Bronchoscopy-Guided High-Power Microwave Ablation in an in vivo Porcine Lung Model.

Introduction: Percutaneous microwave ablation (MWA) is clinically accepted for the treatment of lung tumors and oligometastatic disease. Bronchoscopic MWA is under development and evaluation in the clinical setting. We previously reported on the development of a bronchoscopy-guided MWA system integrated with clinical virtual bronchoscopy and navigation and demonstrated the feasibility of transbronchial MWA, using a maximum power of 60 W at the catheter input.

Directional microwave ablation in spine: experimental assessment of computational modeling.

Background: Despite the theoretical advantages of treating metastatic bone disease with microwave ablation (MWA), there are few reports characterizing microwave absorption and bioheat transfer in bone. This report describes a computational modeling-based approach to simulate directional microwave ablation (dMWA) in spine, supported by and pilot experiments in porcine vertebral bodies.

Materials And Methods: A 3D computational model of microwave ablation within porcine vertebral bodies was developed.

Temporal recruitment of base excision DNA repair factors in living cells in response to different micro-irradiation DNA damage protocols.

Laser micro-irradiation across the nucleus rapidly generates localized chromatin-associated DNA lesions permitting analysis of repair protein recruitment in living cells. Recruitment of three fluorescently-tagged base excision repair factors [DNA polymerase β (pol β), XRCC1 and PARP1], known to interact with one another, was compared in gene-deleted mouse embryonic fibroblasts and in those expressing the endogenous factor. A low energy micro-irradiation (LEMI) forming direct single-strand breaks and a moderate energy (MEMI) protocol that additionally creates oxidized bases were compared.

Comparison of Two Bandage Splint Constructs in an Ex Vivo Equine Metacarpal Fracture Model.

Objectives:  The aim of this study was to compare the deflection distance, deflection angle and pre-loading sub-bandage pressure of a transverse, mid-metacarpal fracture in an equine cadaver limb when loaded in bending while stabilized with either a Robert Jones Bandage (RJB) or a single-stack bandage (SS), each containing two orthogonal splints.

Study Design:  In an ex vivo experimental study, forelimb pairs from eight horses were collected, and one forelimb from each pair was assigned to either the SS or RJB groups. A transverse osteotomy was performed at the midpoint of the metacarpus.

Injectable Peptide Hydrogel Encapsulation of Mesenchymal Stem Cells Improved Viability, Stemness, Anti-Inflammatory Effects, and Early Stage Wound Healing.

Human-adipose-derived mesenchymal stem cells (hADMSCs) are adult stem cells and are relatively easy to access compared to other sources of mesenchymal stem cells (MSCs). They have shown immunomodulation properties as well as effects in improving tissue regeneration. To better stimulate and preserve the therapeutic properties of hADMSCs, biomaterials for cell delivery have been studied extensively.

Shaping the future of microwave tumor ablation: a new direction in precision and control of device performance.

Microwave ablation (MWA) is becoming an increasingly important minimally invasive treatment option for localized tumors in many organ systems due to recent advancements in microwave technology that have conferred many advantages over other tumor ablation modalities. Despite these improvements in technology and development of applicators for site-specific tumor applications, the vast majority of commercially available MWA applicators are generally designed to create large-volume, symmetric, ellipsoid or spherically-shaped treatment zones and often lack the consistency, predictability, and spatial control needed to treat tumor targets near critical structures that are vulnerable to inadvertent thermal injury. The relatively new development and ongoing translation of directional microwave ablation (DMWA) technology, however, has the potential to confer an added level of control over the treatment zone shape relative to applicator position, and shows great promise to expand MWA's clinical applicability in treating tumors in challenging locations.

antimicrobial activity of equine platelet lysate and mesenchymal stromal cells against common clinical pathogens.

Septic arthritis is considered a medical emergency. Disease following bacterial colonization can lead to significant morbidity and mortality and requires costly treatment. Antimicrobial properties of regenerative therapies, including mesenchymal stromal cells and platelet products, have been researched extensively in human medicine.

Structural basis for proficient oxidized ribonucleotide insertion in double strand break repair.

Reactive oxygen species (ROS) oxidize cellular nucleotide pools and cause double strand breaks (DSBs). Non-homologous end-joining (NHEJ) attaches broken chromosomal ends together in mammalian cells. Ribonucleotide insertion by DNA polymerase (pol) μ prepares breaks for end-joining and this is required for successful NHEJ in vivo.

Microwave ablation of lung tumors: A probabilistic approach for simulation-based treatment planning.

Purpose: Microwave ablation (MWA) is a clinically established modality for treatment of lung tumors. A challenge with existing application of MWA, however, is local tumor progression, potentially due to failure to establish an adequate treatment margin. This study presents a robust simulation-based treatment planning methodology to assist operators in comparatively assessing thermal profiles and likelihood of achieving a specified minimum margin as a function of candidate applied energy parameters.

Epidemiology of Heart Failure Stages in Middle-Aged Black People in the Community: Prevalence and Prognosis in the Atherosclerosis Risk in Communities Study.

Background Black individuals have a higher burden of risk factors for heart failure (HF) and subclinical left ventricular remodeling. Methods and Results We evaluated 1871 Black participants in the Atherosclerosis Risk in Communities Study cohort who attended a routine examination (1993-1996, median age 58 years) when they underwent echocardiography. We estimated the prevalences of 4 HF stages: (1) : no risk factors; (2) : presence of HF risk factors (hypertension, diabetes mellitus, obesity, smoking, dyslipidemia, coronary artery disease without clinical myocardial infarction), no cardiac structural/functional abnormality; (3) : presence of prior myocardial infarction, systolic dysfunction, left ventricular hypertrophy, regional wall motion abnormality, or left ventricular enlargement; and (4) : prevalent HF.

Watching a double strand break repair polymerase insert a pro-mutagenic oxidized nucleotide.

Oxidized dGTP (8-oxo-7,8-dihydro-2´-deoxyguanosine triphosphate, 8-oxodGTP) insertion by DNA polymerases strongly promotes cancer and human disease. How DNA polymerases discriminate against oxidized and undamaged nucleotides, especially in error-prone double strand break (DSB) repair, is poorly understood. High-resolution time-lapse X-ray crystallography snapshots of DSB repair polymerase μ undergoing DNA synthesis reveal that a third active site metal promotes insertion of oxidized and undamaged dGTP in the canonical anti-conformation opposite template cytosine.

DNA polymerase β: Closing the gap between structure and function.

DNA polymerase (dpol) β has served as a model for structural, kinetic, and computational characterization of the DNA synthesis reaction. The laboratory directed by Samuel H. Wilson has utilized a multifunctional approach to analyze the function of this enzyme at the biological, chemical, and molecular levels for nearly 50 years.

Bronchoscopically delivered microwave ablation in an porcine lung model.

Background: Percutaneous microwave ablation is clinically used for inoperable lung tumour treatment. Delivery of microwave ablation applicators to tumour sites within lung parenchyma under virtual bronchoscopy guidance may enable ablation with reduced risk of pneumothorax, providing a minimally invasive treatment of early-stage tumours, which are increasingly detected with computed tomography (CT) screening. The objective of this study was to integrate a custom microwave ablation platform, incorporating a flexible applicator, with a clinically established virtual bronchoscopy guidance system, and to assess technical feasibility for safely creating localised thermal ablations in porcine lungs .

Effect of position on transdiaphragmatic pressure and hemodynamic variables in anesthetized horses.

Recumbency affects respiratory mechanics and oxygenation in anesthetized horses. Changes in pleural and abdominal pressures that can impair ventilation have not been described in all recumbencies. The objective of this study was to determine the effects of patient positioning on transdiaphragmatic pressure and selected hemodynamic variables.

Preferential DNA Polymerase β Reverse Reaction with Imidodiphosphate.

DNA replication and repair reactions involve the addition of a deoxynucleoside monophosphate onto a growing DNA strand with the loss of pyrophosphate. This chemical reaction is also reversible; the addition of pyrophosphate generates a deoxynucleoside triphosphate, thereby shortening the DNA by one nucleotide. The forward DNA synthesis and reverse pyrophosphorolysis reactions strictly require the presence of divalent metals, usually magnesium, at the reactive center as cofactors.

Directional Microwave Ablation: Experimental Evaluation of a 2.45-GHz Applicator in Ex Vivo and In Vivo Liver.

Purpose: To experimentally characterize a microwave (MW) ablation applicator designed to produce directional ablation zones.

Materials And Methods: Using a 14-gauge, 2.45-GHz side-firing MW ablation applicator, 36 ex vivo bovine liver ablations were performed.

DNA polymerase β nucleotide-stabilized template misalignment fidelity depends on local sequence context.

DNA polymerase β has two DNA-binding domains that interact with the opposite sides of short DNA gaps. These domains contribute two activities that modify the 5' and 3' margins of gapped DNA during base excision repair. DNA gaps greater than 1 nucleotide (nt) pose an architectural and logistical problem for the two domains to interact with their respective DNA termini.

DNA polymerase beta and other gap-filling enzymes in mammalian base excision repair.

DNA polymerase β plays a central role in the base excision DNA repair pathway that cleanses the genome of apurinic/apyrimidinic (AP) sites. AP sites arise in DNA from spontaneous base loss and DNA damage-specific glycosylases that hydrolyze the N-glycosidic bond between the deoxyribose and damaged base. AP sites are deleterious lesions because they can be mutagenic and/or cytotoxic.

Using microwave thermal ablation to develop a subtotal, cortical-sparing approach to the management of primary aldosteronism.

To investigate the feasibility and efficacy of localized, subtotal, cortical-sparing microwave thermal ablation (MTA) as a potential curative management for primary aldosteronism. The study investigated with equal importance the selected ablation of small volumes of adrenal cortex while sparing adjacent cortex. An study was carried out in swine ( = 8) where MTA was applied under direct visualization, to the adrenal glands at 45 W or 70 W for 60 s, using a lateral, side-firing probe and a non-penetrative approach.

Eukaryotic Base Excision Repair: New Approaches Shine Light on Mechanism.

Genomic DNA is susceptible to endogenous and environmental stresses that modify DNA structure and its coding potential. Correspondingly, cells have evolved intricate DNA repair systems to deter changes to their genetic material. Base excision DNA repair involves a number of enzymes and protein cofactors that hasten repair of damaged DNA bases.

A guardian residue hinders insertion of a Fapy•dGTP analog by modulating the open-closed DNA polymerase transition.

4,6-Diamino-5-formamidopyrimidine (Fapy•dG) is an abundant form of oxidative DNA damage that is mutagenic and contributes to the pathogenesis of human disease. When Fapy•dG is in its nucleotide triphosphate form, Fapy•dGTP, it is inefficiently cleansed from the nucleotide pool by the responsible enzyme in Escherichia coli MutT and its mammalian homolog MTH1. Therefore, under oxidative stress conditions, Fapy•dGTP could become a pro-mutagenic substrate for insertion into the genome by DNA polymerases.

Effect of bandaging techniques on sub-bandage pressures in the equine distal limb, carpus, and tarsus.

Objective: To determine the influence of 3 types of bandages on sub-bandage pressures over the distal limb, carpus, and tarsus.

Study Design: Observational study.

Animals: Eight healthy horses.

Transitions in DNA polymerase β μs-ms dynamics related to substrate binding and catalysis.

DNA polymerase β (pol β) plays a central role in the DNA base excision repair pathway and also serves as an important model polymerase. Dynamic characterization of pol β from methyl-TROSY 13C-1H multiple quantum CPMG relaxation dispersion experiments of Ile and Met sidechains and previous backbone relaxation dispersion measurements, reveals transitions in μs-ms dynamics in response to highly variable substrates. Recognition of a 1-nt-gapped DNA substrate is accompanied by significant backbone and sidechain motion in the lyase domain and the DNA binding subdomain of the polymerase domain, that may help to facilitate binding of the apoenzyme to the segments of the DNA upstream and downstream from the gap.

Probing DNA Base-Dependent Leaving Group Kinetic Effects on the DNA Polymerase Transition State.

We examine the DNA polymerase β (pol β) transition state (TS) from a leaving group pre-steady-state kinetics perspective by measuring the rate of incorporation of dNTPs and corresponding novel β,γ-CXY-dNTP analogues, including individual β,γ-CHF and -CHCl diastereomers with defined stereochemistry at the bridging carbon, during the formation of right (R) and wrong (W) base pairs. Brønsted plots of log k versus p K of the leaving group bisphosphonic acids are used to interrogate the effects of the base identity, the dNTP analogue leaving group basicity, and the precise configuration of the C-X atom in R and S stereoisomers on the rate-determining step ( k). The dNTP analogues provide a range of leaving group basicity and steric properties by virtue of monohalogen, dihalogen, or methyl substitution at the carbon atom bridging the β,γ-bisphosphonate that mimics the natural pyrophosphate leaving group in dNTPs.

Mapping Functional Substrate-Enzyme Interactions in the pol β Active Site through Chemical Biology: Structural Responses to Acidity Modification of Incoming dNTPs.

We report high-resolution crystal structures of DNA polymerase (pol) β in ternary complex with a panel of incoming dNTPs carrying acidity-modified 5'-triphosphate groups. These novel dNTP analogues have a variety of halomethylene substitutions replacing the bridging oxygen between Pβ and Pγ of the incoming dNTP, whereas other analogues have alkaline substitutions at the bridging oxygen. Use of these analogues allows the first systematic comparison of effects of 5'-triphosphate acidity modification on active site structures and the rate constant of DNA synthesis.