Dental Correction Does Not Alter Postprandial Nutrient Concentrations in Healthy Mares.

Irregular wear patterns are theorized to cause poor feed digestion and weight loss in the horse. The objective of this study was to test the hypothesis that dental correction would increase postprandial nutrient concentrations and reduce fecal particle size (FPS) in clinically healthy mares. The study was conducted in 16 mares of mature age (4-17) who had not received dental care in the previous year. A diet consisting of ad libitum Coastal Bermudagrass hay and 1.36 kg of a pelleted feed was fed daily prior to and during the study. Eight mares received dental work and eight served as untreated controls. While the consumption of a concentrate meal increased plasma concentrations of glucose and amino acids at 90 minutes postfeeding (P < .001), dental correction did not have an influence on plasma nutrient concentrations (P > .1). On day 56, untreated control horses had a larger percent of large FPS than horses having received dental correction (14.7 ± 0.1 vs. 12.5 ± 0.1; P = .028). Dental correction may improve mechanical digestion of feed, but this does not translate to altered postprandial plasma nutrient concentrations following the consumption of a concentrate meal.

Impact of Oral Phytozen EQ Supplementation on Plasma Cortisol and Behavior Responses of Young Horses Exposed to Stressful Stimuli.

Calming supplements are common in the equine industry. This study tested the hypothesis that Phytozen EQ, a blend of citrus botanical oils, magnesium, and yeast would reduce startle response as well as reduce behavioral and physiological signs of stress in young (1.5-6 years of age) horses (n = 14) when tied in isolation and when trailered in isolation. During the 59-day trial, horses were assigned to either the control (CON; n = 7) or treatment (PZEN; n = 7) group that received 56 g of Phytozen EQ daily. Horses underwent a 10-minute isolation test on d 30 and a 15 minute individual trailering test on day 52 or 55. For both tests, blood samples were obtained pre, immediately after, and 1-hour post for analysis of plasma cortisol concentrations, which were analyzed by repeated measures ANOVA. On day 59, horses underwent a startle test, for which time to travel 3 m and total distance traveled were recorded. These data were analyzed using a T-test. During trailering, PZEN horses tended to have lower overall geometric mean (lower, upper 95% confidence interval) cortisol concentrations than CON (81 [67, 98] vs. 61 [48, 78] ng/mL; P = .071). For the startle test, PZEN horses tended to have longer geometric mean times to travel 3 m than CON horses (1.35 [0.39, 4.70] vs. 0.26 [0.07, 0.91 seconds, P = 0.064). Other data points were not different between treatments (P > .1). It is possible that this dietary supplement could have beneficial calming effects on horses undergoing trailering or in novel situations.

Anticoagulation-Free Pediatric Extracorporeal Membrane Oxygenation: Single-Center Retrospective Study.

OBJECTIVES: To analyze hemorrhage and thrombosis data related to anticoagulation-free pediatric extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective cohort study. SETTINGS: High-volume ECMO single institution data. PATIENTS: Children (0-18 yr) supported with ECMO (>24 hr) with initial anticoagulation-free period of greater than or equal to 6 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Utilizing consensus American Thoracic Society definitions for hemorrhage and thrombosis on ECMO, we evaluated thrombosis and associated patient and ECMO characteristics during anticoagulation-free period. Thirty-five patients met inclusion criteria from 2018 to 2021 having a median age (interquartile range [IQR]) of 13.5 months (IQR, 3-91 mo), median ECMO duration of 135 hours (IQR, 64-217 hr), and 964 anticoagulation-free hours. Increased RBC transfusion needs were associated with longer anticoagulation-free periods ( p = 0.03). We identified 20 thrombotic events: only four during the anticoagulation-free period and occurring in three of 35 (8%) patients. Compared with those without thrombotic events, anticoagulation-free clotting events were associated with younger age (i.e., 0.3 mo [IQR, 0.2-0.3 mo] vs 22.9 mo [IQR, 3.6-112.9 mo]; p = 0.02), lower weight (2.7 kg [IQR, 2.7-3.25 kg] vs 13.2 kg [5.9-36.4 kg]; p = 0.006), support with lower median ECMO flow rate (0.5 kg [IQR, 0.45-0.55 kg] vs 1.25 kg [IQR, 0.65-2.5 kg]; p = 0.04), and longer anticoagulation-free ECMO duration (44.5 hr [IQR, 40-85 hr] vs 17.6 hr [IQR, 13-24.1]; p = 0.008). CONCLUSIONS: In selected high-risk-for-bleeding patients, our experience is that we can use ECMO in our center for limited periods without systemic anticoagulation, with lower frequency of patient or circuit thrombosis. Larger multicentered studies are required to assess weight, age, ECMO flow, and anticoagulation-free time limitations that are likely to pose risk for thrombotic events.

Effects of Crude Rice Bran Oil and a Flaxseed Oil Blend in Young Horses Engaged in a Training Program.

Rice bran oil and flaxseed oil contain omega-3 fatty acids with the potential to reduce post-exercise inflammation and muscle damage. This study measures plasma interleukin-1ß and creatine kinase and fatty acid profiles in lightly worked, young horses (Equus caballus) undergoing an exercise test after 60 days (d) of oil consumption, where the oil replaced 25% of concentrate calories. Treatments consisted of CON (no oil), FLAX (flaxseed oil blend), and RICE (crude rice bran oil). Blood was collected pre-exercise, and again at 1 min, 30 min, 24 h, 48 h, and 72 h post-IET. Data were analyzed by repeated measures ANOVA. Plasma creatine kinase activity was not different in CON during the study, greater (p < 0.05) in RICE from pre-exercise to 30 min post-exercise across all exercise tests, and lesser (p < 0.05) in FLAX at 30 min post-exercise on d 30 compared to d 0. Plasma interleukin-1ß was greater (p < 0.01) in CON on d 60, but no differences were observed in FLAX and RICE throughout the study. Plasma alpha-linolenic and linoleic acids were greatest (p < 0.05) in FLAX after 30 d of inclusion, while CON horses had greater (p < 0.05) EPA across all exercise tests and DHA after 60 d. These results indicate that 60 d of inclusion of crude rice bran oil or a flaxseed oil blend may benefit lightly worked, young horses by reducing training-program-related increases in interleukin-1ß, while a flaxseed oil blend may reduce exercise-induced increases in creatine kinase. Additionally, the flaxseed oil blend has the potential to increase plasma omega-3 and omega-6 fatty acids. Replacing 25% of concentrate calories with flaxseed or rice bran oil has potential benefits for young horses in training.

The impact of a "Residents as Teachers" Workshop at one year follow-up.

INTRODUCTION: "Residents as Teachers" (RaT) Workshops have been implemented in many General Surgery residency programs to improve resident teaching ability. The aim of this project was to assess whether there was significant degradation of teaching skills and knowledge one year after a RaT workshop. METHODS: A 4-h interactive workshop was delivered at an academic general surgery residency program. Pre- and post-workshop assessments evaluated participants' knowledge and confidence regarding teaching skills and they were re-evaluated one-year later. RESULTS: On a 5-point Likert scale, residents improved confidence and self-perception following the workshop was stable after one year. A decrease was found in the resident's perception of the education-related training received and scores on the knowledge-based questions. CONCLUSION: The confidence residents obtained from single-day RaT workshop was maintained at one year, but the knowledge was not. Resident perception of their educational training may benefit from more frequent reinforcement.

"Residents as Teachers" Workshop Improves Knowledge, Confidence, and Feedback Skills for General Surgery Residents.

OBJECTIVE: Surgical residents receive limited formal training in education, yet they are expected to teach medical students and one another. A "Residents as Teachers" curriculum was developed and implemented to improve residents' knowledge of educational strategies, confidence in teaching abilities, and quality of feedback given to learners. DESIGN: A 6-hour workshop was delivered at an academic general surgery residency program. It included 3 interactive sessions: "Teaching on the wards", "How to give and receive feedback", and "Teaching in the operating room (OR)". Pre- and postsession surveys were administered to evaluate participants' knowledge and confidence regarding teaching skills. Standard statistical analyses were used to compare pre- and postcurriculum scores. SETTING: General surgery residents at Case Western Reserve University/University Hospitals Cleveland Medical Center Program attended a 6-hour educational seminar entitled "Residents as Teachers". Three attending surgeons with expertise in surgical education administered the curriculum. PARTICIPANTS: Twenty-four residents completed the course and surveys (5 PGY-5s, 6 PGY-4s, 4 PGY-3s, 5 PGY-2s, and 4 PGY-1s). RESULTS: On a 5-point Likert scale, residents' self-rating of teaching skills (pre = 1.8, post = 3.04, p < 0.001) and understanding of adult learning (pre = 1.88, post = 4.42, p < 0.001) improved significantly. The greatest gain was in describing effective strategies for teaching in the OR (pre = 1.75, post = 4.38, p < 0.001). Residents reported improved understanding of effective feedback characteristics (pre = 2.5, post = 4.33, p < 0.001), and felt more prepared to provide feedback to learners (pre = 2.73, post = 3.17, p = 0.01). Scores on 5 of 10 knowledge-based questions significantly improved following the intervention. All participants agreed or strongly agreed that the workshop improved the program's surgical education curriculum (mean score 4.42 of 5). CONCLUSIONS: A "Residents as Teachers" workshop improved resident confidence in teaching and feedback skills, particularly for intraoperative instruction, and improved knowledge in the 3 specific educational domains included in the session.

Gastric Per Oral Pyloromyotomy for Post-Vagotomy-Induced Gastroparesis Following Esophagectomy.

BACKGROUND: Following the success of per-oral endoscopic myotomy (POEM) for achalasia, application of this minimally invasive skillset has broadened to other disease processes. Since 2013, gastric per-oral pyloromyotomy (GPOP) has become an increasingly accepted therapy for refractory gastroparesis. Although it does not treat the underlying etiology of the disease, pyloromyotomy has demonstrated measurable improvements in gastric emptying scintigraphy, nausea, and quality of life. Gastroparesis is a common complication of esophagectomy due to the inherent vagotomy that occurs during creation of the gastric conduit. Fifteen to 30% of post-esophagectomy patients develop gastroparesis with a large portion of them reporting symptoms refractory to medical therapy, botox injection, and endoscopic dilation. Therefore, GPOP may have the potential to offer symptomatic relief to a significant population of debilitated post-esophagectomy patients. MATERIALS AND METHODS: The procedure was recorded using standard operating room equipment. Materials utilized included high-definition single-channel gastroscope, therapeutic overtube, clear endoscopic cap, triangle tip (TT) knife, ERBE energy source, endoscopic clips, sclerotherapy needle, methylene blue with epinephrine, and CO2 insufflator. RESULTS: We present a video of GPOP for a 71-year-old male with post-vagotomy-induced gastroparesis after esophagectomy. His pre-operative course was significant for persistent nausea and vomiting, diet intolerance, 20 lb weight loss, and frequent hospitalizations for aspiration pneumonia. Post-operatively, the patient recovered well and was discharged home on post-operative day 1 on a liquid diet. At 3-week follow-up, his nausea, vomiting, and PO intolerance had improved. At 6-month follow-up, he had no recent admissions for aspiration pneumonia and his pylorus remained widely patent on EGD. CONCLUSIONS: GPOP status post-esophagectomy presented multiple challenges: difficulty maintaining field of view and insufflation, establishing tension and counter tension for the mucosotomy, and a limited working space. With care and patience, endoscopists trained to perform POEM may apply their skillset to help a large population of patients suffering with post-esophagectomy gastroparesis.

Fog Harvesting with Harps.

Fog harvesting is a useful technique for obtaining fresh water in arid climates. The wire meshes currently utilized for fog harvesting suffer from dual constraints: coarse meshes cannot efficiently capture microscopic fog droplets, whereas fine meshes suffer from clogging issues. Here, we design and fabricate fog harvesters comprising an array of vertical wires, which we call "fog harps". Under controlled laboratory conditions, the fog-harvesting rates for fog harps with three different wire diameters were compared to conventional meshes of equivalent dimensions. As expected for the mesh structures, the mid-sized wires exhibited the largest fog collection rate, with a drop-off in performance for the fine or coarse meshes. In contrast, the fog-harvesting rate continually increased with decreasing wire diameter for the fog harps due to efficient droplet shedding that prevented clogging. This resulted in a 3-fold enhancement in the fog-harvesting rate for the harp design compared to an equivalent mesh.

ECMO for Pediatric Lung Transplantation.

Extracorporeal membrane oxygenation (ECMO) has been reported as an alternative to cardiopulmonary bypass during lung transplantation. The reports in the literature have been limited to adult practice and associated with decreased pulmonary and renal complications, lower mortality, and lower in-hospital mortality. We present four pediatric lung transplantations performed on ECMO and discuss relevant perfusion management.

Mixed acinar-neuroendocrine-ductal carcinoma of the pancreas: a tale of three lineages.

Most pancreatic cancers arise from a single cell type, although mixed pancreatic carcinomas represent a rare exception. The rarity of these aggressive malignancies and the limitations of fine-needle aspiration (FNA) pose significant barriers to diagnosis and appropriate management. We report a case of a 54-year-old man presenting with abdominal pain, jaundice and a hypodense lesion within the uncinate process on CT. FNA suggested poorly differentiated adenocarcinoma, which was subsequently resected via pancreaticoduodenectomy. Pathological analysis yielded diagnosis of invasive mixed acinar-neuroendocrine-ductal pancreatic carcinoma. Given the rare and deadly nature of these tumours, clinicians must be aware of their pathophysiology and do practice with a high degree of clinical suspicion, when appropriate. Surgical resection and thorough pathological analysis with immunohistochemical staining and electron microscopy remain the standards of care for mixed pancreatic tumours without gross evidence of metastasis. Diligent characterisation of the presentation and histological findings associated with these neoplasms should continue in order to promote optimal diagnostic and therapeutic strategies.

A cell-free expression and purification process for rapid production of protein biologics.

Cell-free protein synthesis has emerged as a powerful technology for rapid and efficient protein production. Cell-free methods are also amenable to automation and such systems have been extensively used for high-throughput protein production and screening; however, current fluidic systems are not adequate for manufacturing protein biopharmaceuticals. In this work, we report on the initial development of a fluidic process for rapid end-to-end production of recombinant protein biologics. This process incorporates a bioreactor module that can be used with eukaryotic or prokaryotic lysates that are programmed for combined transcription/translation of an engineered DNA template encoding for specific protein targets. Purification of the cell-free expressed product occurs through a series of protein separation modules that are configurable for process-specific isolation of different proteins. Using this approach, we demonstrate production of two bioactive human protein therapeutics, erythropoietin and granulocyte-macrophage colony-stimulating factor, in yeast and bacterial extracts, respectively, each within 24 hours. This process is flexible, scalable and amenable to automation for rapid production at the point-of-need of proteins with significant pharmaceutical, medical, or biotechnological value.

The effect of mitral valve surgery on ventricular arrhythmia in patients with bileaflet mitral valve prolapse.

BACKGROUND: Bileaflet mitral valve prolapse (biMVP) is associated with frequent ventricular ectopy (VE) and malignant ventricular arrhythmia. We examined the effect of mitral valve (MV) surgery on VE burden in biMVP patients. METHODS: We included 32 consecutive patients undergoing MV surgery for mitral regurgitation secondary to biMVP between 1993 and 2012 at Mayo Clinic who had available pre- and post-operative Holter monitoring data. Characteristics of patients with a significant reduction in postoperative VE (group A, defined as >10% reduction in VE burden compared to baseline) were compared with the rest of study patients (group B). RESULTS: In the overall cohort, VE burden was unchanged after the surgery (41 interquartile range [16, 196] pre-surgery vs. 40 interquartile range [5186] beats/hour [bph] post-surgery; P = 0.34). However, in 17 patients (53.1%), VE burden decreased by at least 10% after the surgery. These patients (group A) were younger than the group B (59 ± 15 vs. 68 ± 7 years; P = 0.04). Other characteristics including pre- and postoperative left ventricular function and size were similar in both groups. Age <60 years was associated with a reduction in postoperative VE (odds ratio 5.8; 95% confidence interval, 1.1-44.7; P = 0.03). Furthermore, there was a graded relationship between age and odds of VE reduction with surgery (odds ratio 1.9; 95% confidence interval 1.04-4.3 per 10-year; P = 0.04). CONCLUSIONS: MV surgery does not uniformly reduce VE burden in patients with biMVP. However, those patients who do have a reduction in VE burden are younger, perhaps suggesting that early surgical intervention could modify the underlying electrophysiologic substrate.

Implementing a Community-Driven Research Partnership: The Backyard Initiative Community Health Survey Methods and Approach.

BACKGROUND: In community-based participatory research (CBPR), issues such as creating a setting where community members drive decisions and creating culturally relevant processes remain largely underachieved. The Backyard Initiative (BYI) provided the setting for implementing a community-centered collaborative research process. The BYI is a partnership between Allina Health, the Cultural Wellness Center (CWC), and community residents to improve health. OBJECTIVES: To describe the unique community-centered method used in the 2013 BYI Community Health Survey (CHS) as a viable approach for collecting meaningful and valid health related data. With this approach, the community operates as the agent of change rather than the target. METHODS: At the core was the BYI assessment team, which brought together conventional researchers and community members to collaboratively design, implement, analyze, interpret, and disseminate the CHS results. Focusing on the CHS, this structure and process permitted and facilitated important and difficult discussions about approach, content and outcomes of the research. RESULTS: We held seven sessions (239 participants). Participants were 37% African American/African and 34% Native American, 65% female, and 72% spoke English at home. Achievement of our recruitment goals, participation of groups typically underrepresented in research, and positive community feedback were indications that the BYI approach to survey research was successful. CONCLUSIONS: The BYI CHS community-centered methods built trust among research partners and participants, engaged populations often underrepresented in research, and collected meaningful data. Our success indicates that it is possible to co-design and implement a lengthy survey to inform future research and community activities.

Energizing eukaryotic cell-free protein synthesis with glucose metabolism.

Eukaryotic cell-free protein synthesis (CFPS) is limited by the dependence on costly high-energy phosphate compounds and exogenous enzymes to power protein synthesis (e.g., creatine phosphate and creatine kinase, CrP/CrK). Here, we report the ability to use glucose as a secondary energy substrate to regenerate ATP in a Saccharomyces cerevisiae crude extract CFPS platform. We observed synthesis of 3.64±0.35 µg mL(-1) active luciferase in batch reactions with 16 mM glucose and 25 mM phosphate, resulting in a 16% increase in relative protein yield (µg protein/$ reagents) compared to the CrP/CrK system. Our demonstration provides the foundation for development of cost-effective eukaryotic CFPS platforms.

Characterizing and alleviating substrate limitations for improved in vitro ribosome construction.

Complete cell-free synthesis of ribosomes could make possible minimal cell projects and the construction of variant ribosomes with new functions. Recently, we reported the development of an integrated synthesis, assembly, and translation (iSAT) method for in vitro construction of Escherichia coli ribosomes. iSAT allows simultaneous rRNA synthesis, ribosome assembly, and reporter protein expression as a measure of ribosome activity. Here, we explore causes of iSAT reaction termination to improve efficiency and yields. We discovered that phosphoenolpyruvate (PEP), the secondary energy substrate, and nucleoside triphosphates (NTPs) were rapidly degraded during iSAT reactions. In turn, we observed a significant drop in the adenylate energy charge and termination of protein synthesis. Furthermore, we identified that the accumulation of inorganic phosphate is inhibitory to iSAT. Fed-batch replenishment of PEP and magnesium glutamate (to offset the inhibitory effects of accumulating phosphate by repeated additions of PEP) prior to energy depletion prolonged the reaction duration 2-fold and increased superfolder green fluorescent protein (sfGFP) yield by ~75%. By adopting a semi-continuous method, where passive diffusion enables substrate replenishment and byproduct removal, we prolonged iSAT reaction duration 5-fold and increased sfGFP yield 7-fold to 7.5 ± 0.7 µmol L(-1). This protein yield is the highest ever reported for iSAT reactions. Our results underscore the critical role energy substrates play in iSAT and highlight the importance of understanding metabolic processes that influence substrate depletion for cell-free synthetic biology.

Substrate replenishment and byproduct removal improve yeast cell-free protein synthesis.

Cell-free protein synthesis (CFPS) platforms are now considered a powerful tool for synthesizing a variety of proteins at scales from pL to 100 L with accelerated process development pipelines. We previously reported the advancement of a novel yeast-based CFPS platform. Here, we studied factors that cause termination of yeast CFPS batch reactions. Specifically, we characterized the substrate and byproduct concentrations in batch, fed-batch, and semi-continuous reaction formats through high-performance liquid chromatography (HPLC) and chemical assays. We discovered that creatine phosphate, the secondary energy substrate, and nucleoside triphosphates were rapidly degraded during batch CFPS, causing a significant drop in the reaction's energy charge (E.C.) and eventual termination of protein synthesis. As a consequence of consuming creatine phosphate, inorganic phosphate accumulated as a toxic byproduct. Additionally, we measured amino acid concentrations and found that aspartic acid was rapidly consumed. By adopting a semi-continuous reaction format, where passive diffusion enables substrate replenishment and byproduct removal, we achieved over a 70% increase in active superfolder green fluorescent protein (sfGFP) as compared with the batch system. This study identifies targets for the future improvement of the batch yeast CFPS reaction. Moreover, it outlines a detailed, generalized method to characterize and improve other CFPS platforms.

Melanoma simulation model: promoting opportunistic screening and patient counseling.

IMPORTANCE: Lack of training hampers melanoma recognition by physicians. OBJECTIVE: To evaluate a melanoma simulation model to teach visual assessment and counseling skills. DESIGN AND SETTING: Simulation model study in an academic research setting. PARTICIPANTS: A convenience sample of third-year medical students was randomly assigned to receive the intervention before or after a standardized patient. INTERVENTION: During the primary care clerkship, medical students participated in melanoma skills training using 2 simulation models replicating melanomas and abnormal or benign nevi. Scoring threshold rules for visual assessment and management of pigmented lesions and videos of patient counseling were provided. MAIN OUTCOME MEASURES: Identifying a melanoma moulage and counseling the standardized patient. Secondary measures were preintervention and 2-week postintervention knowledge, attitudes about and confidence in their ability to perform opportunistic surveillance and counseling, as well as identification on the model of clinically suspicious pigmented lesions, lesions needing a biopsy, and lesions to be monitored for change. RESULTS Among 74 students, confidence in their ability to perform opportunistic surveillance improved significantly after skills training (P < .05, χ2 test). Monitoring clinically suspicious lesions for change decreased from 16% (12 of 74) to 3% (2 of 74) and performing a biopsy increased from 80% (59 of 74) to 96% (71 of 74), monitoring benign lesions for change decreased from 43% (32 of 74) to 3% (2 of 74), and biopsying melanoma in situ increased from 10% (7 of 74) to 26% (20 of 74) (P < .05 for all, χ2 test). Detection of the melanoma moulage on the standardized patient occurred more often by trained students (P < .05, χ2 test). CONCLUSION AND RELEVANCE: A 1-hour melanoma simulation education and skills training experience improved performance of opportunistic surveillance, management, and patient counseling by third-year medical students. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01191294.

Radar observations of individual rain drops in the free atmosphere.

Atmospheric remote sensing has played a pivotal role in the increasingly sophisticated representation of clouds in the numerical models used to assess global and regional climate change. This has been accomplished because the underlying bulk cloud properties can be derived from a statistical analysis of the returned microwave signals scattered by a diverse ensemble comprised of numerous cloud hydrometeors. A new Doppler radar, previously used to track small debris particles shed from the NASA space shuttle during launch, is shown to also have the capacity to detect individual cloud hydrometeors in the free atmosphere. Similar to the traces left behind on film by subatomic particles, larger cloud particles were observed to leave a well-defined radar signature (or streak), which could be analyzed to infer the underlying particle properties. We examine the unique radar and environmental conditions leading to the formation of the radar streaks and develop a theoretical framework which reveals the regulating role of the background radar reflectivity on their observed characteristics. This main expectation from theory is examined through an analysis of the drop properties inferred from radar and in situ aircraft measurements obtained in two contrasting regions of an observed multicellular storm system. The observations are placed in context of the parent storm circulation through the use of the radar's unique high-resolution waveforms, which allow the bulk and individual hydrometeor properties to be inferred at the same time.

Anatomical form defines color: function, form, and aesthetics.

Contemporary composite materials enable the reproduction of polychromatic effects within a tooth. A broader definition of color that incorporates the anatomy and optical properties of a tooth must be developed so the dental professional can better understand the infinite possibilities of color that exist within the tooth and restoration. This article describes a direct protocol for the development of natural restorations in the posterior dentition through the integration of function, form, and color.