The rat as an animal model in chronic wound research: An update.

The increasing global prevalence of chronic wounds underscores the growing importance of developing effective animal models for their study. This review offers a critical evaluation of the strengths and limitations of rat models frequently employed in chronic wound research and proposes potential improvements. It explores these models in the context of key comorbidities, including diabetes, venous and arterial insufficiency, pressure-induced blood flow obstruction, and infections. Additionally, the review examines important wound factors including age, sex, smoking, and the impact of anesthetic and analgesic drugs, acknowledging their substantial effects on research outcomes. A thorough understanding of these variables is crucial for refining animal models and can provide valuable insights for future research endeavors.

Injectable and rapidly expandable thrombin-decorated cryogels achieve rapid hemostasis and high survival rates in a swine model of lethal junctional hemorrhage.

Effective therapies are urgently needed to stabilize patients with marginally compressible junctional hemorrhage long enough to get them to the hospital alive. Herein, we report injectable and rapidly expandable cryogels consisting of polyacrylamide and thrombin (AT cryogels) created by cryo-polymerization for the efficient management of lethal junctional hemorrhage in swine. The produced cryogels have small pore sizes and highly interconnected porous architecture with robust mechanical strength. The cryogels exhibit rapid shape memory properties and prove to be resilient against fatigue. These cryogels also show high water/blood absorption capacity, fast blood clotting effect, and enhanced adhesion of red blood cells and platelets in vitro. Further, in vivo, hemostatic efficacy tests in a lethal swine junctional hemorrhage model suggest that treatment with AT cryogels, especially AT-2 cryogels, achieves the least blood loss and the highest survival rate (100 %) compared to currently employed products such as XStat® and combat gauze. The high hemostatic performance of the cryogels may be attributed to highly interconnected porous architecture with small pore size and the use of thrombin as a pro-coagulant agent. Collectively, injectable and rapidly expandable thrombin-decorated polyacrylamide-based cryogels show significant promise as hemostatic material, offering effective management of marginally compressible junctional hemorrhages in prehospital settings.

Decreased Noise and Identification of Very Low Voltage Signals Using a Novel Electrophysiology Recording System.

Aims: The interpretation of intracardiac electrograms recorded from conventional electrophysiology recording systems is frequently impacted by powerline (50/60 Hz) noise and distortion due to notch filtering. This study compares unipolar electrograms recorded simultaneously from a conventional electrophysiology recording system and one of two 3D mapping systems (control system) with those from a novel system (ECGenius, CathVision ApS) designed to reduce noise without the need for conventional filtering. Methods: Unipolar electrograms were recorded simultaneously from nine consecutive patients undergoing catheter ablation for AF (five patients), atrioventricular nodal re-entrant tachycardia (three patients), or ventricular tachycardia (one patient) over the course of 1 week in 2020. Results: The noise spectral power of the novel system (49-51 Hz) was 6.1 ± 6.2 times lower than that of the control system. Saturation artefact following pacing (duration 97 ± 85 ms) occurred in eight control recordings and no novel system recordings (p<0.001). High frequency, low amplitude signals and fractionated electrograms apparent on unfiltered novel system unipolar recordings were not present on control recordings. Control system notch filtering obscured His bundle electrograms observable without such filtering using the novel system and induced electrogram distortion that was not present on novel system recordings. Signal saturation occurred in five of seven control system recordings but none of the novel system recordings. Conclusion: In this study, novel system recordings exhibited less noise and fewer signal artefacts than the conventional control system and did not require notch filtering that distorted electrograms on control recordings. The novel recording system provided superior electrogram data not apparent with conventional systems.

Evaluation of Five Mammalian Models for Human Disease Research Using Genomic and Bioinformatic Approaches.

The suitability of an animal model for use in studying human diseases relies heavily on the similarities between the two species at the genetic, epigenetic, and metabolic levels. However, there is a lack of consistent data from different animal models at each level to evaluate this suitability. With the availability of genome sequences for many mammalian species, it is now possible to compare animal models based on genomic similarities. Herein, we compare the coding sequences (CDSs) of five mammalian models, including rhesus macaque, marmoset, pig, mouse, and rat models, with human coding sequences. We identified 10,316 conserved CDSs across the five organisms and the human genome based on sequence similarity. Mapping the human-disease-associated single-nucleotide polymorphisms (SNPs) from these conserved CDSs in each species has identified species-specific associations with various human diseases. While associations with a disease such as colon cancer were prevalent in multiple model species, the rhesus macaque showed the most model-specific human disease associations. Based on the percentage of disease-associated SNP-containing genes, marmoset models are well suited to study many human ailments, including behavioral and cardiovascular diseases. This study demonstrates a genomic similarity evaluation of five animal models against human CDSs that could help investigators select a suitable animal model for studying their target disease.

Treatment of aged wound healing models with FGF2 and ABT-737 reduces the senescent cell population and increases wound closure rate.

Delayed tissue repair in the aged presents a major socio-economic and clinical problem. Age-associated delay in wound healing can be attributed to multiple factors, including an increased presence of senescent cells persisting in the wound. Although the transient presence of senescent cells is physiologic during the resolution phase of normal healing, increased senescent cell accumulation with age can negatively impact tissue repair. The objective of the study was to test interventional strategies that could mitigate the negative effect of senescent cell accumulation and possibly improve the age-associated delay in wound healing. We utilised a 3D in vitro senescent fibroblast populated collagen matrix (FPCM) to study cellular events associated with senescence and delayed healing. Senescent fibroblasts showed an increase in anti-apoptotic B-cell lymphoma 2 (BCL-2) family proteins. We hypothesized that reducing the senescent cell population and promoting non-senescent cell functionality would mitigate the negative effect of senescence and improve healing kinetics. BCL-2 inhibition and mitogen stimulation (FGF2) improved healing in the in vitro senescent models. These results were confirmed with an ex vivo human skin biopsy model. These data suggested that modulation of the senescent cell population with soluble factors improved the healing outcome in our in vitro and ex vivo healing models.

Mucins as contrast agent targets for fluorescence-guided surgery of pancreatic cancer.

Pancreatic cancer is difficult to resect due to its unique challenges, often leading to incomplete tumor resections. Fluorescence-guided surgery (FGS), also known as intraoperative molecular imaging and optical surgical navigation, is an intraoperative tool that can aid surgeons in complete tumor resection through an increased ability to detect the tumor. To target the tumor, FGS contrast agents rely on biomarkers aberrantly expressed in malignant tissue compared to normal tissue. These biomarkers allow clinicians to identify the tumor and its stage before surgical resection and provide a contrast agent target for intraoperative imaging. Mucins, a family of glycoproteins, are upregulated in malignant tissue compared to normal tissue. Therefore, these proteins may serve as biomarkers for surgical resection. Intraoperative imaging of mucin expression in pancreatic cancer can potentially increase the number of complete resections. While some mucins have been studied for FGS, the potential ability to function as a biomarker target extends to the entire mucin family. Therefore, mucins are attractive proteins to investigate more broadly as FGS biomarkers. This review summarizes the biomarker traits of mucins and their potential use in FGS for pancreatic cancer.

Multifunctional Microgel-Based Cream Hydrogels for Postoperative Abdominal Adhesion Prevention.

Postoperative abdominal adhesions are a common problem after surgery and can produce serious complications. Current antiadhesive strategies focus mostly on physical barriers and are unsatisfactory and inefficient. In this study, we designed and synthesized advanced injectable cream-like hydrogels with multiple functionalities, including rapid gelation, self-healing, antioxidation, anti-inflammation, and anti-cell adhesion. The multifunctional hydrogels were facilely formed by the conjugation reaction of epigallocatechin-3-gallate (EGCG) and hyaluronic acid (HA)-based microgels and poly(vinyl alcohol) (PVA) based on the dynamic boronic ester bond. The physicochemical properties of the hydrogels including antioxidative and anti-inflammatory activities were systematically characterized. A mouse cecum-abdominal wall adhesion model was implemented to investigate the efficacy of our microgel-based hydrogels in preventing postoperative abdominal adhesions. The hydrogels, with a high molecular weight HA, significantly decreased the inflammation, oxidative stress, and fibrosis and reduced the abdominal adhesion formation, compared to the commercial Seprafilm group or Injury-only group. Label-free quantitative proteomics analysis demonstrated that S100A8 and S100A9 expressions were associated with adhesion formation; the microgel-containing hydrogels inhibited these expressions. The microgel-containing hydrogels with multifunctionality decreased the formation of postoperative intra-abdominal adhesions in a murine model, demonstrating promise for clinical applications.

Induction of pancreatic neoplasia in the KRAS/TP53 Oncopig.

The 5-year survival of pancreatic cancer (PC) remains low. Murine models may not adequately mimic human PC and can be too small for medical device development. A large-animal PC model could address these issues. We induced and characterized pancreatic tumors in Oncopigs (transgenic swine containing KRASG12D and TP53R167H). The oncopigs underwent injection of adenovirus expressing Cre recombinase (AdCre) into one of the main pancreatic ducts. Resultant tumors were characterized by histology, cytokine expression, exome sequencing and transcriptome analysis. Ten of 14 Oncopigs (71%) had gross tumor within 3 weeks. At necropsy, all of these subjects had gastric outlet obstruction secondary to pancreatic tumor and phlegmon. Oncopigs with injections without Cre recombinase and wild-type pigs with AdCre injection did not show notable effect. Exome and transcriptome analysis of the porcine pancreatic tumors revealed similarity to the molecular signatures and pathways of human PC. Although further optimization and validation of this porcine PC model would be beneficial, it is anticipated that this model will be useful for focused research and development of diagnostic and therapeutic technologies for PC. This article has an associated First Person interview with the joint first authors of the paper.

Validation of the Burden Transfer Inventory-abbreviated and examination across veterinary medicine positions and settings in the United States.

Background: Burden transfer, when veterinary client caregiver burden underlies stressful encounters with providers, elevates risk for occupational distress in veterinary medicine. To date, burden transfer has been primarily examined in veterinarians working in general practice, using methods that are time consuming. The current work validates an abbreviated Burden Transfer Inventory (BTI-A) and explores burden transfer across positions of employment and veterinary settings. Methods: Participants completed online measures of burden transfer, stress and burnout. A BTI-A with items representing each BTI domain was created with an initial validation sample (n = 1151 veterinarians). Confirmatory psychometric analyses were conducted in a cross-validation sample (n = 440 veterinarians and support staff), followed by exploration of the BTI and BTI-A across veterinary settings and position of employment. Results: The BTI-A correlated with the full-length BTI (r = 0.89-0.96) shows good internal consistency (α = 0.72-0.88) and 1-month test-retest reliability (r = 0.69-0.74). The BTI-A correlated significantly (p < 0.001) with stress and burnout. Exploratory comparisons suggested group differences including greater reactivity in general compared to specialty referral/emergency practice (p = 0.02). Conclusion: The BTI-A can be used in place of the original measure when brevity is important. Use of the BTI-A may help guide allied mental health professionals in providing support for wellbeing in veterinary healthcare team members.

Nanofiber capsules for minimally invasive sampling of biological specimens from gastrointestinal tract.

Accurate and rapid point-of-care tissue and microbiome sampling is critical for early detection of cancers and infectious diseases and often result in effective early intervention and prevention of disease spread. In particular, the low prevalence of Barrett's and gastric premalignancy in the Western world makes population-based endoscopic screening unfeasible and cost-ineffective. Herein, we report a method that may be useful for prescreening the general population in a minimally invasive way using a swallowable, re-expandable, ultra-absorbable, and retrievable nanofiber cuboid and sphere produced by electrospinning, gas-foaming, coating, and crosslinking. The water absorption capacity of the cuboid- and sphere-shaped nanofiber objects is shown ∼6000% and ∼2000% of their dry mass. In contrast, unexpanded semicircular and square nanofiber membranes showed <500% of their dry mass. Moreover, the swallowable sphere and cuboid were able to collect and release more bacteria, viruses, and cells/tissues from solutions as compared with unexpanded scaffolds. In addition to that, an expanded sphere shows higher cell collection capacity from the esophagus inner wall as compared with the unexpanded nanofiber membrane. Taken together, the nanofiber capsules developed in this study could provide a minimally invasive method of collecting biological samples from the duodenal, gastric, esophagus, and oropharyngeal sites, potentially leading to timely and accurate diagnosis of many diseases. STATEMENT OF SIGNIFICANCE: Recently, minimally invasive technologies have gained much attention in tissue engineering and disease diagnosis. In this study, we engineered a swallowable and retrievable electrospun nanofiber capsule serving as collection device to collect specimens from internal organs in a minimally invasive manner. The sample collection device could be an alternative endoscopy to collect the samples from internal organs like jejunum, stomach, esophagus, and oropharynx without any sedation. The newly engineered nanofiber capsule could be used to collect, bacteria, virus, fluids, and cells from the abovementioned internal organs. In addition, the biocompatible and biodegradable nanofiber capsule on a string could exhibit a great sample collection capacity for the primary screening of Barret Esophagus, acid reflux, SARS-COVID-19, Helicobacter pylori, and gastric cancer.

Preclinical Evaluation of a Humanized, Near-Infrared Fluorescent Antibody for Fluorescence-Guided Surgery of MUC16-Expressing Pancreatic Cancer.

Surgery remains the only potentially curative treatment option for pancreatic cancer, but resections are made more difficult by infiltrative disease, proximity of critical vasculature, peritumoral inflammation, and dense stroma. Surgeons are limited to tactile and visual cues to differentiate cancerous tissue from normal tissue. Furthermore, translating preoperative images to the intraoperative setting poses additional challenges for tumor detection, and can result in undetected and unresected lesions. Thus, pancreatic ductal adenocarcinoma (PDAC) has high rates of incomplete resections, and subsequently, disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to improve intraoperative detection of cancer and ultimately improve surgical outcomes. Initial clinical trials have demonstrated feasibility of FGS for PDAC, but there are limited targeted probes under investigation for this disease, highlighting the need for development of additional novel biomarkers to reflect the PDAC heterogeneity. MUCIN16 (MUC16) is a glycoprotein that is overexpressed in 60-80% of PDAC. In our previous work, we developed a MUC16-targeted murine antibody near-infrared conjugate, termed AR9.6-IRDye800, that showed efficacy in detecting pancreatic cancer. To build on the translational potential of this imaging probe, a humanized variant of the AR9.6 fluorescent conjugate was developed and investigated herein. This conjugate, termed huAR9.6-IRDye800, showed equivalent binding properties to its murine counterpart. Using an optimized dye:protein ratio of 1:1, in vivo studies demonstrated high tumor to background ratios in MUC16-expressing tumor models, and delineation of tumors in a patient-derived xenograft model. Safety, biodistribution, and toxicity studies were conducted. These studies demonstrated that huAR9.6-IRDye800 was safe, did not yield evidence of histological toxicity, and was well tolerated in vivo. The results from this work suggest that AR9.6-IRDye800 is an efficacious and safe imaging agent for identifying pancreatic cancer intraoperatively through fluorescence-guided surgery.

Caregiver burden, treatment complexity, and the veterinarian-client relationship in owners of dog with skin disease.

BACKGROUND: Increasing complexity of treatment plans is associated with higher levels of caregiver burden in owners of dogs with skin disease. It is possible that elevated caregiver burden resulting from treatment complexity could, in turn, affect the veterinarian-client relationship. HYPOTHESES/OBJECTIVES: We expected that treatment complexity, caregiver burden, and the client's perception of the veterinarian-client relationship would be related to each other. We also expected an indirect effect of caregiver burden on the cross-sectional association between treatment complexity and the veterinarian-client relationship, and that this effect would be robust to adjustment for the dog's skin disease course and severity. PARTICIPANTS: Participants were 349 owners of dogs with skin disease recruited through online consumer panels. MATERIALS AND METHODS: Cross-sectional online assessments were completed for caregiver burden, treatment plan complexity, veterinarian-client relationship, and skin disease course and severity. Demographic information also was collected. RESULTS: The indirect effect of caregiver burden on the relationship between treatment complexity and veterinarian-client relationship was statistically significant, accounting for 42.76% of the variance in the model. After controlling for disease severity and course, that effect remained statistically significant, accounting for 37.76% of the variance. CONCLUSIONS AND CLINICAL IMPORTANCE: Findings support the notion that greater treatment complexity is related to the owner's perception of the veterinarian-client relationship via caregiver burden. Efforts to reduce caregiver burden by using the simplest effective treatment may benefit the veterinarian-client relationship.

Contexte - La complexité croissante des plans de traitement est associée à des niveaux plus élevés de fardeau pour les soignants propriétaires de chiens atteints de maladies de peau. Il est possible que le fardeau élevé des soignants résultant de la complexité du traitement pourrait, à son tour, affecter la relation vétérinaire-client. Hypothèses/Objectifs - Nous nous attendions à ce que la complexité du traitement, le fardeau des soignants et la perception du client de la relation vétérinaire-client seraient liés les uns aux autres. Nous nous attendions également à un effet indirect de le fardeau du soignant sur l'association transversale entre la complexité du traitement et le vétérinaire-client relation, et que cet effet serait robuste à l'ajustement de l'évolution et de la gravité de la maladie de peau du chien. Participants - Les participants étaient 349 propriétaires de chiens atteints de maladies de la peau recrutés par le biais de consommateurs en ligne panneaux. Matériels et méthodes - Des évaluations transversales en ligne ont été réalisées pour le fardeau des soignants, le traitement la complexité du plan, la relation vétérinaire-client et l'évolution et la gravité des maladies de la peau. Informations démographiques a également été collecté. Résultats - L'effet indirect du fardeau des soignants sur la relation entre la complexité du traitement et le vétérinaire-la relation client était statistiquement significative, représentant 42,76 % de la variance du modèle. Après contrôle pour la gravité et l'évolution de la maladie, cet effet est resté statistiquement significatif, représentant 37,76 % des la variance. Conclusions et importance clinique - Les résultats appuient l'idée qu'une plus grande complexité du traitement est liée à la perception du propriétaire de la relation vétérinaire-client via le fardeau des soignants. Efforts pour réduire le soignant fardeau en utilisant le traitement efficace le plus simple peut être bénéfique pour la relation vétérinaire-client.

Contexto - O aumento da complexidade dos planos de tratamento está associado a altos níveis de sobrecarga do cuidador de cães com doenças de pele. É possível que a sobrecarga do cuidador elevada resultante da complexidade da terapia possa, desta forma, afetar a relação veterinário-cliente. Hipótese/Objetivos - Nós imaginamos que a complexidade do tratamento, a sobrecarga do cuidador, e a percepção do cliente da relação veterinário-cliente estariam relacionadas. Nós também imaginamos que poderia uma mediação da sobrecarga do cuidador na associação transversal entre a complexidade do tratamento e a relação veterinário-cliente, e que este efeito seria robusto para ajustar o curso e a gravidade da doença de pele do cão. Participantes - Os participantes foram 349 tutores de cães com doença de pele recrutados através de formulários online. Materiais e métodos - Avaliações transversais online foram preenchidas para sobrecarga do cuidador, complexidade do plano de tratamento, relação veterinário-cliente, e curso da doença de pele e gravidade. Dados demográficos também foram coletados. Resultados - O efeito indireto da sobrecarga do cuidador na relação entre a complexidade do tratamento e a relação veterinário-cliente foi significativamente significativa, sendo responsável por 42,76% da variância no modelo. Após controlar para gravidade da doença e curso, esse efeito permaneceu estatisticamente significativo, respondendo por 37,76% da variância. Conclusões e importância clínica - Os achados corroboram com a ideia de que a complexidade do tratamento está relacionada à percepção do tutor sobre a relação veterinário-cliente pela sobrecarga do cuidador. Esforços para reduzir a sobrecarga do cuidador utilizando planos terapêuticos mais simples podem beneficiar a relação veterinário-cliente.

Introducción- el aumento de la complejidad de los planes de tratamiento se asocia a mayores niveles de responsabilidad de los propietarios de perros con enfermedades de la piel. Es posible que esta mayor carga para el propietario resultante de la complejidad del tratamiento pueda, a su vez, afectar a la relación veterinario-cliente. Hipótesis/Objetivos- esperábamos que la complejidad del tratamiento, la mayor responsabilidad para cuidadores y la percepción de los propietarios de la relación veterinario-cliente estuvieran relacionadas entre sí. También esperábamos un efecto de mediación de la mayor carga del cuidador en la asociación transversal entre la complejidad del tratamiento y la relación veterinario-cliente, y que este efecto sería sólido para el ajuste del curso y la gravedad de la enfermedad de la piel del perro. Participantes- los participantes fueron 349 propietarios de perros con enfermedades de la piel reclutados a través de paneles de consumidores vía telemática. Materiales y métodos- se completaron evaluaciones transversales en línea sobre la carga del cuidador, la complejidad del plan de tratamiento, la relación veterinario-cliente y el curso y la gravedad de la enfermedad de la piel. También se recopiló información demográfica. Resultados - El efecto indirecto de la carga del cuidador sobre la relación entre la complejidad del tratamiento y la relación veterinario-cliente fue estadísticamente significativo, explicando el 42,76% de la varianza del modelo. Después de controlar la gravedad y el curso de la enfermedad, ese efecto siguió siendo estadísticamente significativo y representó el 37,76 % de la varianza. Conclusiones e importancia clínica- los hallazgos respaldan la noción de que una mayor complejidad del tratamiento está relacionada con la percepción del propietario de la relación veterinario-cliente mediante una mayor carga del cuidador. Esfuerzos para reducir la carga del cuidador mediante el uso de tratamientos efectivos más simples pueden beneficiar a la relación veterinario-cliente.

Isolating and cryopreserving pig skin cells for single-cell RNA sequencing study.

The pig skin architecture and physiology are similar to those of humans. Thus, the pig model is very valuable for studying skin biology and testing therapeutics. The single-cell RNA sequencing (scRNA-seq) technology allows quantitatively analyzing cell types, compositions, states, signaling, and receptor-ligand interactome at single-cell resolution and at high throughput. scRNA-seq has been used to study mouse and human skins. However, studying pig skin with scRNA-seq is still rare. A critical step for successful scRNA-seq is to obtain high-quality single cells from the pig skin tissue. Here we report a robust method for isolating and cryopreserving pig skin single cells for scRNA-seq. We showed that pig skin could be efficiently dissociated into single cells with high cell viability using the Miltenyi Human Whole Skin Dissociation kit and the Miltenyi gentleMACS Dissociator. Furthermore, the obtained single cells could be cryopreserved using 90% FBS + 10% DMSO without causing additional cell death, cell aggregation, or changes in gene expression profiles. Using the developed protocol, we were able to identify all the major skin cell types. The protocol and results from this study are valuable for the skin research scientific community.

Large Animal Models of Breast Cancer.

In this mini review the status, advantages, and disadvantages of large animal modeling of breast cancer (BC) will be discussed. While most older studies of large animal BC models utilized canine and feline subjects, more recently there has been interest in development of porcine BC models, with some early promising results for modeling human disease. Widely used rodent models of BC were briefly reviewed to give context to the work on the large animal BC models. Availability of large animal BC models could provide additional tools for BC research, including availability of human-sized subjects and BC models with greater biologic relevance.

Preperitoneal insufflation pressure of the abdominal wall in a porcine model.

BACKGROUND: Most complications and adverse events during laparoscopic surgery occur during initial entry into the peritoneal cavity. Among them, preperitoneal insufflation occurs when the insufflation needle is incorrectly placed, and the abdominal wall is insufflated. The objective of this study was to find a range for static pressure which is low enough to allow placement of a Veress needle into the peritoneal space without causing preperitoneal insufflation, yet high enough to separate abdominal viscera from the parietal peritoneum. METHODS: A pressure test was performed on twelve fresh porcine carcasses to determine the minimum preperitoneal insufflation pressure and the minimum initial peritoneal cavity insufflation pressure. Each porcine model had five needle placement categories. One category tested the initial peritoneal cavity insufflation pressure beneath the umbilicus. The four remaining categories tested the preperitoneal insufflation pressure at four different anatomical locations on the abdomen that can be used for initial entry. The minimum initial insufflation pressures from each carcass were then compared to the preperitoneal insufflation pressures to obtain an optimal range for initial insufflation. RESULTS: Increasing the insufflation pressure increased the probability of preperitoneal insufflation. Also, there was a statistically significant difference (p < 0.05) between the initial peritoneal cavity insufflation pressures (8.83 ± 4.19 mmHg) and the lowest preperitoneal pressures (32.54 ± 7.84 mmHg) (mean ± SD). CONCLUSION: Pressures greater than 10 mmHg resulted in initial cavity insufflation and pressures greater than 20 mmHg resulted in preperitoneal insufflation in porcine models. By knowing the minimum pressure required to separate the layers of the abdominal wall, the risk of preperitoneal insufflation can be mitigated while obtaining safe and efficient entry into the peritoneal cavity. The findings in this research are not a guideline for trocar or Veress needle placement, but instead reveal preliminary data which may lead to more studies, technology, etc.

Electrostatic Flocking of Insulative and Biodegradable Polymer Microfibers for Biomedical Applications.

Electrostatic flocking, a textile engineering technique, uses Coulombic driving forces to propel conductive microfibers toward an adhesive-coated substrate, leaving a forest of aligned fibers. Though an easy way to induce anisotropy along a surface, this technique is limited to microfibers capable of accumulating charge. This study reports a novel method, utilizing principles from the percolation theory to make electrically insulative polymeric microfibers flockable. A variety of well-mixed, conductive materials are added to multiple insulative and biodegradable polymer microfibers during wet spinning, which enables nearly all types of polymer microfibers to accumulate sufficient charges required for flocking. Biphasic, biodegradable scaffolds are fabricated by flocking silver nanoparticle (AgNP)-filled poly(ε-caprolactone) (PCL) microfibers onto substrates made from 3D printing, electrospinning, and thin-film casting. The incorporation of AgNP into PCL fibers and use of chitosan-based adhesive enables antimicrobial activity against methicillin-resistant Staphylococcus aureus. The fabricated scaffolds demonstrate both favorable in vitro cell response and new tissue formation after subcutaneous implantation in rats, as evident by newly formed blood vessels and infiltrated cells. This technology opens the door for using previously unflockable polymer microfibers as surface modifiers or standalone structures in various engineering fields.

Porcine pancreatic ductal epithelial cells transformed with KRASG12D and SV40T are tumorigenic.

We describe our initial studies in the development of an orthotopic, genetically defined, large animal model of pancreatic cancer. Primary pancreatic epithelial cells were isolated from pancreatic duct of domestic pigs. A transformed cell line was generated from these primary cells with oncogenic KRAS and SV40T. The transformed cell lines outperformed the primary and SV40T immortalized cells in terms of proliferation, population doubling time, soft agar growth, transwell migration and invasion. The transformed cell line grew tumors when injected subcutaneously in nude mice, forming glandular structures and staining for epithelial markers. Future work will include implantation studies of these tumorigenic porcine pancreatic cell lines into the pancreas of allogeneic and autologous pigs. The resultant large animal model of pancreatic cancer could be utilized for preclinical research on diagnostic, interventional, and therapeutic technologies.

The effect of pre-resection obesity on post-resection body composition after 75% small bowel resection in rats.

In patients with short bowel syndrome, an elevated pre-resection Body Mass Index may be protective of post-resection body composition. We hypothesized that rats with diet-induced obesity would lose less lean body mass after undergoing massive small bowel resection compared to non-obese rats. Rats (CD IGS; age = 2 mo; N = 80) were randomly assigned to either a high-fat (obese rats) or a low-fat diet (non-obese rats), and fed ad lib for six months. Each diet group then was randomized to either underwent a 75% distal small bowel resection (massive resection) or small bowel transection with re-anastomosis (sham resection). All rats then were fed ad lib with an intermediate-fat diet (25% of total calories) for two months. Body weight and quantitative magnetic resonance-determined body composition were monitored. Preoperative body weight was 884 ± 95 versus 741 ± 75 g, and preoperative percent body fat was 35.8 ± 3.9 versus 24.9 ± 4.6%; high-fat vs. low fat diet, respectively (p < 0.0001); preoperative diet type had no effect on lean mass. Regarding total body weight, massive resection produced an 18% versus 5% decrease in high-fat versus low-fat rats respectively, while sham resection produced a 2% decrease vs. a 7% increase, respectively (p < 0.0001, preoperative vs. necropsy data). Sham resection had no effect on lean mass; after massive resection, both high-fat and low-fat rats lost lean mass, but these changes were not different between the latter two rat groups. The high-fat diet and low-fat diet induced obesity and marginal obesity, respectively. The massive resection produced greater weight loss in high-fat rats compared to low-fat rats. The type of dietary preconditioning had no effect on lean mass loss after massive resection. A protective effect of pre-existing obesity on lean mass after massive intestinal resection was not demonstrated.

Owner quality of life, caregiver burden and anticipatory grief: How they differ, why it matters.

BACKGROUND: Understanding client perspective is important for veterinary communications, particularly during problem visits. Key client experiences of caregiver burden, anticipatory grief and quality of life (QoL) have been previously examined in this context, but never simultaneously considered. METHODS: A sample of 393 owners of an elderly or seriously ill companion animal was recruited online to complete cross-sectional measures of psychosocial function, companion animal presentation and demographics. RESULTS: Exploratory factor analysis demonstrated that owner caregiver burden, anticipatory grief and QoL reflect distinct constructs. Cluster analysis showed these experiences occur in four separate owner profiles: 'distressed', 'resilient', 'non-distressed' and owners experiencing strain due to 'other influences'. These groups appear to be differentially influenced by various factors, such as the companion animal's QoL, nature of the illness and the owner's attachment. They also show distinct differences in consideration of euthanasia and emotional functioning, including experience of stress and depressive symptoms. CONCLUSIONS: Constructs of caregiver burden, anticipatory grief and QoL are not interchangeable and may differentially impact owner decisions and behaviour. The veterinarian's understanding of owner profiles relevant to these issues and distinguishing underlying features may foster effective communication.

Minimally Invasive Delivery of 3D Shape Recoverable Constructs with Ordered Structures for Tissue Repair.

Minimally invasive procedures are becoming increasingly more common in surgery. However, the biomaterials capable of delivering biomimetic, three-dimensional (3D) functional tissues in a minimally invasive manner and exhibiting ordered structures after delivery are lacking. Herein, we reported the fabrication of gelatin methacryloyl (GelMA)-coated, 3D expanded nanofiber scaffolds, and their potential applications in minimally invasive delivery of 3D functional tissue constructs with ordered structures and clinically appropriate sizes (4 cm × 2 cm × 1.5 mm). GelMA-coated, expanded 3D nanofiber scaffolds produced by combining electrospinning, gas-foaming expansion, hydrogel coating, and cross-linking are extremely shape recoverable after release of compressive strain, displaying a superelastic property. Such scaffolds can be seeded with various types of cells, including dermal fibroblasts, bone marrow-derived mesenchymal stem cells, and human neural stem/precursor cells to form 3D complex tissue constructs. Importantly, the developed 3D tissue constructs can be compressed and loaded into a 4 mm diameter glass tube for minimally invasive delivery without compromising the cell viability. Taken together, the method developed in this study could hold great promise for transplantation of biomimetic, 3D functional tissue constructs with well-organized structures for tissue repair and regeneration using minimally invasive procedures like laparoscopy and thoracoscopy.