Safety of mapping the motor networks in the spinal cord using penetrating microelectrodes in Yucatan minipigs.

OBJECTIVE: The goal of this study was to assess the safety of mapping spinal cord locomotor networks using penetrating stimulation microelectrodes in Yucatan minipigs (YMPs) as a clinically translational animal model. METHODS: Eleven YMPs were trained to walk up and down a straight line. Motion capture was performed, and electromyographic (EMG) activity of hindlimb muscles was recorded during overground walking. The YMPs underwent a laminectomy and durotomy to expose the lumbar spinal cord. Using an ultrasound-guided stereotaxic frame, microelectrodes were inserted into the spinal cord in 8 animals. Pial cuts were made to prevent tissue dimpling before microelectrode insertion. Different locations within the lumbar enlargement were electrically stimulated to map the locomotor networks. The remaining 3 YMPs served as sham controls, receiving the laminectomy, durotomy, and pial cuts but not microelectrode insertion. The Porcine Thoracic Injury Behavioral Scale (PTIBS) and hindlimb reflex assessment results were recorded for 4 weeks postoperatively. Overground gait kinematics and hindlimb EMG activity were recorded again at weeks 3 and 4 postoperatively and compared with preoperative measures. The animals were euthanized at the end of week 4, and the lumbar spinal cords were extracted and preserved for immunohistochemical analysis. RESULTS: All YMPs showed transient deficits in hindlimb function postoperatively. Except for 1 YMP in the experimental group, all animals regained normal ambulation and balance (PTIBS score 10) at the end of weeks 3 and 4. One animal in the experimental group showed gait and balance deficits by week 4 (PTIBS score 4). This animal was excluded from the kinematics and EMG analyses. Overground gait kinematic measures and EMG activity showed no significant (p > 0.05) differences between preoperative and postoperative values, and between the experimental and sham groups. Less than 5% of electrode tracks were visible in the tissue analysis of the animals in the experimental group. There was no statistically significant difference in damage caused by pial cuts between the experimental and sham groups. Tissue damage due to the pial cuts was more frequently observed in immunohistochemical analyses than microelectrode tracks. CONCLUSIONS: These findings suggest that mapping spinal locomotor networks in porcine models can be performed safely, without lasting damage to the spinal cord.

The development of lateral flow devices for urinary biomarkers to assess kidney health.

Serum creatinine levels are insensitive to real-time changes in kidney function or injury. There is a growing interest in assessing kidney injury by measuring biomarkers in body fluid. From our previous studies, we identified and reported three urinary biomarkers namely Uromodulin (UMOD), Osteopontin (OPN), and Interleukin-9 (IL-9) to be associated with kidney health. The availability of a rapid point-of-care test for these urinary biomarkers will potentially accelerate its applicability and accessibility. In this study, we aimed to develop novel lateral flow device (LFD) for UMOD, OPN and IL-9. We tested paired antibodies using Enzyme Linked Immunosorbent Assay wherein we observed functionality only for UMOD and OPN and not for IL-9. A conjugation buffer pH of 7.8 and 8.5 was found suitable at a detection antibody concentration of 15 µg/mL for LFD development. The developed LFDs were found to quantitatively measure UMOD standard (LLOD of 80,000 pg/mL) and OPN standard (LLOD of 8600 pg/mL) respectively. The LFD was also able to measure human urinary UMOD and OPN with a percent CV of 12.12 and 5.23 respectively.

Adhesive capsulitis: Utility of magnetic resonance imaging as a primary diagnostic tool and clinical management support.

OBJECTIVE: Adhesive capsulitis (AC) has traditionally been a clinical diagnosis characterized by progressive shoulder pain and decreased range of motion. Our aim is to examine the role of shoulder MRI in making the diagnosis of AC, and to identify the frequency of cases where MRI was the primary method in diagnosing AC amongst medical providers. METHODS: This was an anonymized retrospective analysis. Patients with positive MRI features suggestive for AC from 2015 to 2018 were included. Pre and post MRI clinical notes were assessed in order to ascertain the clinical suspicion of AC. A total of 117 cases were included for this study. RESULTS: Our results demonstrated the number of patients whose management were influenced by shoulder MRI. When all of the imaging parameters by MRI are taken into account by aggregate, there is a statistically significant difference (p-value < 0.01) with regards to orthopedists having their working diagnosis of AC confirmed by the MRI results as compared to the primary care physicians. CONCLUSION: This study supports the role of shoulder MRI in the evaluation of AC. Not only does shoulder MRI assist ordering clinicians with providing additional evidence to support a suspected diagnosis of AC, but also plays a primary role in making the diagnosis of AC in cases in which it was not initially suspected, ultimately impacting management.

Urinary Biomarkers and Kidney Injury in VA NEPHRON-D: Phenotyping Acute Kidney Injury in Clinical Trials.

RATIONALE & OBJECTIVE: Urinary biomarkers of injury, inflammation, and repair may help phenotype acute kidney injury (AKI) observed in clinical trials. We evaluated the differences in biomarkers between participants randomized to monotherapy or to combination renin-angiotensin-aldosterone system (RAAS) blockade in VA NEPHRON-D, where an increased proportion of observed AKI was acknowledged in the combination arm. STUDY DESIGN: Longitudinal analysis. SETTING & PARTICIPANTS: A substudy of the VA NEPHRON-D trial. PREDICTOR: Primary exposure was the treatment arm (combination [RAAS inhibitor] vs monotherapy). AKI is used as a stratifying variable. OUTCOME: Urinary biomarkers, including albumin, EGF (epidermal growth factor), MCP-1 (monocyte chemoattractant protein-1), YKL-40 (chitinase 3-like protein 1), and KIM-1 (kidney injury molecule-1). ANALYTICAL APPROACH: Biomarkers measured at baseline and at 12 months in trial participants were compared between treatment groups and by AKI. AKI events occurring during hospitalization were predefined safety end points in the original trial. The results were included in a meta-analysis with other large chronic kidney disease trials to assess global trends in biomarker changes. RESULTS: In 707 participants followed for a median of 2.2 years, AKI incidence was higher in the combination (20.7%) versus the monotherapy group (12.7%; relative risk [RR], 1.64 [95% CI, 1.16-2.30]). Compared with the monotherapy arm, in the combination arm the urine biomarkers at 12 months were either unchanged (MCP-1: RR, -3% [95% CI, -13% to 9%], Padj=0.8; KIM-1: RR, -10% [95% CI, -20% to 1%], Padj=0.2; EGF, RR-7% [95% CI, -12% to-1%], Padj=0.08) or lower (albuminuria: RR, -24% [95% CI, -37% to-8%], Padj=0.02; YKL: RR, -40% to-44% [95% CI, -58% to-25%], Padj<0.001). Pooled meta-analysis demonstrated reduced albuminuria in the intervention arm across 3 trials and similar trajectories in other biomarkers. LIMITATIONS: Biomarker measurement was limited to 2 time points independent of AKI events. CONCLUSIONS: Despite the increased risk of serum creatinine-defined AKI, combination RAAS inhibitor therapy was associated with unchanged or decreased urinary biomarkers at 12 months. This suggests a possible role for kidney biomarkers to further characterize kidney injury in clinical trials. PLAIN-LANGUAGE SUMMARY: The VA NEPHRON-D trial investigated inhibition of the renin-angiotensin-aldosterone system (RAAS) hormonal axis on kidney outcomes in a large population of diabetic chronic kidney disease patients. The trial was stopped early due to increased events of serum creatinine-defined acute kidney injury in the combination therapy arm. Urine biomarkers can serve as an adjunct to serum creatinine in identifying kidney injury. We found that urinary biomarkers in the combination therapy group were not associated with a pattern of harm and damage to the kidney, despite the increased number of kidney injury events in that group. This suggests that serum creatinine alone may be insufficient for defining kidney injury and supports further exploration of how other biomarkers might improve identification of kidney injury in clinical trials.

Conservation tools: the next generation of engineering-biology collaborations.

The recent increase in public and academic interest in preserving biodiversity has led to the growth of the field of conservation technology. This field involves designing and constructing tools that use technology to aid in the conservation of wildlife. In this review, we present five case studies and infer a framework for designing conservation tools (CT) based on human-wildlife interaction. Successful CT range in complexity from cat collars to machine learning and game theory methodologies and do not require technological expertise to contribute to conservation tool creation. Our goal is to introduce researchers to the field of conservation technology and provide references for guiding the next generation of conservation technologists. Conservation technology not only has the potential to benefit biodiversity but also has broader impacts on fields such as sustainability and environmental protection. By using innovative technologies to address conservation challenges, we can find more effective and efficient solutions to protect and preserve our planet's resources.

The ASSESS-AKI Study found urinary epidermal growth factor is associated with reduced risk of major adverse kidney events.

Biomarkers of tubular function such as epidermal growth factor (EGF) may improve prognostication of participants at highest risk for chronic kidney disease (CKD) after hospitalization. To examine this, we measured urinary EGF (uEGF) from samples collected in the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study, a multi-center, prospective, observational cohort of hospitalized participants with and without AKI. Cox proportional hazards regression was used to investigate the association of uEGF/Cr at hospitalization, three months post-discharge, and the change between these time points with major adverse kidney events (MAKE): CKD incidence, progression, or development of kidney failure. Clinical findings were paired with mechanistic studies comparing relative Egf expression in mouse models of kidney atrophy or repair after ischemia-reperfusion injury. MAKE was observed in 20% of 1,509 participants over 4.3 years of follow-up. Each 2-fold higher level of uEGF/Cr at three months was associated with decreased risk of MAKE (adjusted hazards ratio 0.46, 95% confidence interval: 0.39-0.55). Participants with the highest increase in uEGF/Cr from hospitalization to three-month follow-up had a lower risk of MAKE (adjusted hazards ratio 0.52; 95% confidence interval: 0.36-0.74) compared to those with the least change in uEGF/Cr. A model using uEGF/Cr at three months combined with clinical variables yielded moderate discrimination for MAKE (area under the curve 0.73; 95% confidence interval: 0.69-0.77) and strong discrimination for kidney failure at four years (area under the curve 0.96; 95% confidence interval: 0.92-1.00). Accelerated restoration of Egf expression in mice was seen in the model of adaptive repair after injury, compared to a model of progressive atrophy. Thus, urinary EGF/Cr may be a biomarker of distal tubular health, with higher concentrations and increased uEGF/Cr post-discharge independently associated with reduced risk of MAKE in hospitalized patients.

Estimating Risk of Locoregional Failure and Overall Survival in Anal Cancer Following Chemoradiation: A Machine Learning Approach.

BACKGROUND: Optimal treatment of anal squamous cell carcinoma (ASCC) is definitive chemoradiation. Patients with persistent or recurrent disease require abdominoperineal resection (APR). Current models for predicting need for APR and overall survival are limited by low accuracy or small datasets. This study sought to use machine learning (ML) to develop more accurate models for locoregional failure and overall survival for ASCC. METHODS: This study used the National Cancer Database from 2004-2018, divided into training, validation, and test sets. We included patients with stage I-III ASCC who underwent chemoradiation. Our primary outcomes were need for APR and 3-year overall survival. Random forest (RF), gradient boosting (XGB), and neural network (NN) ML-based models were developed and compared with logistic regression (LR). Accuracy was assessed using area under the receiver operating characteristic curve (AUROC). RESULTS: APR was required in 5.3% (1,015/18,978) of patients. XGB performed best with AUROC of 0.813, compared with 0.691 for LR. Tumor size, lymphovascular invasion, and tumor grade showed the strongest influence on model predictions. Mortality was 23.6% (7,988/33,834). AUROC for XGB and LR were similar at 0.766 and 0.748, respectively. For this model, age, radiation dose, sex, and insurance status were the most influential variables. CONCLUSIONS: We developed and internally validated machine learning-based models for predicting outcomes in ASCC and showed higher accuracy versus LR for locoregional failure, but not overall survival. After external validation, these models may assist clinicians with identifying patients with ASCC at high risk of treatment failure.

Urinary flow through urethras with a rough lumen.

AIMS: This study investigates how lumen roughness and urethral length influence urinary flow speed. METHODS: We used micro-computed tomography scans to measure the lumen roughness and dimensions for rabbits, cats, and pigs. We designed and fabricated three-dimensional-printed urethra mimics of varying roughness and length to perform flow experiments. We also developed a corresponding mathematical model to rationalize the observed flow speed. RESULTS: We update the previously reported relationship between body mass and urethra length and diameter, now including 41 measurements for urethra length and 10 measurements for diameter. We report the relationship between lumen diameter and roughness as a function of position down the urethra for rabbits, cats, and pigs. The time course of urinary speed from our mimics is reported, as well as the average speed as a function of urethra length. CONCLUSIONS: Based on the behavior of our mimics, we conclude that the lumen roughness in mammals reduces flow speed by up to 25% compared to smooth urethras. Urine flows fastest when the urethra length exceeds 25 times its diameter. Longer urethras do not drain faster due to viscous effects counteracting the additional gravitational head. However, flows with our urethra mimics are still 6 times faster than those observed in nature, suggesting that further work is needed to understand flow resistance in the urethra.

Canine-inspired Unidirectional Flows for Improving Memory Effects in Machine Olfaction.

A dog's nose differs from a human's in that air does not change direction but flows in a unidirectional path from inlet to outlet. Previous simulations showed that unidirectional flow through a dog's complex nasal passageways creates stagnant zones of trapped air. We hypothesize that these zones give the dog a "physical memory," which it may use to compare recent odors to past ones. In this study, we conducted experiments with our previously built Gaseous Recognition Oscillatory Machine Integrating Technology (GROMIT) and performed corresponding simulations in two dimensions. We compared three settings: a control setting that mimics the bidirectional flow of the human nose; a short-circuit setting where odors exit before reaching the sensors; and a unidirectional configuration using a dedicated inlet and outlet that mimics the dog's nose. After exposure to odors, the sensors in the unidirectional setting showed the slowest return to their baseline level, indicative of memory effects. Simulations showed that both short-circuit and unidirectional flows created trapped recirculation zones, which slowed the release of odors from the chamber. In the future, memory effects such as the ones found here may improve the sensitivity and utility of electronic noses.

Onggi's permeability to carbon dioxide accelerates kimchi fermentation.

Since ancient times, Korean chefs have fermented foods in an onggi, a traditional earthenware vessel. The porous structure of the onggi mimics the loose soil where lactic acid bacteria is naturally found. This permeability has been purported to facilitate the growth of lactic acid bacteria, but the details of the process remain poorly understood. In this combined experimental and theoretical study, we ferment salted napa cabbage in onggi and hermetic glassware and measure the time course of carbon dioxide concentration, which is a signature of fermentation. We present a mathematical model for carbon dioxide generation rate during fermentation using the onggi's gas permeability as a free parameter. Our model provides a good fit for the data, and we conclude that porous walls help the onggi to 'exhale' carbon dioxide, lowering internal levels to those favoured by lactic acid bacteria. The positive pressure inside the onggi and the constant outflow through its walls act as a safety valve for bacteria growth by blocking the entry of external contaminants without mechanical components. We hope this study draws attention to the work of traditional artisans and inspires energy-efficient methods for fermenting and storing food products.

ForageFeeder: A low-cost open source feeder for randomly distributing food.

Automated feeders have long fed mice, livestock, and poultry, but are incapable of feeding zoo animals such as gorillas. In captivity, gorillas eat cut vegetables and fruits in pieces too large to be dispensed by automated feeders. Consequently, captive gorillas are fed manually at set times and locations, keeping them from the exercise and enrichment that accompanies natural foraging. We designed and built ForageFeeder, an automated gorilla feeder that spreads food at random intervals throughout the day. ForageFeeder is an open source and easy to manufacture and modify device, making the feeder more accessible for zoos. The design presented here reduces manual labor for zoo staff and may be a useful tool for studies of animal ethology.

Quantitative assessment of automated purification and concentration of E. coli bacteria.

Automated methods for rapidly purifying and concentrating bacteria from environmental interferents are needed in next-generation applications for anything from water purification to biological weapons detection. Though previous work has been performed by other researchers in this area, there is still a need to create an automated system that can both purify and concentrate target pathogens in a timely manner with readily available and replaceable components that could be easily integrated with a detection mechanism. Thus, the objective of this work was to design, build, and demonstrate the effectiveness of an automated system, the Automated Dual-filter method for Applied Recovery, or aDARE. aDARE uses a custom LABVIEW program that guides the flow of bacterial samples through a pair of size-based separation membranes to capture and elute the target bacteria. Using aDARE, we eliminated 95% of the interfering beads of a 5 mL-sample volume containing 107 CFU/mL of E. coli contaminated with 2 µm and 10 µm polystyrene beads at 106 beads/mL concentration., The target bacteria were concentrated to more than twice the initial concentration in 900 µL of eluent, resulting in an enrichment ratio for the target bacteria of 42 ± 13 in 5.5 min. These results show the feasibility and effectiveness of using size-based filtration membranes to purify and concentrate a target bacterium, in this case E. coli, in an automated system.

Drying dynamics of pellet feces.

Pellet feces are generated by a number of animals important to science or agriculture, including mice, rats, goats, and wombats. Understanding the factors that lead to fecal shape may provide a better understanding of animal health and diet. In this combined experimental and theoretical study, we test the hypothesis that pellet feces are formed by drying processes in the intestine. Inspirational to our work is the formation of hexagonal columnar jointings in cooling lava beds, in which the width L of the hexagon scales as L ∼ J-1 where J is the heat flux from the bed. Across 22 species of mammals, we report a transition from cylindrical to pellet feces if fecal water content drops below 0.65. Using a mathematical model that accounts for water intake rate and intestinal dimensions, we show pellet feces length L scales as L ∼ J-2.08 where J is the flux of water absorbed by the intestines. We build a mimic of the mammalian intestine using a corn starch cake drying in an open trough, finding that corn starch pellet length scales with water flux-0.46. The range of exponents does not permit us to conclude that formation of columnar jointings is similar to the formation of pellet feces. Nevertheless, the methods and physical picture shown here may be of use to physicians and veterinarians interested in using feces length as a marker of intestinal health.

Elephant trunks use an adaptable prehensile grip.

Elephants have long been observed to grip objects with their trunk, but little is known about how they adjust their strategy for different weights. In this study, we challenge a female African elephant at Zoo Atlanta to lift 20-60 kg barbell weights with only its trunk. We measure the trunk's shape and wrinkle geometry from a frozen elephant trunk at the Smithsonian. We observe several strategies employed to accommodate heavier weights, including accelerating less, orienting the trunk vertically, and wrapping the barbell with a greater trunk length. Mathematical models show that increasing barbell weights are associated with constant trunk tensile force and an increasing barbell-wrapping surface area due to the trunk's wrinkles. Our findings may inspire the design of more adaptable soft robotic grippers that can improve grip using surface morphology such as wrinkles.

Jumping of flea beetles onto inclined platforms.

The flea beetle, Altica cirsicola, escapes predators by jumping and landing in a dense maze of leaves. How do they land on such varied surfaces? In this experimental study, we filmed the take-off, flight, and landing of flea beetles on a configurable angled platform. We report three in-flight behaviors: winged, wingless, and an intermediate winged mode. These modes significantly affected take-off speed, acceleration, and the duration that wings were deployed. When wings were closed, flea beetles rolled or pitched up to five times in the air. This work may help to understand how insects can jump and right themselves onto variable surfaces.

Deriving International Classification of Diseases, 9th and 10th revision, codes for identifying and following up patients with diabetic lower extremity ulcers.

Objective: Administrative claims data offer a rich data source for clinical research. However, its application to the study of diabetic lower extremity ulceration is lacking. Our objective was to create a widely applicable framework by which investigators might derive and refine the International Classification of Diseases, 9th and 10th revision (ICD-9 and ICD-10, respectively) codes for use in identifying diabetic, lower extremity ulceration. Methods: We created a seven-step process to derive and refine the ICD-9 and ICD-10 coding lists to identify diabetic lower extremity ulcers. This process begins by defining the research question and the initial identification of a list of ICD-9 and ICD-10 codes to define the exposures or outcomes of interest. These codes are then applied to claims data, and the rates of clinical events are examined for consistency with prior research and changes across the ICD-9 to ICD-10 transition. The ICD-9 and ICD-10 codes are then cross referenced with each other to further refine the lists. Results: Using this method, we started with 8 ICD-9 and 43 ICD-10 codes used to identify lower extremity ulcers in patients with known diabetes and peripheral arterial disease and examined the association of ulceration with lower extremity amputation. After refinement, we had 45 ICD-9 codes and 304 ICD-10 codes. We then grouped the codes into eight clinical exposure groups and examined the rates of amputation as a rudimentary test of validity. We found that the rate of lower extremity amputation correlated with the severity of lower extremity ulceration. Conclusions: We identified 45 ICD-9 and 304 ICD-10 ulcer codes, which identified patients at risk of amputation from diabetes and peripheral artery disease. Although further validation at the medical record level is required, these codes can be used for claims-based risk stratification for long-term outcomes assessment in the treatment of patients at risk of limb loss.

Food as Medicine Clinic: Early Results and Lessons Learned.

INTRODUCTION: Hospital-based food pantries are commonly used to address food insecurity. However, few studies have examined the impact of these food pantries on patients with chronic health conditions. In this study, we sought to assess the effect of a hospital-based food pantry clinic on self-reported dietary changes, health outcomes, and resource utilization. METHODS: This study included food insecure participants with suboptimally controlled congestive heart failure, hypertension, or diabetes who visited a Food as Medicine (FAM) clinic at an academic healthcare system between October 2018 and November 2019. The clinic provided a three-day supply of food for participants and their families up to two times per month for up to 12 months. Baseline, three-month, and six-month surveys were used to assess dietary behaviors, and electronic health record (EHR) data were used to assess health outcomes and utilization. Multivariable Poisson regression was used to explore variables associated with FAM clinic use. RESULTS: At three months, participants self-reported improved dietary behaviors, including increased consumption of fruits and vegetables as snacks and an increased variety of fruits and vegetables consumed. There were no statistically significant changes in clinical or healthcare utilization measures, despite small absolute improvements in systolic blood pressure (SBP), hospitalizations, and emergency department (ED) visits. There was a weak association between FAM clinic visit frequency and changes in dietary behaviors. CONCLUSION: Among patients with chronic diseases, the use of the FAM clinic was associated with improved self-reported dietary behaviors and a nonsignificant improvement in health outcomes and resource utilization.

Point prevalence of Hip Symptoms, Radiographic, And Symptomatic OA at Five Time Points: The Johnston County Osteoarthritis Project, 1991-2018.

Objective: To describe the point prevalence of hip symptoms, radiographic hip osteoarthritis (rHOA), severe rHOA, and symptomatic rHOA (sxHOA) at five time points in the longitudinal, population-based Johnston County Osteoarthritis Project (JoCoOA). Design: Data were from 3068 JoCoOA participants who attended up to five study visits (1991-2018). Standardized supine pelvis radiographs were read by a single, expert musculoskeletal radiologist with high reliability. The four outcomes were: 1) self-reported hip symptoms: "On most days, do you have pain, aching, or stiffness in your right/left hip?"; 2) rHOA: Kellgren-Lawrence grade (KLG) of 2-4; 3) severe rHOA: KLG of 3-4; and 4) sxHOA: both symptoms and rHOA in the same joint. Weighted point prevalence and 95% confidence intervals (CI) were generated overall and by age group (45-54, 55-64, 65-74, 75+ years), sex, race (Black/White), and body mass index (BMI; 18.5-24.9; 25-29.9; 30+ kg/m2). Results: At the most recent follow-up (2017-2018), the point prevalence (%) of hip symptoms, rHOA, severe rHOA, and sxHOA were 30% (95% CI 25%, 35%), 53% (95% CI 48%, 58%), 9% (95% CI 6%, 12%), and 15% (95% CI 11%, 19%), respectively. RHOA and severe rHOA were most prevalent in those 75+ years. Women were more likely than men to have hip symptoms and sxHOA. No consistent trends were noted by race or BMI. Conclusion: These updated point prevalence estimates demonstrate a large and increasing burden of HOA in the general population, particularly with aging. Black and White individuals were affected similarly in this cohort.