Ninerafaxstat in the Treatment of Cardiometabolic Disease: Shifting Metabolic Paradigms.

Cardiovascular disease (CVD) refers to a wide array of conditions that damage the heart muscle and impede its ability to effectively circulate blood throughout the body. In damaged or pathological states, the heart muscle might not function as effectively as it would have had there been no insult to it. Understanding this, certain CVDs can put the heart in a "metabolic disadvantage"-a state in which it cannot synthesize energy stores, in the form of adenosine triphosphate (ATP), as efficiently as it was once able to do. While the heart typically uses fatty acids for its ATP synthesis, the metabolic processes required to do so consume more oxygen per mole than the processes required to convert glucose (or carbohydrates) to ATP. In conditions when oxygen demand outweighs supply-such as angina, heart failure, and certain inherited CVDs-the myocardium can more efficiently run via glucose oxidation. Despite this knowledge, there are no currently approved therapeutics or interventions that encourage this "metabolic shift" in the myocardial cells. Currently in phase II clinical trials, however, is a novel medication called ninerafaxstat. This novel drug is a partial inhibitor of fatty acid oxidation and thus pushes the heart to convert glucose (instead of fatty acids) to ATP-ultimately cutting down on oxygen supply. While still completing clinical trials, ninerafaxstat must undergo further safety and efficacy evaluation before it can be used as a standard of care. If, however, the drug makes it to market, it might offer a unique way to improve both the symptoms and quality of life of the millions of Americans who suffer from CVDs.

The potential for carbon dioxide removal by enhanced rock weathering in the tropics: An evaluation of Costa Rica.

Tropical environments show great potential to sequester CO2 by enhanced rock weathering (ERW) of powdered mafic rocks applied to agricultural fields. This study seeks to assess carbon dioxide reduction (CDR) potential in the humid tropics (1) by experimental weathering of mafic rock powders in conditions simulating humid tropical soils, and (2) from weathering rates determined from a Holocene tropical soil chronosequence where parent material is andesitic sediments. Experimentally determined weathering rates by leaching of basaltic andesites from Costa Rica (Arenal and Barva) for 50 t ha-1 applications indicate potential sequestration of 2.4 to 4.5 t CO2 ha-1 yr-1, whereas the USGS basalt standard BHVO-1 yields a rate of 11.9 t ha-1 yr-1 (influenced by more mafic composition and finer particle size). The chronosequence indicates a rate of 1.7 t CO2 ha-1 yr-1. The weathering experiment consisted of 0.6 mm of powdered rock applied atop 12 mm of Ultisol at 35 °C. To simulate a tropical soil solution, 100-mL aliquots of a dilute solution of oxalic acid in carbonated DI water were rained onto soils over a 14-day period to simulate soil moisture in the humid tropics. Solutions were collected and analyzed by ICPMS for concentrations of leached cations. A potential ERW scenario for Costa Rica was assessed assuming that one-half of lowland agricultural kaolinitic soils (mainly Ultisols, common crop and pasture soils, excluding protected areas) were to receive 50 t ha-1 of annual or biennial applications of powdered mafic rock. With an experimentally determined humid tropical CDR rate for basaltic andesite (3.5 t ha-1 yr-1) and allowances for carbon costs (e.g. emissions from processing and delivery) that reduce CDR to a net 3.2 t ha-1 yr-1, potential annual CDR of this tropical nation is ∼2-4 million tons, amounting to ∼25-50 % of annual CO2 emissions (mainly from transportation in Costa Rica).

A comparison between field measurements of vapour concentrations of plant protection products and predictions by the BROWSE model.

A database of field measurements of air concentrations of pesticide active ingredients has previously been compiled by CropLife Europe with an aim to revise the default air concentration values and assumptions applied in assessing vapour exposure in the risk assessment of bystanders and residents. The BROWSE model, released in 2014, which is a regulatory risk assessment model that includes the exposure of residents and bystanders has a component relating to post-application vapour inhalation. Predictions of concentration deduced from exposures obtained using the BROWSE model were compared with field measurements of 24-h and 7-day average concentrations. The methodology for obtaining concentration estimates from the BROWSE model is described, and the criteria for including field studies in the comparison are given. The field data were adjusted to account for differences between the field experiment and the BROWSE scenario using factors derived from a separate plume dispersion model. This showed that BROWSE provides a satisfactory level of conservatism in determining potential exposures of residents and bystanders to vapour and could be a reliable alternative to replace the current EFSA approach for predicting vapour inhalation exposures for pesticides where no compound-specific data are available.

INTERVERTEBRAL DISC DISEASE IN THREE LARGE FELIDS (PANTHERA SPP.) TREATED SURGICALLY.

Intervertebral disc disease (IVDD) in captive large felids is a commonly encountered syndrome that is usually treated medically, with surgical cases only sparsely documented in the literature. This case series describes the diagnosis, surgical treatment, and postoperative care of three cases of IVDD in large felids: an 8-yr-old male Bengal tiger (Panthera tigris tigris) with acute paraplegia, a 10-yr-old male tiger of unknown subspecies (Panthera tigris) with progressive tetraparesis, and a 17-yr-old female African lion (Panthera leo) with mild paraparesis. Two cases were diagnosed via magnetic resonance imaging (MRI) and the third was diagnosed with computed tomography myelography. Disc herniations were confirmed during surgery in all cases and via necropsy in two cases. Surgical procedures included a thoracolumbar dorsal hemilaminectomy in one tiger, a cervical hemilaminectomy in the other tiger, and a continuous lumbar dorsal hemilaminectomy in the lion. One tiger was euthanized approximately 1 wk after surgery and the other tiger was euthanized approximately 1 mon after surgery, following a lack of clinical improvement in both cases. The lion, however, improved markedly over several months after surgery before acutely declining secondary to spinal neoplasia. Analysis of these cases suggests that pursuing MRI and surgery as soon as possible after the onset of clinical signs and marking affected disc sites based on imaging to provide landmarks for the surgeon may improve long-term prognosis. Additionally, strict postoperative confinement in an accessible cage is beneficial to facilitate care and prevent overexertion while allowing early movement.

In vitro analysis and in vivo assessment of fracture complications associated with use of locking plate constructs for stabilization of caprine tibial segmental defects.

PURPOSE: Locking plate fixation of caprine tibial segmental defects is widely utilized for translational modeling of human osteopathology, and it is a useful research model in tissue engineering and orthopedic biomaterials research due to its inherent stability while maintaining unobstructed visualization of the gap defect and associated healing. However, research regarding surgical technique and long-term complications associated with this fixation method are lacking. The goal of this study was to assess the effects of surgeon-selected factors including locking plate length, plate positioning, and relative extent of tibial coverage on fixation failure, in the form of postoperative fracture. METHODS: In vitro, the effect of plate length was evaluated using single cycle compressive load to failure mechanical testing of locking plate fixations of caprine tibial gap defects. In vivo, effects of plate length, positioning, and relative tibial coverage were evaluated using data from a population of goats enrolled in ongoing orthopedic research which utilized locking plate fixation of 2 cm tibial diaphyseal segmental defects to evaluate bone healing over 3, 6, 9, and 12 months. RESULTS: In vitro, no significant differences in maximum compressive load or total strain were noted between fixations using 14 cm locking plates and 18 cm locking plates. In vivo, both plate length and tibial coverage ratio were significantly associated with postoperative fixation failure. The incidence of any cortical fracture in goats stabilized with a 14 cm plate was 57%, as compared with 3% in goats stabilized with an 18 cm plate. Craniocaudal and mediolateral angular positioning variables were not significantly associated with fixation failure. Decreasing distance between the gap defect and the proximal screw of the distal bone segment was associated with increased incidence of fracture, suggesting an effect on proximodistal positioning on overall fixation stability. CONCLUSIONS: This study emphasizes the differences between in vitro modeling and in vivo application of surgical fixation methods, and, based on the in vivo results, maximization of plate-to-tibia coverage is recommended when using locking plate fixation of the goat tibial segmental defect as a model in orthopedic research.

Silver Carboxylate-Eluting Titanium-Dioxide Polydimethylsiloxane Coating Inhibits Multi-Drug-Resistant Acinetobacterium baumannii and Vancomycin-Resistant Enterococcus faecalis Adherence and Proliferation on Orthopedic Trauma Fixation and Spinal Fusion Materials.

Background: Vancomycin-resistant Enterococcus faecalis and multi-drug-resistant (MDR) Acinetobacter baumannii are rising contributors to spinal fusion and fracture-associated infections (FAI), respectively. These MDR bacteria can form protective biofilms, complicating traditional antibiotic treatment. This study explores the effects of the antibiotic-independent antimicrobial silver carboxylate (AgCar)-doped coating on the adherence sand proliferation of these pathogens on orthopedic implant materials utilized in spinal fusion and orthopedic trauma fixation. Methods: Multi-drug-resistant Acinetobacter baumannii and vancomycin-resistant Enterococcus faecalis were inoculated on five common implant materials: cobalt chromium, titanium, titanium alloy, polyether ether ketone, and stainless steel. Dose response curves were generated to assess antimicrobial potency. Scanning electron microscopy and confocal laser scanning microscopy were utilized to characterize and quantify growth and adherence on each material. Results: The optimal AgCar concentration was a 95% titanium dioxide (TiO2)-5% polydimethylsiloxane (PDMS) matrix combined with 10 × silver carboxylate, which inhibited bacterial proliferation by 89.40% (p = 0.001) for MDR Acinetobacter baumannii and 84.02% (p = 0.001) for vancomycin-resistant Enterococcus faecalis compared with uncoated implants. A 95% TiO2-5% PDMS matrix combined with 10 × AgCar was equally effective at inhibiting bacterial proliferation across all implant materials for MDR Acinetobacter baumannii (p = 0.19) and vancomycin-resistant Enterococcus faecalis (p = 0.07). A 95% TiO2-5% PDMS matrix with 10 × AgCar is effective at decreasing bacterial adherence of both MDR Acinetobacter baumannii and vancomycin-resistant Enterococcus faecalis on implant materials. Conclusions: Application of this antibiotic-independent coating for surgery in which these implant materials might be used may prevent adherence, biofilm formation, spinal infections, and FAI by MDR Acinetobacter baumannii and vancomycin-resistant Enterococcus faecalis.

Quantifying the computational capability of a nanomagnetic reservoir computing platform with emergent magnetisation dynamics.

Devices based on arrays of interconnected magnetic nano-rings with emergent magnetization dynamics have recently been proposed for use in reservoir computing applications, but for them to be computationally useful it must be possible to optimise their dynamical responses. Here, we use a phenomenological model to demonstrate that such reservoirs can be optimised for classification tasks by tuning hyperparameters that control the scaling and input-rate of data into the system using rotating magnetic fields. We use task-independent metrics to assess the rings' computational capabilities at each set of these hyperparameters and show how these metrics correlate directly to performance in spoken and written digit recognition tasks. We then show that these metrics, and performance in tasks, can be further improved by expanding the reservoir's output to include multiple, concurrent measures of the ring arrays' magnetic states.

Genotypic variation and covariation in wheat seedling seminal root architecture and grain yield under field conditions.

KEY MESSAGE: Greater embryo size in a large and carefully phenotyped mapping population was genetically associated with a greater number of longer seminal roots to increase grain yield in droughted field environments. Breeding modification of root architecture is challenging in field environments owing to genetic and phenotypic complexity, and poor repeatability with root sampling. Seeds from a large mapping population varying in embryo size were harvested from a common glasshouse and standardised to a common size before assessing in rolled germination paper at 12 and 20 °C for seedling growth. Differences in genotype means were large and heritabilities high (h2 = 0.55-0.93) indicating strong and repeatable genotypic differences for most root traits. Seminal roots 1 to 3 were produced on all seedlings, whereas growth of seminal roots 4, 5 and 6 was associated with differences in embryo size. Increases in seminal root number from 4 to 6 per plant were strongly, genetically correlated with increases in total seminal length (rg = 0.84, < 0.01). Multivariate analysis confirmed initiation and growth of seminal roots 1, 2 and 3, and of roots 4, 5 and 6 behaved as genetically independent (rPg = 0.15 ns) cohorts. Tails representing extremes in seedling root length and number were associated with significant differences in grain yield of up to 35% in droughted field environments but were not different in irrigated environments. Increases in grain yield were linked to greater lengths of seminal roots 4, 5 and 6 and were largely independent of plant height or development. This is the first report on the genetic relationship of seedling root architecture and embryo size, and potential in selection of seminal root size for accessing deep-soil moisture in droughted environments.

Improved bandwidth and F/B ratio of a CPW-fed planar monopole antenna.

A directional planar monopole antenna is described. The antenna comprises of a circular monopole, coplanar waveguide (CPW) feed line and a ground plane. To achieve unidirectional radiation, a stub is also attached to on the ground plane to increase the lower end impedance bandwidth and also increase the Front-to-Back ratio (F/B). The proposed antenna is etched on a 50 × 50 mm2 FR4 substrate. Simulated and experimental results reveal that the proposed antenna can achieve an impedance bandwidth from 2.3 - 10.5 GHz for S11 < -10 dB, and unidirectional radiation patterns with high gain and high efficiency.

Antibiotic Cement Utilization for the Prophylaxis and Treatment of Infections in Spine Surgery: Basic Science Principles and Rationale for Clinical Use.

Antibiotic bone cement (ABC) is an effective tool for the prophylaxis and treatment of osteomyelitis due to the controlled, sustained release of local antibiotics. ABC has been proven to be effective in the orthopedic fields of arthroplasty and extremity trauma, but the adoption of ABC in spine surgery is limited. The characteristics of ABC make it an optimal solution for treating vertebral osteomyelitis (VO), a serious complication following spine surgery, typically caused by bacterial and sometimes fungal and parasitic pathogens. VO can be devastating, as infection can result in pathogenic biofilms on instrumentation that is dangerous to remove. New techniques, such as kyphoplasty and novel vertebroplasty methods, could amplify the potential of ABC in spine surgery. However, caution should be exercised when using ABC as there is some evidence of toxicity to patients and surgeons, antibiotic allergies, bone cement structural impairment, and possible development of antibiotic resistance. The purpose of this article is to describe the basic science of antibiotic cement utilization and review its usage in spine surgery.

Indolent Infection After Lumbar Interbody Fusion: An Under-recognized Cause of Pseudarthrosis, Which Can Be Successfully Treated With Anterior Revision Fusion.

INTRODUCTION: Bacterial infection is a common etiology for pseudarthrosis after transforaminal lumbar interbody fusion, although it is often difficult to identify because of a delayed presentation and normal laboratory values. The primary goal of this study was to present a series of cases demonstrating patients with infection-related pseudarthrosis successfully managed with anterior revision. METHODS: We retrospectively reviewed patients presenting to a single academic spine center who were found to have evidence of Cutibacterium acnes or coagulase-negative Staphylococcus infection on routine culturing of lumbar interbody fusion revisions from July 2019 to January 2021. All patients underwent salvage of a transforaminal lumbar interbody fusion pseudarthrosis through an anterior lumbar approach. RESULTS: A total of six patients managed for pseudarthrosis secondary to suspected infection were eligible for this study (mean age 64.8 years, range 54-70 years; mean body mass index, range 24.5-39.1). Persistent radiculopathy was the primary presenting symptom in all patients with a mean time to revision of 17 months. Coagulase-negative Staphylococcus was the primary pathogen, identified from intraoperative samples in 50% of the cases. All patients demonstrated a resolution of symptoms after placement of an anterior lumbar interbody cage, without intraoperative complications, and a subsequent antibiotic regimen. DISCUSSION: Indolent infection is an under-recognized cause of pseudarthrosis of the lumbar spine. Revision surgery through an anterior lumbar approach, which promotes ease of cage removal and optimized alignment and surface area available for revision fusion, is sufficient to manage pseudarthrosis due to infection.

Synergistic Effects of Silver Carboxylate and Chlorhexidine Gluconate for Wound Care and Prevention of Surgical Site Infections by Cutibacterium acnes and Methicillin-Resistant Staphylococcus aureus.

Background: This study presents the effectiveness of a combined silver carboxylate (AgCar) and chlorohexidine gluconate (AgCar:CHG) chemistry assessed against two commonly encountered nosocomial pathogens, Methicillin-resistant Staphylococcus aureus (MRSA) and Cutibacterium acnes, within the context of surgical antisepsis and wound care. Methods: Through an Institutional Review Board- and Institutional Animal Care and Use Committee (IACUC)-approved protocol, AgCar:CHG was applied to live Yucatan porcine skin and visualized by fast red and green staining to assess level of skin penetration. Dose response curves for Cutibacterium acnes and MRSA were generated to determine the optimal therapeutic ratio of AgCar to CHG. Coatings were applied to two different clinically available sutures and antimicrobial efficacy was evaluated at 24-hour intervals using Kirby-Bauer (KB) assays. Graphite furnace atomic absorption spectroscopy was used to measure AgCar elution from sutures over time. Results: Synergistic application of AgCar:CHG demonstrated deep pilosebaceous gland penetration on Yucatan pig skin. The therapeutic concentration range of AgCar was determined to be between 120 × -150 × and 30 × -60 × dopage for MRSA and Cutibacterium acnes, respectively. A 1:1 therapeutic ratio of AgCar to CHG was found to have 100% bactericidal activity against both pathogens. Sutures coated with AgCar:CHG showed sustained antimicrobial activity against MRSA and Cutibacterium acnes, and were significantly more efficacious than antimicrobial sutures over the three- to four-day period (p < 0.01). Conclusions: This AgCar:CHG chemistry demonstrates deep skin penetration, extended elution, and broad-spectrum antimicrobial activity compared with commercially available options. This chemistry shows promise as an additional tool for the prophylaxis of surgical site infections.

Analysis of Patients' Online Reviews of Orthopaedic Surgeons.

INTRODUCTION: Physician rating websites (PRWs) are an increasingly popular interface between patient and surgeon. Despite the growing popularity of PRWs, little guidance exists for orthopaedic surgeons regarding online reviews. We analyzed online ratings and comments to provide a better understanding of patients' values and expectations so that surgeons can tailor their practice accordingly to enhance their clinical care and online reputation. METHODS: Three common PRWs (Vitals, HealthGrades, and RateMDs) were queried from January 1, 2006, to May 18, 2020. Publicly available ratings, both quantitative (1 to 5 stars) and qualitative (free text comments), were collected. Comments were qualitatively tabulated as having positive or negative assessments for categories including outcome, personality, staff, surgical skill, visit time, bedside manner, wait time, diagnosis, knowledge, treatment, and advanced practice providers and analyzed using chi square goodness of fit. Quantitative comparisons of star ratings were made across surgeon years in practice, sex, practice setting, and PRW and compared using chi square independence testing. RESULTS: In total, 81% of patient comments were found to have a positive assessment. Comments regarding outcome (P < 0.001), staff (P = 0.001), surgical skill (P < 0.001), or knowledge (P = 0.001) were more likely to be positive. Reviews regarding bedside manner (P < 0.001), wait time (P < 0.001), diagnosis (P < 0.001), treatment (P < 0.001), or advanced practice providers (P < 0.001) were more likely to be negative. Surgeon sex was not associated with a difference in quantitative ratings (P = 0.131), unlike practice setting (P < 0.001) and PRW (P < 0.001). DISCUSSION: PRWs are a growing interface between surgeon and patient with a considerable effect on surgeon marketability. This study reveals a statistical association between certain patient-centered medical practices and positive patient reviews. This emphasizes the importance of ensuring that high standards are maintained throughout a physician's practice of maintaining a constant awareness of the fundamentals for effective patient care and of taking care to curate a physician's online presence.

Silver carboxylate-doped titanium dioxide-polydimethylsiloxane coating decreases Cutibacterium acnes adherence and biofilm formation on polyether ether ketone.

BACKGROUND CONTEXT: Cutibacterium acnes (C. acnes) is a gram-positive facultative anaerobe found in the deep sebaceous follicles of the skin on the shoulder and back. C. acnes has been increasingly recognized as a pathogen in spinal surgical site infection (SSI) especially in the presence of instrumentation. PURPOSE: This study assesses whether a silver carboxylate-doped titanium dioxide-polydimethylsiloxane (TiO2-PDMS) coating can decrease C. acnes adherence and biofilm formation on PEEK and four other commonly used spinal implant materials, stainless steel, cobalt chromium, titanium, and titanium alloy. STUDY DESIGN: We compared the adherence of C. acnes over 24 hours between uncoated, 95:5 TiO2 to PDMS ratio with 10× silver carboxylate coating and a 100% silver carboxylate coating on each implant material, which were uniformly saw cut and sterilized. Implants were then subjected to scanning electron microscopy (SEM) and confocal scanning laser microscopy (CSLM). METHODS: Samples were coated using 95:5 TiO2-PDMS 10× silver carboxylate, 100% silver carboxylate, or left uncoated. C. acnes was applied onto the samples and allowed to adhere for periods of 4, 8, 12, 16, or 20 hours. Nonadherent bacteria were then washed from the samples. These samples were then allowed to continue incubating for a total of 24 hours. SEM and confocal laser scanning microscope were used to visualize all samples for the presence of biofilm and quantification of C. acnes adherence at each time point. RESULTS: The 95:5 TiO2-PDMS 10× silver carboxylate coating was able to significantly decrease C. acnes adherence on PEEK after 8, 12, 16, and 20 hours of adherence. No statistical difference was found between the 95:5 TiO2-PDMS 10× silver carboxylate coating and the 100% silver carboxylate positive control. We previously observed extensive C. acnes biofilm formation on uncoated PEEK, but none on PEEK coated with either the 95:5 TiO2-PDMS 10× silver carboxylate or 100% Ag coating . Furthermore, no biofilm formation was observed on stainless steel, cobalt chromium, titanium, and titanium alloy coated with 95:5 TiO2-PDMS 10× silver carboxylate or 100% Ag coating. CONCLUSION: A 95:5 TiO2-PDMS 10× silver carboxylate coating decreases C. acnes adhesion and prevents biofilm formation on PEEK and other common orthopedic implant materials. CLINICAL SIGNIFICANCE: A 95:5 TiO2-PDMS 10× silver carboxylate coating may help decrease spinal SSI due to C. acnes, especially in procedures with instrumentation.

Functional siRNA Delivery by Extracellular Vesicle-Liposome Hybrid Nanoparticles.

The therapeutic use of RNA interference is limited by the inability of siRNA molecules to reach their site of action, the cytosol of target cells. Lipid nanoparticles, including liposomes, are commonly employed as siRNA carrier systems to overcome this hurdle, although their widespread use remains limited due to a lack of delivery efficiency. More recently, nature's own carriers of RNA, extracellular vesicles (EVs), are increasingly being considered as alternative siRNA delivery vehicles due to their intrinsic properties. However, they are difficult to load with exogenous cargo. Here, EV-liposome hybrid nanoparticles (hybrids) are prepared and evaluated as an alternative delivery system combining properties of both liposomes and EVs. It is shown that hybrids are spherical particles encapsulating siRNA, contain EV-surface makers, and functionally deliver siRNA to different cell types. The functional behavior of hybrids, in terms of cellular uptake, toxicity, and gene-silencing efficacy, is altered as compared to liposomes and varies among recipient cell types. Moreover, hybrids produced with cardiac progenitor cell (CPC) derived-EVs retain functional properties attributed to CPC-EVs such as activation of endothelial signaling and migration. To conclude, hybrids combine benefits of both synthetic and biological drug delivery systems and might serve as future therapeutic carriers of siRNA.

In vitro visualization and quantitative characterization of Pseudomonas aeruginosa biofilm growth dynamics on polyether ether ketone.

Prevention and treatment of orthopedic device-related infection (ODRI) is complicated by the formation of bacterial biofilms. Biofilm formation involves dynamic production of macromolecules that contribute to the structure of the biofilm over time. Limitations to clinically relevant and translational biofilm visualization and measurement hamper advances in this area of research. In this paper, we present a multimodal methodology for improved characterization of Pseudomonas aeruginosa grown on polyether ether ketone (PEEK) as a model for ODRI. PEEK discs were inoculated with P. aeruginosa, incubated for 4-48 h time intervals, and fixed with 10% neutral-buffered formalin. Samples were stained with fluorescent dyes to measure biofilm components, imaged with confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM), and quantified. We were able to visualize and quantify P. aeruginosa biofilm growth on PEEK implants over 48 h. Based on imaging data, we propose a generalized growth cycle that can inform orthopedic diagnostic and treatment for this pathogen on PEEK. These results demonstrate the potential of using a combined CLSM and SEM approach for determining biofilm structure, composition, post-adherence development on orthopedic materials. This model may be used for quantitative biofilm analysis for other pathogens and other materials of orthopedic relevance for translational study of ODRI.

Time-varying Spectral Index of Electrodermal Activity to Predict Central Nervous System Oxygen Toxicity Symptoms in Divers: Preliminary results.

The most effective method to mitigate decompression sickness in divers is hyperbaric oxygen (HBO2) pre-breathing. However, divers breathing HBO2 are at risk for developing central nervous system oxygen toxicity (CNS-OT), which can manifest as symptoms that might impair a diver's performance, or cause more serious symptoms like seizures. In this study, we have collected electrodermal activity (EDA) signals in fifteen subjects at elevated oxygen partial pressures (2.06 ATA, 35 FSW) in the "foxtrot" chamber pool at the Duke University Hyperbaric Center, while performing a cognitive stress test for up to 120 minutes. Specifically, we have computed the time-varying spectral analysis of EDA (TVSymp) as a tool for sympathetic tone assessment and evaluated its feasibility for the prediction of symptoms of CNS-OT in divers. The preliminary results show large increase in the amplitude TVSymp values derived from EDA recordings ~2 minutes prior to expert human adjudication of symptoms related to oxygen toxicity. An early detection based on TVSymp might allow the diver to take countermeasures against the dire consequences of CNS-OT which can lead to drowning.Clinical Relevance-This study provides a sensitive analysis method which indicates a significant increase in the electrodermal activity prior to human expert adjudication of symptoms related to CNS-OT.

Heavy Ion Minibeam Therapy: Side Effects in Normal Brain.

The purpose of this work was to investigate whether minibeam therapy with heavy ions might offer improvements of the therapeutic ratio for the treatment of human brain cancers. To assess neurotoxicity, we irradiated normal juvenile rats using 120 MeV lithium-7 ions at an absorbed integral dose of 20 Gy. Beams were configured either as a solid parallel circular beam or as an array of planar parallel minibeams having 300-micron width and 1-mm center-to-center spacing within a circular array. We followed animals for 6 months after treatment and utilized behavioral testing and immunohistochemical studies to investigate the resulting cognitive impairment and chronic pathologic changes. We found both solid-beam therapy and minibeam therapy to result in cognitive impairment compared with sham controls, with no apparent reduction in neurotoxicity using heavy ion minibeams instead of solid beams under the conditions of this study.

Does Age Affect the Short- and Long-Term Outcomes of Coronary Bypass Grafting?

The etiology of coronary artery disease (CAD) is multifactorial, stemming from both modifiable and nonmodifiable risk factors such as age. Several studies have reported the effects of age on various outcomes of coronary artery bypass grafting (CABG). This article reviews age-related outcomes of CABG and offers direction for further studies in the field to create comprehensive, evidence-based guidelines for the treatment of CAD. Ninety-two primary sources were analyzed for relevance to the subject matter, of which 17 were selected for further analysis: 14 retrospective cohort studies, 2 randomized clinical trials, and 1 meta-analysis. Our review revealed four broad age ranges into which patients can be grouped: those with CAD (1) below the age of 40 years, (2) between the ages of 40 and 60 years, (3) between the ages of 60 and 80 years, and (4) at or above 80 years. Patients below the age of 40 years fare best overall with total arterial revascularization (TAR). Patients between the ages of 40 and 60 years also fare well with the use of multiarterial grafts (MAGs) whereas either MAGs or single-arterial grafts may be of significant benefit to patients at or above the age of 60 years, with younger and diabetic patients benefitting the most. Arterial grafting is superior to vein grafting until the age of 80 years, at which point there is promising evidence supporting the continued use of the saphenous vein as the favored graft substrate. Age is a factor affecting the outcomes of CABG but should not serve as a barrier to offering patients CABG at any age from either a cost or a health perspective. Operative intervention starts to show significant mortality consequences at the age of 80 years, but the increased risk is countered by maintenance or improvement to patients' quality of life.

Comparison of Pediatric Otolaryngology clinical and operative case volume among surgical specialties in the COVID-19 pandemic.

OBJECTIVES: To report changes in clinical and surgical volume impacting a Pediatric Otolaryngology division one year prior to and following the onset of the COVID-19 pandemic in comparison to five other pediatric surgical subspecialties. METHODS: The number of clinical visits and surgical cases per month for six pediatric surgical specialties (Otolaryngology, Orthopedic Surgery, Urology, Neurosurgery, Plastic Surgery, and General Surgery) for 12 months prior to the pandemic and 12 months following the onset of the pandemic was collected. Poisson regression analysis was performed for the number of visits and cases per season adjusting for specialty, season, staffing changes, and the pandemic to determine adjusted rate ratios (aRR) post-pandemic for the surgical fields compared to Otolaryngology. RESULTS: A percentage decrease in median visits per paired month (-15.63%, IQR = -23.01, -1.66) and operative cases (-19.86%, IQR = -29.39, -10.17) was seen for Pediatric Otolaryngology. Regression analysis showed a significant negative effect on the number of visits (aRR = 0.74, 95% CI = 0.70-0.77) and cases (aRR = 0.65, 95% CI = 0.60-0.71) due to the pandemic. While many of the other specialties had predicted reductions in volume (notably Orthopedics), they all experienced significant predicted increases in productivity following the pandemic compared to Otolaryngology. CONCLUSIONS: These findings suggest that Pediatric Otolaryngology is particularly vulnerable to this change in clinical pattern, which could be due to a decline in community infections from mask wearing and social distancing, and may result in a longer-term volume deficit when compared to other pediatric surgical subspecialties.