Microplastic-induced hepatic adverse effects evaluated in advanced quadruple cell human primary models following three weeks of repeated exposure.

Nano and microplastics are defined as particles smaller than 100 nm and 5 mm respectively. The widespread production and use of plastics in everyday life has resulted in significant accumulation of plastic debris in the environment. Over the last two decades there are increased concerns regarding the potential entry and accumulation of plastics in the human body with ingestion being one of the most important routes of exposure.

Trimodal wireless intramuscular device detects muscle pressure, flow, and oxygenation changes in porcine model of lower extremity compartment syndrome.

Purpose: Compartment syndrome remains difficult to diagnose early in its clinical course. Pressure transducer catheters have been used to directly measure intracompartmental pressure (ICP), but this method is unreliable, with a false positive rate of 35%. We have previously used intramuscular near infrared spectroscopy to detect changes in tissue oxygen saturation (StO) in response to increasing ICP using a novel implantable probe.

Surface Modification of PEEKs with Cyclic Peptides to Support Endothelialization and Antithrombogenicity.

Synthetic polymers are often utilized in the creation of vascular devices, and need to possess specific qualities to prevent thrombosis. Traditional strategies for this include surface modification of vascular devices through covalent attachment of substrates such as heparin, antiplatelet agents, thrombolytic agents, or hydrophilic polymers. One promising prosthetic material is polyether ether ketone (PEEK), which is utilized in various FDA-approved medical devices, including vascular and endovascular prostheses.

Vaso-Lock for sutureless anastomosis in a pig arteriovenous loop model.

A vascular anastomosis is a critical surgical skill that involves connecting blood vessels. Traditional handsewn techniques can be challenging and resource intensive. To address these issues, we have developed a unique sutureless anastomotic device called Vaso-Lock.

Translation and validation of the German version of the FACE-Q paralysis module in adult patients with unilateral peripheral facial palsy.

The aim was to develop and validate a German version of the FACE-Q paralysis module, a patient-reported outcome measure to assess health-related quality of life in adult patients with unilateral facial palsy. The FACE-Q craniofacial questionnaire, which includes the paralysis module, was translated. 213 patients with facial palsy completed the German FACE-Q paralysis along with the established FDI and FaCE questionnaires.

From Augmented to Virtual Reality in Plastic Surgery: Blazing the Trail to a New Frontier.

Background:  Augmented reality (AR) and virtual reality (VR)-termed mixed reality-have shown promise in the care of operative patients. Currently, AR and VR have well-known applications for craniofacial surgery, specifically in preoperative planning. However, the application of AR/VR technology to other reconstructive challenges has not been widely adopted.

Assessing an Online Patient Decision Aid about Upper Extremity Reconstructive Surgery for Cervical Spinal Cord Injury: Pilot Testing Knowledge, Decisional Conflict, and Acceptability.

Unlabelled: While nerve and tendon transfer surgery can restore upper extremity function and independence after midcervical spinal cord injury, few individuals (∼14%) undergo surgery. There is limited information regarding these complex and time-sensitive treatment options. Patient decision aids (PtDAs) convey complex health information and help individuals make informed, preference-consistent choices.

Drug induced liver injury - a 2023 update.

Drug-Induced Liver Injury (DILI) constitutes hepatic damage attributed to drug exposure. DILI may be categorized as hepatocellular, cholestatic or mixed and might also involve immune responses. When DILI occurs in dose-dependent manner, it is referred to as intrinsic, while if the injury occurs spontaneously, it is termed as idiosyncratic.

Point-of-Care Tissue Oxygenation Assessment with SnapshotNIR for Alloplastic and Autologous Breast Reconstruction.

Unlabelled: In breast reconstruction, mastectomy and free flaps are susceptible to vascular compromise and tissue necrosis. The SnapshotNIR device (Kent Imaging, Calgary, AB, Canada) utilizes near-infrared spectroscopy to measure tissue oxygen saturation (StO) and hemoglobin concentration. Here, we report on the use of this device for StO monitoring among patients receiving alloplastic or autologous breast reconstruction.

KATP channels are necessary for glucose-dependent increases in amyloid-β and Alzheimer's disease-related pathology.

Elevated blood glucose levels, or hyperglycemia, can increase brain excitability and amyloid-β (Aβ) release, offering a mechanistic link between type 2 diabetes and Alzheimer's disease (AD). Since the cellular mechanisms governing this relationship are poorly understood, we explored whether ATP-sensitive potassium (KATP) channels, which couple changes in energy availability with cellular excitability, play a role in AD pathogenesis. First, we demonstrate that KATP channel subunits Kir6.

Assessing the transferability and reproducibility of 3D in vitro liver models from primary human multi-cellular microtissues to cell-line based HepG2 spheroids.

To reduce, replace, and refine in vivo testing, there is increasing emphasis on the development of more physiologically relevant in vitro test systems to improve the reliability of non-animal-based methods for hazard assessment. When developing new approach methodologies, it is important to standardize the protocols and demonstrate the methods can be reproduced by multiple laboratories. The aim of this study was to assess the transferability and reproducibility of two advanced in vitro liver models, the Primary Human multicellular microtissue liver model (PHH) and the 3D HepG2 Spheroid Model, for nanomaterial (NM) and chemical hazard assessment purposes.

Intramuscular Microvascular Flow Sensing for Flap Monitoring in a Porcine Model of Arterial and Venous Occlusion.

Background:  Commercially available near infrared spectroscopy devices for continuous free flap tissue oxygenation (StO) monitoring can only be used on flaps with a cutaneous component. Additionally, differences in skin quality and pigmentation may alter StO measurements. Here, we present a novel implantable heat convection probe that measures microvascular blood flow for peripheral monitoring of free flaps, and is not subject to the same issues that limit the clinical utility of near-infrared spectroscopy.

A Biomimetic High Throughput Model of Cancer Cell Spheroid Dissemination onto Aligned Fibrillar Collagen.

Cell dissemination during tumor development is a characteristic of cancer metastasis. Dissemination from three-dimensional spheroid models on extracellular matrices designed to mimic tissue-specific physiological microenvironments may allow us to better elucidate the mechanism behind cancer metastasis and the response to therapeutic agents. The orientation of fibrillar collagen plays a key role in cellular processes and mediates metastasis through contact-guidance.

Percutaneously introduced wireless intramuscular near-infrared spectroscopy device detects muscle oxygenation changes in porcine model of lower extremity compartment syndrome.

Serial examination and direct measurement of intracompartmental pressure (ICP) are suboptimal strategies for the detection of acute compartment syndrome (CS) because they are operator-dependent and yield information that only indirectly reflects intracompartmental muscle perfusion. As a result, instances of unnecessary fasciotomy and unrecognized CS are relatively common. Recently, near-infrared spectroscopy (NIRS)-based systems for compartment monitoring have generated interest as an adjunct tool.

The History and Innovations of Blood Vessel Anastomosis.

Surgical technique and technology frequently coevolve. The brief history of blood vessel anastomosis is full of famous names. While the techniques pioneered by these surgeons have been well described, the technology that facilitated their advancements and their inventors deserve recognition.

Particulate and drug-induced toxicity assessed in novel quadruple cell human primary hepatic disease models of steatosis and pre-fibrotic NASH.

In an effort to replace, reduce and refine animal experimentation, there is an unmet need to advance current in vitro models that offer features with physiological relevance and enhanced predictivity of in vivo toxicological output. Hepatic toxicology is key following chemical, drug and nanomaterials (NMs) exposure, as the liver is vital in metabolic detoxification of chemicals as well as being a major site of xenobiotic accumulation (i.e.

A Model-Based Workflow to Benchmark the Clinical Cholestasis Risk of Drugs.

We present a generic workflow combining physiology-based computational modeling and in vitro data to assess the clinical cholestatic risk of different drugs systematically. Changes in expression levels of genes involved in the enterohepatic circulation of bile acids were obtained from an in vitro assay mimicking 14 days of repeated drug administration for 10 marketed drugs. These changes in gene expression over time were contextualized in a physiology-based bile acid model of glycochenodeoxycholic acid.

Evolution of initiation rites during the Austronesian dispersal.

As adaptive systems, kinship and its accompanying rules have co-evolved with elements of complex societies, including wealth inheritance, subsistence, and power relations. Here we consider an aspect of kinship evolution in the Austronesian dispersal that began from about 5500 BP in Taiwan, reaching Melanesia about 3200 BP, and dispersing into Micronesia by 1500 BP. Previous, foundational work has used phylogenetic comparative methods and ethnolinguistic information to infer matrilocal residence in proto-Austronesian societies.

NMR microsystem for label-free characterization of 3D nanoliter microtissues.

Performing chemical analysis at the nanoliter (nL) scale is of paramount importance for medicine, drug development, toxicology, and research. Despite the numerous methodologies available, a tool for obtaining chemical information non-invasively is still missing at this scale. Observer effects, sample destruction and complex preparatory procedures remain a necessary compromise.

Comparing in vitro human liver models to in vivo human liver using RNA-Seq.

The liver plays an important role in xenobiotic metabolism and represents a primary target for toxic substances. Many different in vitro cell models have been developed in the past decades. In this study, we used RNA-sequencing (RNA-Seq) to analyze the following human in vitro liver cell models in comparison to human liver tissue: cancer-derived cell lines (HepG2, HepaRG 3D), induced pluripotent stem cell-derived hepatocyte-like cells (iPSC-HLCs), cancerous human liver-derived assays (hPCLiS, human precision cut liver slices), non-cancerous human liver-derived assays (PHH, primary human hepatocytes) and 3D liver microtissues.

The EU-ToxRisk method documentation, data processing and chemical testing pipeline for the regulatory use of new approach methods.

Hazard assessment, based on new approach methods (NAM), requires the use of batteries of assays, where individual tests may be contributed by different laboratories. A unified strategy for such collaborative testing is presented. It details all procedures required to allow test information to be usable for integrated hazard assessment, strategic project decisions and/or for regulatory purposes.

A Novel Lipidomics-Based Approach to Evaluating the Risk of Clinical Hepatotoxicity Potential of Drugs in 3D Human Microtissues.

The importance of adsorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis is expected to grow substantially due to recent failures in detecting severe toxicity issues of new chemical entities during preclinical/clinical development. Traditionally, safety risk assessment studies for humans have been conducted in animals during advanced preclinical or clinical phase of drug development. However, potential drug toxicity in humans now needs to be detected in the drug discovery process as soon as possible without reliance on animal studies.

Assessment of nanomaterial-induced hepatotoxicity using a 3D human primary multi-cellular microtissue exposed repeatedly over 21 days - the suitability of the in vitro system as an in vivo surrogate.

Background: With ever-increasing exposure to engineered nanomaterials (NMs), there is an urgent need to evaluate the probability of consequential adverse effects. The potential for NM translocation to distal organs is a realistic prospect, with the liver being one of the most important target organs. Traditional in vitro or ex vivo hepatic toxicology models are often limiting (i.

Tracing Clonal Dynamics Reveals that Two- and Three-dimensional Patient-derived Cell Models Capture Tumor Heterogeneity of Clear Cell Renal Cell Carcinoma.

Background: Extensive DNA sequencing has led to an unprecedented view of the diversity of individual genomes and their evolution among patients with clear cell renal cell carcinoma (ccRCC).

Objective: To understand subclonal architecture and dynamics of patient-derived two-dimensional (2D) and three-dimensional (3D) ccRCC models in vitro, in order to determine whether they mirror ccRCC inter- and intratumor heterogeneity.

Design, Setting, And Participants: We have established a comprehensive platform of living renal cancer cell models from ccRCC surgical specimens.