence occurred, subsequent operations, and outcome at final follow-up. Results The charts of 172 patients undergoing either arthroscopic or open dorsal ganglion excision were reviewed. Nine of 54 (16.7%) arthroscopic excisions resulted in cyst recurrence, while 8 of 118 (6.8%) open excisions resulted in cyst recurrence ( P = .044). Two of 9 (22%) recurrences after arthroscopic ganglion excision versus 2 of 8 (25%) recurrences after open ganglion excision underwent repeat surgical intervention. Time to recurrence, as well as final follow-up, was not statistically different between groups. Conclusions Dorsal wrist ganglion cysts are the most common benign soft tissue mass of the upper extremity, but it remains unknown whether arthroscopic or open surgical excision leads to lower recurrence rate. Scant literature exists directly comparing these 2 methods of surgical excision. This study suggests that open excision of dorsal wrist ganglia leads to a lower recurrence rate than does arthroscopic excision.

Soybean (Glycine max [L.] Merrill) yield losses as a result of plant diseases were estimated by university and government plant pathologists in 29 soybean producing states in the United States and in Ontario, Canada, from 2015 through 2019. In general, the estimated losses that resulted from each of 28 plant diseases or pathogens varied by state or province as well as year. Soybean cyst nematode (SCN) (Heterodera glycines Ichinohe) caused more than twice as much loss as any other disease during the survey period. Seedling diseases (caused by various pathogens), Sclerotinia stem rot (white mold) (caused by Sclerotinia sclerotiorum [Lib.] de Bary), and sudden death syndrome (caused by Fusarium virguliforme O’Donnell & T. Aoki) caused the next greatest yield losses, in descending order. Following SCN, the most damaging diseases in the northern United States and Ontario differed from those in the southern United States. The estimated mean economic loss from all soybean diseases, averaged across the United States and Ontario, Canada was US$45 per acre (US$111 per hectare). The outcome from the current survey will provide pertinent information regarding the important soybean diseases and their overall severity in the soybean crop and help guide future research and Extension efforts on managing soybean diseases.

Matthew W Konigsberg, John D Mueller, Jordan A Lebovic, R Kumar Kadiyala Department of Orthopedic Surgery, Columbia University Medical Center, New York, NY, USACorrespondence: Matthew W KonigsbergDepartment of Orthopedic Surgery, Columbia University Medical Center, 622 W. 168th St. 11th Floor, New York, NY 10032, USATel +1-212-305-5976Fax +1-212-305-6193Email Mk3294@cumc.columbia.eduIntroduction: The purpose of this study was to describe four cases of patients who developed concomitant upper extremity and gluteal compartment syndrome in the context of substance abuse. In somnolent patients unable to provide a reliable physical exam, the healthcare provider must be aware of patients presenting with concomitant upper extremity and gluteal compartment syndrome.Methods: Retrospective chart review identified cases of the combined upper extremity and gluteal compartment syndrome following illicit drug abuse at a single academic center during the years 2009– 2019.Results: During the 11-year period examined, a total of eight patients were diagnosed with compartment syndrome secondary to illicit drug use and prolonged immobilization. Four (50%) patients presented with combined upper extremity and gluteal compartment syndrome. All of these patients underwent prompt surgical release of the affected compartments. All eventually returned to normal activities of daily living.Discussion: Compartment syndrome is primarily a clinical diagnosis, with physical exam being extremely important. In patients presenting with somnolence secondary to illicit drug use, physical exam may not be reliable. It is critical to have a high clinical suspicion in this patient population, understanding that these patients may present with concomitant upper extremity and gluteal compartment syndrome.Level of Evidence: Level IV, case series.Keywords: compartment syndrome, fasciotomy, trauma, upper extremity, gluteal

Aims Medical comorbidities are a critical factor in the decision-making process for operative management and risk-stratification. The Hierarchical Condition Categories (HCC) risk adjustment model is a powerful measure of illness severity for patients treated by surgeons. The HCC is utilized by Medicare to predict medical expenditure risk and to reimburse physicians accordingly. HCC weighs comorbidities differently to calculate risk. This study determines the prevalence of medical comorbidities and the average HCC score in Medicare patients being evaluated by neurosurgeons and orthopaedic surgeon, as well as a subset of academic spine surgeons within both specialities, in the USA. Methods The Medicare Provider Utilization and Payment Database, which is based on data from the Centers for Medicare and Medicaid Services’ National Claims History Standard Analytic Files, was analyzed for this study. Every surgeon who submitted a valid Medicare Part B non-institutional claim during the 2013 calendar year was included in this study. This database was queried for medical comorbidities and HCC scores of each patient who had, at minimum, a single office visit with a surgeon. This data included 21,204 orthopaedic surgeons and 4,372 neurosurgeons across 54 states/territories in the USA. Results Orthopaedic surgeons evaluated patients with a mean HCC of 1.21, while neurosurgeons evaluated patients with a mean HCC of 1.34 (p < 0.05). The rates of specific comorbidities in patients seen by orthopaedic surgeons/neurosurgeons is as follows: Ischemic heart disease (35%/39%), diabetes (31%/33%), depression (23%/31%), chronic kidney disease (19%/23%), and heart failure (17%/19%). Conclusion Nationally, comorbidity rate and HCC value for these Medicare patients are higher than national averages for the US population, with ischemic heart disease being six-times higher, diabetes two-times higher, depression three- to four-times higher, chronic kidney disease three-times higher, and heart failure nine-times higher among patients evaluated by orthopaedic surgeons and neurosurgeons. Cite this article: Bone Joint Open 2020;1-6:257–260.

Background: Total shoulder arthroplasty (TSA) is an increasingly common procedure. This study looked at trends in TSA using a nationwide registry, with a focus on patient demographics, comorbidities, and complications. Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried for patients who underwent TSA from 2005 to 2018. Cohorts were created based on year of surgery: 2005-2010 (N = 1116), 2011-2014 (N = 5920), and 2015-2018 (N = 16,717). Patient demographics, comorbidities, operative time, hospital length of stay, discharge location, and complications within 30 days of surgery were compared between cohorts using bivariate and multivariate analysis. Results: Bivariate analysis revealed significantly more comorbidities among patients in the 2015-2018 cohort compared with the 2005-2010 cohort, specifically American Society of Anesthesiologist class III or IV (57.0% vs. 44.3%, P < .001), morbid obesity (10.8% vs. 7.8%, P < .001), diabetes (17.8% vs. 12.1%, P < .001), and chronic obstructive pulmonary disease (6.7% vs. 4.1%, P = .003). The use of regional anesthesia has decreased (5.6% in 2005-2010 vs. 2.8% in 2015-2018, P < .001), as has operative time (▵: −16 minutes, P < .001) and length of stay (▵: −0.6 days, P < .001). There were also significant decreased rates of perioperative blood transfusion (OR [odds ratio], 0.46), non-home discharge (OR, 0.79), urinary tract infection (OR, 0.47), and sepsis (OR, 0.17), (P < .001 for all comparisons) between the 2005-2010 and 2015-2018 cohorts. Conclusions: Between 2005 and 2018, patients undergoing TSA had increasingly more comorbidities but experienced lower rates of short-term complications, in the context of shorter hospitalizations and more frequent discharge to home.

Increasingly resistant Enterobacteriaceae have emerged as a health threat in both hospital and community settings. Infections of the urinary tract, once often treated with oral agents in the community, are requiring increased hospitalization and use of intravenously administered agents for effective treatment. These isolates often carry extended spectrum β-lactamases (ESBLs) and carbapenemases that necessitate the need for an inhibitor to cover a broad range of β-lactamases. ETX1317 is a novel diazabicyclooctane class serine β-lactamase inhibitor that restores the antibacterial activity of several classes of β-lactams, including third-generation cephalosporins such as cefpodoxime. ETX1317 is currently being developed as an orally available prodrug, ETX0282, to be administered with cefpodoxime proxetil (CPDP). The combination has demonstrated oral efficacy in murine models of infection. Pharmacokinetics established in preclinical species and pharmacokinetic/pharmacodynamic attributes suggest the orally administered combination ETX0282 + CPDP could serve as an effective treatment option against contemporary ESBL and carbapenemase-producing Enterobacteriaceae.

The Centers for Disease Control and the World Health Organization have issued a list of priority pathogens for which there are dwindling therapeutic options, including antibiotic-resistant Neisseri...

Multi-drug-resistant Enterobacteriales expressing a wide array of β-lactamases are emerging as a global health threat in both hospitals and communities. Although several intravenous drugs have recently been approved to address this need, there are no oral Gram-negative agents that are both safe and broadly effective against such pathogens. The lack of an effective oral agent is of concern for common infections which could otherwise be treated in the community but, due to antibiotic resistance, require hospitalization to allow for intravenous therapy. ETX1317 is a novel, broad spectrum, serine β-lactamase inhibitor of the diazabicyclooctane class that restores the antibacterial activity of multiple β-lactams against multiple species of multi-drug-resistant Enterobacteriales, including carbapenem-resistant strains. A combination of its oral prodrug, ETX0282, and the oral prodrug of a third-generation cephalosporin, cefpodoxime proxetil, is currently in clinical development. This report describes the biochemical and microbiological properties of ETX1317, which is more potent and demonstrates a greater breadth of inhibition than avibactam, the parenteral prototype of this class of β-lactamase inhibitors.

There are multiple techniques which attempt to maintain anatomic length-tension relationship during biceps tenodesis. However, no direct comparison has been performed with respect to the timing of biceps tenotomy during biceps tenodesis.Assess the incidence of Popeye deformity and clinical outcomes of two all-arthroscopic techniques for biceps tenodesis based on timing of the biceps tenotomy.A consecutive series of patients undergoing arthroscopic biceps tenodesis with concomitant rotator cuff tears were enrolled from 2019 to 2021. Biceps tenodesis performed after tenotomy formed the first cohort (Group 1). The other cohort had biceps tenodesis performed prior to biceps tenotomy (Group 2). Postoperative anterior arm pain, biceps muscle spasms, and patient perceptions of the appearance of the bicep muscle were assessed. In addition, Patient Reported Outcomes (PROs) were collected at 3 months and minimum 6 months postoperatively RESULTS: A total of 71 patients were eligible for participation and 62 patients (53% female, age 58.7 ± 9.0 years) were enrolled (n=33 in Group 1 and n=29 in Group 2). There were no differences between groups with respect to gender, age, and laterality of biceps tenodesis, as well as type and size of rotator cuff repair. At 3-month follow-up, VR12 Physical Health Scores were significantly improved in Group 2 (44.8 ± 9.7) compared to Group 1 (34.1 ± 3.4) (p=0.03). In addition, patients in Group 2 experienced significantly less pain in their anterior arm than patients in Group 1 (19% vs. 33%, p=0.02). There were no differences in biceps muscle spasm (3.4% vs. 5.2%; p=0.21) and no other differences in PROs between groups. Final follow-up which averaged 11.6 ± 3.3 months in Group 1 and 11.8 ± 5.5 months in Group 2. There were no significant differences in patient perceived biceps Popeye deformity between Group 1 (12.1%) and Group 2 (0%) (p=0.652). Furthermore, there were no differences in ASES, EQ5D, PROMIS 10 Physical Health, PROMIS 10 Depression, VR12 Physical Health, and SANE scores between the two technique groups.Patients with tenotomy performed after tenodesis had better VR12 Physical Health scores and less arm pain than patients with tenotomy performed before tenodesis at 3-month follow-up. However, there were no differences in any outcome at final follow-up of nearly 1-year. In addition, there were no differences in perceived Popeye deformity between groups at any time period.

To identify and analyze the 50 most-cited articles in patellar tendon injury research.The ISI Web of Science and SCOPUS databases were used to conduct a search for articles pertaining to patellar tendon injury. For the top 50 most-cited articles, bibliometric data (title, first and senior author, citation count, journal, publication year, citation density, country of origin, Level of Evidence [LOE]) and topic of article were recorded.The mean number of citations was 172.0 ± 88.2 (range 101-546). There was a statistically significant correlation between publication year and citation density (r = 0.61, P.01). The earliest article was the third most-cited article (362 citations), published by Blazina et al. in 1973, which discussed the epidemiology of patellar tendinopathy. The first and second most-cited articles (546 and 466 citations, respectively) covered surgical outcomes of patellar tendinopathy and prevalence of patellar tendinopathy among elite athletes. A total of 14 articles (28%) discussed nonoperative management, whereas only 5 articles discussed surgical management (10%). The most frequent LOE category was a LOE of IV (n = 18, 36%), but 19 studies (38%) were LOE I or LOE II.Among the top 50 most-cited studies regarding patellar tendon injury, a relatively high number were of a high LOE (19 Level I or II, 38%), affirming that these articles in patellar tendon injury research are not only influential, but also of high-quality evidence.This bibliometric analysis provides an efficient tool for educators, researchers, and evidence-based practitioners to identify and evaluate the most influential articles in patellar tendon injury research.

Epilepsy can be interpreted as altered brain rhythms from overexcitation or insufficient inhibition. Chemogenetic tools have revolutionized neuroscience research because they allow “on demand” excitation or inhibition of neurons with high cellular specificity. Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are the most frequently used chemogenetic techniques in epilepsy research. These engineered muscarinic receptors allow researchers to excite or inhibit targeted neurons with exogenous ligands. As a result, DREADDs have been applied to investigate the underlying cellular and network mechanisms of epilepsy. Here, we review the existing literature that has applied DREADDs to understand the pathophysiology of epilepsy. The aim of this review is to provide a general introduction to DREADDs with a focus on summarizing the current main findings in experimental epilepsy research using these techniques. Furthermore, we explore how DREADDs may be applied therapeutically as highly innovative treatments for epilepsy.

We investigated the causes and impact of procrastination on “slippery deadlines,” where the due date is ill-defined and can be autonomously extended, using the unique applied setting of grievance arbitration across two studies. In Study One, using 3 years of observed performance data derived from Canadian arbitration cases and a survey of leading arbitrators, we examined the effect of individual differences, self-regulatory skills, workloads and task characteristics on time delay. Observed delay here is a critical criterion, where justice is emphasized to beswiftand sure. Multilevel Modeling established trait procrastination as a substantive predictor of observed delay, equivalent to the environmental contributors of expediting the arbitration procedure or grievance complexity. Also, despite substantive negative consequence of delay for both arbitrators and their clients, arbitrators who scored one standard deviation above the mean in procrastination took approximately 83 days to write their decisions compared to the 26 days for arbitrators one standard deviation below the mean. In Study Two, we conducted a replication and extension survey with a much larger group of American arbitrators. Consistent with Temporal Motivation Theory (TMT), trait procrastination was largely explained by expectancy, value, and sensitivity to time related traits and skills, which together accounted for majority of the variance in trait procrastination, leaving little left for other explanations. For example, perfectionism connection to procrastination appears to be distal, being largely mediated by each of TMT’s core variables. Finally, procrastination was largely synonymous with a deadline pacing style, indicating that observed delay can be used as a proxy for procrastination as long as little or no prior work was done (e.g., a u-shaped pacing style is not synonymous). In all, our results indicate that procrastination is rampant in the workplace and has seriously detrimental effects.