Epidemiological Characteristics of School Playground Injuries.

Reports of children's play-related injuries have remained stagnant according to epidemiology studies of the past 3 decades. This article provides a unique look into the context of playground injuries within an entire school district, demonstrating the prevalence of these injuries. This study reports that playgrounds are the leading location of school injury, comprising one-third of all elementary school injuries. This study found that while head/neck injuries were the most commonly injured body region within the playground environment, the proportion of head/neck injuries decreased with age, whereas the proportion of extremity injuries increased with age. At least 1 upper extremity injury required outside medical attention for every 4 that were treated on-site, making upper extremity injuries roughly twice as likely to require outside medical attention as injuries to other body regions. The data in this study are useful for interpreting injury patterns in the context and evaluation of existing safety standards for playgrounds.

Bisbenzamidine and Bisbenzguanidine Ureas Act as Antibacterial Agents against Pseudomonas aeruginosa.

Due to the global rise in the number of antibiotic resistant bacterial infections over the past 20 years, there is a dire need for the development of small molecule antibiotics capable of overcoming resistance mechanisms in pathogenic bacteria. Antibiotic development against Gram-negative pathogens, such as Pseudomonas aeruginosa, is especially challenging due to their additional outer membrane which reduces antibiotic entry. Recently, it has been shown that a broad range of nitrogen functionality, including guanidines, amidines, primary amines, imidazolines, and imidazoles, promote antibiotic and adjuvant activity in Gram-negative bacteria, but few of these have been targeted towards Pseudomonas aeruginosa specifically despite this pathogen being deemed a critical threat by the United States Centers for Disease Control and Prevention. Herein, we examined a small series of known and unknown nitrogenous dimers, with guanidine, amidine, dimethyl amine, and pyridine functionality, for antibacterial activity against multidrug resistant Pseudomonas aeruginosa. We found that two, with bisbenzguanidine and bisbenzamidine functionality, are potent against clinical isolates of multidrug resistant and biofilm forming Pseudomonas aeruginosa.

Poor Sensitivity of the MALDI Biotyper® MBT Subtyping Module for Detection of Klebsiella pneumoniae Carbapenemase (KPC) in Klebsiella Species.

Rapid detection of Klebsiella pneumoniae carbapenemase (KPC) in the Klebsiella species is desirable. The MALDI Biotyper® MBT Subtyping Module (Bruker Daltonics) uses an algorithm that detects a peak at ~11,109 m/z corresponding to a protein encoded by the p019 gene to detect KPC simultaneously with organism identification by a matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-ToF MS). Here, the subtyping module was evaluated using 795 clinical Klebsiella isolates, with whole genome sequences used to assess for blaKPC and p019. For the isolates identified as KPC positive by sequencing, the overall sensitivity of the MALDI-ToF MS subtyping module was 239/574 (42%) with 100% specificity. For the isolates harboring p019, the subtyping module showed a sensitivity of 97% (239/246) and a specificity of 100%. The subtyping module had poor sensitivity for the detection of blaKPC-positive Klebsiella isolates, albeit exhibiting excellent specificity. The poor sensitivity was a result of p019 being present in only 43% of the blaKPC-positive Klebsiella isolates.

Antimicrobial Susceptibility of Elizabethkingia Species: Report from a Reference Laboratory.

Elizabethkingia species are Gram-negative bacilli that were most recently linked to a cluster of infections in the Midwestern United States from 2016 to 2017. Inappropriate empirical and directed antibiotic selection for this organism is common among providers and is an independent risk factor for mortality. Trends in antimicrobial susceptibility profiles of Elizabethkingia species from a referral laboratory over a 10-year period were reviewed. Identification methods used over time varied and included biochemical panels, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and 16S rRNA gene sequencing. Agar dilution was used to conduct antimicrobial susceptibility testing. One hundred seventy-four clinical isolates were included. The lower respiratory tract (20/37; 54%) was the most common specimen source in pediatric patients, whereas blood isolates (62/137; 45%) constituted the most prevalent source in adults. Among the identified species, Elizabethkingia meningoseptica (72/121; 59%) constituted the majority. All Elizabethkingia species tested against minocycline were susceptible (18/18; 100%), and 90% of isolates tested against trimethoprim-sulfamethoxazole (TMP-SMX) (117/130) were susceptible. Of the 12 Elizabethkingia miricola isolates, most of the tested isolates were susceptible to piperacillin-tazobactam (11/12; 92%) and levofloxacin (11/12; 92%), whereas the Elizabethkingia anophelis isolates most often tested susceptible to piperacillin-tazobactam (13/14; 93%). In this study, Elizabethkingia species showed high rates of in vitro susceptibility to minocycline and TMP-SMX. Further studies are needed to investigate the clinical implications of species-level differences in antimicrobial susceptibilities in this genus.

Glenoid Component Position Does Not Affect Short-Term Clinical and Radiologic Outcomes in Total Shoulder Arthroplasty.

BACKGROUND: Malpositioning of the glenoid component in total shoulder arthroplasty (TSA) remains the primary source of loosening. The purpose of this study is firstly, to quantify postoperative glenoid component position in patients having a TSA and secondly, to explore whether glenoid component radiolucency is associated with glenoid position, clinical outcomes and patient-reported measures in the short-term (two year) follow-up period. METHODS: This study was a sub-study of a larger clinical trial that included patients who underwent a TSA and who were randomized into two different glenoid types with a minimum two-year follow-up period. Post-operative radiographic assessments (six weeks and two years) were used to measure glenoid component position (version, inclination, offset) and humeral head centering anterior-posterior (AP) and superior-inferior (SI), and to assess glenoid component radiolucent scoring (modified Lazarus). Pre-operative X-rays were used to measure glenoid version, inclination and Walch classification. Patient-reported measures (PROMs) included the EQ-5D health slider and the Western Ontario Osteoarthritis (WOOS) and American Shoulder and Elbow Surgeons (ASES) score and were captured at baseline and two years postoperative. Clinical outcomes including range of motion and complications were also documented. Statistical analysis included t-tests and regression modeling. RESULTS: Ninety-one patients with an average age of 69.9 ± 6.2 years were included in this study. Glenoid component position improved significantly in version (-19.4 ± 8.6° to -17.7 ± 8.5°; p < 0.045) and inclination (11.5 ± 7.1° to 5.9 ± 6.3°; p < 0.00001) from preoperative to six weeks postoperative. Glenoid component offset in SI and humeral head centering in AP remained unchanged throughout the follow-up. Radiolucency (Lazarus classification) was recorded in 21 cases (17.3%) with a Lazarus score of 1 (15 cases) and 2 (6 cases). The EQ-5D health slider, WOOS and ASES, and ROM confirmed continuous improvements from the preoperative scores to the two-year follow-up (p < 0.05). Regression models showed no correlation between glenoid component radiolucency at two years and the postoperative week six glenoid component position; however, female gender was a significant variable. CONCLUSION: Glenoid component changes from its original native glenoid were observed following TSA. Glenoid inclination was improved more than version from baseline, and the humeral head remained well-centered in AP and SI at two years. Radiolucency of the glenoid at two years is not negatively associated with PROMs or component position; however, female gender was identified as a significant predictor and warrants further investigation. Complications are not associated with glenoid position or radiolucency, but longer-term follow-up is required.

The KRAS-regulated kinome identifies WEE1 and ERK coinhibition as a potential therapeutic strategy in KRAS-mutant pancreatic cancer.

Oncogenic KRAS drives cancer growth by activating diverse signaling networks, not all of which have been fully delineated. We set out to establish a system-wide profile of the KRAS-regulated kinase signaling network (kinome) in KRAS-mutant pancreatic ductal adenocarcinoma (PDAC). We knocked down KRAS expression in a panel of six cell lines and then applied multiplexed inhibitor bead/MS to monitor changes in kinase activity and/or expression. We hypothesized that depletion of KRAS would result in downregulation of kinases required for KRAS-mediated transformation and in upregulation of other kinases that could potentially compensate for the deleterious consequences of the loss of KRAS. We identified 15 upregulated and 13 downregulated kinases in common across the panel of cell lines. In agreement with our hypothesis, all 15 of the upregulated kinases have established roles as cancer drivers (e.g., SRC, TGF-ß1, ILK), and pharmacological inhibition of one of these upregulated kinases, DDR1, suppressed PDAC growth. Interestingly, 11 of the 13 downregulated kinases have established driver roles in cell cycle progression, particularly in mitosis (e.g., WEE1, Aurora A, PLK1). Consistent with a crucial role for the downregulated kinases in promoting KRAS-driven proliferation, we found that pharmacological inhibition of WEE1 also suppressed PDAC growth. The unexpected paradoxical activation of ERK upon WEE1 inhibition led us to inhibit both WEE1 and ERK concurrently, which caused further potent growth suppression and enhanced apoptotic death compared with WEE1 inhibition alone. We conclude that system-wide delineation of the KRAS-regulated kinome can identify potential therapeutic targets for KRAS-mutant pancreatic cancer.

Two-year results of a multi-centre, randomized controlled trial comparing a second-generation uncemented trabecular metal-backed versus cemented polyethylene glenoid component in total shoulder arthroplasty.

AIMS: To report early (two-year) postoperative findings from a randomized controlled trial (RCT) investigating disease-specific quality of life (QOL), clinical, patient-reported, and radiological outcomes in patients undergoing a total shoulder arthroplasty (TSA) with a second-generation uncemented trabecular metal (TM) glenoid versus a cemented polyethylene glenoid (POLY) component. METHODS: Five fellowship-trained surgeons from three centres participated. Patients aged between 18 and 79 years with a primary diagnosis of glenohumeral osteoarthritis were screened for eligibility. Patients were randomized intraoperatively to either a TM or POLY glenoid component. Study intervals were: baseline, six weeks, six-, 12-, and 24 months postoperatively. The primary outcome was the Western Ontario Osteoarthritis Shoulder QOL score. Radiological images were reviewed for metal debris. Mixed effects repeated measures analysis of variance for within and between group comparisons were performed. RESULTS: A total of 93 patients were randomized (46 TM; 47 POLY). No significant or clinically important differences were found with patient-reported outcomes at 24-month follow-up. Regarding the glenoid components, there were no complications or revision surgeries in either group. Grade 1 metal debris was observed in three (6.5%) patients with TM glenoids at 24 months but outcomes were not negatively impacted. CONCLUSION: Early results from this RCT showed no differences in disease-specific QOL, radiographs, complication rates, or shoulder function between uncemented second-generation TM and cemented POLY glenoids at 24 months postoperatively. Revision surgeries and reoperations were reported in both groups, but none attributed to glenoid implant failure. At 24 months postoperatively, Grade 1 metal debris was found in 6.5% of patients with a TM glenoid but did not negatively influence patient-reported outcomes. Longer-term follow-up is needed and is underway. Cite this article: Bone Jt Open 2021;2(9):728-736.

A genetically encoded tool for reconstituting synthetic modulatory neurotransmission and reconnect neural circuits in vivo.

Chemogenetic and optogenetic tools have transformed the field of neuroscience by facilitating the examination and manipulation of existing circuits. Yet, the field lacks tools that enable rational rewiring of circuits via the creation or modification of synaptic relationships. Here we report the development of HySyn, a system designed to reconnect neural circuits in vivo by reconstituting synthetic modulatory neurotransmission. We demonstrate that genetically targeted expression of the two HySyn components, a Hydra-derived neuropeptide and its receptor, creates de novo neuromodulatory transmission in a mammalian neuronal tissue culture model and functionally rewires a behavioral circuit in vivo in the nematode Caenorhabditis elegans. HySyn can interface with existing optogenetic, chemogenetic and pharmacological approaches to functionally probe synaptic transmission, dissect neuropeptide signaling, or achieve targeted modulation of specific neural circuits and behaviors.

Transaural experiments and a revised duplex theory for the localization of low-frequency tones.

The roles of interaural time difference (ITD) and interaural level difference (ILD) were studied in free-field source localization experiments for sine tones of low frequency (250-750 Hz). Experiments combined real-source trials with virtual trials created through transaural synthesis based on real-time ear canal measurements. Experiments showed the following: (1) The naturally occurring ILD is physically large enough to exert an influence on sound localization well below 1000 Hz. (2) An ILD having the same sign as the ITD modestly enhances the perceived azimuth of tones for all values of the ITD, and it eliminates left-right confusions that otherwise occur when the interaural phase difference (IPD) passes 180°. (3) Increasing the ILD to large, implausible values can decrease the perceived laterality while also increasing front-back confusions. (4) Tone localization is more directly related to the ITD than to the IPD. (5) An ILD having a sign opposite to the ITD promotes a slipped-cycle ITD, sometimes with dramatic effects on localization. Because the role of the ITD itself is altered by the ILD, the duplex processing of ITD and ILD reflects more than mere trading; the effect of the ITD can be reversed in sign.

Determination of caffeic acid in wine using PEDOT film modified electrode.

A novel method using PEDOT (poly(3,4-ethylenedioxy) thiophene) modified electrode was developed for the determination of caffeic acid (CA) in wine. Cyclic voltammetry (CV) with the additions standard method was used to quantify the analyte at PEDOT modified electrodes. PEDOT films were electrodeposited on Platinum electrode (Pt) in aqueous medium by galvanostatic method using sodium poly(styrene-4-sulfonate) (PSS) as electrolyte and surfactant. CV allows detecting the analyte over a wide concentration range (10.0nmoll(-1)-6.5mmoll(-1)). The electrochemical method proposed showed good statistical and analytical parameters as linearity range, LOD, LOQ and sensitivity.

Ultrafast time-gated ballistic-photon imaging and shadowgraphy in optically dense rocket sprays.

Time-gated ballistic-photon imaging is a form of shadowgraphy in which an ultrashort, optical-Kerr-effect (order 2 ps) time gate is used to enhance the relative intensity of ballistic versus multiply scattered photons. In the current work, this technique is adapted for what is believed to be the first time for use in the moderately dense environment (optical density approximately 1.5 to 2) of a high-speed 5 to 15 mm diameter rocket spray to improve image contrast and observe liquid-breakup phenomena. Unlike coherence gating, which is another form of ballistic imaging, the time-gating approach allows sufficient signal levels from ballistic and near-ballistic photons to enable time-resolved single-shot imaging. Direct comparisons with non-time-gated shadowgraphy indicate that the two techniques are sensitive to different features of the flowfield, with regions composed of a dense field of droplets being highly attenuated in conventional shadowgrams but appearing transparent to ballistic photons. This enables significant image contrast enhancement (approximately 6.6:1) of liquid-core structures and facilitates improved understanding of the primary and secondary breakup processes in sprays of moderate optical density.

Childhood injuries due to falls from apartment balconies and windows.

BACKGROUND: Falls from balconies and windows are an important cause of childhood injury. This study investigated the circumstances around such falls and attempted to identify possible measures for their prevention. POPULATION: Children <15 years living in Dallas County, Texas. METHODS: Each child treated because of a fall from a building in 1997-99 had information about the injury collected, and a parent was contacted to obtain further information. For apartment related falls, an attempt was made to visit the apartment to measure windows and balcony rails. RESULTS: Ninety eight children were injured in falls from buildings during the three year period; 39 (40%) were admitted to hospital. Seventy five of the falls (77%) involved apartments, and most occurred around noon or evening meal times. Among apartment falls, 39 (52%) fell from windows, 34 (45%) from balconies, and two (3%) from unknown sites. For more than two thirds of balcony related falls, the child fell from between the balcony rails, all of which were spaced more than 4 inches (10 cm) apart. On-site measurement showed the rails were an average of 7.5 inches (19 cm) apart; all of these apartments were built before 1984. For more than two thirds of window related falls, the window was situated within 2 feet (61 cm) of the floor. CONCLUSIONS: Two factors are important in falls from apartment windows and balconies: balcony rails more than 4 inches (10 cm) apart, and windows positioned low to the floor. Current building codes do not apply to older apartments, where most of these falls occurred. Nevertheless, these factors may be amenable to environmental modifications that may prevent most of these falls.

Single-strand reconstruction of the lateral ulnar collateral ligament restores varus and posterolateral rotatory stability of the elbow.

Because of a lack of biomechanical studies of lateral elbow ligament reconstruction in the literature, the initial stability afforded by 3 different techniques of lateral ulnar collateral ligament reconstruction was evaluated in 8 cadaveric elbows. The arm was mounted in a testing apparatus, and passive flexion was performed with the arm in varus and valgus orientations. A pivot shift test was performed with the arm in the vertical orientation. An electromagnetic tracking device was used to quantify motion pathways. After intact testing, each specimen underwent sectioning of the radial collateral and lateral ulnar collateral ligaments from the lateral epicondyle. Reconstruction of the lateral ulnar collateral ligament was performed in a randomized sequence, consisting of proximal single-strand, distal single-strand, and double-strand tendon grafts. Division of the radial collateral and lateral ulnar collateral ligaments from the lateral epicondyle caused a significant decrease in rotational stability when the pivot shift test was being performed (P <.0001). Varus-valgus stability also decreased after transection of the radial collateral and lateral ulnar collateral ligaments (P <.0001). Reconstruction of the lateral ulnar collateral ligament restored elbow stability to that of the intact state. There was no significant difference in stability between the single- and double-strand repair techniques (P >.05). This study demonstrates that both single- and double-strand reconstructions restore varus and posterolateral elbow stability and may be considered appropriate reconstructive procedures in patients with symptomatic insufficiency of the lateral ligaments of the elbow.

Evaluation of a bicycle helmet giveaway program--Texas, 1995.

OBJECTIVE: To determine the effect of a bicycle helmet giveaway program on helmet use among children. METHODS: In 1995, a bicycle helmet giveaway program was conducted in two rural towns in Texas. Helmets were given to all 403 school children in kindergarten through grade 8. Helmet education, a bicycle rodeo, and incentives to increase helmet use were part of the program. Observations of helmet use were made before the helmet program began and after the program at several intervals throughout the school year and during the summer. A self-reported survey questionnaire was administered to children in grades 4 through 8 before the helmet program began and at several intervals during the school year to determine their attitudes about helmet use, safety perceptions, and peer pressure. A questionnaire also was administered to the parents of these children to determine attitudes and bicycle helmet use among parents. RESULTS: Helmet use increased from 3% before the giveaway to 38% at the end of the school year, 7 months later. However, during the subsequent summer, helmet use decreased to 5%. Helmet use among 7th- and 8th-grade students was 0% at all observations periods after the giveaway. Even though 96% of all students thought that helmet use increased riding safety and 68% thought helmets should be worn at all times when riding, only 25% thought that their friends would approve of helmet use. Most parents also believed that helmets increased riding safety and should be worn, but only 23% reported always wearing one when riding a bicycle. CONCLUSIONS: Bicycle helmet giveaway programs can increase helmet use temporarily, but they may not be sufficient to sustain it. This program was not effective among 7th- and 8th-grade students.