Magnetic resonance-guided focused ultrasound treatment of facet joint pain: summary of preclinical phase

STUDY DESIGN: A phantom experiment, two thermocouple experiments, three in vivo pig experiments, and a simulated treatment on a healthy human volunteer were conducted to test the feasibility, safety, and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for treating facet joint pain. OBJECTIVE: The goal of the current study was to develop a novel method for accurate and safe noninvasive facet joint ablation using MRgFUS. SUMMARY OF BACKGROUND DATA: Facet joints are a common source of chronic back pain. Direct facet joint interventions include medial branch nerve ablation and intra-articular injections, which are widely used, but limited in the short and long term. MRgFUS is a breakthrough technology that enables accurate delivery of high-intensity focused ultrasound energy to create a localized temperature rise for tissue ablation, using MR guidance for treatment planning and real-time feedback. METHODS: We validated the feasibility, safety, and efficacy of MRgFUS for facet joint ablation using the ExAblate 2000® System (InSightec Ltd., Tirat Carmel, Israel) and confirmed the system's ability to ablate the edge of the facet joint and all terminal nerves innervating the joint. A phantom experiment, two thermocouple experiments, three in vivo pig experiments, and a simulated treatment on a healthy human volunteer were conducted. RESULTS: The experiments showed that targeting the facet joint with energies of 150–450 J provides controlled and accurate heating at the facet joint edge without penetration to the vertebral body, spinal canal, or root foramina. Treating with reduced diameter of the acoustic beam is recommended since a narrower beam improves access to the targeted areas. CONCLUSIONS: MRgFUS can safely and effectively target and ablate the facet joint. These results are highly significant, given that this is the first study to demonstrate the potential of MRgFUS to treat facet joint pain

How parents choose to use CAM: a systematic review of theoretical models

Background: Complementary and Alternative Medicine (CAM) is widely used throughout the UK and the Western world. CAM is commonly used for children and the decision-making process to use CAM is affected by numerous factors. Most research on CAM use lacks a theoretical framework and is largely based on bivariate statistics. The aim of this review was to identify a conceptual model which could be used to explain the decision-making process in parental choice of CAM. Methods: A systematic search of the literature was carried out. A two-stage selection process with predetermined inclusion/exclusion criteria identified studies using a theoretical framework depicting the interaction of psychological factors involved in the CAM decision process. Papers were critically appraised and findings summarised. Results: Twenty two studies using a theoretical model to predict CAM use were included in the final review; only one examined child use. Seven different models were identified. The most commonly used and successful model was Andersen's Sociobehavioural Model (SBM). Two papers proposed modifications to the SBM for CAM use. Six qualitative studies developed their own model. Conclusion: The SBM modified for CAM use, which incorporates both psychological and pragmatic determinants, was identified as the best conceptual model of CAM use. This model provides a valuable framework for future research, and could be used to explain child CAM use. An understanding of the decision making process is crucial in promoting shared decision making between healthcare practitioners and parents and could inform service delivery, guidance and policy

Comparative Genomic Analysis of Clinical and Environmental Vibrio Vulnificus Isolates Revealed Biotype 3 Evolutionary Relationships

In 1996 a common-source outbreak of severe soft tissue and bloodstream infections erupted among Israeli fish farmers and fish consumers due to changes in fish marketing policies. The causative pathogen was a new strain of Vibrio vulnificus, named biotype 3, which displayed a unique biochemical and genotypic profile. Initial observations suggested that the pathogen erupted as a result of genetic recombination between two distinct populations. We applied a whole genome shotgun sequencing approach using several V. vulnificus strains from Israel in order to study the pan genome of V. vulnificus and determine the phylogenetic relationship of biotype 3 with existing populations. The core genome of V. vulnificus based on 16 draft and complete genomes consisted of 3068 genes, representing between 59% and 78% of the whole genome of 16 strains. The accessory genome varied in size from 781 kbp to 2044 kbp. Phylogenetic analysis based on whole, core, and accessory genomes displayed similar clustering patterns with two main clusters, clinical (C) and environmental (E), all biotype 3 strains formed a distinct group within the E cluster. Annotation of accessory genomic regions found in biotype 3 strains and absent from the core genome yielded 1732 genes, of which the vast majority encoded hypothetical proteins, phage-related proteins, and mobile element proteins. A total of 1916 proteins (including 713 hypothetical proteins) were present in all human pathogenic strains (both biotype 3 and non-biotype 3) and absent from the environmental strains. Clustering analysis of the non-hypothetical proteins revealed 148 protein clusters shared by all human pathogenic strains; these included transcriptional regulators, arylsulfatases, methyl-accepting chemotaxis proteins, acetyltransferases, GGDEF family proteins, transposases, type IV secretory system (T4SS) proteins, and integrases. Our study showed that V. vulnificus biotype 3 evolved from environmental populations and formed a genetical

F11R expression upon hypoxia is regulated by RNA editing.

F11R is a cell adhesion molecule found on the surface of human platelets. It plays a role in platelet aggregation, cell migration and cell proliferation. F11R is subjected to RNA editing, a post-transcriptional modification which affects RNA structure, stability, localization, translation and splicing. RNA editing in the 3'UTR of F11R and RNA levels are increased upon hypoxia. We therefore set to examine if RNA editing plays a role in the increase of F11R RNA seen upon hypoxic conditions. We show that ADAR1, but not ADAR2, takes part in the editing of F11R however editing alone is not sufficient for obtaining an elevation in RNA levels. In addition we show that hyper-edited mature mRNAs are retained in the nucleus and are associated with p54(nrb). We therefore conclude that hypoxia-induced edited RNAs of F11R are preferentially stabilized and accumulate in the nucleus preventing their export to the cytoplasm for translation. This mechanism may be used by additional proteins in the cell as part of the cell's effort to reduce metabolism upon hypoxic stress

A proposed model for the regulation of F11R expression following hypoxic stress.

<p>Upon normoxia, F11R mRNA is transcribed and a fraction of the molecules are exported to the cytoplasm for translation. Upon hypoxia, editing of F11R is increased. The majority of the hyperedited molecules binds p54^nrb and is retained in the nucleus in large amounts. Translation of the small number of edited transcripts which escape nuclear retention, is attenuated by a yet to be determined mechanism. We propose that when oxygen levels return to normal, a large amount of F11R hyperedited molecules disengage from p54^nrb and thus are released to the cytoplasm for translation enabling protein levels to return to normal very quickly.</p