Relating appendicular skeletal variation of sigmodontine rodents to locomotion modes in a phylogenetic context

Abstract

Sigmodontinae rodents constitute the second-largest subfamily among mammals. Alongside the taxonomic diversity, they are also ecologically diverse, exhibiting a wide array of locomotion modes, with semifossorial, terrestrial, semiaquatic, scansorial, arboreal, and saltatorial forms. To understand the ecomorphologic aspects that allow these rodents to display such locomotion diversity, we analyzed 35 qualitative characters of the appendicular skeleton (humerus, ulna, radius, scapula, femur, tibia, ilium, ischium and pubis) in 795 specimens belonging to 64 species, 34 genera and 10 tribes, representing all locomotion modes assigned to this subfamily. We performed a statistical analysis based upon the coefficient of trait differentiation to test the congruence of character states and the different locomotion modes. We also mapped characters states in a molecular phylogeny in order to reconstruct ancestral states and to evaluate how appendicular characters evolved within main lineages of Sigmodontinae radiation under a phylogenetic framework. The statistical analyses revealed six characters related to specific locomotion modes, except terrestrial. The mapping and parsimony ancestral states reconstruction identified two characters with phylogenetical signal and eight characters that are exclusively or more frequently recorded in certain modes of locomotion, four of them also detected by the statistical analysis. Notwithstanding the documented morphological variation, few changes characterize the transition to each of the locomotion modes, at least regarding the appendicular skeleton. This finding corroborates previous results that showed that sigmodontines exhibit an all-purpose appendicular morphology that allows them to use and explore a great variety of habitats.

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Morphology, topology and dimensions of the heart and arteries of genetically normal and mutant mouse embryos at stages S21–S23

Abstract

Accurate identification of abnormalities in the mouse embryo depends not only on comparisons with appropriate, developmental stage-matched controls, but also on an appreciation of the range of anatomical variation that can be expected during normal development. Here we present a morphological, topological and metric analysis of the heart and arteries of mouse embryos harvested on embryonic day (E)14.5, based on digital volume data of whole embryos analysed by high-resolution episcopic microscopy (HREM). By comparing data from 206 genetically normal embryos, we have analysed the range and frequency of normal anatomical variations in the heart and major arteries across Theiler stages S21–S23. Using this, we have identified abnormalities in these structures among 298 embryos from mutant mouse lines carrying embryonic lethal gene mutations produced for the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme. We present examples of both commonly occurring abnormal phenotypes and novel pathologies that most likely alter haemodynamics in these genetically altered mouse embryos. Our findings offer a reference baseline for identifying accurately abnormalities of the heart and arteries in embryos that have largely completed organogenesis.

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Assessment of the involvement of the macrophage migration inhibitory factor–glucocorticoid regulatory dyad in the expression of matrix metalloproteinase-2 during periodontitis

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine and counter-regulator of endogenous glucocorticoids (GCs). It is implicated in acute and chronic inflammatory diseases. This study investigated the role of the MIF–GC regulatory dyad in the expression and release of matrix metalloproteinase-2 (MMP-2) during periodontitis, in vivo and in vitro. In a Mif-knockout (KO) mouse model of ligature-induced periodontitis, gingival tissues and blood were collected and analysed for levels of interleukin-6 (IL-6), MIF, MMP-2, and corticosterone. In addition, human gingival fibroblasts (HGFs) were tested for production of IL-6 and MMP-2 after stimulation with hydrocortisone (HC), MIF, tumour necrosis factor-alpha (TNF-α), or Fusobacterium nucleatum, a pathogen known to elicit immune responses during periodontitis. Wild-type (WT) mice showed a local and systemic increase of MIF levels during inflammation, which was confirmed by increased local IL-6 concentrations. Systemic GC levels were reduced in WT and Mif-KO mice during inflammation, with overall lower concentrations in Mif-KO mice. In vivo and in vitro, MMP-2 production was not dependent on MIF or inflammatory stimuli, but was inhibited by HC. Therefore, MIF does not appear to stimulate expression of MMP-2 in the gingival tissues, whereas GC upregulates MIF and downregulates MMP-2. Our findings further suggest that MIF may regulate systemic GC levels.

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New Developments in the Prophylactic Drug Treatment of Pediatric Migraine: What Is New in 2017 and Where Does It Leave Us?

Abstract

Purpose of Review

Headaches in children are quite common; however, the study and characterization of headache disorders in the pediatric age group has historically been limited. Because of the lack of controlled studies on prophylactic treatment of headache disorders in this age group, the diagnosis of migraine rests on criteria similar those in adults. Likewise, data from adult studies is often inferred and applied to children. Although it appears that many preventives are safe in children, currently none are FDA or EMA approved for this age group. Consequently, many children who present to their primary care physicians with migraines do not receive any preventive therapy despite experiencing significant disability.

Recent Findings

Controlled clinical trials investigating the use of preventive medications in children have suffered from high placebo response rates. The shorter duration of headaches and other characteristic features seen in children are such that designing randomized controlled trials in this age group is more problematic and limiting. Treatment practices vary widely, even among specialists, due to the absence of evidence-based guidelines from clinical trials. The Childhood and Adolescent Migraine Prevention Study (CHAMP) was developed to examine the effectiveness of two of the most widely prescribed preventive medications for pediatric migraine and help narrow this gap. To date, it has been the largest enrolling study of its kind within the pediatric migraine world; its results and implications will be discussed and considered here.

Summary

The CHAMP trial was discontinued early on account of futility and exhibited that neither of two preventive medications for pediatric migraine was more effective than placebo in reducing the number of headache days over a period of 24 weeks. Subjects in the amitriptyline and topiramate groups had higher rates of adverse events than those who had received placebo.

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Age-Related Remodeling of the JAK/STAT/SOCS Signaling Pathway and Associated Myocardial Changes: From Histological to Molecular Level

Publication date: Available online 4 August 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Basma Emad aboulhoda
BackgroundThe cellular and molecular mechanisms implicated in age-associated changes in myocardial structure are of paramount importance since they cause profound alterations in the functional response and represent targets for alleviating age-related pathologies. One of these mechanisms is the JAK/STAT/SOCS signaling pathway.Aim of the studyThe present study is designed to elucidate age-dependent changes of the myocardium to provide morphological basis displaying the pathogenesis of myocardial hypertrophy, fibrosis and inflammation with aging.Material and MethodsThirty male Sprague Dawley rats aged; 6, 30 and 36 months were used in this study. The animals were divided into three age groups, young adult, senile and very senile rats, respectively. The heart weight/body weight ratio was determined. The heart was subjected to gross morphologic examination, microscopic examination using H&E and Masson's trichrome stains and immunohistochemical examination for detection of JAK, pSTAT3, α-SMA, β-MHC and CD45. Western blotting was also carried out to detect SOCS genes. Real-time PCR was used to detect the inflammatory markers TNFα and IL1β and the hypertrophy marker α −SKA. Biochemical analysis of cardiac troponin I and creatine kinase-MB was done. Quantitative histomorphometric estimations included estimation of cardiac myocyte cross sectional area, estimation of the area percent of collagen fibers in Masson's trichrome stained sections and determination of optical density in immunostained sections. Electron microscopic examination was done to determine capillary density.ResultsJak and pSTAT3 were predominantly localized to the nuclei and exhibited progressive decline with aging, while SOCS3 activity displayed an age-related increase. The aged myocardium displayed profound age associated structural changes as well as myocardial hypertrophy, fibrosis and inflammation in senile and very senile rats.ConclusionThe age-related modifications in the JAK/STAT/SOCS signaling as well as the age-associated pathological changes in myocardial structure are of particular interest as they provide further insight in age-associated heart pathologies and represent potential targets for cardioprotective and therapeutic approaches.



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British Rhinological Society 16th Annual Meeting Jersey, 19 May 2017

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Postoperative seizure freedom does not normalize altered connectivity in temporal lobe epilepsy

Summary

Objectives

Specific changes in the functional connectivity of brain networks occur in patients with epilepsy. Yet whether such changes reflect a stable disease effect or one that is a function of active seizure burden remains unclear. Here, we longitudinally assessed the connectivity of canonical cognitive functional networks in patients with intractable temporal lobe epilepsy (TLE), both before and after patients underwent epilepsy surgery and achieved seizure freedom.

Methods

Seventeen patients with intractable TLE who underwent epilepsy surgery with Engel class I outcome and 17 matched healthy controls took part in the study. The functional connectivity of a set of cognitive functional networks derived from typical cognitive tasks was assessed in patients, preoperatively and postoperatively, as well as in controls, using stringent methods of artifact reduction.

Results

Preoperatively, functional networks in TLE patients differed significantly from healthy controls, with differences that largely, but not exclusively, involved the default mode and temporal/auditory subnetworks. However, undergoing epilepsy surgery and achieving seizure freedom did not lead to significant changes in network connectivity, with postoperative functional network abnormalities closely mirroring the preoperative state.

Significance

This result argues for a stable chronic effect of the disease on brain connectivity, with changes that are largely "burned in" by the time a patient with intractable TLE undergoes epilepsy surgery, which typically occurs years after the initial diagnosis. The result has potential implications for the treatment of intractable epilepsy, suggesting that delaying surgical intervention that may achieve seizure freedom may lead to functional network changes that are no longer reversible by the time of epilepsy surgery.

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Issue Information

Cover of this issue. DDX4 is localized on the mitotic spindle. See also Schudrowitz et al. (pages 1612–1619 of this issue).

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In This Issue

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Oral administration of geranylgeranylacetone to protect vestibular hair cells

We recently reported that the heat shock response played a major role in the protection of hair cells against stress. Oral administration of the heat shock inducer, geranylgeranylacetone (GGA) protected hair cells against intense noise. In our present study, we investigated the effect of GGA on vestibular hair cell death induced by an aminoglycoside.

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Microbiome of peri-implantitis affected and healthy dental sites in patients with a history of chronic periodontitis

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Danae Apatzidou, David F. Lappin, Graham Hamilton, Christos A. Papadopoulos, Antonis Konstantinidis, Marcello P. Riggio
ObjectiveTo determine the composition of the microbiome of peri-implantitis sites and corresponding dental sites in subjects with a history of chronic periodontitis.DesignClinical and radiographic examination assessed the periodontal/peri-implant disease status. Plaque samples were collected from one diseased implant with peri-implantitis, functional for at least two years and healthy sites in ten non-smokers who had received periodontal treatment prior to implant placement. Following DNA extraction, the bacteria present in each sample were determined by high-throughput sequencing of V3-V4 region of the 16S rRNA gene using the Illumina MiSeq platform. OTUs were picked using QIIME. Differences between dental and implant sites were determined using linear discriminant analysis, effect size and diversity analyses were conducted using PAST v3.02.ResultsThe microbiomes of healthy samples were more diverse than those found in disease, although disease was associated with a higher abundance of taxa relative to health. The genera Actinobacillus and Streptococcus were most closely associated with health, whereas Prevotella and Porphyromonas were most discriminative for disease. Synergistetes were highly associated with peri-implantitis.ConclusionIn patients with a history of periodontitis, putative periodontal pathogens prevailed in the microbiome of diseased implants. Diseased implants and corresponding healthy sites appear to have distinct microbiological ecosystems.



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Anti-PD-1 Antibody Therapy Induces Hashimoto's Disease with an Increase in Peripheral Blood Follicular Helper T Cells

Thyroid , Vol. 0, No. 0.


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Prevalence and Characterization of Thyroid Hemiagenesis in Japan: The Fukushima Health Management Survey

Thyroid Aug 2017, Vol. 27, No. 8: 1011-1016.


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Future Meetings

Thyroid Aug 2017, Vol. 27, No. 8: 1107-1107.


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Influence of radiotherapy on the dentin properties and bond strength

Abstract

Objectives

The objective of this study was to evaluate the biomechanical properties of dentin and the microtensile bond strength (μTBS) performed before or after radiotherapy (RT).

Material and methods

Dentin chemical composition (infrared spectroscopy—FTIR), SEM images, and mechanical properties (Vickers microhardness—VHN and elastic modulus—E) were evaluated comparing no irradiated and irradiate dentin (n = 5). RT was defined by application of 72 Gy (1.8 Gy daily, 5 days per week, during 8 weeks) with sample immersed in distilled water. μTBS evaluated three groups (n = 10): NI—no irradiated; IB—irradiation before restoration; and IA—irradiation after restoration. Resin-dentin sticks (1.0 mm²) were obtained and submitted to μTBS. Analysis of the bonding interface was made by confocal microscopy.

Results

After RT, percentage ratio of FTIR analysis showed increased absorption for all bands. SEM image showed a disorganized dentin structure. Two-way ANOVA showed increased VHN (p = 0.005) and decreased E (p < 0.001). For μTBS, one-way ANOVA and Duncan test showed significant differences among groups (p = 0.018). IB group presented the lowest bond strength values.

Conclusions

RT alters the absorption bands and SEM images showed a disorganization of the dentin structure. Mechanical properties were changed with increased VHN and decreased E. μTBS was affected by the radiotherapy and restoration period (before or after).

Clinical relevance

RT causes changes that contribute to increased risk of tooth decay. Restorative treatments can be performed using adhesive procedures, but it is preferable to be performed before of the irradiation protocol, to guarantee better adhesive properties to restoration.

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Laser treatments of active acne

Abstract

The utility of laser therapy is increasingly being recognized in the treatment of active acne vulgaris. We aimed to perform a narrative review of the medical literature on the use of laser therapy for the treatment of active acne vulgaris. We performed a PubMed literature search on September 1, 2016 using the search terms "active acne," "acne," "laser therapy," and "laser surgery." Case reports, case series, cohort, and controlled trials were included. Studies of lasers in the treatment of acne, including erbium glass, Nd:YAG, pulse dye laser (PDL), potassium titanyl phosphate (KTP) laser, and laser-based photodynamic therapy, have been published. While treatment of active acne with lasers has been successful, many studies are limited by small patient number and lack of control populations and comparison to standard therapies for active acne. Laser therapies are increasingly becoming part of or an adjunct to the medical treatment of active acne and are a useful treatment modality.

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Lewis-Sumner Syndrome Manifesting as Unilateral Vocal Fold Paresis and Laryngeal Fasciculations

Lewis-Sumner syndrome (LSS) is a rare disease characterized by asymmetrical and multifocal mononeuropathy commonly located in the upper limbs. Some rare cases affecting cranial nerve have been described, but LSS is unknown to affect especially laryngeal nerves. This paper presents the first case of unilateral vocal fold paresis caused by an LSS in a 59-year-old man complaining of dysphonia, breathy voice, and vocal fatigue. Epidemiology, clinical features, diagnosis, and treatment will be described.

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DNA methylation profiles of 22 apoptosis-related genes in odontogenic keratocysts before and after marsupialization

Publication date: Available online 3 August 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Karuza Maria Alves Pereira, Sara Ferreira dos Santos Costa, Núbia Braga Pereira, Marina Gonçalves Diniz, Wagner Henriques Castro, Carolina Cavaliéri Gomes, Ricardo Santiago Gomez
Objective: Odontogenic keratocysts (OKCs) are cystic lesions of the jaws, which tend to recur after treatment. Marsupialization is an effective preliminary treatment for large OKCs. This procedure induces epithelial lining changes in association with Bcl-2 protein expression reduction, but the underlying mechanisms are unknown. The purpose of our study was to compare the methylation profile of apoptosis-related genes of OKCs before and after marsupialization. Study design: We assessed the methylation percentages of the promoter region of 22 apoptosis-related genes in 13 OKCs, marsupialized (m-OKCs) and non-marsupialized lesions by using methylation qPCR array. We validated the expression of genes that showed the greatest differences in methylation percentage between the two groups. Results:LTBR and BCLAF1 showed higher DNA methylation percentage in the m-OKCs, but this difference did not affect gene expression (p > 0.05). The other 20 genes showed similar DNA methylation in both OKC groups. Conclusions: OKC shows a distinct methylation profile after marsupialization, but this is not followed by gene expression alterations.



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Oral lichen sclerosus- a review of clinical presentation, treatment, and clinical outcomes

Publication date: Available online 3 August 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Stephanie L. Bevans, Jordan M. Keeley, Naveed Sami
ObjectiveTo evaluate disease involvement, treatment and response, and malignant potential of oral LS.Study DesignWe conducted a review of the literature of 37 cases of oral LS. We looked specifically for the following data: patient demographics, disease involvement, treatment, treatment response, follow-up duration, symptoms, risk factors for oral malignancy, and malignant transformation.ResultsThe most common area of oral involvement included the labial mucosa (67.6%). 38.5% with oral involvement reported symptoms, and 35.1% exhibited extra-oral manifestations. Patients were less likely to receive treatment if asymptomatic (62.5%) than if symptomatic (80%). Topical steroids were more efficacious (66.7%) compared to other treatments. 25.0% of patients were found to have risk factors for malignancy. No patients had malignant transformation of oral lesions at follow-up (mean follow-up 22.1 months; median 12 months).ConclusionMore data and longer follow-up is required to determine the long-term clinical outcomes of oral LS.



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Is cone beam computed tomography accurate for post-operative evaluation of implants? an in vitro study

Publication date: Available online 3 August 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Michele Machado Vidor, Gabriela Salatino Liedke, Mathias Pante Fontana, Heraldo Luis Dias da Silveira, Nadia Assein Arus, André Lemos, Mariana Boessio Vizzotto
ObjectiveTo evaluate the accuracy of CBCT images for bone/implant interface diagnosis in comparison to periapical radiographs.Study DesignTitanium implants were inserted in 74 bovine rib blocks in intimate contact to the bone walls, and with a gap of 0.125 mm (simulating a failure in the osseointegration process). Periapical radiographs were taken with conventional film, and CBCT scans were acquired with i-CAT (0.2mm and 0.125mm voxel) and Kodak (0.2mm and 0.076mm voxel) units. Three examiners evaluated the images using a 5-point scale. Diagnostic accuracy was analyzed through sensitivity, specificity, and the area under the ROC curve (AUC) with 95% confidence intervals (CI). Intra- and inter-examiner agreements were analyzed through Kendall's concordance test.ResultsIntra- and inter-examiner agreements showed satisfactory results. The greatest accuracy was observed with conventional radiographs (AUC = 0.963 / CI 95% = 0.891-0.993). I-CAT 0.125mm images showed good accuracy (AUC = 0.885 / CI 95% = 0.790-0.947), with no significant difference compared to conventional radiography. Kodak images had high specificity and low sensitivity, presenting more false-negative results.ConclusionConventional radiographs showed the highest accuracy for bone/implant interface diagnosis. However, CBCT scans (i-CAT 0.125 mm voxel), if available or if performed for pre-surgical assessment of another implant site, may provide similar accuracy.



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FDA Approval Summary: Trabectedin for Unresectable or Metastatic Liposarcoma or Leiomyosarcoma Following an Anthracycline-Containing Regimen

On October 23, 2015, the U.S. Food and Drug Administration approved trabectedin, a new molecular entity for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen. Approval was based on results of a single, randomized, active-controlled, 518-patient, multicenter study comparing the safety and efficacy of trabectedin 1.5 mg/m² as a 24-hour continuous intravenous (i.v.) infusion once every 3 weeks to dacarbazine 1000 mg/m² i.v. once every 3 weeks. Treatment with trabectedin resulted in a statistically significant improvement in progression-free survival (PFS) of 4.2 months and 1.5 months for trabectedin and dacarbazine, respectively. (HR= 0.55; 95% CI: 0.44, 0.70; unstratified log-rank test p<0.001). The most common adverse reactions (≥20%) were nausea, fatigue, vomiting, constipation, decreased appetite, diarrhea, peripheral edema, dyspnea, and headache. Serious adverse reactions included anaphylaxis, neutropenic sepsis, rhabdomyolysis, hepatotoxicity, cardiomyopathy, and extravasation resulting in tissue necrosis. A post-marketing trial was required to evaluate the serious risk of cardiomyopathy. This approval provides another treatment option in a setting where no drug has been shown to improve overall survival. A key regulatory consideration during review of this application was use of PFS as an endpoint to support regular approval of trabectedin.

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Analgesics and Sport Performance: Beyond the Pain Modulating Effects

Analgesics are widely used in sport to treat pain and inflammation associated with injury. However, there is growing evidence that some athletes might be taking these substances in an attempt to enhance performance. While the pharmacological action of analgesics and their use in treating pain with and without anti-inflammatory effect is well established, their effect on sport performance is debated. The aim of this review was to evaluate the evidence of whether analgesics are capable of enhancing exercise performance, and if so, to what extent.

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Professor David Burns Moffat VRD MD FRCS, 1921–2017

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A bifunctional MAPK/PI3K antagonist for inhibition of tumor growth and metastasis

Responses to targeted therapies frequently are brief with patients relapsing with drug resistant tumors. For oncogenic MEK and BRAF inhibition, drug resistance commonly occurs through activation of PI3K/AKT/mTOR signaling and immune checkpoint modulation, providing a robust molecular target for concomitant therapy. Here, we evaluated the efficacy of a bifunctional kinase inhibitor (ST-162) that concurrently targets MAPK and PI3K signaling pathways. Treatment with ST-162 produced regression of mutant KRAS or BRAF addicted xenograft models of colorectal cancer and melanoma and stasis of BRAF/PTEN mutant melanomas. Combining ST-162 with immune checkpoint blockers further increased efficacy in a syngeneic KRAS mutant colorectal cancer model. Nascent transcriptome analysis revealed a unique gene set regulated by ST-162 related to melanoma metastasis. Subsequent mouse studies revealed ST-162 was a potent inhibitor of melanoma metastasis to the liver. These findings highlight the significant potential of a single molecule with multi-kinase activity to achieve tumor control, overcome resistance and prevent metastases through modulation of interconnected cell signaling pathways.

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The tumor suppressor protein OPCML potentiates anti-EGFR and anti-HER2 targeted therapy in HER2-positive ovarian and breast cancer

OPCML is a tumor suppressor gene that is frequently inactivated in ovarian cancer and many other cancers by somatic methylation. We have previously shown that OPCML exerts its suppressor function by negatively regulating a spectrum of receptor tyrosine kinases (RTKs), such as ErbB2/HER2, FGFR1 and EphA2, thus attenuating their related downstream signaling. The physical interaction of OPCML with this defined group of RTKs is a prerequisite for their downregulation. Overexpression/gene amplification of EGFR and HER2 is a frequent event in multiple cancers including ovarian and breast cancers. Molecular therapeutics against EGFR/HER2 or EGFR only, such as lapatinib and erlotinib respectively, were developed to target these receptors but resistance often occurs in relapsing cancers. Here we show that, though OPCML interacts only with HER2 and not with EGFR, the interaction of OPCML with HER2 disrupts the formation of the HER2-EGFR heterodimer and this translates into a better response to both lapatinib and erlotinib in HER2-expressing ovarian and breast cancer cell lines. Also, we show that high OPCML expression is associated with better response to lapatinib therapy in breast cancer patients and better survival in HER2-overexpressing ovarian cancer patients, suggesting that OPCML co-therapy could be a valuable sensitizing approach to RTK inhibitors.

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Bypassing drug-resistance mechanisms of prostate cancer with small-molecules that target androgen receptor chromatin interactions

Human androgen receptor (AR) is a hormone-activated transcription factor that is an important drug-target in the treatment of prostate cancer. Current small molecule AR-antagonists, such as enzalutamide, compete with androgens that bind to the steroid binding pocket of the AR ligand binding domain (LBD). In castration-resistant prostate cancer (CRPC), drug-resistance can manifest through AR-LBD mutations that convert AR-antagonists into agonists, or by expression of AR-variants lacking the LBD. Such treatment resistance underscores the importance of novel ways of targeting the AR.  Previously, we reported the development a series of small molecules that were rationally designed to selectively target the AR DNA binding domain (DBD) and, hence, to directly interfere with AR-DNA interactions. In the current work we have confirmed that the lead AR DBD inhibitor indeed directly interacts with the AR-DBD and tested that substance across multiple clinically relevant CRPC cell lines. We have also performed a series of experiments that revealed that genome-wide chromatin binding of AR was dramatically impacted by the lead compound (although with lesser effect on AR variants). Collectively, these observations confirm the novel mechanism of anti-androgen action of the developed AR-DBD inhibitors, establishing proof-of-principle for targeting DNA-binding domains of nuclear receptors in endocrine cancers.

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Combination Therapy With c-Met and Src Inhibitors Induces Caspase-Dependent Apoptosis of Merlin-Deficient Schwann Cells and Suppresses Growth of Schwannoma Cells

Neurofibromatosis type 2 (NF2) is a nervous system tumor disorder caused by inactivation of the merlin tumor suppressor encoded by the NF2 gene. Bilateral vestibular schwannomas (VS) are a diagnostic hallmark of NF2. Mainstream treatment options for NF2-associated tumors have been limited to surgery and radiotherapy; however, off-label uses of targeted molecular therapies are becoming increasingly common. Here we investigated drugs targeting two kinases activated in NF2-associated schwannomas, c-Met and Src. We demonstrated that merlin-deficient mouse Schwann cells (MD-MSCs) treated with the c-Met inhibitor, cabozantinib, or the Src kinase inhibitors, dasatinib and saracatinib, underwent a G₁ cell cycle arrest. However, when MD-MSCs were treated with a combination of cabozantinib and saracatinib, they exhibited caspase-dependent apoptosis. The combination therapy also significantly reduced growth of MD-MSCs in an orthotopic allograft mouse model by greater than 80% of vehicle. Moreover, human vestibular schwannoma cells with NF2 mutations had a 40% decrease in cell viability when treated with cabozantinib and saracatinib together compared to the vehicle control. This study demonstrates that simultaneous inhibition of c-Met and Src signaling in MD-MSCs triggers apoptosis, and reveals vulnerable pathways that could be exploited to develop NF2 therapies.

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Inhibition of the V-ATPase by Archazolid A - a new strategy to inhibit EMT

Epithelial-mesenchymal transition (EMT) induces tumor-initiating cells (TICs) which account for tumor recurrence, metastasis and therapeutic resistance. Strategies to interfere with EMT are rare but urgently needed to improve cancer therapy. By using the myxobacterial natural compound Archazolid A as a tool, we elucidate the V-ATPase, a multimeric proton pump that regulates lysosomal acidification, as a crucial player in EMT and identify the inhibition of V-ATPase by Archazolid A as promising strategy to block EMT. Genetic knockdown and pharmacologic inhibition of the V-ATPase by Archazolid A interfere with the EMT process and inhibit TIC generation, as shown by a reduced formation of mammospheres and decreased cell motility. As underlying mechanism, V-ATPase-inhibition by Archazolid A disturbs the turnover of E-cadherin: Archazolid abrogates E-cadherin loss during EMT by interfering with its internalization and recycling. Our study elucidates V-ATPase as essential player in EMT by regulating E-cadherin turnover.  Archazolid A is suggested as a promising therapeutic agent to block EMT and the generation of TICs.

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Repression of Stress-Induced LINE-1 Expression Protects Cancer Cell Subpopulations from Lethal Drug Exposure

Publication date: Available online 3 August 2017
Source:Cancer Cell
Author(s): Gulfem Dilek Guler, Charles Albert Tindell, Robert Pitti, Catherine Wilson, Katrina Nichols, Tommy KaiWai Cheung, Hyo-Jin Kim, Matthew Wongchenko, Yibing Yan, Benjamin Haley, Trinna Cuellar, Joshua Webster, Navneet Alag, Ganapati Hegde, Erica Jackson, Tracy Leah Nance, Paul Garrett Giresi, Kuan-Bei Chen, Jinfeng Liu, Suchit Jhunjhunwala, Jeff Settleman, Jean-Philippe Stephan, David Arnott, Marie Classon
Maintenance of phenotypic heterogeneity within cell populations is an evolutionarily conserved mechanism that underlies population survival upon stressful exposures. We show that the genomes of a cancer cell subpopulation that survives treatment with otherwise lethal drugs, the drug-tolerant persisters (DTPs), exhibit a repressed chromatin state characterized by increased methylation of histone H3 lysines 9 and 27 (H3K9 and H3K27). We also show that survival of DTPs is, in part, maintained by regulators of H3K9me3-mediated heterochromatin formation and that the observed increase in H3K9me3 in DTPs is most prominent over long interspersed repeat element 1 (LINE-1). Disruption of the repressive chromatin over LINE-1 elements in DTPs results in DTP ablation, which is partially rescued by reducing LINE-1 expression or function.

Graphical abstract

Teaser

Guler et al. show that drug-tolerant persisters (DTPs), a cancer cell subpopulation surviving lethal drugs, are partly maintained by a repressed chromatin state, prominently at LINE-1 elements. Disrupting the repressive chromatin results in death of DTPs, which is partially rescued by reducing LINE-1 expression.


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Liver Transplantation for Hepatocellular Carcinoma: Kent Hospital Experience

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Rajeunissement jugal et traitement des bajoues

Publication date: Available online 2 August 2017
Source:Annales de Chirurgie Plastique Esthétique
Author(s): A. Fogli
Le but de cette étude est, d'une part, d'analyser les modifications anatomiques conduisant à l'aspect du vieillissement jugal avec l'apparition des bajoues. D'autre part, il est, après avoir évoqué les différentes techniques, de mettre en exergue celles qui sont le plus efficaces avec le souci permanent de l'obtention d'un résultat naturel avec un ovale bien défini et une répartition des volumes jugaux harmonieuse. Pour cela, les techniques de lifting avec remise en place des volumes déplacés et la lipostructure sont souvent associées avec le strict respect de vecteurs différents dans leur direction pour les tissus sous-jacents et pour le redrapage cutané. Plus ciblé, la dissection de l'espace pré-massétérin permet de répondre aux problèmes spécifiques posés par les bajoues et les sillons labio-mentonniers lourds. En répondant à la demande psychosociologique de notre époque, deux grands types d'indications se dégagent avec le lifting du sujet jeune qui permet d'obtenir un résultat pérenne et un retour à une vie sociale et professionnelle rapide, une chirurgie d' indication plus tardive qui nécessite des techniques plus invasives entraînant des suites opératoires plus lourdes.The aim of this study is to analyze the anatomical changes leading to the appearance of jugal aging with the appearance of jowls. It is also to describe the different techniques and to highlight those that are most effective with the permanent concern of obtaining a natural result with a well-defined jawline and a harmonious distribution of jugal volumes. For this purpose, the techniques of lifting with relocation of the displaced volumes and lipostructure are often associated with the strict respect of different directional vectors for the underlying tissues and for the skin redraping. More precisely, the dissection of the pre-masseteric space makes it possible to address the specific problems posed by the jowls and the heavy labio-mental grooves. In responding to the psycho-sociological demand of our time, two major types of indications emerge with the facelift of the young patient, which makes it possible to obtain a long lasting result and a fast return to social and professional life and a later indication surgery, which requires more invasive techniques resulting in heavier surgical procedures and follow-up.



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JCAD Promotes Progression of Non-alcoholic Steatohepatitis to Liver Cancer by Inhibiting LATS2 Kinase Activity

Non-alcoholic steatohepatitis-associated hepatocellular carcinoma (NASH-HCC) is a malignancy whose incidents is rapidly increasing. However, the mechanisms that drive development of HCC in a steatotic microenvironment remain unknown. Here we report that the obesity-associated protein JCAD is expressed at significantly higher levels in human NASH-HCC specimens compared to peri-carcinoma specimens. High JCAD expression was verified in multiple hepatoma cell lines. Forced overexpression of JCAD in hepatoma cells promoted tumor growth and proliferation; whereas JCAD silencing yielded opposite effects. JCAD interacted with the kinase domain of the tumor suppressor kinase LATS2, a core component of the Hippo signaling pathway. JCAD overexpression inhibited the ability of LATS2 to phosphorylate YAP in this pathway, in turn upregulating CCND1 and GLI2 to promote hepatoma cell proliferation. JCAD was induced by fatty acid overload in hepatic cells and was highly expressed in a mouse model of NASH-precarcinoma lesions, where the ratio of phospho-YAP to YAP was decreased. In human NASH-HCC specimens, JCAD expression and YAP phosphorylation patterns paralleled with the mouse model. Our findings illuminate a new role for JCAD and its critical interplay in the Hippo signaling cascade during the transition of NASH to HCC, with potential implications for therapeutic development in this setting.

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Aneuploid cell survival relies upon sphingolipid homeostasis.

Aneuploidy, a hallmark of cancer cells, poses an appealing opportunity for cancer treatment and prevention strategies. Using a cell-based screen to identify small molecules that could selectively kill aneuploid cells, we identified the compound N-[2-hydroxy-1-(4-morpholinylmethyl)-2-phenylethyl]-decanamide monohydrochloride (DL-PDMP), an antagonist of UDP-glucose ceramide glucosyltransferase. DL-PDMP selectively inhibited proliferation of aneuploid primary mouse embryonic fibroblasts and aneuploid colorectal cancer cells. Its selective cytotoxic effects were based on further accentuating the elevated levels of ceramide which characterize aneuploid cells, leading to increased apoptosis. We observed that DL-PDMP could also enhance the cytotoxic effects of paclitaxel, a standard of care chemotherapeutic agent that causes aneuploidy, in human colon cancer and mouse lymphoma cells. Our results offer pharmacological evidence that the aneuploid state in cancer cells can be targeted selectively for therapeutic purposes, or for reducing the toxicity of taxane-based drug regimens.

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EZH2 palmitoylation mediated by ZDHHC5 in p53 mutant glioma drives malignant development and progression

Gilomas with mutant p53 occurring in 30% of giloma patients exhibit therapeutic resistance and poor outcomes. In this study, we identify a novel mechanism through which mutant p53 drives cancer cell survival and malignant growth. We documented overexpression of the zinc finger protein ZDHHC5 in glioma compared to normal brain tissue and that this event to be tightly correlated with p53 mutations. Mechanistic investigations revealed that mutant p53 transcriptionally upregulated ZDHHC5 along with the nuclear transcription factor NF-Y. These events contributed to the development of glioma by promoting the self-renewal capacity and tumorigenicity of glioma stem-like cells, by altering the palmitoylation and phosphorylation status of the tumor suppressor EZH2. Taken together, our work highlighted ZDHHC5 as a candidate therapeutic target for management of p53-mutated gliomas.

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Using Pretend Play to Promote Foundations for Text Comprehension: Examples From a Program for Children Who Are Deaf and Hard of Hearing

This review article starts with an overview of changing education paradigms and the literature on cognitive and linguistic relationships in imaginative play related to comprehension of oral and written texts. Strategies for developing the cognitive and linguistic foundations for text comprehension through play are described. A review of current literature on children who are deaf or hard of hearing (DHH) indicates that many of them are at risk for deficits in imaginative play and text comprehension related to deficits in language, cognition, theory of mind, and social–emotional skills. The article concludes with description of a play-based educational program that was implemented with preschool children who are DHH. It is an example of how play-based interventions could be implemented with other populations facing language and literacy challenges.

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Play as Regulation: Promoting Self-Regulation Through Play

The nature of play and an overview of the stages of play in the first 5 years of childhood are discussed. The core features of sensorimotor, functional, and symbolic play are identified. Vignettes describing how play serves a regulatory function punctuate each section. A conceptual framework for the construct of regulation is presented and counterpointed against the primary sources of dysregulation in young children, including excessive psychosensory stimulation, states of intense emotional arousal, anxiety, and conditions of toxic stress. Factors are reviewed that contribute to the development of self-regulatory capacity, including temperament and constitutional factors, cognitive control in the form of executive function; positive parenting, attachment, and internal representation; and the capacity for symbolization, along with the expected progression of the acquisition of self-regulatory capacity. Specific regulatory functions of play are identified and explicated including play as regulatory practice, novelty and investigation, and roles and rules. The article concludes by summarizing the state of current empirical evidence with regard to play and self-regulation.

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Issue Editor Foreword: The Power of Play and Its Role in Developmental Integration

No abstract available

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From the Editor: Thinking Deeper About Play

No abstract available

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What Exactly Is Play, and Why Is It Such a Powerful Vehicle for Learning?

"Play" is a word used commonly to refer to children's preferred activities and to some adult activities, and it is often said that play promotes learning. But what is play exactly, and what and how do children learn through play? This essay begins with a description of an evolutionary, practice theory of play by German philosopher and naturalist, Karl Groos, followed by a system of categorizing play according to the kinds of skills most obviously practiced: physical/locomotor play, constructive play, language play, fantasy play, social play, and play with formal rules. Play is then defined as activity that (1) is self-chosen and self-directed, (2) is motivated by means more than ends, (3) is guided by mental rules, and (4) includes a strong element of imagination. These characteristics are elaborated upon to show how each contributes to play's developmental value. Two final sections describe the special developmental value of age-mixed play and deleterious changes in children's well-being that have accompanied the decline of play in recent decades.

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The Power of Symbolic Play in Emotional Development Through the DIR Lens

Symbolic play is a powerful vehicle for supporting emotional development and communication. It embraces all developmental capacities. This article describes how symbols are formed and how emotional themes are symbolized whereby children reveal their understanding of the world, their feelings and relationships, and how they see themselves in the symbols they choose in play. The DIR (Developmental, Individual Difference, Relationship) model provides the framework and context for understanding the unique profiles of all children, including those with autism, and the importance of elevating feelings and impulses to the level of symbolic ideas that support emotional and behavioral regulation. Children need play where interactive relationships with parents and caregivers help them climb the symbolic–emotional ladder, even when development is uneven, as in autism spectrum disorders. Examples illustrate children solving emotional challenges, exploring the range of emotions, developing reality testing, and reaching abstract levels of thought and empathy through symbolic play and conversations unifying emotions and intellect in early childhood development.

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Embracing the Potential of Play for Children on the Autism Spectrum: Facilitating the Earliest Stages of Developmental Integration

In this article, the breadth and depth of play as an integrating process for children with developmental challenges are explored. The fact that play is a source of developmental growth suggests that its role in intervention with children with language and communication disorders cannot be overstated. Several contemporary play-based intervention programs for children with autism spectrum disorders are briefly reviewed. Models of child development that emphasize developmental integration are discussed. Clinical vignettes, dilemmas, and scenarios illustrate how language interventions can be designed to address engagement and meaning, the foundations of language development. Finally, the role of the adult or the attuned play partner is considered relative to current thinking about the caregiver–child relationship.

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Methylene blue mediated photobiomodulation on human osteoblast cells

Abstract

Photobiomodulation (PBM) and photodynamic therapy (PDT) are two major methods, which use light in medicine and dentistry. PBM uses low-level laser light to induce cell proliferation and activity. In contrast, PDT use laser light combined with a photosensitizer (PS) to cause cell death. Due to similar, not fully understood mechanisms and biphasic response of light, unexpected and complex outcomes may be observed. In the present study, the effect of 635 nm laser light, with power density 50 mW/cm², at three different energy densities (0.5, 1, and 2 J/cm² which last 10, 20, and 40 s, respectively) mediated by methylene blue (MB) on the human osteoblast cell line (ATCC-CRL-11372, Rockville, MD, USA) was investigated. Cell viability (MTT assay and acridine orange/propidium iodide staining) and proliferation (Alamar Blue assay) were assessed at 24, 48, and 72 h post irradiation. Alkaline phosphatase (ALP) activity, mineralization (Alizarin Red staining) and gene expressions (RT-PCR analysis) were analyzed at 7th and 14th days after treatment. Five groups were formed as the control group (no MB, no irradiation), MB (only 0.05 μM MB), MB + 0.5 J/cm², MB + 1 J/cm², and MB + 2 J/cm². Cell viability was decreased at 72 h (ANOVA; p < 0.05) for MB + 0.5 J/cm², MB + 1 J/cm², and MB + 2 J/cm² groups. Although proliferation does not seem to be effected by MB-mediated laser application, osteo-anabolic activity is altered. ALP activity was significantly increased at day 7 (ANOVA; p < 0.05) for MB-combined laser groups; on the other hand, mineralization was significantly decreased (ANOVA; p < 0.05) in all treatment groups. Alkaline phosphatase and collagen-I expressions were upregulated in MB + 2 J/cm² group at 7th and 14th days, respectively. These results may contribute to the low-dose PDT researches and understanding PBM effects on osteoblast behavior but further studies are needed since inappropriate conditions may lead to undesirable results for both therapies.

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Relevance of Spatial Heterogeneity of Immune Infiltration for Predicting Risk of Recurrence After Endocrine Therapy of ER+ Breast Cancer

Abstract

Background

Despite increasing evidence supporting the clinical utility of immune infiltration in the estrogen receptor–negative (ER-) subtype, the prognostic value of immune infiltration for ER+ disease is not well defined.

Methods

Quantitative immune scores of cell abundance and spatial heterogeneity were computed using a fully automated hematoxylin and eosin–stained image analysis algorithm and spatial statistics for 1178 postmenopausal patients with ER+ breast cancer treated with five years' tamoxifen or anastrozole. The prognostic significance of immune scores was compared with Oncotype DX 21-gene recurrence score (RS), PAM50 risk of recurrence (ROR) score, IHC4, and clinical treatment score, available for 963 patients. Statistical tests were two-sided.

Results

Scores of immune cell abundance were not associated with recurrence-free survival. In contrast, high immune spatial scores indicating increased cell spatial clustering were associated with poor 10-year, early (0–5 years), and late (5–10 years) recurrence-free survival (Immune Hotspot: LR-χ² = 14.06, P < .001, for 0–10 years; LR-χ² = 6.24, P = .01, for 0–5 years; LR-χ² = 7.89, P = .005, for 5–10 years). The prognostic value of spatial scores for late recurrence was similar to that of IHC4 and RS in both populations, but was not as strong as other tests in comparison for recurrence across 10 years.

Conclusions

These results provide a missing link between tumor immunity and disease outcome in ER+ disease by examining tumor spatial architecture. The association between spatial scores and late recurrence suggests a lasting memory of protumor immunity that may impact disease progression and evolution of endocrine treatment resistance, which may be exploited for therapeutic advances.

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The Emergency Department's Impact on Inpatient Critical Care Resources

Abstract

Critical care is an expensive and limited resource in the United States. Estimates from more than a decade ago suggest that over $100 billion a year is spent on critical care services.¹ Over the past two decades, the number of patients presenting to the Emergency Department (ED) requiring critical care services has increased at a much higher rate than the growth in overall ED volume.^2,3 The proportion of ED patients requiring Intensive Care Unit (ICU) admission has increased 75% over the first decade of the twenty-first century. In addition to the increase in the absolute number of patients requiring critical care admission, the ED length of stay for critically ill patients increased by 60 minutes. This resulted in a total nationwide increase in critical care provided in the ED by more than threefold. This disproportionate increase in critical care time reflects both the increase in critical care volume and the increase in ED boarding of critically ill patients. Data from 2008 reported the median boarding time for a patient waiting in the ED for an ICU bed was more than 5 hours, and 30% of patients waited more than 6 hours for an ICU bed.^2,3

This article is protected by copyright. All rights reserved.

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Wogonoside inhibits invasion and migration through suppressing TRAF2/4 expression in breast cancer

Twist1 is involved in tumor initiation and progression, which especially contributes to tumor invasion and metastasis. Wogonoside is the main in-vivo metabolite of wogonin, and it is also a natural product wit...

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Modeling tumor cell adaptations to hypoxia in multicellular tumor spheroids

Under hypoxic conditions, tumor cells undergo a series of adaptations that promote evolution of a more aggressive tumor phenotype including the activation of DNA damage repair proteins, altered metabolism, and...

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A new technique for creating a neo-umbilicus in abdominoplasty

The umbilicus is an essential feature of the abdomen. In this article we describe a new technique for creating a neo-umbilicus in abdominoplasties.

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Brazilian Portuguese version of the Female Genital Self Image Scale (FGSIS) for women seeking abdominoplasty

Female body image is a multifaceted construct associated with satisfaction with specific body parts (e.g., abdomen, arms, thighs, among others), body size, and feeling comfortable showing the body to the partner or others1,2. These perceptions and feelings about the body are influenced by socio-cultural aspects and personal views, and may affect sexual performance and satisfaction3. Changes in body image are particularly evident in women who have experienced changes in the body, including pregnancy, weight gain, serious diseases such as cancer, and aging.

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Re: Impact of the Method and Success of Pharyngeal Reconstruction on the Outcome of Treating Laryngeal and Hypopharyngeal Cancers with Pharyngolaryngectomy: A National Analysis

Life expectancy is crucial to evaluate in patients that undergo pharyngolaryngectomy, in order to be able to choose the best reconstructive strategy for each case. Ileocolon free flap represents our preference when voice reconstruction is aimed, especially in patients with long life expectancy.

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The bacterial species associated with aspirated foreign bodies in children

Publication date: Available online 2 August 2017
Source:Auris Nasus Larynx
Author(s): Maayan Gruber, Graeme van Der Meer, Benjamin Ling, Colin Barber, Nikki Mills, Michel Neeff, Lesley Salkeld, Murali Mahadevan
ObjectiveInhaled foreign bodies in children are common and may be complicated by secondary airway tract infection. The inhaled foreign body may act as carrier of infectious material and the aim of this study was to explore the bacterial species associated with aspirated foreign bodies in a cohort of children.MethodsRetrospective case series of 34 patients who underwent rigid laryngobronchoscopy because of foreign body aspiration. Each patient had a sample taken from tracheobronchial secretions during the procedure.ResultsThe average patient age was 31.2 months and the average hospital stay was 2.5 days. Of the foreign bodies 24 (71%) were organic in nature and 10 (29%) were non-organic. Twenty eight (82.3%) patients had mixed oropharyngeal flora organisms growth. Fifteen (44%) samples were positive for organisms other than oropharyngeal flora with the most common cultured organisms being: Streptococcus pneumonia (4/12%), Haemophilus influenza (4/12%), Moraxella catarrhalis (4/12%). Four samples (12%) grew a fungus; Candida albicans was cultured in 3 patients and Aspergillus glaucus was identified in one sample. Of the non-oropharyngeal organisms 7(47%) demonstrated antibiotic resistance with four having resistance to amoxycillin, two resistant to penicillin and one resistant to cotrimoxazole.ConclusionSome children who present with aspirated foreign body may be complicated with secondary airway infection. Antibacterial treatment might be considered in some of these cases. The regimen of antibiotics should aim to cover oropharyngeal flora, S. pneumonia, H. influenza and Moraxella catarrhalis.



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The Otology Questionnaire Amsterdam: a generic patient reported outcome measure about the severity and impact of ear complaints. A cross-sectional study on the development of this questionnaire

Abstract

Objective

Development of the Otology Questionnaire Amsterdam (OQUA); a patient reported outcome measure (PROM), measuring the severity and impact of ear complaints of patients visiting an ENT surgeon.

Design

Multicenter, cross-sectional study.Phase 1: qualitative research. In depth interviews (N=16) to identify relevant types of ear complaints and to formulate items. Pilot study of the first and second draft of the OQUA (N=32, N=39). Phase 2: quantitative research. Field-testing of the OQUA (N=352). Item reduction based on inter-item correlation, factor analysis and expert opinion.

Setting

Two secondary and two tertiary ENT clinics.

Participants

Patients over the age of sixteen visiting an ENT surgeon with an ear complaint.

Main outcome measures

Phase 1: meaning units and frequency of selected descriptions. Phase 2:inter-item correlation, factor loading and Cronbach's Alpha (α).

Results

Phase 1: eight relevant types of ear complaints were identified: earache, pressure in ear, hearing loss, tinnitus, otorrhoea, itch, dizziness and loss of taste. Phase 2: factor analysis generated a factor 'impact' (α = 0.913). The current version of the OQUA consists of 34 items, covers eight types of ear complaints and consists of two constructs: complaints and impact.

Conclusion

The OQUA is a generic, otologic PROM designed to evaluate the severity of ear complaints and their impact on patients lives.

This article is protected by copyright. All rights reserved.

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All That Wheezes…

Foreword. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors' commentary follows. Stage. A 20-year-old woman presented to…

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Medical Knowledge Assessment by Hematology and Medical Oncology In-Training Examinations Are Better Than Program Director Assessments at Predicting Subspecialty Certification Examination Performance

Abstract

The Accreditation Council for Graduate Medical Education's Next Accreditation System requires training programs to demonstrate that fellows are achieving competence in medical knowledge (MK), as part of a global assessment of clinical competency. Passing American Board of Internal Medicine (ABIM) certification examinations is recognized as a metric of MK competency. This study examines several in-training MK assessment approaches and their ability to predict performance on the ABIM Hematology or Medical Oncology Certification Examinations. Results of a Hematology In-Service Examination (ISE) and an Oncology In-Training Examination (ITE), program director (PD) ratings, demographic variables, United States Medical Licensing Examination (USMLE), and ABIM Internal Medicine (IM) Certification Examination were compared. Stepwise multiple regression and logistic regression analyses evaluated these assessment approaches as predictors of performance on the Hematology or Medical Oncology Certification Examinations. Hematology ISE scores were the strongest predictor of Hematology Certification Examination scores (β = 0.41) (passing odds ratio [OR], 1.012; 95 % confidence interval [CI], 1.008–1.015), and the Oncology ITE scores were the strongest predictor of Medical Oncology Certification Examination scores (β = 0.45) (passing OR, 1.013; 95 % CI, 1.011–1.016). PD rating of MK was the weakest predictor of Medical Oncology Certification Examination scores (β = 0.07) and was not significantly predictive of Hematology Certification Examination scores. Hematology and Oncology ITEs are better predictors of certification examination performance than PD ratings of MK, reinforcing the effectiveness of ITEs for competency-based assessment of MK.

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Flipping The Practice Based Pathology Laboratory—Can It Support Development Of Practitioner Capability For Trainee Pathologists in Gynaecological Cytopathology?

Abstract

This study investigated the role of 'flipping', the practice-based pathology laboratory and classroom to support the development of trainee pathologist practitioners' in the field of gynaecological cytopathology, addressing development of their knowledge and practical application in the clinical setting. Content-rich courses traditionally involve lecture led delivery which restricts tutors from adopting approaches that support greater student engagement in the topic area and application of knowledge to practice. We investigated the role of 'flipping', the practice-based pathology laboratory and classroom where 'virtual lectures' were accessed outside of 'class time' allowing more time for students to engage in active learning under the supervision of a consultant histopathologist. 'Flipping' was used to support two gynaecological cytopathology training courses with cohorts of eight trainee pathologists on the first course and six on the second. Lectures were made available to the trainees to watch before attending the workshops. The workshops consisted of group activities and individual practical exercises allowing trainees to review and report on patient practice cases with the support of their peers and tutors. Focus group sessions were held after each course, allowing trainee pathologists to reflect on their experiences. Discussions were transcribed and thematic analysis was used to capture key themes discussed by the trainees. Trainees' identified that 'flipping' provided them with more time during face-to-face sessions, enabling a greater depth of questioning and engagement with the consultant histopathologists. Having already watched the lectures, trainees were able to attend the sessions having identified areas in which they needed additional support and development. Trainee pathologists reported they had more time to concentrate on developing their skills and practise under the guidance of the consultant histopathologists so developing their capability in gynaecological cytopathology. The role of alternative methods of delivery such as 'flipping' is suggested for short courses designed to support practitioner capability and continued professional development.

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New Approaches to Continuing Medical Education: a QStream (spaced education) Program for Research Translation in Ovarian Cancer

Abstract

Continuing medical education (CME) is challenging and often has limited impact on clinician behavior or patient outcomes. This study examined the impact of an online Qstream education program on senior clinicians to determine its utility for increasing clinician knowledge about the latest guidelines regarding genetic assessment and consideration of genetic testing for women with particular types of ovarian, fallopian tube and primary peritoneal cancer. Participants were recruited into a pilot study that involved responding to case-based scenarios at spaced and repeated intervals. At the completion of the program, semi-structured interviews were conducted to ascertain the impact on their knowledge and referral behavior. Findings from interviews were subject to thematic analysis that involved the identification of categories and themes. Twenty-one participants commenced the program, seventeen completed and twelve participated in semi-structured interviews. Thematic analysis yielded several themes including knowledge change, curriculum and format and changes in referral patterns. A majority of participants (n = 10) agreed the program had helped update their knowledge about referring women, and eight agreed they would now change their referral patterns. The use of QStream as an approach to CME has significant advantages when working with busy clinicians. QStream has a well accepted format and most participants indicated it is very appropriate for disseminating updates to clinical guidelines and protocols. It is important to supplement CME programs with other implementation techniques, such as audit and feedback as multifaceted approaches are more likely to result in behavior change.

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Determinants of Skin Cancer Preventive Behaviors Among Rural Farmers in Iran: an Application of Protection Motivation Theory

Abstract

Skin cancer is one of the most prevalent cancers, worldwide, which happens more among those with more sunlight exposure like farmers. The aim of this study was to explore the determinants of skin cancer preventive behaviors (SCPBs) among rural farmers using Protection Motivation Theory (PMT). In this cross-sectional study, multistage random sampling was employed to enroll 238 farmers referring to rural health houses (HH) in Chaldoran County, Iran. A valid and reliable instrument based on PMT variables was used. Significant correlations were found between all PMT variables with SCPBs (p < 0.05). Hierarchical multiple linear regressions were performed with Protection Motivation and SCPBs as outcome variables. Predictors for these two outcome variables were classified in two different blocks according to their natures. Demographic characteristics (p > 0.05) and PMT constructs (p < 0.001) explained 3 and 63.6 % of the observed variance in Protection Motivation, respectively. Also, no significant effect was found on SCPBs by demographic variables, in the first block (∆R ² = 0.025); however, in the second block, Perceived Susceptibility (p = 0.000), Rewards (p = 0.022), Self-efficacy (p = 0.000), and Response Cost (p = 0.001) were significant predictors of SCPBs (∆R ² = 0.432). Health care providers may consider PMT as a framework for developing educational interventions aiming at improving SCPBs among rural farmers.

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Medical Knowledge Assessment by Hematology and Medical Oncology In-Training Examinations Are Better Than Program Director Assessments at Predicting Subspecialty Certification Examination Performance

Abstract

The Accreditation Council for Graduate Medical Education's Next Accreditation System requires training programs to demonstrate that fellows are achieving competence in medical knowledge (MK), as part of a global assessment of clinical competency. Passing American Board of Internal Medicine (ABIM) certification examinations is recognized as a metric of MK competency. This study examines several in-training MK assessment approaches and their ability to predict performance on the ABIM Hematology or Medical Oncology Certification Examinations. Results of a Hematology In-Service Examination (ISE) and an Oncology In-Training Examination (ITE), program director (PD) ratings, demographic variables, United States Medical Licensing Examination (USMLE), and ABIM Internal Medicine (IM) Certification Examination were compared. Stepwise multiple regression and logistic regression analyses evaluated these assessment approaches as predictors of performance on the Hematology or Medical Oncology Certification Examinations. Hematology ISE scores were the strongest predictor of Hematology Certification Examination scores (β = 0.41) (passing odds ratio [OR], 1.012; 95 % confidence interval [CI], 1.008–1.015), and the Oncology ITE scores were the strongest predictor of Medical Oncology Certification Examination scores (β = 0.45) (passing OR, 1.013; 95 % CI, 1.011–1.016). PD rating of MK was the weakest predictor of Medical Oncology Certification Examination scores (β = 0.07) and was not significantly predictive of Hematology Certification Examination scores. Hematology and Oncology ITEs are better predictors of certification examination performance than PD ratings of MK, reinforcing the effectiveness of ITEs for competency-based assessment of MK.

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Flipping The Practice Based Pathology Laboratory—Can It Support Development Of Practitioner Capability For Trainee Pathologists in Gynaecological Cytopathology?

Abstract

This study investigated the role of 'flipping', the practice-based pathology laboratory and classroom to support the development of trainee pathologist practitioners' in the field of gynaecological cytopathology, addressing development of their knowledge and practical application in the clinical setting. Content-rich courses traditionally involve lecture led delivery which restricts tutors from adopting approaches that support greater student engagement in the topic area and application of knowledge to practice. We investigated the role of 'flipping', the practice-based pathology laboratory and classroom where 'virtual lectures' were accessed outside of 'class time' allowing more time for students to engage in active learning under the supervision of a consultant histopathologist. 'Flipping' was used to support two gynaecological cytopathology training courses with cohorts of eight trainee pathologists on the first course and six on the second. Lectures were made available to the trainees to watch before attending the workshops. The workshops consisted of group activities and individual practical exercises allowing trainees to review and report on patient practice cases with the support of their peers and tutors. Focus group sessions were held after each course, allowing trainee pathologists to reflect on their experiences. Discussions were transcribed and thematic analysis was used to capture key themes discussed by the trainees. Trainees' identified that 'flipping' provided them with more time during face-to-face sessions, enabling a greater depth of questioning and engagement with the consultant histopathologists. Having already watched the lectures, trainees were able to attend the sessions having identified areas in which they needed additional support and development. Trainee pathologists reported they had more time to concentrate on developing their skills and practise under the guidance of the consultant histopathologists so developing their capability in gynaecological cytopathology. The role of alternative methods of delivery such as 'flipping' is suggested for short courses designed to support practitioner capability and continued professional development.

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New Approaches to Continuing Medical Education: a QStream (spaced education) Program for Research Translation in Ovarian Cancer

Abstract

Continuing medical education (CME) is challenging and often has limited impact on clinician behavior or patient outcomes. This study examined the impact of an online Qstream education program on senior clinicians to determine its utility for increasing clinician knowledge about the latest guidelines regarding genetic assessment and consideration of genetic testing for women with particular types of ovarian, fallopian tube and primary peritoneal cancer. Participants were recruited into a pilot study that involved responding to case-based scenarios at spaced and repeated intervals. At the completion of the program, semi-structured interviews were conducted to ascertain the impact on their knowledge and referral behavior. Findings from interviews were subject to thematic analysis that involved the identification of categories and themes. Twenty-one participants commenced the program, seventeen completed and twelve participated in semi-structured interviews. Thematic analysis yielded several themes including knowledge change, curriculum and format and changes in referral patterns. A majority of participants (n = 10) agreed the program had helped update their knowledge about referring women, and eight agreed they would now change their referral patterns. The use of QStream as an approach to CME has significant advantages when working with busy clinicians. QStream has a well accepted format and most participants indicated it is very appropriate for disseminating updates to clinical guidelines and protocols. It is important to supplement CME programs with other implementation techniques, such as audit and feedback as multifaceted approaches are more likely to result in behavior change.

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Determinants of Skin Cancer Preventive Behaviors Among Rural Farmers in Iran: an Application of Protection Motivation Theory

Abstract

Skin cancer is one of the most prevalent cancers, worldwide, which happens more among those with more sunlight exposure like farmers. The aim of this study was to explore the determinants of skin cancer preventive behaviors (SCPBs) among rural farmers using Protection Motivation Theory (PMT). In this cross-sectional study, multistage random sampling was employed to enroll 238 farmers referring to rural health houses (HH) in Chaldoran County, Iran. A valid and reliable instrument based on PMT variables was used. Significant correlations were found between all PMT variables with SCPBs (p < 0.05). Hierarchical multiple linear regressions were performed with Protection Motivation and SCPBs as outcome variables. Predictors for these two outcome variables were classified in two different blocks according to their natures. Demographic characteristics (p > 0.05) and PMT constructs (p < 0.001) explained 3 and 63.6 % of the observed variance in Protection Motivation, respectively. Also, no significant effect was found on SCPBs by demographic variables, in the first block (∆R ² = 0.025); however, in the second block, Perceived Susceptibility (p = 0.000), Rewards (p = 0.022), Self-efficacy (p = 0.000), and Response Cost (p = 0.001) were significant predictors of SCPBs (∆R ² = 0.432). Health care providers may consider PMT as a framework for developing educational interventions aiming at improving SCPBs among rural farmers.

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Stretch-reflex threshold modulation during active elbow movements in post-stroke survivors with spasticity

Spasticity is a common complication of stroke, occurring in ∼20-50% of patients in the first year (Wissel et al., 2013) and often associated with other sensory and motor impairments (e.g., muscle weakness, loss of dexterity). Spasticity is generally assessed by resistance or EMG responses to passive muscle stretches and has been attributed to exaggerated spinal stretch reflexes (SRs) and alterations in intrinsic muscle properties (Dietz and Sinkjaer, 2007). For example, motor units of spastic muscles often have an impaired ability to relax (Lewek et al., 2007), prolonged spontaneous firing (Mottram et al., 2010) and low firing rates (Young and Mayer, 1982; Gemperline et al., 1995).

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Cortical involvement in myopathies: insights from transcranial magnetic stimulation

There is increasing evidence that a significant brain dysfunction occurs in patients affected by several myopathies. For instance, some patients with muscle diseases, such as dystrophinopathies, exhibit intellectual disabilities and mental retardation (Emery, 1987; North et al., 1996; Mehler, 2000), while in subjects with facioscapulohumeral muscular dystrophy (FSHD) epilepsy is one of the most frequent manifestations of cerebral involvement (Saito et al., 2007; Grosso et al., 2011).

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Subepithelial esophageal tumors: a single-center review of resected and surveilled lesions

Subepithelial esophageal tumors (SETs) are frequent incidental findings. Although symptomatic tumors are surgically or endoscopically resected, there is no consensus on the management of asymptomatic esophageal leiomyomas.

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Clinical practice guideline for enhanced recovery after colon and rectal surgery from the American Society of Colon and Rectal Surgeons (ASCRS) and Society of American Gastrointestinal and Endoscopic Surgeons (SAGES)

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Lytic eosinophils produce extracellular DNA traps as well as free eosinophil granules

Publication date: Available online 3 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Carl Persson, Shigeharu Ueki




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Reply

Publication date: Available online 3 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Anne M. Fitzpatrick, Daniel J. Jackson, David Mauger, Stanley J. Szefler




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Reply

Publication date: Available online 3 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Elien Gevaert, Shida Yousefi, Claus Bachert, Hans-Uwe Simon




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Nonatopic persistent asthma in children, a missed phenotype of asthma?

Publication date: Available online 3 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Giorgio Longo, Ester Conversano, Elisa Panontin, Giovanna Ventura, Alessandro Ventura




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Diagnosis and management of anaphylaxis in precision medicine

Publication date: August 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 2
Author(s): Mariana Castells
Anaphylaxis is the most severe and frightening of the allergic reactions, placing patients at high risk and demanding prompt recognition and immediate management by health care providers. Yet because its symptoms imitate those of other diseases, such as asthma and urticaria, current data suggest that its diagnosis is often missed, with underuse of tryptase measurement; its treatment is delayed, with little use of epinephrine; and its underlying cause or causes are poorly investigated. Deaths from anaphylaxis are difficult to investigate because of miscoding. Surprisingly, patients treated with new and powerful chemotherapy agents and humanized mAbs present with nonclassical symptoms of anaphylaxis, and patients may present with unrecognized clonal mast cell disorders with KIT mutations may present as Hymenoptera-induced or idiopathic anaphylaxis. The goal of this review is to recognize the presentations of anaphylaxis with the description of its current phenotypes, to provide new insight and understanding of its mechanisms and causes through its endotypes, and to address its biomarkers for broad clinical use. Ultimately, the aim is to empower allergists and heath care providers with new tools that can help alleviate patients' symptoms, preventing and protecting them against anaphylaxis.



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TCRαβ+ and CD19+ cell depleted Haploidentical and Mismatched Hematopoietic Stem Cell Transplantation in Primary Immune Deficiency

Publication date: Available online 3 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Ravi M. Shah, Reem Elfeky, Zohreh Nademi, Waseem Qasim, Persis Amrolia, Robert Chiesa, Kanchan Rao, Giovanna Lucchini, Juliana M.F. Silva, Austen Worth, Dawn Barge, David Ryan, Jane Conn, Andrew J. Cant, Roderick Skinner, Intan Juliana Abd Hamid, Terence Flood, Mario Abinun, Sophie Hambleton, Andrew R. Gennery, Paul Veys, Mary Slatter
BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is used as a therapeutic approach for primary immunodeficiencies (PIDs). The best outcomes have been achieved using HLA-matched donors, but when a matched donor is not available, a haploidentical or mismatched unrelated donor (mMUD) can be useful. Various strategies are used to mitigate the risk of graft versus host disease (GvHD) and rejection associated with such transplants.ObjectiveWe sought to evaluate the outcomes of haploidentical or mMUD HSCT after depleting GvHD causing TCRαβCD3+ cells from the graft.MethodsCD3+TCRαβ+/CD19⁺ depleted grafts were given in conditioned (except three) children with PIDs. Treosulfan (busulfan in one), fludarabine, thiotepa and ATG or alemtuzumab conditioning was used in 77% cases, and all but four received GvHD prophylaxis.Results25 patients with 12 types of PIDs received 26 HSCTs. Three were transplanted for refractory GvHD developing after first cord transplantation. At 20.8 months (5 month- 3.3 years) median follow up, 21/25 patients survived and were cured of underlying immunodeficiency. Overall and Event Free Survival at 3 years was 83.9% and 80.4% respectively. Cumulative incidence (CI) of Grade II-IV acute GvHD was 22±8.7%. No case of visceral or chronic GvHD was seen. CI of graft failure, CMV or/and adeno viral infections and transplant related mortality at 1 year were 4.2±4.1%, 58.8±9.8% and 16.1±7.4% respectively. Patients going into transplant with systemic viral infections had poor survival in comparison to those with absent or resolved infection (33.3% vs.100%).ConclusionCD3+TCRαβ⁺ and CD19⁺ depleted haploidentical or mMUD HSCT is a practical and viable alternative for children with a range of PIDs.

Teaser

CD3+TCRαβ⁺ and CD19+ cell depleted haploidentical or mMUD HSCT has reproducible outcomes in children with a range of PIDs resulting in good immune reconstitution. Viral infections before or after HSCT are major contributors to mortality and morbidity.


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Diagnosis and management of anaphylaxis in precision medicine

Publication date: August 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 2





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The pathophysiology of anaphylaxis

Publication date: August 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 2
Author(s): Laurent L. Reber, Joseph D. Hernandez, Stephen J. Galli
Anaphylaxis is a severe systemic hypersensitivity reaction that is rapid in onset; characterized by life-threatening airway, breathing, and/or circulatory problems; and usually associated with skin and mucosal changes. Because it can be triggered in some persons by minute amounts of antigen (eg, certain foods or single insect stings), anaphylaxis can be considered the most aberrant example of an imbalance between the cost and benefit of an immune response. This review will describe current understanding of the immunopathogenesis and pathophysiology of anaphylaxis, focusing on the roles of IgE and IgG antibodies, immune effector cells, and mediators thought to contribute to examples of the disorder. Evidence from studies of anaphylaxis in human subjects will be discussed, as well as insights gained from analyses of animal models, including mice genetically deficient in the antibodies, antibody receptors, effector cells, or mediators implicated in anaphylaxis and mice that have been "humanized" for some of these elements. We also review possible host factors that might influence the occurrence or severity of anaphylaxis. Finally, we will speculate about anaphylaxis from an evolutionary perspective and argue that, in the context of severe envenomation by arthropods or reptiles, anaphylaxis might even provide a survival advantage.



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Mast cell activation syndromes

Publication date: August 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 2
Author(s): Cem Akin
Mast cell activation is common and possibly necessary for maintenance of survival. Disordered mast cell activation occurs when mast cells are pathologically overproduced or if their activation is out of proportion to the perceived threat to homeostasis. Mast cell activation syndrome refers to a group of disorders with diverse causes presenting with episodic multisystem symptoms as the result of mast cell mediator release. Despite introduction of diagnostic criteria and some advances in treatment in the last decade, many areas of mast cell activation syndrome are in need of research. This article reviews our current knowledge about the various types of mast cell activation disorders, their treatment, and areas of uncertainty in need of future investigation.



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The Editors' Choice

Publication date: August 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 2
Author(s): Cezmi A. Akdis, Zuhair K. Ballas




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News Beyond Our Pages

Publication date: August 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 2
Author(s): Marc E. Rothenberg, Jean Bousquet




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Mandibular osteomyelitis following implant placement

Publication date: Available online 3 August 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Matthias Schlund, Gwenael Raoul, Joel Ferri, Romain Nicot
Mandibular osteomyelitis is relatively rare except in cases of osteoradionecrosis or medication-related osteonecrosis. The most frequent etiologies are odontogenic and traumatic, however, hematogenous spread also exists. It usually affects patients suffering from systemic diseases such as diabetes mellitus, malnutrition, malignancy or immune deficiency. The infection is nearly always polymicrobial.Related to dental implant complications, the literature is comprehensive related to mechanical etiologies of implant failure as well as on the infectious side, on the subject of peri-implantitis. Mandibular osteomyelitis treatment is a long and challenging process requiring long-term antibiotic therapy and multiple surgeries.The purpose of this case report is to highlight a rare but devastating complication of dental implant surgery. The pathophysiology and the treatment of mandibular osteomyelitis are discussed. The case of a patient who developed mandibular osteomyelitis following implant placement, which was resistant to long-term antibiotic therapy requiring radical surgical treatment with fibular free flap reconstruction, is reviewed as well as the related literature.



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Is it truly wise to remove the ‘Safe Surgery Checklist Use’ reporting requirements?

Publication date: Available online 3 August 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Yisi D. Ji, Jeffrey T. Hajibandeh




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Proper Choice of Donor Site Veins for Patients Undergoing Free Radial Forearm Flap Reconstruction for the Defects of Head and Neck

Publication date: Available online 3 August 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Zhai Qin-kai, Dai Wei, Tan Xue-xin, Sun Jian, Zhang Chen-ping, Qin Xing-jun
BackgroundThe purpose of this study was to analyze the reliability of the deep venous drainage system of the free radial forearm flap.MethodsThe authors implemented a retrospective cohort study and enrolled patients admitted for the evaluation and management of head and neck tumors with radial forearm flap reconstruction. The primary predictor variables were defined as the donor site veins including the deep, dual, and superficial venous drainage systems. The primary outcome measure was defined as the incidence of venous compromise. Potential confounders included patient demographics, history of chemotherapy and/or radiotherapy, defect sites, and the recipient artery and vein. The chi-square test and logistic regression analysis were used for statistical analysis.ResultsThe final study population comprised 520 subjects (mean age, 54 years), who underwent free radial forearm flap for head and neck soft tissue reconstruction. Patients with the deep system (odds ratio [OR]: 0.251, 95% confidence interval [CI]: 0.108–0.581) or dual system (OR: 0.197, 95% CI: 0.064–0.605) had a significantly lower risk of venous compromise than those with the superficial system. The overall incidence of inadequate outflow was 2.5% (5/204) when the deep system was used alone, and 8.9% (19/212) when the superficial system was used alone (P = 0.004).ConclusionsPatients with the deep venous drainage system had a significantly lower risk of venous compromise. This study recommends using the deep system as a drainage vein for the free radial forearm flap.



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The Use of Platelet Rich Fibrin for Immediate Closure of Acute Oroantral Communications: An Alternative Approach

Publication date: Available online 3 August 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Kani Bilginaylar
Currently, buccal advancement flap, palatal rotational flap or buccal fat pad techniques are frequently used to close an oroantral communication (OAC). In this study,platelet rich fibrin (PRF) clots were used for immediate closure of acute oroantral communications after the extraction of posterior maxillary molars. Acute oroantral perforations of more than 3 mm in diameter in 21 patients were treated uneventfully by using PRF clots. None of the patients had systemic diseases nor symptoms of sinus disease. After tooth extraction, the diagnosis of acute oroantral communication was examined by Valsalva's maneuver test (compression of nostrils with the fingers and blowing out the air). After the detection of an air leak, modification of a ball burnisher instrument of 3 mm diameter was used to determine whether the size of perforation was greater than 3 mm. The post-extraction socket of the tooth was cleaned with a sterile physiologic saline solution, and the cavity was filled with PRF. PRF clots were sutured to the gingiva to prevent them from migrating to the sinus and for stabilization. On the 7th day of follow-up, healthy granulation tissue was observed, and on the third week of follow-up, epithelialized oral mucosa was detected at the extraction site across all cases. This technique (PRF) enables the closure of OACs without a primary flap closure or any other surgical interventions. Thus, the use of PRF for immediate closure of acute OACs will make the treatment of OACs less traumatic and easier and will eliminate the need for special surgical expertise.



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Evaluation of mandibular bone after dental extraction in rats treated with antiresorptive drugs

Publication date: Available online 3 August 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Victor Lousan Do Nascimento Poubel, Diogo Lenzi Capella, Adair Roberto Soares Santos, Márcio Correa, Letícia Ruhland Correa, Elena Riet Correa Rivero
PurposeZoledronic acid (ZOL) and denosumab (Dmab) are commonly used to treat bone pathologies. Given that both drugs suppress bone metabolism, this study sought to compare their effect on bone repair after tooth extraction.Materials and MethodsFour-week-old male Wistar rats were randomly assigned to three groups receiving either 0.125 mg/kg ZOL or 0.25 mg/kg Dmab (treatment groups), or 10 ml/kg saline solution (control group). After 1 week of treatment, the first left molar was extracted; the rats were euthanized at 28 days. The jaws were removed and photographed for macroscopic analysis of wound healing, and then, were subjected to tomographic analysis and histological analysis. Immunohistochemistry was carried out against receptor activator of nuclear Kappa-B ligand (RANKL) and osteoprotegerin (OPG).ResultsNo difference was found between the groups in terms of wound healing, presence of inflammatory infiltrate and bone sequestration, or osteocyte expression of RANKL and OPG. On tomography analysis, the ZOL group showed less alveolar resorption and more complete alveolar repair compared with the other groups. There was a statistically significant difference in OPG marker in the control (P=0.008) and ZOL group (P=0.05) when comparing the extracted and non-extracted sides.ConclusionThe systemic use of ZOL can improve alveolar bone healing; however, the potential risk for the development of osteonecrosis should be considered. Higher expression of OPG seems to be associated with osteoclastogenesis control during bone repair.



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Effect of resveratrol on critical-sized calvarial defects of diabetic rats: Histometric and gene expression analysis

Publication date: Available online 3 August 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Danilo Siqueira Pino, Renato Correa Casarin, Suzana Peres Pimentel, Fabiano Ribeiro Cirano, Mônica Grazieli Corrêa, Fernanda Vieira Ribeiro
PurposeThis study aimed to determine the influence of resveratrol (RESV) on the repair of bone critical defects in calvaria of animals with induced diabetes mellitus (DM).Material and methodsOne hundred rats were divided into five groups: induced DM + RESV administration (DM+RESV; n = 20); induced DM + placebo solution administration (DM+PLAC; n = 20); induced DM + insulin therapy (DM+INS; n = 20); induced DM + administration of resveratrol and insulin (DM+RESV+INS; n = 20); and non-diabetic controls (NDM; n = 20). Diabetes was induced by intraperitoneal injection of 50 mg/kg streptozotocin, three days before surgical procedures. Two critical calvarial defects were created in each animal at the start of the study (day zero). Treatments were administered from day zero to day 30 of the experiment, when animals were euthanized. One of the defects was processed for histometric analysis to measure the closure of the bone defect. The tissue of the other defect was analyzed for quantification of BMP-2, OPN, OPG, RANKL, Runx2, Osx, β-catenin, Lrp-5, and Dkk-1 mRNA by quantitative PCR.ResultsHistometric results showed that the DM+RESV, DM+RESV+INS, and NDM groups exhibited greater closure of the bone defects as compared to the placebo- or insulin-treated groups (p < 0.05). Diabetic animals treated with RESV+INS showed higher levels of BMP-2 and Osx; Osx was also positively increased in animals treated with INS alone (p < 0.05).ConclusionsThe use of RESV, regardless of the presence of INS, positively influenced bone repair in DM-induced animals. Further, the combination of insulin with RESV is necessary for the modulation of BMP-2 gene expression.



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Clinicopathologic and surgical study of pleomorphic adenoma of the parotid gland: Analysis of risk factors for recurrence and facial nerve dysfunction

Publication date: Available online 3 August 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Carlos A. Espinosa, Álvaro Fernández-Valle, Paloma Lequerica-Fernández, Lucas de Villalaín, Juan Carlos de Vicente
ObjectiveTo determine whether clinicopathologic or surgical features are risk factors for recurrence and facial nerve dysfunction in pleomorphic adenoma (PA) of the parotid gland.Patients and methodsThe records of 198 patients surgically treated for a PA of the parotid gland between 1999 and 2013 were retrospectively reviewed to identify patients who developed a tumor recurrence. Fisher's exact test and Mann-Whitney U test were used to analyze patient characteristics between recurrent and non-recurrent PAs. Logistic regression was used to determine the risks of recurrence and facial nerve dysfunction.Results23 (11.6%) patients developed a recurrence. Patients with tumor recurrence were significantly younger than patients that remained recurrence free. Of the 14 patients who underwent enucleation, 11 cases (78.6%) experienced residual disease, as did 10 of 165 (6%) of patients managed by a superficial parotidectomy (p < 0.0005). Furthermore, the risk of residual disease was 9.3 to 21.6 times higher in patients who underwent enucleation than in those who underwent a total or superficial parotidectomy. Regarding tumor histology, recurrence was observed in 3 (15.8%) of the 19 cellular types, in 18 (11.5%) of the 157 classic cases, and in 1 (4.8%) of the 21 myxoid cases (p = 0.5). The risk of recurrence if the resection margins were positive was 49 times higher than when they were not affected (p = 0.001).ConclusionYoung age, enucleation, and positive margins are risk factors for residual pleomorphic adenoma, and surgical technique and histomorphologic features are associated with increased facial nerve dysfunction.



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Sponsoring Organizations and Liaisons

Publication date: August 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 2





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Table of Contents

Publication date: August 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 2





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The Essentials

Publication date: August 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 2





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Editorial Board

Publication date: August 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 2





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News and Notes

Publication date: August 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 2





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Piezosurgery in Modified Pterional Orbital Decompression Surgery in Graves Disease

Publication date: October 2017
Source:World Neurosurgery, Volume 106
Author(s): Juergen Grauvogel, Christian Scheiwe, Waseem Masalha, Nadja Jarc, Tanja Grauvogel, Andreas Beringer
ObjectivePiezosurgery uses microvibrations to selectively cut bone, preserving the adjacent soft tissue. The present study evaluated the use of piezosurgery for bone removal in orbital decompression surgery in Graves disease via a modified pterional approach.MethodsA piezosurgical device (Piezosurgery medical) was used in 14 patients (20 orbits) with Graves disease who underwent orbital decompression surgery in additional to drills and rongeurs for bone removal of the lateral orbital wall and orbital roof. The practicability, benefits, and drawbacks of this technique in orbital decompression surgery were recorded. Piezosurgery was evaluated with respect to safety, preciseness of bone cutting, and preservation of the adjacent dura and periorbita. Preoperative and postoperative clinical outcome data were assessed.ResultsThe orbital decompression surgery was successful in all 20 orbits, with good clinical outcomes and no postoperative complications. Piezosurgery proved to be a safe tool, allowing selective bone cutting with no damage to the surrounding soft tissue structures. However, there were disadvantages concerning the intraoperative handling in the narrow space and the efficiency of bone removal was limited in the orbital decompression surgery compared with drills.ConclusionsPiezosurgery proved to be a useful tool in bone removal for orbital decompression in Graves disease. It is safe and easy to perform, without any danger of damage to adjacent tissue because of its selective bone-cutting properties. Nonetheless, further development of the device is necessary to overcome the disadvantages in intraoperative handling and the reduced bone removal rate.



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