Advanced artificial intelligence-guided hemodynamic management within cardiac enhanced recovery after surgery pathways: A multi-institution review.

Objective: The study objective was to report early outcomes of integrating Hypotension Prediction Index-guided hemodynamic management within a cardiac enhanced recovery pathway on total initial ventilation hours and length of stay in the intensive care unit. Methods: A multicenter, historical control, observational analysis of implementation of a hemodynamic management tool within enhanced recovery pathways was conducted by identifying cardiac surgery cases from 3 sites during 2 time periods, August 1 to December 31, 2019 (preprogram), and April 1 to August 31, 2021 (program). Reoperations, emergency (salvage), or cases requiring mechanical assist were excluded. Data were extracted from electronic medical records and chart reviews. Two primary outcome variables were length of stay in the intensive care unit (using Society of Thoracic Surgeons definitions) and acute kidney injury (using modified Kidney Disease Improving Global Outcomes criteria). One secondary outcome variable, total initial ventilation hours, used Society of Thoracic Surgeons definitions. Differences in length of stay in the intensive care unit and total ventilation time were analyzed using Kruskal-Wallis and stepwise multiple linear regression. Acute kidney injury stage used chi-square and stepwise cumulative logistic regression. Results: A total of 1404 cases (795 preprogram; 609 program) were identified. Overall reductions of 6.8 and 4.4 hours in intensive care unit length of stay (P = .08) and ventilation time (P = .03) were found, respectively. No significant association between proportion of patients identified with acute kidney injury by stage and period was found. Conclusions: Adding artificial intelligence-guided hemodynamic management to cardiac enhanced recovery pathways resulted in associated reduced time in the intensive care unit for patients undergoing nonemergency cardiac surgery across institutions in a real-world setting.

A Reproducible and Effective Technique for Coronary Sinus Injury Repair.

Objective: Coronary sinus injury related to the use of a retrograde cardioplegia catheter is a rare but potentially life-threatening complication with mortality reported as high as 20%. We present a series of iatrogenic coronary sinus injuries as well as an effective method of repair without any ensuing mortality. Methods: There were 3,004 cases that utilized retrograde cardioplegia at our institution from 2007 to 2018. Of these, 15 patients suffered a coronary sinus injury, an incidence of 0.49%. A pericardial roof repair was performed in 14 cases in which autologous pericardium was sutured circumferentially to normal epicardium around the injury with purified bovine serum albumin and glutaraldehyde injected into the newly created space as a sealant. Incidence of perioperative morbidity and mortality, operative time, and length of stay were collected. Results: In our series, there were no intraoperative or perioperative mortalities. Procedure types included coronary artery bypass grafting (CABG), valve replacement and repair, or combined CABG and valve procedures. Median (interquartile range) cross-clamp time was 100 (88 to 131) minutes, cardiopulmonary bypass duration was 133 (114 to 176) minutes, and length of stay was 6 (4 to 8) days. None of the patients returned to the operating room for hemorrhage, and there were no complications associated with the repair of a coronary sinus injury when using the pericardial roof technique. Conclusions: Coronary sinus injuries can result in difficult to manage perioperative bleeding and potentially lethal consequences from cardiac manipulation. Our series supports the pericardial roof technique as an effective solution to a challenging intraoperative complication.

Publisher Correction: In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer.

Mitochondria are essential regulators of cellular energy and metabolism, and have a crucial role in sustaining the growth and survival of cancer cells. A central function of mitochondria is the synthesis of ATP by oxidative phosphorylation, known as mitochondrial bioenergetics. Mitochondria maintain oxidative phosphorylation by creating a membrane potential gradient that is generated by the electron transport chain to drive the synthesis of ATP1. Mitochondria are essential for tumour initiation and maintaining tumour cell growth in cell culture and xenografts2,3. However, our understanding of oxidative mitochondrial metabolism in cancer is limited because most studies have been performed in vitro in cell culture models. This highlights a need for in vivo studies to better understand how oxidative metabolism supports tumour growth. Here we measure mitochondrial membrane potential in non-small-cell lung cancer in vivo using a voltage-sensitive, positron emission tomography (PET) radiotracer known as 4-[18F]fluorobenzyl-triphenylphosphonium (18F-BnTP)4. By using PET imaging of 18F-BnTP, we profile mitochondrial membrane potential in autochthonous mouse models of lung cancer, and find distinct functional mitochondrial heterogeneity within subtypes of lung tumours. The use of 18F-BnTP PET imaging enabled us to functionally profile mitochondrial membrane potential in live tumours.

Optical Bioluminescence Protocol for Imaging Mice.

The presence, growth, or decline of transfected cell populations expressing the enzyme Luciferase can be followed in live mice using bioluminescence optical imaging techniques. This protocol describes how to verify the imaging equipment, options for injecting the substrate Luciferin into mice, image acquisition considerations, and commonly used data analysis techniques.

A versatile three-dimensional foam fabrication strategy for soft and hard tissue engineering.

The fabrication strategies of three-dimensional porous biomaterials have been extensively studied and well established in the past few decades, yet the biocompatibility and versatility of porous architecture preparation is still lacking. Herewith, we present a novel and green 3D porous foam fabrication technique for both soft and hard engineering. By utilizing the gelatinization and retrogradation properties of starches, stabilized porous constructs made of various building blocks, from living cells to ceramic particles, were created for the first time. In soft tissue engineering applications, 3D cultured tissue foam (CTF) with controlled cell release properties was developed, and foams constituting osteoblasts, fibroblasts and vascular endothelial cells all exhibited high mechanical stability and preservation of cell viability or functions. More importantly, the CTF achieved sustained self-release of cells controlled by serum concentration (containing amylase) and the released cells also maintained high viability and functions. In the context of hard tissue engineering applications, ceramic/bioglass (BG) foam scaffolds were developed by a similar starch-assisted foaming strategy where the resultant bone scaffolds of hydroxyapatite (HA)/BG and Si3N4/BG possessed >70% porosity with interconnected macropores (sizes 200 âˆ¼ 400 µm), fine pores (sizes 1 âˆ¼ 10 µm) and superior mechanical properties despite the high porosity. Additionally, in vitro and in vivo evaluations of the biological properties revealed that porous HA/BG foam exhibits the desired biocompatibility and osteogenesis. The in vivo study indicated new bone ingrowth after 1 week and significant increases in new bone volume after 2 weeks. In conclusion, the presented foaming strategy provides opportunities for biofabricating CTF with different cells for different target soft tissues and preparing porous ceramic/BG foams with different material components and high strengths, showing great versatility in soft and hard tissue engineering.

Antibacterial properties and toxicity from metallic nanomaterials.

The era of antibiotic resistance is a cause of increasing concern as bacteria continue to develop adaptive countermeasures against current antibiotics at an alarming rate. In recent years, studies have reported nanoparticles as a promising alternative to antibacterial reagents because of their exhibited antibacterial activity in several biomedical applications, including drug and gene delivery, tissue engineering, and imaging. Moreover, nanomaterial research has led to reports of a possible relationship between the morphological characteristics of a nanomaterial and the magnitude of its delivered toxicity. However, conventional synthesis of nanoparticles requires harsh chemicals and costly energy consumption. Additionally, the exact relationship between toxicity and morphology of nanomaterials has not been well established. Here, we review the recent advancements in synthesis techniques for silver, gold, copper, titanium, zinc oxide, and magnesium oxide nanomaterials and composites, with a focus on the toxicity exhibited by nanomaterials of multidimensions. This article highlights the benefits of selecting each material or metal-based composite for certain applications while also addressing possible setbacks and the toxic effects of the nanomaterials on the environment.

Guidance for Efficient Small Animal Imaging Quality Control.

Routine quality control is a critical aspect of properly maintaining high-performance small animal imaging instrumentation. A robust quality control program helps produce more reliable data both for academic purposes and as proof of system performance for contract imaging work. For preclinical imaging laboratories, the combination of costs and available resources often limits their ability to produce efficient and effective quality control programs. This work presents a series of simplified quality control procedures that are accessible to a wide range of preclinical imaging laboratories. Our intent is to provide minimum guidelines for routine quality control that can assist preclinical imaging specialists in setting up an appropriate quality control program for their facility.

Nanotechnology Treatment Options for Osteoporosis and Its Corresponding Consequences.

Unfortunately, osteoporosis, as a worldwide disease, is challenging human health with treatment only available for the symptoms of osteoporosis without managing the disease itself. Osteoporosis can be linked as the common cause of fractures and increased mortality among post-menopausal women, men, and the elderly. Regrettably, due to osteoporosis, incidents of fractures are more frequent among the presented populations and can be afflictive for carrying out everyday life activities. Current treatments of osteoporosis encompass changing lifestyles, taking orthopedic drugs, and invasive surgeries. However, these treatment options are not long lasting and can lead to complications after post-surgical life. Therefore, to solve this impairment, researchers have turned to nanotechnologies and nanomaterials to create innovative and alternative treatments associated with the consequences of osteoporosis. This review article provides an introduction to osteoporotic compression vertebral fractures (OVCFs) and current clinical treatments, along with the rationale and efficacy of utilizing nanomaterials to modify and improve biomaterials or instruments. The methods of applying bioactive agents (bone morphogenetic protein-2 (BMP-2), parathyroid hormone 1-34 (PTH 1-34)), as well as 3D printing will be presented from an osteoporosis treatment perspective. Additionally, the application of nanoparticles and nanotube arrays onto the current surgical treatments and orthopedic drug administration methods addressed will show that these systems reinforce a better mechanical performance and provide precise and slow-releasing drug delivery for better osseointegration, bone regeneration, and bone strength. In summary, nanomaterials can be seen as an alternative and more effective treatment for individuals with osteoporosis.

Mean deformation metrics for quantifying 3D cell-matrix interactions without requiring information about matrix material properties.

Mechanobiology relates cellular processes to mechanical signals, such as determining the effect of variations in matrix stiffness with cell tractions. Cell traction recorded via traction force microscopy (TFM) commonly takes place on materials such as polyacrylamide- and polyethylene glycol-based gels. Such experiments remain limited in physiological relevance because cells natively migrate within complex tissue microenvironments that are spatially heterogeneous and hierarchical. Yet, TFM requires determination of the matrix constitutive law (stress-strain relationship), which is not always readily available. In addition, the currently achievable displacement resolution limits the accuracy of TFM for relatively small cells. To overcome these limitations, and increase the physiological relevance of in vitro experimental design, we present a new approach and a set of associated biomechanical signatures that are based purely on measurements of the matrix's displacements without requiring any knowledge of its constitutive laws. We show that our mean deformation metrics (MDM) approach can provide significant biophysical information without the need to explicitly determine cell tractions. In the process of demonstrating the use of our MDM approach, we succeeded in expanding the capability of our displacement measurement technique such that it can now measure the 3D deformations around relatively small cells (∼10 micrometers), such as neutrophils. Furthermore, we also report previously unseen deformation patterns generated by motile neutrophils in 3D collagen gels.

Pretargeted Positron Emission Tomography Imaging That Employs Supramolecular Nanoparticles with in Vivo Bioorthogonal Chemistry.

A pretargeted oncologic positron emission tomography (PET) imaging that leverages the power of supramolecular nanoparticles with in vivo bioorthogonal chemistry was demonstrated for the clinically relevant problem of tumor imaging. The advantages of this approach are that (i) the pharmacokinetics (PKs) of tumor-targeting and imaging agents can be independently altered via chemical alteration to achieve the desired in vivo performance and (ii) the interplay between the two PKs and other controllable variables confers a second layer of control toward improved PET imaging. In brief, we utilized supramolecular chemistry to synthesize tumor-targeting nanoparticles containing transcyclooctene (TCO, a bioorthogonal reactive motif), called TCO⊂SNPs. After the intravenous injection and subsequent concentration of the TCO⊂SNPs in the tumors of living mice, a small molecule containing both the complementary bioorthogonal motif (tetrazine, Tz) and a positron-emitting radioisotope ((64)Cu) was injected to react selectively and irreversibly to TCO. High-contrast PET imaging of the tumor mass was accomplished after the rapid clearance of the unreacted (64)Cu-Tz probe. Our nanoparticle approach encompasses a wider gamut of tumor types due to the use of EPR effects, which is a universal phenomenon for most solid tumors.

Three-Dimensional Stem Cell Bioprinting.

Stem cells have become a revived biotechnology that is beginning to expand the field of regenerative medicine. Although stem cells are capable of regenerating tissues, current research trends tend to side on developing fully functional organs and other clinical uses including in situ stem cell repair through three-dimensional printing methods. Through several tests and techniques, it can be shown that most stem cell printing methods are possible and that most tests come out with high cell viability. Furthermore, the importance of bioprinting is to benefit the field of regenerative medicine, which looks into artificial organ transplants for the thousands of patients without donors. Although the field is not brand new, understanding the integration and use of additive manufacturing with biomaterials is essential in developing fully functional organs. There is a heavy emphasis on the biomaterials themselves since they have a crucial role in creating an organ that is mechanically robust and adaptable in vivo. Covered in this review article are many featured tests, which also touch on the importance of including a biomaterial that is capable of maintaining a viable microenvironment. These include biomaterials such as hydrogels, biopolymers, and synthetic extra cellular matrices (ECM) built for stem cells to proliferate, differentiate, and give freedom to cell communication after printing.

Nanomaterials for Cardiac Myocyte Tissue Engineering.

Since their synthesizing introduction to the research community, nanomaterials have infiltrated almost every corner of science and engineering. Over the last decade, one such field has begun to look at using nanomaterials for beneficial applications in tissue engineering, specifically, cardiac tissue engineering. During a myocardial infarction, part of the cardiac muscle, or myocardium, is deprived of blood. Therefore, the lack of oxygen destroys cardiomyocytes, leaving dead tissue and possibly resulting in the development of arrhythmia, ventricular remodeling, and eventual heart failure. Scarred cardiac muscle results in heart failure for millions of heart attack survivors worldwide. Modern cardiac tissue engineering research has developed nanomaterial applications to combat heart failure, preserve normal heart tissue, and grow healthy myocardium around the infarcted area. This review will discuss the recent progress of nanomaterials for cardiovascular tissue engineering applications through three main nanomaterial approaches: scaffold designs, patches, and injectable materials.

Heightening Energetic Stress Selectively Targets LKB1-Deficient Non-Small Cell Lung Cancers.

Inactivation of the LKB1 tumor suppressor is a frequent event in non-small cell lung carcinoma (NSCLC) leading to the activation of mTOR complex 1 (mTORC1) and sensitivity to the metabolic stress inducer phenformin. In this study, we explored the combinatorial use of phenformin with the mTOR catalytic kinase inhibitor MLN0128 as a treatment strategy for NSCLC bearing comutations in the LKB1 and KRAS genes. NSCLC is a genetically and pathologically heterogeneous disease, giving rise to lung tumors of varying histologies that include adenocarcinomas and squamous cell carcinomas (SCC). We demonstrate that phenformin in combination with MLN0128 induced a significant therapeutic response in KRAS/LKB1-mutant human cell lines and genetically engineered mouse models of NSCLC that develop both adenocarcinomas and SCCs. Specifically, we found that KRAS/LKB1-mutant lung adenocarcinomas responded strongly to phenformin + MLN0128 treatment, but the response of SCCs to single or combined treatment with MLN0128 was more attenuated due to acquired resistance to mTOR inhibition through modulation of the AKT-GSK signaling axis. Combinatorial use of the mTOR inhibitor and AKT inhibitor MK2206 robustly inhibited the growth and viability of squamous lung tumors, thus providing an effective strategy to overcome resistance. Taken together, our findings define new personalized therapeutic strategies that may be rapidly translated into clinical use for the treatment of KRAS/LKB1-mutant adenocarcinomas and squamous cell tumors.

Planar Gradient Diffusion System to Investigate Chemotaxis in a 3D Collagen Matrix.

The importance of cell migration can be seen through the development of human life. When cells migrate, they generate forces and transfer these forces to their surrounding area, leading to cell movement and migration. In order to understand the mechanisms that can alter and/or affect cell migration, one can study these forces. In theory, understanding the fundamental mechanisms and forces underlying cell migration holds the promise of effective approaches for treating diseases and promoting cellular transplantation. Unfortunately, modern chemotaxis chambers that have been developed are usually restricted to two dimensions (2D) and have complex diffusion gradients that make the experiment difficult to interpret. To this end, we have developed, and describe in this paper, a direct-viewing chamber for chemotaxis studies, which allows one to overcome modern chemotaxis chamber obstacles able to measure cell forces and specific concentration within the chamber in a 3D environment to study cell 3D migration. More compelling, this approach allows one to successfully model diffusion through 3D collagen matrices and calculate the coefficient of diffusion of a chemoattractant through multiple different concentrations of collagen, while keeping the system simple and user friendly for traction force microscopy (TFM) and digital volume correlation (DVC) analysis.

A reporter mouse for optical imaging of inflammation in mdx muscles.

BACKGROUND: Duchenne muscular dystrophy (DMD) is due to mutations in the gene coding for human DMD; DMD is characterized by progressive muscle degeneration, inflammation, fat accumulation, and fibrosis. The mdx mouse model of DMD lacks dystrophin protein and undergoes a predictable disease course. While this model has been a valuable resource for pre-clinical studies aiming to test therapeutic compounds, its utility is compromised by a lack of reliable biochemical tools to quantifiably assay muscle disease. Additionally, there are few non-invasive assays available to researchers for measuring early indicators of disease progression in mdx mice. METHODS: Mdx mice were crossed to knock-in mice expressing luciferase from the Cox2 promoter. These reporter mice (Cox2 (FLuc/+) DMD (-/-) ) were created to serve as a tool for researchers to evaluate muscle inflammation. Luciferase expression was assayed by immunohistochemistry to insure that it correlated with muscle lesions. The luciferase signal was quantified by optical imaging and luciferase assays to verify that the signal correlated with muscle damage. As proof of principle, Cox2 (FLuc/+) DMD (-/-) mice were also treated with prednisolone to validate that a reduction in luciferase signal correlated with prednisone treatment. RESULTS: In this investigation, a novel reporter mouse (Cox2 (FLuc/+) DMD (-/-) mice) was created and validated for non-invasive quantification of muscle inflammation in vivo. In this dystrophic mouse, luciferase is expressed from cyclooxygenase 2 (Cox2) expressing cells and bioluminescence is detected by optical imaging. Bioluminescence is significantly enhanced in damaged muscle of exercised Cox2 (FLuc/+) DMD (-/-) mice compared to non-exercised Cox2 (FLuc/+) DMD (+/+) mice. Moreover, the Cox2 bioluminescent signal is reduced in Cox2 (FLuc/+) DMD (-/-) mice in response to a course of steroid treatment. Reduction in bioluminescence is detectable prior to measurable therapy-elicited improvements in muscle strength, as assessed by traditional means. Biochemical assay of luciferase provides a second means to quantify muscle inflammation. CONCLUSIONS: The Cox2 (FLuc/+) DMD (-/-) mouse is a novel tool to evaluate the therapeutic benefits of drugs intended to target inflammatory aspects of dystrophic pathology. This mouse model will be a useful adjunct to traditional outcome measures in assessing potential therapeutic compounds.

The Impact of Social Support and Attachment Style on Quality of Life and Readiness to Change in a Sample of Individuals Receiving Medication-Assisted Treatment for Opioid Dependence.

BACKGROUND: A basic principle within the addictions treatment field is that social support is a vital ingredient in the recovery process. This study examines the nature of social support in a sample of opioid-dependent men and women who are currently being treated in a medication-assisted treatment program (methadone). This research examines the types of social support behaviors that the opioid-dependent individuals consider helpful and explores whether attachment style (i.e., secure, ambivalent, or anxious attachment) was a determining factor in whether social support was perceived as helpful. The dependent variables included readiness to change addictive behaviors and abstinence from other mood-altering drugs. METHODS: Participants (N = 159) completed a demographic questionnaire, the Significant Others Scale, the Experiences in Close Relationships Scale, the Multidimensional Scale of Perceived Social Support Assessment, the Readiness to Change Scale, and an Attachment Style Questionnaire. The demographic questionnaire included subjective ratings of self-improvement. RESULTS: Social support predicted perceived improvement in all of the areas examined (e.g., health, family/social relationships) and abstinence; however, attachment style did not predict improvement or with readiness to change. CONCLUSIONS: Social support is an important factor in one's recovery from substance use disorders. Yet attachment style (i.e., anxious, avoidant, or secure) did not predict abstinence or overall improvement in functioning.

Recent advancements in carbon nanofiber and carbon nanotube applications in drug delivery and tissue engineering.

Since the discovery and synthesis of carbon nanotubes (CNTs) and carbon nanofibers (CNFs) over a decade ago, researchers have envisioned and discovered new potential applications for these materials. CNTs and CNFs have rapidly become a platform technology for a variety of uses, including biomedical applications due to their mechanical, electrical, thermal, optical and structural properties. CNTs and CNFs are also advantageous due to their ability to be produced in many different shapes and sizes. Since their discovery, of the many imaginable applications, CNTs and CNFs have gained a significant amount of attention and therapeutic potential in tissue engineering and drug delivery applications. In recent years, CNTs and CNFs have made significant contributions in designing new strategies for, delivery of pharmaceuticals, genes and molecular probes into cells, stem cell therapies and assisting in tissue regeneration. Furthermore, it is widely expressed that these materials will significantly contribute to the next generation of health care technologies in treating diseases and contributing to tissue growth. Hence, this review seeks to explore the recent advancements, current status and limitations of CNTs and CNFs for drug delivery and tissue engineering applications.