Resection margins in oral cancer surgery: Room for improvement

The purpose of this review was to identify publications on resection margins in oral cancer surgery and compare these with the results from 2 Dutch academic medical centers. Eight publications were considered relevant for this study, reporting 30% to 65% inadequate resection margins (ie, positive and close margins), compared to 85% in Dutch centers. However, clinical outcome in terms of overall survival and recurrence seemed comparable. The misleading difference is caused by lack of unanimous margin definition and differences in surgicopathological approaches. This prevents comparison between the centers. Data from Dutch centers showed that inadequate resection margins have a significantly negative effect on local recurrence, regional recurrence, distant metastasis, and overall survival. These results confirm the need for improvement in oral cancer surgery. We underline the need for consistent protocols and optimization of frozen section procedures. We comment on development of optical techniques for intraoperative assessment of resection margins. © 2015 Wiley Periodicals, Inc. Head Neck 38 : E2197–E2203, 2016     

The design, construction, and operation of a whole-body inhalation chamber for use in avian toxicity studies

Environmental risk assessments are broadening to include evaluations of avian species exposed to gaseous and particulate materials (Mineau, 2002b; Irvine, 2004; Carmalt, 2005). Since the avian respiratory tract is fundamentally different from the respiratory tract of rodents, the effects of gaseous materials on birds cannot validly be extrapolated from data derived from rodent exposure studies (Briant & Driver, 1992; Brown et al., 1997). To address the lack of avian-specific lowest observable effect levels used to calculate reference concentrations for airborne pollutants, a system was designed to facilitate research on inhalation toxicology in small birds. Birds have long been used as early indicators of poor air quality (Brown et al., 1997), and various chambers have been designed for head only exposures of larger birds (Briant & Driver, 1992). Smaller birds with short tracheal lengths and hooked beaks however require less restrictive exposure apparatus, thus warranting the proposed design. The chamber described in this article was designed to accommodate a small falcon, the American kestrel, a species frequently used in toxicological risk assessments (Wiemeyer & Lincer, 1987a; Smits & Bortolotti, 2001; Bortolotti et al., 2003; Fisher et al., 2006). To accomplish this, a 41-L closed inhalation system capable of exposing 12 adult American kestrels was constructed primarily of galvanized steel, polyvinyl chloride, and copper tubing. Humidified air was passed over the birds and subsequently decontaminated by an activated carbon filter and released to a HEPA filtration system. The proposed inhalation chamber was successfully used in 2005 and 2006 to expose a total of 55 male American kestrels to benzene and toluene. Measurements of various biochemical endpoints associated with benzene and toluene toxicity allowed us to study the effects of airborne pollutants on small nondomesticated birds in a controlled laboratory setting.     

Cardiac sodium channels and inherited electrophysiologic disorders: a pharmacogenetic overview

Sodium (Na) channels are essential for cardiac electrical activity. Cardiac Na channel dysfunction, inherited or acquired, can induce life-threatening conduction and arrhythmia disorders. Inherited Na channel dysfunction may put affected patients at a greater risk for these complications when channel-modifying drugs are prescribed. This study addressed pharmacogenetic effects in three well-described Na channel-related diseases: long QT syndrome type 3, Brugada syndrome and inherited cardiac conduction disease. A review of the currently available literature on cardiac Na channel-modulating drugs was undertaken. An overview is given of the known risks of development of the previously mentioned complications of commonly prescribed drugs in patients affected with Na channel-related diseases and the underlying mechanisms.     

Retention of cast crown copings cemented to implant abutments

Background: The cementation of crowns to dental implant abutments is an accepted form of crown retention that requires consideration of the properties of available cements within the applied clinical context. Dental luting agents are exposed to a number of stressors that may reduce crown retention in vivo, not the least of which is occlusal loading. This study investigated the influence of compressive cyclic loading on the physical retention of cast crown copings cemented to implant abutments. Methods: Cast crown copings were cemented to Straumann synOcta titanium implant abutments with three different readily used and available cements. Specimens were placed in a humidifier, thermocycled and subjected to one of four quantities of compressive cyclic loading. The uniaxial tensile force required to remove the cast crown copings was then recorded. Results: The mean retention values for crown copings cemented with Panavia‐F cement were statistically significantly greater than both KetacCem and TempBond non‐eugenol cements at each compressive cyclic loading quantity. KetacCem and TempBond non‐eugenol cements produced relatively low mean retention values that were not statistically significantly different at each quantity of compressive cyclic loading. Compressive cyclic loading had a statistically significant effect on Panavia‐F specimens alone, but increased loading quantities produced no further statistically significant difference in mean retention. Conclusions: Within the limitations of the current in vitro conditions employed in this study, the retention of cast crown copings cemented to Straumann synOcta implant abutments with a resin, glass ionomer and temporary cement was significantly affected by cement type but not compressive cyclic loading. Resin cement is the cement of choice for the definitive non‐retrievable cementation of cast crown copings to Straumann synOcta implant abutments out of the three cements tested.     

The Wnt/frizzled/GSK-3 beta pathway: a novel therapeutic target for cardiac hypertrophy

An excessive hypertrophic response of the heart to an increased workload is a leading cause of heart failure. At present, cardiac hypertrophy is treated with inhibitors of the renin-angiotensin system or with beta-adrenoceptor antagonists. These current therapeutic strategies inhibit prohypertrophic signaling pathways, but this therapy is inadequate in a substantial number of patients. However, the hypertrophic response of the heart is the net result of activation of prohypertrophic and antihypertrophic pathways. Glycogen synthase kinase-3 beta (GSK-3 beta) has a powerful antihypertrophic effect, but is inhibited by growth factors and hypertrophic stimuli through phosphorylation at the Ser9 residue of GSK-3 beta. Activation of the Wnt/frizzled pathway also results in inactivation of GSK-3 beta through sequestration of the kinase rather than phosphorylation at Ser9. In this Opinion article we will review the current evidence for the involvement of Wnt/frizzled signaling and the activation of GSK-3 beta in the regulation of cardiac hypertrophy, and subsequently discuss the potential of this pathway to serve as a novel therapeutic approach for cardiac hypertrophy.     

Current Status and Future Direction of Hepatic Radioembolisation

Radioembolisation is a locoregional treatment modality for hepatic malignancies. It consists of several stages that are vital to its success, which include a pre-treatment angiographic simulation followed by nuclear medicine imaging, treatment activity choice, treatment procedure and post-treatment imaging. All these stages have seen much advancement over the past decade. Here we aim to provide an overview of the practice of radioembolisation, discuss the limitations of currently applied methods and explore promising developments.     

The miR-143/145 Cluster,a Novel Diagnostic Biomarker in Chondrosarcoma,Acts as a Tumor Suppressor and Directly Inhibits Fascin-1

Chondrosarcoma is the second most frequent bone sarcoma. Due to the inherent chemotherapy and radiotherapy resistance and absence of known therapeutic targets, clinical management is limited to surgical resection. Consequently, patients with advanced disease face a poor prognosis. Hence, elucidating regulatory networks governing chondrosarcoma pathogenesis is vital for development of effective therapeutic strategies. Here, miRNA and mRNA next generation sequencing of different subtypes of human chondrogenic tumors in combination with in silico bioinformatics tools were performed with the aim to identify key molecular factors. We identified miR-143/145 cluster levels to inversely correlate with tumor grade. This deregulation was echoed in the miRNA plasma levels of patients and we provided the first evidence that circulating miR-145 is a potential noninvasive diagnostic biomarker and can be valuable as an indicator to improve the currently challenging diagnosis of cartilaginous bone tumors. Additionally, artificial upregulation of both miRNAs impelled a potent tumor suppressor effect in vitro and in vivo in an orthotopic xenograft mouse model. A combined in silico/sequencing approach revealed FSCN1 as a direct target of miR-143/145, and its depletion phenotypically resembled miR-143/145 upregulation in vitro. Last, FSCN1 is a malignancy-promoting factor associated with aggressive chondrosarcoma progression. Our findings underscore miR-143/145/FSCN1 as important players in chondrosarcoma and may potentially open new avenues for specific therapeutic intervention options. © 2020 American Society for Bone and Mineral Research.     

Science review: Cell membrane expression (connectivity) regulates neutrophil delivery,function and clearance

As the principal cellular component of the inflammatory host defense and contributor to host injury after severe physiologic insult, the neutrophil is inherently coupled to patient outcome in both health and disease. Extensive research has focused on the mechanisms that regulate neutrophil delivery, function, and clearance from the inflammatory microenvironment. The neutrophil cell membrane mediates the interaction of the neutrophil with the extracellular environment; it expresses a complex array of adhesion molecules and receptors for various ligands, including mediators, cytokines, immunoglobulins, and membrane molecules on other cells. This article presents a review and analysis of the evidence that the neutrophil membrane plays a central role in regulating neutrophil delivery (production, rolling, adhesion, diapedesis, and chemotaxis), function (priming and activation, microbicidal activity, and neutrophil-mediated host injury), and clearance (apoptosis and necrosis). In addition, we review how change in neutrophil membrane expression is synonymous with change in neutrophil function in vivo. Employing a complementary analysis of the neutrophil as a complex system, neutrophil membrane expression may be regarded as a measure of neutrophil connectivity, with altered patterns of connectivity representing functionally distinct neutrophil states. Thus, not only does the neutrophil membrane mediate the processes that characterize the neutrophil lifecycle, but characterization of neutrophil membrane expression represents a technology with which to evaluate neutrophil function.