Cancer-testis gene PIWIL1 promotes cell proliferation, migration, and invasion in lung adenocarcinoma

Abstract

Piwi-like RNA-mediated gene silencing 1 (PIWIL1) has been identified as a novel extremely highly expressed cancer-testis (CT) gene in lung adenocarcinoma. However, the exact function and mechanism of PIWIL1 in lung adenocarcinoma remains unclear. Herein, we sought to investigate the role of PIWIL1 in the occurrence and development of lung adenocarcinoma. We examined the expression pattern of PIWIL1 in The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples, and validated it by Real-Time PCR (RT-PCR) in additional 21 paired lung adenocarcinoma tissues and 16 normal tissues. Subsequently, we explored the biological function of PIWIL1 in A549 and H1299 cell lines by gain and loss-of-function analyses. Using TCGA lung adenocarcinoma data, we further performed coexpression and Gene Ontology (GO) analyses, and analyzed the association of DNA methylation levels in PIWIL1 promoter region with its expression. Finally, we evaluated its expression in different mutation status of significantly mutated genes (SMGs) in TCGA lung adenocarcinoma data. We observed that PIWIL1 was expressed in testis and lung adenocarcinoma but not in other normal tissues, and its high expression was associated with shortened survival of lung cancer patients. Overexpression of PIWIL1 could facilitate the proliferation, invasion and migration of lung adenocarcinoma cells and vice versa. GO analysis revealed that PIWIL1 upregulated genes were enriched in embryonic development, cell proliferation and regulation of transcription. Moreover, promoter DNA hypomethylation of PIWIL1 could contribute to its aberrant expression in tumors. Interestingly, PIWIL1 expression was significantly higher in patients without hepatocyte growth factor (HGF) or serine/threonine kinase 11 (STK11) mutation (P = 0.006 and 0.005, respectively). PIWIL1 is an epidriver gene in lung adenocarcinoma, indicating a potential target for further therapy.

PIWIL1 is a novel extremely highly expressed cancer-testis gene in lung adenocarcinoma. PIWIL1 could promote the ability of proliferation, invasion, and migration in lung adenocarcinoma. The expression status of PIWIL1 is regulated by methylation in promoter region.

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Prognostic value of PD-L1 expression in combination with CD8+ TILs density in patients with surgically resected non-small cell lung cancer

Abstract

To investigate the prognostic value of PD-L1 expression combined with CD8⁺ TILs density in patients with resected NSCLC and correlations with clinicopathological features. We retrospectively enrolled 178 patients with resected NSCLC from 2011 to 2015. All surgical primary and 58 matched metastatic lymph node specimens were tested for PD-L1, CD8⁺ TILs, and oncogenic alterations. PD-L1⁺ was detected in 71 (39.9%) and CD8^high TILs in 74 (41.6%) cases. Smoking, SqCC, and EGFR⁻ were associated with both PD-L1⁺ and CD8^high TILs. Patients with CD8^high TILs had longer OS (P = 0.012). PD-L1⁻ was significantly associated with longer OS in patients with oncogenic alterations (P = 0.047). By multivariate analysis, CD8^high TILs (HR = 0.411; 95% CI, 0.177–0.954; P = 0.038), rather than PD-L1, was the independent predictive factor for OS. The longest and shortest OS were achieved in patients with PD-L1⁺/CD8^high and PD-L1⁺/CD8^low, respectively (P = 0.025). Inconsistent PD-L1 expression levels were observed in 23 of 58 (39.7%) patients with primary and matched metastatic lymph node specimens. Of them, CD8^high TILs was significantly associated with longer OS in patients with metastatic lymph nodes and/or consistent PD-L1 expression (P = 0.017 and 0.049, respectively). The combination of PD-L1 and CD8⁺ TILs density, instead of PD-L1 alone, suggested impressive prognostic values in NSCLC patients. Less than half of patients with resected NSCLC experienced inconsistent PD-L1 expression between primary and metastatic lesions. The level of PD-L1 expression in advanced NSCLC needs to be evaluated more comprehensively.

Combination of PD-L1 and CD8⁺ TILs density may suggest impressive prognostic value in NSCLC patients instead of PD-L1 alone. Less than half of patients with resected NSCLC experienced inconsistent PD-L1 expression between primary and metastatic lesions, and significance of PD-L1 expression in a single-biopsy specimen in advanced NSCLC may be overestimated in clinical practice.

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Patient satisfaction with information on oral anticancer agent use

Abstract

Adequate information on oral anticancer agent (OACA) use is an essential element of optimal cancer care. The present study aimed to get insight into the experiences of patients with information on OACA treatment and their characteristics regarding information dissatisfaction. Patients of four Dutch university hospitals using OACA participated in this observational study and completed the Satisfaction with Information about Medicines Scale (SIMS), EORTC Quality of Life Questionnaire-C30, Brief Illness Perception Questionnaire, and Beliefs about Medicines Questionnaire-Specific. Logistic regression analyses were used to determine factors associated with dissatisfaction with information. Patients (n = 208) using capecitabine (35%), lenalidomide (15%), imatinib (14%), temozolomide (12%), sunitinib (11%), thalidomide (5%), dasatinib (4%), erlotinib (2%), and nilotinib (2%) participated. Information on the following SIMS-items was inadequate: how OACA elicit their effect, how long it takes before treatment works, how to conclude that treatment is effective, the risk of side effects and its management, interference with sex life, drowsiness, interference with other medication and alcohol and what to do in case of a missed dose. Younger age, hematological malignancy, dyspnoea, positive perception of consequences of the cancer, low perception of treatment control, and indifferent attitude towards OACA were associated with dissatisfaction with information. In conclusion, a considerable number of patients would have appreciated receiving more information on specific issues relating to the consequences of OACA treatment such as the effects and side effects of OACA and the interference of treatment with various aspects of their daily life. Oncologists, hematologists, lung-oncologists and pharmacists may reconsider the provision of information on OACA treatment.

This observational study showed that a substantial number of cancer patients perceived a lack of information on oral anticancer agent (OACA) treatment. Particularly information on the following subjects should be improved: self-monitoring of treatment effectiveness, side effects and their management, interference of treatment with sex life, interference of treatment with other medicines and alcohol use, and what to do in case of missed doses. Healthcare providers may reconsider the provision of information on OACA treatment.

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Effectiveness of Gastrostomy for Improving Nutritional Status and Quality of Life in Patients with Epidermolysis Bullosa: A Systematic Review

Abstract

Inherited epidermolysis bullosa (EB) is a group of rare genetic disorders clinically characterized by a wide range of skin and mucosal blistering after minor trauma¹. This condition is caused by mutations on genes coding for structural proteins of the skin and affects both genders from all ethnic groups, and its estimated prevalence is about 500,000 cases worldwide².

This article is protected by copyright. All rights reserved.

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Acknowledgements to Reviewers

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Author Guidelines

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The COL5A3 and MMP9 genes interact in eczema susceptibility

Abstract

Background

Genetic studies of eczema have identified many genes, which explain only 14% of the heritability. Missing heritability may be partly due to ignored Gene–Gene (G-G) interactions.

Objective

Our aim was to detect new interacting genes involved in eczema.

Methods

The search for G-G interaction in eczema was conducted using a two-step approach, which included as a first step, a biological selection of genes, which are involved either in the skin or epidermis development or in the collagen metabolism, and as a second-step, an interaction analysis of the selected genes. Analyses were carried out at both SNP and gene levels in three asthma-ascertained family samples: the discovery dataset of 388 EGEA (Epidemiological study on the Genetics and Environment of Asthma) families and the two replication datasets of 253 SLSJ (Saguenay-Lac-Saint-Jean) families and 207 MRCA (Medical Research Council) families.

Results

One pair of SNPs, rs2287807 in COL5A3 and rs17576 in MMP9, that were detected in EGEA at P ≤ 10^-5 showed significant interaction by meta-analysis of EGEA, SLSJ and MRCA samples (P=1.1x10^-8 under the significant threshold of 10^-7). Gene-based analysis confirmed strong interaction between COL5A3 and MMP9 (P=4x10^-8 under the significant threshold of 4x10^-6) by meta-analysis of the three datasets. When stratifying the data on asthma, this interaction remained in both groups of asthmatic and non-asthmatic subjects.

Conclusion

This study identified significant interaction between two new genes, COL5A3 and MMP9, which may be accounted for by a degradation of COL5A3 by MMP9 influencing eczema susceptibility.

Further confirmation of this interaction as well as functional studies are needed to better understand the role of these genes in eczema.

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Nasal Cytology: a Precision Medicine tool in clinical practice

Abstract

The BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis represents a precise and accurate document in defining the different sub-groups of patients suffering from allergic rhinitis (AR) and non-allergic rhinitis (NAR). We would like to stimulate the debate about this matter, mainly concerning the definition and classification of NAR. In particular, we would convince the readers that there are different phenotypes/endotypes of NAR in addition to non-allergic rhinitis with eosinophils (NARES). This concept is clinically relevant as deserves an adequate work-up and constitutes the background for the Precision Medicine (PM) approach.

This article is protected by copyright. All rights reserved.

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Genomic risk prediction of aromatase inhibitor-related arthralgia in patients with breast cancer using a novel machine-learning algorithm

Abstract

Many breast cancer (BC) patients treated with aromatase inhibitors (AIs) develop aromatase inhibitor-related arthralgia (AIA). Candidate gene studies to identify AIA risk are limited in scope. We evaluated the potential of a novel analytic algorithm (NAA) to predict AIA using germline single nucleotide polymorphisms (SNP) data obtained before treatment initiation. Systematic chart review of 700 AI-treated patients with stage I-III BC identified asymptomatic patients (n = 39) and those with clinically significant AIA resulting in AI termination or therapy switch (n = 123). Germline DNA was obtained and SNP genotyping performed using the Affymetrix UK BioBank Axiom Array to yield 695,277 SNPs. SNP clusters that most closely defined AIA risk were discovered using an NAA that sequentially combined statistical filtering and a machine-learning algorithm. NCBI PhenGenI and Ensemble databases defined gene attribution of the most discriminating SNPs. Phenotype, pathway, and ontologic analyses assessed functional and mechanistic validity. Demographics were similar in cases and controls. A cluster of 70 SNPs, correlating to 57 genes, was identified. This SNP group predicted AIA occurrence with a maximum accuracy of 75.93%. Strong associations with arthralgia, breast cancer, and estrogen phenotypes were seen in 19/57 genes (33%) and were functionally consistent. Using a NAA, we identified a 70 SNP cluster that predicted AIA risk with fair accuracy. Phenotype, functional, and pathway analysis of attributed genes was consistent with clinical phenotypes. This study is the first to link a specific SNP/gene cluster to AIA risk independent of candidate gene bias.

Aromatase inhibitor-related arthralgias (AIA) are common and may lead to therapy noncompliance. Whereas traditional gene studies to identify arthralgia risk have been limited in scope, we employed a novel analytic algorithm to link a specific SNP/gene cluster to AIA risk independent of candidate gene bias.

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Dose warping uncertainties for the accumulated rectal wall dose in cervical cancer brachytherapy

Publication date: Available online 22 November 2017
Source:Brachytherapy
Author(s): Laura E. van Heerden, Niek van Wieringen, Kees Koedooder, Coen R.N. Rasch, Bradley R. Pieters, Arjan Bel
PurposeStructure-based deformable image registration (DIR) can be used to calculate accumulated dose volume histogram parameters for cervical cancer brachytherapy (BT). The purpose of this study is to investigate dose warping uncertainties for the accumulated dose to the 2 cm³ receiving the highest dose (D2cm3) in the rectal wall, using a physically realistic model (PRM) describing rectal wall deformation.Methods and materialsFor 10 patients, treated with MRI-guided pulsed dose rate BT (two times 24 × 0.75 Gy, given in two applications BT1 and BT2), the planning images were registered with structure-based DIR. The resulting transformation vectors were used to accumulate the total rectum dose from BT. To investigate the dose warping uncertainty, a PRM describing rectal deformation was used. For point pairs on rectumBT1 and rectumBT2 that were at the same location according to the PRM, the dose for BT1 and BT2 was added (DPRM) and compared to the DIR-accumulated dose (DDIR) in the BT2 point. The remaining distance after DIR between corresponding point pairs, defined as the residual distance, was calculated.ResultsFor points within the D2cm3 volume, more than 75% was part of the D2cm3 volume according to both PRM and DIR. The absolute dose difference was <7.3 GyEQD2, and the median (95th percentile) of the residual distance was 8.7 (22) mm.ConclusionsDIR corresponded with the PRM for on average 75% of the D2cm3 volume. Local absolute dose differences and residual distances were large. Care should therefore be taken with DIR for dose-warping purposes in BT.



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Reduction of MRI signal distortion from titanium intracavitary brachytherapy applicator by optimizing pulse sequence parameters

Publication date: Available online 22 November 2017
Source:Brachytherapy
Author(s): Thomas P. Sullivan, Matthew M. Harkenrider, Murat Surucu, Abbie M. Wood, Joseph H. Yacoub, Steven M. Shea
PurposeTo demonstrate that optimized pulse sequence parameters for a T2-weighted (T2w) fast spin echo acquisition reduced artifacts from a titanium brachytherapy applicator compared to conventional sequence parameters.Methods and materialsFollowing Institutional Review Board approval and informed consent, seven patients were successfully imaged with both standard sagittal T2w fast spin echo parameters (voxel size of 0.98 × 0.78 × 4.0 mm³; readout bandwidth of 200 Hz/px; repetition time of 2800 ms; echo time of 91 ms; echo train length of 15; 36 slices; and imaging time of 3:16 min) and an additional optimized T2w sequence (voxel size of 0.98 × 0.98 × 4.0 mm³; readout bandwidth of 500 Hz/px; repetition time of 3610 ms; echo time of 91 ms; echo train length of 25; 18–36 slices; and imaging time of 1:15–2:30 min), which had demonstrated artifact reduction in prior phantom work. Visualized intracavitary tandem was hand-segmented by two of the authors. Three body imaging radiologists assessed image quality and intraobserver agreement scores were analyzed.ResultsThe average segmented volume of the intracavitary applicator significantly (p < 0.05) decreased with the experimental pulse sequence parameters as compared to the standard pulse sequence. Comparison of experimental and standard T2w sequence qualitative scores for each reviewer showed no significant differences between the two techniques.ConclusionsThis study demonstrated that pulse sequence parameter optimization can significantly reduce distortion artifact from titanium applicators while maintaining image quality and reasonable imaging times.



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Wnt/{beta}-catenin pathway activation mediates adaptive resistance to BRAF inhibition in colorectal cancer

One of the most encouraging developments in oncology has been the success of BRAF inhibitors in BRAF-mutant melanoma. However, in contrast to its striking efficacy in BRAF-mutant melanomas, BRAF inhibitor monotherapy is ineffective in BRAF-mutant colorectal cancer (CRC). While many studies on BRAF inhibitor resistance in CRC have focused on mechanisms underlying the reactivation of the EGFR/RAS/RAF/MEK/ERK pathway, the current study focuses on identifying novel adaptive signaling mechanisms, a fresh angle on CRC resistance to BRAF inhibition. We found that treatment with BRAF inhibitors (both current and next generation BRAF inhibitors) upregulated the Wnt/β-catenin pathway in BRAFV600E-mutant CRC cell lines through activating the cytoplasmic tyrosine kinase FAK (focal adhesion kinase). The results showed that FAK activation upon BRAF inhibitor treatment did not require EGFR (Epidermal Growth Factor Receptor) or ERK1/2 (extracellular-signal-regulated kinases1/2) activation, implying that BRAF inhibitor treatment-induced hyperactivation of Wnt signaling is "pathway reactivation"-independent. BRAF inhibition-induced Wnt pathway activation was further validated in preclinical models of BRAFV600E-mutant CRC including cell line xenograft model and a PDX (patient-derived xenograft) model. Combined inhibition of BRAF/Wnt pathways or BRAF/FAK pathways exerted strong synergistic antitumor effects in cell culture model and mouse xenograft model. Overall, the current study has identified activation of the Wnt/β-catenin pathway as a novel fundamental cause of colon cancer resistance to BRAF inhibition. Our results suggest that while complete vertical pathway blockade is pivotal for effective and durable control of BRAF-mutant CRC, co-targeting parallel adaptive signaling-the Wnt/β-catenin pathway-is also essential.

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A Novel YAP1 Inhibitor targets CSCs-enriched Radiation Resistant Cells and Exerts Strong Antitumor Activity in Esophageal Adenocarcinoma

Mounting evidence suggests that the Hippo co-activator Yes-associated protein 1 (YAP1) is a major mediator of cancer stem cell (CSC) properties, tumor progression, and therapy resistance as well as often a terminal node of many oncogenic pathways. Thus, targeting YAP1 may be a novel therapeutic strategy for many types of tumors with high YAP1 expression, including esophageal adenocarcinoma (EAC). However, effective YAP1 inhibitors are currently lacking. Here, we identify a small molecule (CA3) that not only has remarkable inhibitory activity on YAP1/Tead transcriptional activity but also demonstrates strong inhibitory effects on EAC cell growth especially on YAP1 high expressing EAC cells both in vitro and in vivo. Remarkably, radiation resistant cells acquire strong CSC properties and aggressive phenotype, while CA3 can effectively suppresses these phenotypes by inhibiting proliferation, inducing apoptosis, reducing tumor sphere formation, and reducing the fraction of ALDH1+ cells. Further, CA3 combined with 5-FU, synergistically inhibits EAC cell growth especially in YAP1 high EAC cells. Taken together, these findings demonstrated that CA3 represents a new inhibitor of YAP1 and primarily targets YAP1 high and therapy resistant EC cells endowed with CSCs properties.

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Mechanism informed repurposing of minocycline overcomes resistance to topoisomerase inhibition for peritoneal carcinomatosis

Mechanism-inspired drug repurposing that augments standard treatments offers a cost-effective and a rapid route toward addressing the burgeoning problem of plateauing of effective therapeutics for drug-resistant micrometastases. We show that the antibiotic minocycline, by its ability to minimize DNA repair via reduced expression of tyrosyl-DNA phosphodiesterase-1 (Tdp1), removes a key process attenuating the efficacy of irinotecan, a frequently used chemotherapeutic against metastatic disease. Moreover, minocycline and irinotecan cooperatively mitigate each other's undesired cytokine inductions of VEGF and IL-8 respectively, thereby reinforcing the benefits of each modality. These mechanistic interactions result in synergistic enhancement of irinotecan-induced platinum-resistant epithelial ovarian cancer cell death, reduced micrometastases in the omenta and mesentery by >75%, and an extended overall survival by 50% in a late-stage peritoneal carcinomatosis mouse model. Economic incentives and easy translatability make the repurposing of minocycline as a reinforcer of the topoisomerase class of chemotherapeutics extremely valuable and merits further investigations.

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Inhibition of O-GlcNAcase sensitizes apoptosis and reverses bortezomib resistance in mantle cell lymphoma through modification of truncated Bid

Aberrant energy metabolism represents a hallmark of cancer and contributes to numerous aggressive behaviors of cancer cells, including cell death and survival. Despite the poor prognosis of mantle cell lymphoma (MCL), due to the inevitable development of drug resistance, metabolic reprograming of MCL cells remains an unexplored area. Post-translational modification of proteins via O-GlcNAcylation is an ideal sensor for nutritional changes mediated by O-GlcNAc transferase (OGT) and is removed by O-GlcNAcase (OGA). Using various small molecule inhibitors of OGT and OGA, we found for the first time that O-GlcNAcylation potentiates MCL response to bortezomib (BTZ). CRISPR interference of MGEA5 (encoding OGA) validated the apoptosis sensitization by O-GlcNAcylation and OGA inhibition. To identify the potential clinical candidates, we tested MCL response to drug-like OGA inhibitor, ketoconazole (KCZ), and verified that it exerts similar sensitizing effect on BTZ-induced apoptosis. Investigations into the underlying molecular mechanisms reveal that BTZ and KCZ act in concert to cause the accumulation of truncated Bid (tBid). Not only does KCZ potentiate tBid induction, but also increases tBid stability through O-GlcNAcylation that interferes with tBid ubiquitination and proteasomal degradation. Remarkably, KCZ strongly enhances BTZ-induced apoptosis in de novo BTZ-resistant MCL cells and in patient-derived primary cells with minimal cytotoxic effect on normal peripheral blood mononuclear cells and hepatocytes, suggesting its potential utility as a safe and effective adjuvant for MCL. Together, our findings provide novel evidence that combination of BTZ and KCZ or other OGA inhibitors may present a promising strategy for the treatment of drug-resistant MCL.

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Response Regarding Surgical Techniques for Retrograde Parotidectomy

Publication date: Available online 22 November 2017
Source:American Journal of Otolaryngology
Author(s): Maxwell Kligerman, Uchechukwu Megwalu, Davud Sirjani




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Residual Convolutional Neural Network for Determination of IDH Status in Low- and High-grade Gliomas from MR Imaging

Purpose: Isocitrate dehydrogenase (<IDH) mutations in glioma patients confer longer survival and may guide treatment decision-making. We aimed to predict the IDH status of gliomas from MR imaging by applying a residual convolutional neural network to pre-operative radiographic data. Experimental Design: Preoperative imaging was acquired for 201 patients from the Hospital of University of Pennsylvania (HUP), 157 patients from Brigham and Women's Hospital (BWH), and 138 patients from The Cancer Imaging Archive (TCIA) and divided into training, validation, and testing sets. We trained a residual convolutional neural network for each MR sequence (FLAIR, T2, T1 pre-contrast, and T1 post-contrast) and built a predictive model from the outputs. To increase the size of training set and prevent overfitting, we augmented the training set images by introducing random rotations, translations, flips, shearing, and zooming. Results: With our neural network model, we achieved IDH prediction accuracies of 82.8% (AUC = 0.90), 83.0% (AUC = 0.93), and 85.7% (AUC = 0.94) within training, validation, and testing sets, respectively. When age at diagnosis was incorporated into the model, the training, validation, and testing accuracies increased to 87.3% (AUC = 0.93), 87.6% (AUC = 0.95), and 89.1% (AUC = 0.95), respectively. Conclusions: We developed a deep learning technique to non-invasively predict IDH genotype in grade II-IV glioma using conventional MR imaging using a multi-institutional dataset.

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PTEN loss promotes intratumoral androgen synthesis and tumor microenvironment remodeling via aberrant activation of RUNX2 in castration-resistant prostate cancer

Purpose: Intratumoral androgen synthesis (IAS) is a key mechanism promoting androgen receptor (AR) reactivation and anti-androgen resistance in castration-resistant prostate cancer (CRPC). However, signaling pathways driving aberrant IAS remain poorly understood.  Experimental Design: The effect of components of the AKT-RUNX2-osteocalcin (OCN)-GPRC6A-CREB signaling axis on expression of steroidogenesis genes CYP11A1 and CYP17A1 and testosterone level were examined in PTEN-null human PCa cell lines. Pten knockout mice were employed to examine the effect of Runx2 heterozygous deletion or abiraterone acetate (ABA), a prodrug of the CYP17A1 inhibitor abiraterone on Cyp11a1 and Cyp17a1 expression, testosterone level and tumor microenvironment (TME) remodeling in vivo.  Results: We uncovered that activation of the AKT-RUNX2-OCN-GPRC6A-CREB signaling axis induced expression of CYP11A1 and CYP17A1 and testosterone production in PTEN-null PCa cell lines in culture. Deletion of Runx2 in Pten homozygous knockout prostate tumors decreased Cyp11a1 and Cyp17a1 expression, testosterone level and tumor growth in castrated mice. ABA treatment also inhibited testosterone synthesis and alleviated Pten loss-induced tumorigenesis in vivo. Pten deletion induced TME remodeling, but Runx2 heterozygous deletion or ABA treatment reversed the effect of Pten loss by decreasing expression of the collagenase Mmp9. Conclusions:Abnormal RUNX2 activation plays a pivotal role in PTEN loss-induced IAS and TME remodeling, suggesting that the identified signaling cascade represents a viable target for effective treatment of PTEN-null PCa including CRPC.

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The impact of spatio-temporal calcium dynamics within presynaptic active zones on synaptic delay at the frog neuromuscular junction

The spatio-temporal calcium dynamics within presynaptic neurotransmitter release sites (active zones, AZs) at the time of synaptic vesicle fusion is critical for neurotransmitter release. Specifically, the relative arrangement and density of voltage gated calcium channels (VGCCs) as well as the concentration of calcium buffering proteins can play a large role in the timing, magnitude and plasticity of release by shaping the AZ calcium profile. However, a high-resolution understanding of the role of AZ structure on the spatiotemporal calcium dynamics and how that may contribute to functional heterogeneity at an adult synapse is currently lacking. We demonstrate that synaptic delay varies considerably across, but not within, individual synapses at the frog neuromuscular junction (NMJ). To determine how elements of the AZ could contribute to this variability, we performed a parameter search using a spatially realistic diffusion-reaction based computational model of a frog NMJ active zone (Dittrich et al., 2013, Ma et al., 2015). We demonstrate using our model that synaptic delay is sensitive to significant alterations in the spatio-temporal calcium dynamics within an AZ at the time of release caused by manipulations to the density and organization of VGCCs or by the concentration of calcium buffering proteins. Further, our data provide a framework for understanding how AZ organization and structure is important for understanding presynaptic function and plasticity.

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LEARNING-INDUCED MODULATION OF THE EFFECT OF ENDOCANNABINOIDS ON INHIBITORY SYNAPTIC TRANSMISSION

Endocannabinoids are key modulators that regulate central brain functions and behaviours, including learning and memory. At the cellular and molecular levels, endocannabinoids are potent modulators of excitatory and inhibitory synaptic function. Most effects of cannabinoids are thought to be mediated via G protein-coupled cannabinoids receptors. In particular, cannabinoids released from post-synaptic neurons are suggested to act as retrograde messengers, activating presynaptic Type-1 Cannabinoid receptors (CB1R), thereby inducing suppression of synaptic release. Another central mechanism of cannabinoids-induced action requires activation of astroglial CB1R. CB1R are also implicated in self-modulation of cortical neurons. Rats that are trained in a particularly difficult olfactory-discrimination task show a dramatic increased ability to acquire memories of new odors. The memory of the acquired high skill acquisition, termed 'rule learning' or 'learning set' lasts for many months. Using this behavioural paradigm, we show a novel function of action for CB1R; supporting long-term memory by maintaining persistent enhancement of inhibitory synaptic transmission. Long-lasting enhancement of inhibitory synaptic transmission is blocked by a CB1R inverse agonist. This effect is mediated by a novel purely post-synaptic mechanism, obtained by enhancing the single GABAA channel conductance that is PKA-dependent. The significant role that CB1R has in maintaining learning-induced long-term strengthening of synaptic inhibition suggests that endocannabinoids have a key role in maintaining long-term memory by enhancing synaptic inhibition.

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The Modulation of Hippocampal Theta Rhythm by the Vestibular System.

The vestibular system is a sensory system that has evolved over millions of years to detect acceleration of the head, both rotational and translational, in three dimensions. One of its most important functions is to stabilize gaze during unexpected head movement; however, it is also important in the control of posture and autonomic reflexes. Theta rhythm is a 3-12 Hz oscillating EEG signal that is intimately linked to self-motion and is also known to be important in learning and memory. Many studies over the last two decades have shown that selective activation of the vestibular system, either using natural rotational or translational stimulation, or electrical stimulation of the peripheral vestibular system, can induce and modulate theta activity. Furthermore, inactivation of the vestibular system has been shown to significantly reduce theta in freely moving animals, which may be linked to its impairment of place cell function as well as spatial learning and memory. The pathways through which vestibular information modulate theta rhythm remain debatable. However, vestibular responses have been found in the pedunculopontine tegmental nucleus (PPTg) and activation of the vestibular system causes an increase in acetylcholine release into the hippocampus, probably from the medial septum. Therefore, a pathway from the vestibular nucleus complex and/or cerebellum to the PPTg, supramammillary nucleus, posterior hypothalamic nucleus and the septum, to the hippocampus, is likely. The modulation of theta by the vestibular system may have implications for vestibular effects on cognitive function and the contribution of vestibular impairment to the risk of dementia.

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Prefrontal cortical specific differences in behavior and synaptic plasticity between adolescent and adult mice

Adolescence is a highly vulnerable period for the emergence of major neuropsychological disorders and is characterized by decreased cognitive control and increased risk-taking behavior and novelty seeking. The prefrontal cortex (PFC) is involved in the cognitive control of impulsive and risky behavior. Although the PFC is known to reach maturation later than other cortical areas, little information is available regarding the functional changes from adolescence to adulthood in PFC , particularly compared to other primary cortical areas. This study aims to understand the development of PFC-mediated, compared to non PFC-mediated, cognitive functions. Towards this aim, we performed cognitive behavioral tasks in adolescent and adult mice, and subsequently investigated synaptic plasticity in two different cortical areas. Our results showed that adolescent mice exhibit impaired performance in PFC-dependent cognitive tasks compared to adult mice, while their performance in non-PFC dependent tasks is similar to that of adults. Furthermore, adolescent mice exhibited decreased long-term potentiation (LTP) within upper layer synapses of the PFC, but not the barrel cortex (BC). Blocking GABA_A receptor function significantly augments LTP in both the adolescent and adult PFC. No change in intrinsic excitability of PFC pyramidal neurons was observed between adolescent and adult mice. Finally, increased expression of the NR2A subunit of the NMDA receptors is found only in the adult PFC, a change that could underlie the emergence of LTP. In conclusion, our results demonstrate physiological and behavioral changes during adolescence that are specific to the PFC and could underlie the reduced cognitive control in adolescents.

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Perceptual Decisions Based on Previously Learned Information are Independent of Dopaminergic Tone

Both cognitive and motor symptoms in people with Parkinson's disease (PD) arise from either too little or too much dopamine (DA). Akinesia stems from DA neuronal cell loss and dyskinesia often stems from an overdose of DA medication. Cognitive behaviors typically associated with frontal cortical function such as working memory and task switching are also affected by too little or too much DA in PD. Whether motor and cognitive circuits overlap in PD is unknown. Here, we show that whereas motor performance improves in people with PD when on dopaminergic medication compared to off medication, memory-based decision-making performance remains impaired whether on or off medications. To rule out effects of long-term DA treatment and dopaminergic neuronal loss as occur in PD, we also tested a group of people with dopa-unresponsive focal dystonia - a disease that involves primarily the basal ganglia like PD, but has motor symptoms that are insensitive to dopamine treatment and is not thought to involve frontal cortical DA circuits, unlike PD. We found that people with focal dystonia showed intact perceptual decision-making performance, but impaired memory-based decision-making performance, similar to people with PD. Together, the results show a dissociation between motor and cognitive performance in people with PD and reveal a novel cognitive impairment, independent of sensory and motor impairment, in people with focal dystonia. The combined results from people with PD and people with focal dystonia provide mechanistic insights into the role of basal ganglia non-dopaminergic circuits in memory-based perceptual decision-making.

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The humanistic burden of Pompe disease: are there still unmet needs? A systematic review

Humanistic burden considers the impact of an illness on a patient's health-related quality of life (HRQoL), activities of daily living (ADL), caregiver health, and caregiver QoL. Humanistic burden also conside...

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To infinity…. and beyond!!

Wynand Van Der Linden

Annals of Maxillofacial Surgery 2017 7(2):163-164



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Rehabilitation of unilateral congenital microtia by implant-retained prosthesis

Abhay Datarkar, Surendra Daware, Ravi Dande, Ujwala Datarkar

Annals of Maxillofacial Surgery 2017 7(2):291-295

Microtia is a major congenital anomaly of the external ear. It includes a spectrum of deformities from a grossly normal but small ear to the absence of the entire external ear. These deformities account for three in every 10,000 births, with bilaterally missing ears seen in fewer than 10% of all cases. Extraoral implant-retained ear prosthesis has been proven to be a predictable treatment option for rehabilitation of such congenital anomalies. This paper aims to present principles of maxillofacial implants, review of literature, advantages, disadvantages, and considerations in treatment planning and treatment phases of an implant-supported auricular prosthesis and prospective developments for ear prosthesis are also discussed. Implant supported ear reconstruction provides excellent support, good retention, and esthetically acceptable appearance to the patient.

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Understanding and prevention of orofacial clefting: A myth or possibility?

SM Balaji

Annals of Maxillofacial Surgery 2017 7(2):165-165



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Guided bone regeneration for the reconstruction of alveolar bone defects

Arash Khojasteh, Lida Kheiri, Saeed Reza Motamedian, Vahid Khoshkam

Annals of Maxillofacial Surgery 2017 7(2):263-277

Background: Guided bone regeneration (GBR) is the most common technique for localized bone augmentation. Purpose: The purpose of this review was to categorize and assess various GBR approaches for the reconstruction of human alveolar bone defects. Materials and Methods: Electronic search of four databases including PubMed/Medline, EMBASE, Web of Science, and Cochrane and hand searching were performed to identify human trials attempting GBR for the reconstruction of alveolar bony defects for at least 10 patients from January 2000 to August 2015. To meet the inclusion criteria, studies had to report preoperative defect dimensions in addition to outcomes of bone formation and/or resorption. Results: Twenty-five human clinical trials were included of which 17 used conventional technique that is the use of space maintaining membrane with bone grafting particles (GBR I). Application of block bone graft with overlying membrane and particulate fillers was reported in seven studies (GBR II), and utilizing cortical bone block tented over a defect preserving particulate fillers was reported by one study (GBR III). A wide range of initial defects' sizes and treatment results were reported. Conclusions: This review introduces a therapeutically oriented classification system of GBR for treating alveolar bone defects. High heterogeneity among studies hindered drawing definite conclusions in regard to superiority of one to the other GBR technique.

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Fast-track orthognathic surgery: An evidence-based review

Joel Joshi Otero, Olivier Detriche, Maurice Yves Mommaerts

Annals of Maxillofacial Surgery 2017 7(2):166-175

The aim of this study was to establish a fast-track protocol for bimaxillary orthognathic surgery (OGS). Fast-track surgery (FTS) is a multidisciplinary approach where the pre-, intra-, and postoperative management is focusing maximally on a quick patient recovery and early discharge. To enable this, the patients' presurgical stress and postsurgical discomfort should be maximally reduced. Both referral patterns and expenses within the health-care system are positively influenced by FTS. University hospital-literature review through Medline, Embase, and the Cochrane Library (January 2000– July 2016) using the following words – "fast track, enhanced recovery, multimodal, and perioperative care" – to define a protocol evidence based for OGS, as well as evidenced-based medicine search of every term added to the protocol during the same period. The process has resulted in an OGS protocol that may improve the outcome of the patient through several nonoperative and operative measures such as preoperative patient education and intra/postoperative measures that should improve overall patient satisfaction, decrease morbidity such as postoperative nausea, headache, dizziness, pain, and intubation discomfort, and shorten hospital stay. A literature review allowed us to fine-tune a fast-track protocol for uncomplicated OGS that can be prospectively studied against currently applied ones.

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Unusual case of acquired capillary hemangioma of the eyelid in an adult

S Vijayanand, Narahari Ranganatha, Madhumati Singh, Ramesh Babu

Annals of Maxillofacial Surgery 2017 7(2):308-311

Acquired capillary hemangioma of the eyelid is very uncommon in adults. To our knowledge, only eight such cases have been reported in the literature till date. We report the case of a 25-year-old female with acquired capillary hemangioma of the left lower eyelid treated by cutting diathermy followed by reconstruction of the cutaneous and cartilaginous defect. This patient had a history of a similar lesion in the left malar region treated 5 years back. This case is being presented to highlight the occurrence of such lesions in an adult and to discuss the dilemmas in the diagnosis and management.

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Orthognathic surgery or overlay prosthesis: Quality of life in bilateral cleft lip and palate patients

Michelly Lima Moro Alves, José Fernando Scarelli Lopes, Ana Lúcia Pompéia Fraga de Almeida, Karin Hermana Neppelenbroek, Thais Marchini de Oliveira, Simone Soares

Annals of Maxillofacial Surgery 2017 7(2):176-179

Background: The concern to restore and evaluate bilateral cleft lip and palate (BCLP) patients' quality of life, after rehabilitation, is an issue that has been discussed in the literature because it is the ultimate goal of any proposed treatment. Objective: To evaluate the overall and oral quality of life of BCLP patients who had completed their treatment with orthognathic surgery (OrSg) compared to those who completed theirs with prosthetic rehabilitation in the form of overlay prosthesis (OP). Materials and Methods: The study comprised 40 patients, 20 in OrSg group and 20 in OP group. Epidemiological survey and application of two questionnaires (World Health Organization Quality of Life-brief [WHOQOL-bref] and Oral Health Impact Profile-14 [OHIP-14]) were done. The final results were evaluated statistically by the Mann– Whitney test. Results: Regarding the comparison with the WHOQOL-bref, no significant statistical differences between groups were found. In the analysis of the OHIP-14, only in "psychological limitation" field difference could be observed, where OrSg group showed more negative impact when compared to the OP group. Conclusion: Both rehabilitations provide a satisfactory quality of life for patients.

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Tomographic analysis of the impact of mandibular advancement surgery on increased airway volume

Danilo Louzada De Oliveira, Thiago Calcagnotto, Thessio Mina Vago, Hugo Nary Filho, Danilo Pinelli Valarelli, Caio Peres Bellato

Annals of Maxillofacial Surgery 2017 7(2):256-259

Purpose: This study aimed to quantify, using cone-beam computed tomography (CBCT) in patients who underwent a mandibular advancement surgery associated with genioplasty, three-dimensional changes in airway space and to evaluate whether these changes differ between men and women. Materials and Methods: Preoperative and 8-month postoperative CBCT scans of 38 patients aged 18– 45 years of either sex and any ethnicity who underwent mandibular advancement surgery associated with genioplasty were analyzed using the Xoran software (Xoran Technologies, Ann Arbor, MI, USA). The linear distances gonion-gnathion (Go-Gn) and condylion-menton (Co-Me) were obtained. Airway volume was measured using the Dolphin Imaging software, version 11.0. Then, data were tabulated and analyzed using Student's t-test. Results: Mean patient age was 30.3 years; 39.47% were men and 60.63% were women. The mean Go-Gn distance was 72.05 mm before surgery and 78.56 mm after surgery, with a mean gain of 6.51 mm. The mean Co-Me distance was 113.47 mm before surgery and 119.89 mm after surgery, with a mean increase of 6.42 mm. Both differences were statistically significant. The mean volume of airway space was 17,272.92 mm3 before surgery and 24,173.74 mm3 after surgery, with a statistically significant mean increase of 6900.82 mm3. There was no statistically significant difference in mean volumetric gain between men (7566.69 mm3) and women (7456.69 mm3). Conclusion: Mandibular advancement surgery results in significant increase of airway space, and there is no difference in airway volume between men and women.

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A study on dorsal pedicled tongue flap closure of palatal fistulae and oronasal communications

Priya Esther Jeyaraj

Annals of Maxillofacial Surgery 2017 7(2):180-187

Introduction: Residual defects of the palatal region following ablative resection of tumors and Gunshot wounds (GSWs) of the maxillofacial region can be quite painstaking, daunting and challenging to reconstruct, due to the extent and composite nature of the tissue loss. A shortage of available donor areas and local flap options in the intraoral region, add to the difficulty. Further compounding the situation, are factors such as excessive fibrosis and scarring of the palatal tissues as a result of multiple previous surgeries in the region. Objective: To evaluate the effectiveness of the Dorsal Pedicled Tongue Flap in the reconstruction of complex palatal defects resulting from maxillofacial GSWs and ablative tumor resections. To also device techniques to reduce the incidence of postoperative tongue flap detachment, thus improving its efficiency and reliability. Results: The palatal fistulas in all the patients were closed successfully, with no post-operative complications such as bleeding, hematoma formation, congestion, infection, partial or total flap necrosis or flap detachment. The tongue flap at the recipient site remained healthy with no recurrence of the fistula in any of the patients in the two years follow up period. There was a complete resolution of the problem of nasal regurgitation of orally ingested fluids and food particles. There was observed no deformity or articulation defect resulting from the flap harvested from the tongue dorsum, in any of the patients. Conclusion: In GSWs and tumor ablative surgery, where composite tissue defects are involved, the tongue provides a reliable and efficient means of restoring lost tissue bulk as well as ensuring a permanent closure and sealing off of the oronasal fistulas. Its reliability can be further increased by avoiding a common complication, namely, flap detachment in the postoperative period brought on by movements of the tongue, by immobilizing the tongue by tethering it to the maxillary teeth and also, maintaining the patient on Nasogastric feeding for the three weeks postoperative period, until the patient is taken up for surgical separation the pedicle. This helps to ensure a successful and predictable take of the flap at the donor site.

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Multiple dentigerous cysts as a rare presentation of maroteaux– Lamy syndrome

Ajaz Ahmad Shah, Tajamul Ahmad Hakim, Shahid Farooq, Mubashir Younis, Shamina Kosar, Altaf Malik, Latief Najar

Annals of Maxillofacial Surgery 2017 7(2):282-286

Maroteaux– Lamy syndrome is one of the genetic disorders involving disturbances in mucopolysaccaride metabolism, due to deficiency of aryl sulfatase-B which leads to accumulation of dermatan sulfate in tissues and their excretion in urine. The diseases has several oral and dental manifestations, is first diagnosed on the basis of clinical findings. It is characterized by coarse facial features, normal intelligence, organomegaly, enlarged head, short neck, corneal clouding, enlarged tongue, and prominent metachromatic inclusions in leukocytes. Death is usually a result of either respiratory tract infection or cardiac disease, which is caused by the deposition of mucopolysaccharides. An 18-year-old with Maroteaux– Lamy syndrome is described in this article with multiple dentigerous cysts as the first presentation.

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Lugol chromoscopy in the follow-up of head and neck carcinoma

Cesar Augusto Simões, Marcelo Doria Durazzo, Flávia Caló de Aquino Xavier, Marina Helena Cury Gallottini, Sílvia Vanessa Lourenço, Décio dos Santos Pinto Júnior, Natália Martins Magacho de Andrade, Aline Paterno Miazaki, Rogério Aparecido Dedivitis, Cláudio Roberto Cernea

Annals of Maxillofacial Surgery 2017 7(2):188-193

Introduction: Lugol is helpful in identifying early second primary tumors (SPTs) during oroscopy and pharyngoscopy, but this technique has not been assessed during follow-up visits with these patients. Aim: The aim of this study is to describe the use of Lugol (a low-cost method) to diagnose SPTs in the oral cavity and oropharynx. Methods: Patients treated for squamous cell carcinoma of the head and neck were randomly assigned to two groups. Group A was examined with routine oroscopy and pharyngoscopy without Lugol, and Group B was examined with routine oroscopy and pharyngoscopy without stain and with Lugol. A total of 211 patients were included during 4 years. Results: Six oral and oropharynx carcinomas were detected in Group A. Eighteen oral and oropharynx carcinomas were detected in Group B, twelve of which were not seen without chromoscopy but were detected with Lugol. Conclusion: Lugol increases the detection of malignant lesions compared to routine examination alone.

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Karapandzic flap for esthetic and functional reconstruction of large defect of lower lip

Anuj S Dadhich, Seemit Shah, Harish Saluja, Parul Tandon, Vinayak More

Annals of Maxillofacial Surgery 2017 7(2):300-303

Squamous cell carcinoma is the most common cancer occurring in the oral cavity. The lips are one of the most common sites of occurrence with involvement, lower lip being more common than upper. Reconstruction of large defects of lower lip with good functional and esthetic outcome is the biggest challenge faced by the surgeon. Karapandzic flap is one the most commonly used technique for reconstruction of large defects of the lower lip.

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Evaluation of the sternoclavicular graft for the reconstruction of temporomandibular joint after gap arthroplasty

JK Dayashankara Rao, Nahida Dar, Aadya Sharma, Anil K Sheorain, Vijaylaxmi Malhotra, Varun Arya

Annals of Maxillofacial Surgery 2017 7(2):194-201

Introduction: Ankylosis may be defined as the fusion of the articular surfaces with bony or fibrous tissue. The treatment of temporomandibular joint ankylosis poses a significant challenge because of the high incidence of recurrence. A number of interpositional materials have been used including alloplastic materials (acrylic, proplast– teflon, silastic), and autogenous tissues (temporalis muscle flaps, buccal fat pad, dermis, costochondral grafts, metatarsal, fibula, tibia, iliac crest, cranial bone and Sternoclavicular graft SCG and cartilage). Literature suggests that rather than growth centre, we need adaptive centre. SCG is presumed to be a more suitable material for interpositional arthroplasty because Sternoclavicular Joint (SCJ) and TMJ are very similar developmentally, histologically and morphologically throughout the growth period. Material and Method: Patients with TMJ ankylosis (8 males, 2 females) underwent release of the ankylosed joint by the senior author, between June 2013 and Novemeber 2015. The age of the patients ranged from 10 to 19 years. Pre- and post- operative assessment included a thorough history and physical examination to determine the cause of ankylosis, the maximal incisal opening, etiology and type of the ankylosis, recurrence rate. Result: MIO at 6 months follow up was 37.4±2.633 mm (range 32-40 mm), greater than MIO achieved in immediate postoperatively {34.4±2.22 mm (range 30-38 mm). After reconstruction of temporomandibular joint with sternoclavicular graft in the growing child there was a significant increase in the growth of mandible which was stunned due to ankylosis. And the ramal height also increased. Conclusion: The articular reconstruction with alloplastic or autogenous grafts, or gap arthroplasty for the treatment of ankylosis is shown to be efficient in relation to the post-operative maximal incisal opening, recurrence and articular function.

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Dual pathology of mandible

Suday G Rajurkar, Mohan D Deshpande, Noaman Kazi, Dhanashree Jadhav, Pallavi Ranadive, Snehal Ingole

Annals of Maxillofacial Surgery 2017 7(2):316-318

Aneurysmal Bone cyst (ABC)is a rare benign lesion of the bone which is infrequent in craniofacial region (12%). Rapid growth pattern causing bone expansion and facial asymmetry is a characteristic feature of ABC. Giant cell lesion is another distinct pathological entity. Here we present to you a rare case of dual pathology in an 11 year old female patient who presented with a large expansile lesion in the left hemimandible. All radiographic investigations were suggestive of ABC, aspiration of the lesion resulted in blood aspirate. However only after a histologic examination the dual nature of the lesion was revealed.

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A randomized control trial of awake oral to submental conversion versus asleep technique in maxillofacial trauma

Shahna Ali, Manazir Athar, Syed Moied Ahmed, Obaid Ahmad Siddiqi, Amrin Badar

Annals of Maxillofacial Surgery 2017 7(2):202-206

Aim: This study was designed to evaluate the efficacy of awake oral to submental conversion over asleep technique. Materials and Methods: This randomized clinical study was conducted in maxillofacial department of a tertiary care hospital in patients who had panfacial or mandibular fractures requiring elective surgical correction. The patients were randomly divided into two groups of 12 patients each, asleep fiberoptic-assisted submental intubation (SMI) (Group G; n = 12) and awake fiberoptic-assisted SMI (Group A; n = 12). The primary predictor was mean conversion time of oral to SMI while other predictors were overall success rate, ease of conversion, and complications. Data are presented as mean (±standard deviation) and frequencies (%) as appropriate. Statistical analysis done using unpaired t-test or Chi-square test was performed and P < 0.05 was considered statistically significant. Results: Twenty-four patients (19:5;Male:Female) aged 18– 55 years (Group G = 35.96; Group A = 32.43 years) were included in the study. SMI was successful in all except two patients in group G. Overall success rate was similar in both groups. Time to convert orotracheal intubation to SMI was significantly less in group A (Group G = 9.55 ± 1.42, Group A = 5.67 ± 1.73; P < 0.001). Ease of SMI was found Grade I in 30% and 83% of the patients of group G and A, respectively. No serious complications were observed except 2 cases of bleeding, and 1 case of tube damage. Conclusion: Awake oral to submental conversion requires lesser time in comparison to asleep technique besides improving the ease (Δ = 53%) of the procedure.

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Efficacy of exclusive lingual nerve block versus conventional inferior alveolar nerve block in achieving lingual soft-tissue anesthesia

Sasikala Balasubramanian, Elavenil Paneerselvam, T Guruprasad, M Pathumai, Simin Abraham, VB Krishnakumar Raja

Annals of Maxillofacial Surgery 2017 7(2):250-255

Objective: The aim of this randomized clinical trial was to assess the efficacy of exclusive lingual nerve block (LNB) in achieving selective lingual soft-tissue anesthesia in comparison with conventional inferior alveolar nerve block (IANB). Materials and Methods: A total of 200 patients indicated for the extraction of lower premolars were recruited for the study. The samples were allocated by randomization into control and study groups. Lingual soft-tissue anesthesia was achieved by IANB and exclusive LNB in the control and study group, respectively. The primary outcome variable studied was anesthesia of ipsilateral lingual mucoperiosteum, floor of mouth and tongue. The secondary variables assessed were (1) taste sensation immediately following administration of local anesthesia and (2) mouth opening and lingual nerve paresthesia on the first postoperative day. Results: Data analysis for descriptive and inferential statistics was performed using SPSS (IBM SPSS Statistics for Windows, Version 22.0, Armonk, NY: IBM Corp. Released 2013) and a P < 0.05 was considered statistically significant. In comparison with the control group, the study group (LNB) showed statistically significant anesthesia of the lingual gingiva of incisors, molars, anterior floor of the mouth, and anterior tongue. Conclusion: Exclusive LNB is superior to IAN nerve block in achieving selective anesthesia of lingual soft tissues. It is technically simple and associated with minimal complications as compared to IAN block.

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Low-level laser therapy on postoperative pain after mandibular third molar surgery

May Ayad Hamid

Annals of Maxillofacial Surgery 2017 7(2):207-216

Introduction: The analgesic effect of low-level laser therapy (LLLT) after mandibular third molar (MTM) extraction is controversial. The aim is to evaluate the effect of intraoral LLLT on postoperative pain after MTMs extraction. Methods: Thirty patients with bilateral symmetrical impacted MTMs underwent surgical extractions. Experimental and control sides were randomly selected to receive LLLT or placebo. Following suturing, a dental assistant applied 810 nm gallium aluminum arsenide (GaAlAs) at three points for 30 s each with a total energy of 9 J. Pain was recorded on a visual analog scale on the 7 successive days. Results: Data analyzed by IBM SPSS Statistics 23 for Windows with P ≤ 0.05 signifi cance level. LLLT appeared to have a high signifi cant effect on pain reduction; however, there was a mild increase in pain after the 4th day. Conclusion: Intraoral 810 nm GaAlAs is effective in reducing postoperative pain when a dose of 32.86 J/cm2 is used.

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Computed tomographic analysis of the sagittal orbit-globe relationship

Zachary R Abramson, Srinivas M Susarla, Anand R Kumar, Asim F Choudhri

Annals of Maxillofacial Surgery 2017 7(2):260-262

Identifying the normal relationship of the orbital rims to the globes is critical in planning surgical correction of craniofacial deformities affecting the orbit. This article illustrates a technical proof of principle and mathematical basis for a computed tomography-based measurement of the sagittal orbit-globe relationship. The technique does not require subject cooperation and is, therefore, optimal for pediatric craniofacial surgical treatment planning and outcome evaluation.

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Evaluation of knowledge of physical education students on dental trauma

Danilo Louzada de Oliveira, Paulo Domingos Ribeiro-Junior, Ana Camila Sbroggio, Priscila Góis dos Santos, Graziela Garrido Mori

Annals of Maxillofacial Surgery 2017 7(2):217-221

Introduction: Sports' practitioners are vulnerable to dental trauma; if this occurs, the emergency treatment should be fast and efficient. This may be performed by any person at the site of the accident, not only by dental professionals. Physical educators may face dental trauma and should be able to provide proper care. This study had the objective evaluated the knowledge of physical education graduates on dental trauma. Materials and Methods: A questionnaire containing questions on dental trauma was applied to 199 physical education students; after collection of the questionnaires, data were tabulated and processed on the software Epi Info 2000 (Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA 30333, USA). As a result, only 36.7% of participants would take the individual suffering trauma to the dental professional, 56.8% believe that the avulsed tooth should be replanted, and 42.2% would replant it. Only 7.5% would store the avulsed tooth in an ideal storage medium for transportation. Conclusion: It was concluded that there is a lack of knowledge on dental trauma among physical education graduates, evidencing the need of public policies to allow education on this issue.

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Post herpetic frey's syndrome

Jigna S Shah, Vijay K Asrani

Annals of Maxillofacial Surgery 2017 7(2):278-281

Frey's syndrome is characterized by unilateral sweating and flushing of the skin in the area of the parotid gland, occurring during meal, or on salivary stimulation. It is a common complication following surgery/injury in the parotid gland region/temporomandibular joint surgery; however, very few cases have been reported of its occurrence following herpetic infection. It is important for the clinician to recognize its unusual symptoms as early as possible to prevent its potential negative social and psychological effect on the patient. It is diagnosed on clinical presentation and confirmed by objective testing methods. The treatment ranges from topical application of glycopyrrolate to local injections of botulinum toxin and lastly to surgical intervention. An interesting case of Frey's syndrome is presented in a young patient having the previous history of herpes zoster infection, which was diagnosed clinically and confirmed by starch-iodine test and was successfully treated with topical application of glycopyrrolate.

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Small-diameter compression screws completely embedded in bone for rigid internal fixation of the condylar head of the mandible

Complications after open reduction and internal fixation of the condylar head include irritation of the sensitive soft tissues surrounding the temporomandibular joint (TMJ) caused by permanent friction from the screw head,1 and resorption beneath the screw heads because of bony remodelling around the lateral pole.1,2 However, a second operation can risk damage to the facial nerve.

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Diagnosing Kernohan-Woltman notch phenomenon by Somatosensory Evoked Potentials in Intensive Care Unit

Kernohan-Woltman notch phenomenon can occur after hemispheric brain lesions with severe midline herniation. This is clinically defined by the existence of false-localizing signs (such as an ipsilateral hemiparesis) due to a contralateral mesencephalon compression by the tentorial edge, without contralateral hemiparesis by temporal lobe herniation (Codd et al., 2013). Repetitive somatosensory evoked potential (SEP) recordings have been used to help assessing secondary injury related to severe herniation on the intensive care unit (ICU), even if they were not brought to evidence by intracranial pressure (ICP) monitoring (Stocchetti et al., 2014).

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Multisession anodal transcranial direct current stimulation induces motor cortex plasticity enhancement and motor learning generalization in an aging population

Transcranial direct-current stimulation (tDCS) is a non-invasive technique of cortical brain neuromodulation with potential therapeutic effects. Using a constant and low intensity direct current that flows between two electrodes over the scalp (Webster et al., 2006, Fregni et al., 2007), this technique influences trans-membrane neuronal potentials and modifies the level of cortical excitability in the targeted brain region (Priori et al., 1998, Fregni et al., 2007, Nitsche et al., 2008, Bastani et al., 2012).

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Cataplexy plus presence of HLA-DQB1*0602 allele can predict Hypocretin-1 deficiency

Currently, narcolepsy patients are treated with stimulants and other drugs for cataplexy.[1] However, emerging therapies focus on hypocretin-1 "replacement" and immunotherapy.[2] Unfortunately, the hypocretin-1 levels in CSF analysis depend on a lumbar puncture and radioimmunoassay, which are not available for the most part in sleep centers. Thus/Therefore, we studied the areas under the ROC curve of clinical or/and electrophysiology methods to predict Hypocretin-1 deficiency.

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Willis-Ekbom disease/restless legs syndrome in patients with opioid withdrawal

Many patients with opioid use disorder report symptoms similar to restless legs syndrome (RLS) during withdrawal. However, whether these symptoms are true RLS, their predictors and effect of treatment with pregabalin are still unknown.

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Work-Related Musculoskeletal Disorders among Plastic Surgeons: A Systematic Review

J reconstr Microsurg
DOI: 10.1055/s-0037-1608680

Background To date, no review has been conducted on the growing body of literature describing various work-related musculoskeletal disorders (MSDs), ergonomic hazards, and potential interventions relevant to plastic surgeons. This systematic review sought to (1) define the scope of coverage of this important issue in the peer-reviewed literature; (2) critically assess the evidence; and (3) provide recommendations for future directions. Methods We conducted a literature search of MEDLINE, Embase, Web of Science, and PubMed from the inception of each database until 2016. All articles reporting on work-related MSDs or ergonomics among plastic surgeons were reviewed, summarized, and assessed for trends. Results Sixteen articles met our inclusion criteria including five expert opinions, four cross-sectional studies and case reports/series, one review, and six experimental studies. Four articles presented evidence on disease burden. The most commonly described work-related MSD was cervical spine disease, for which one study reported a career prevalence of 24.7% (point prevalence in the general population: 0.1–0.4%); three studies reported 64 cases of surgeon work-related MSD resulting in surgical intervention, decreased productivity, or involuntary early retirement. Eight studies described interventions, most of which aimed to improve the ergonomics of microsurgery. Conclusion This review found low-level evidence of plastic surgeons' vulnerability to a work-related MSD at times severe enough to end careers. Further investigation is needed to clearly define this important problem in plastic surgery. Specifically, future directions should include more methodologically rigorous epidemiologic studies evaluating disease burden.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Does the proposed removal of mitotic count as a prognostic indicator in melanoma, accurately reflect the risk profile for metastasis in UK patients?

We of the Newcastle upon Tyne Hospitals NHS Foundation Trust Specialist Skin Cancer MDT, write with concern regarding the most recently published AJCC 8th edition staging system for malignant melanoma 1 (proposed to be implemented in the UK in January 2018) and its possible implications for accurate risk stratification and prognostic forecasting.

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The effect of supragingival biofilm re-development on the subgingival microbiota in chronic periodontitis

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Fátima Aparecida Rocha Resende Hartenbach, Carina Maciel Silva-Boghossian, Ana Paula Vieira Colombo
ObjectiveIn this study, we hypothesized that in the absence of oral hygiene, re-growth of the climax microbial communities of supra and subgingival biofilm happens in a faster and more intense fashion in individuals with chronic periodontitis (CP) compared to periodontally healthy controls (PH).DesignThirty patients (PH=15 and CP=15) received professional supragingival prophylaxis, and were asked to refrain from oral hygiene for 7days. Supra and subgingival biofilm samples and GCF were collected from randomly selected quadrants at baseline (before prophylaxis), immediately after prophylaxis, 2h, 6h, 24h, and 7days after prophylaxis. The composition of the biofilm was determined by the checkerboard method.ResultsAll subjects developed gingivitis at the end of 7days without oral hygiene. GCF mean volumes were significantly higher in CP than PH patients at baseline, but they started decreasing 2h after prophylaxis, returning to baseline levels after 24h in both groups. Significant increases in mean counts for most of the species evaluated were observed in both groups and biofilms over time (p<0.05). Few hours after prophylaxis, a more marked reduction in microbial counts happened in the supragingival biofilm of the CP group, and re-development of biofilm started later than in the PH group. At 7days, no differences were seen between groups. Significant differences in kinetics of re-colonization between groups were observed only in the subgingival biofilm for T. denticola and F. nucleatum ss vicentii (increased in the CP), and N. mucosa (increased in the PH group; p<0.05).ConclusionsBiofilm re-development was very similar between CP and PH individuals, although microbial re-growth occurred few hours earlier in PH than PC. Only 3 species in the subgingival biofilm differed in re-colonization between groups. Thus, we reject the hypothesis that re-colonization of biofilm in CP patients is more intense and faster than in individuals with PH.



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Aims & Scope/Editorial board

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85





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Homeobox genes and tooth development: Understanding the biological pathways and applications in regenerative dental science

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Anand Ramanathan, Thekkeparambil Chandrabose Srijaya, Prema Sukumaran, Rosnah Binti Zain, Noor Hayaty Abu Kasim
ObjectivesHomeobox genes are a group of conserved class of transcription factors that function as key regulators during the embryonic developmental processes. They act as master regulator for developmental genes, which involves coordinated actions of various auto and cross-regulatory mechanisms. In this review, we summarize the expression pattern of homeobox genes in relation to the tooth development and various signaling pathways or molecules contributing to the specific actions of these genes in the regulation of odontogenesis.Materials and methodsAn electronic search was undertaken using combination of keywords e.g. Homeobox genes, tooth development, dental diseases, stem cells, induced pluripotent stem cells, gene control region was used as search terms in PubMed and Web of Science and relevant full text articles and abstract were retrieved that were written in English. A manual hand search in text books were also carried out. Articles related to homeobox genes in dentistry and tissue engineering and regenerative medicine of odontogenesis were selected.ResultsThe possible perspective of stem cells technology in odontogenesis and subsequent analysis of gene correction pertaining to dental disorders through the possibility of induced pluripotent stem cells technology is also inferred.ConclusionsWe demonstrate the promising role of tissue engineering and regenerative medicine on odontogenesis, which can generate a new ray of hope in the field of dental science.



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Novel methodology for determining the effect of adsorbates on human enamel acid dissolution

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): N. Pechlivani, D.A. Devine, P.D. Marsh, A. Mighell, S.J. Brookes
ObjectiveThe effect of various interventions on enamel demineralisation can be determined by chemically measuring mineral ions dissolved by the attacking acid. Results are usually expressed as mineral loss per surface area of enamel exposed. Acid resistant varnish or adhesive tape are typically used to delineate an area of enamel. However, enamel surface curvature, rugosity and porosity reduce the reliability of simple area measurements made at the macro scale. Our aim was to develop a simple method for investigating the effect of adsorbates on enamel demineralisation that does not rely on knowing the area of enamel exposed. As an exemplar we have used salivary proteins as a model adsorbate.DesignNatural human tooth enamel surfaces were subjected to five sequential acid challenges and then incubated in adsorbate (whole clarified saliva) followed by a further 15 acid challenges. Demineralisation was determined by measuring the phosphate released into the acid during each exposure by a spectrophotometric assay. The initial five challenges established a mean baseline mineral loss for each tooth against which the effect of subsequently adsorbed proteins could be compared.ResultsSalivary proteins significantly reduced the acid demineralisation of human enamel by 43% (p<0.01). Loss of proteins during each challenge corresponded to a gradual reduction in the degree of protection afforded.ConclusionsThe methodology provides a simple and flexible means to investigate the effect of any adsorbate on enamel acid dissolution. Knowledge of the area of exposed enamel is irrelevant as each tooth acts as its own negative control.



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Raloxifene reduces the risk of local alveolar bone destruction in a mouse model of periodontitis combined with systemic postmenopausal osteoporosis

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Ryota Ichimaru, Tsukasa Tominari, Shosei Yoshinouchi, Chiho Matsumoto, Kenta Watanabe, Michiko Hirata, Yukihiro Numabe, Gillian Murphy, Hideaki Nagase, Chisato Miyaura, Masaki Inada
OBJECTIVEPeriodontitis is characterized by local inflammation leading to tooth loss and severe destruction of alveolar bone. Raloxifene is a selective estrogen receptor modulator (SERM) that halts estrogen deficiency-induced systemic bone loss in postmenopausal osteoporosis without the side effects of cancer in breast and uterus. In this study, we examined the effects of raloxifene on alveolar bone mass in a mouse model with estrogen deficiency-induced periodontitis.METHODSPeriodontitis was induced by the injection of lipopolysaccharide (LPS) into the lower gingiva in ovariectomized (OVX) mice, and the alveolar bone and femur bone mineral density (BMD) were analyzed by dual-energy X-ray absorptiometry. To explore the direct osteoclast inhibitory effect of raloxifene, a co-culture system for osteoclast formation and organ culture of alveolar bone was established.RESULTSWhen OVX mice were treated with raloxifene, the bone loss in both alveolar bone and femur were abrogated. Interleukin 1 and/or LPS stimulated the osteoclast formation and bone-resorbing activity; however, raloxifene did not show any inhibitory effect on the osteoclast formation or function. In vivo local injection of raloxifene also did not prevent bone resorption in a mouse model of periodontitis. However, the systemic treatment of raloxifene using a mini-osmotic pump did prevent the loss of BMD of alveolar bone induced by LPS.CONCLUSIONThese results suggest that the SERM raloxifene systemically maintain alveolar bone mass in a mouse model of periodontitis with osteoporosis. Increasing the alveolar bone mass by SERMs treatment in patients with postmenopausal osteoporosis may be a useful approach to preventing the destruction of alveolar bone in late-onset periodontitis.



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Cdc42 is essential for the polarized movement and adhesion of human dental pulp stem cells

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Mingwei Li, Liang Ma, Bing Song, Dingyi Yu, Min Xiao, Xiaohan Mei, Huihui Guo, Qing Yu
ObjectiveStem cell-based tissue repair and regeneration require the regulation of cell migration and adhesion. As a regulator of cell polarization, Cdc42 (cell division control protein 42) plays a basic role at the initial stage of cell migration and adhesion. This study explores the effect of Cdc42 on the polarized migration and adhesion of hDPSCs (human dental pulp stem cells).DesignHDPSCs were isolated from extracted third molars and transfected with siRNA targeted against Cdc42. Scratch wound assays and transwell assays were performed to detect the migration of human dental pulp stem cells. Polarization assays were applied to explore the polarized movement of Golgi bodies and nuclei.Western blot was used to examine the expression of related proteins.ResultsThe expression of Cdc42 was knocked down by siRNA transfection, which inhibited the migration of hDPSCs in both the scratch wound assays and transwell assays. Meanwhile, the proportion of polarized hDPSCs during migration was also decreased, and the adhesion ability of hDPSCs was downregulated. Western blot demonstrated that these effects were dependent on FAK (focal adhesion kinase), β-catenin and GSK3β (Glycogen synthase kinase-3β).ConclusionOur study demonstrates that Cdc42 plays an essential role during the polarized movement and adhesion of hDPSCs.



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Inhibitory effect of probiotic lactobacilli supernatants on single and mixed non-albicans Candida species biofilm

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Yulong Tan, Matthias Leonhard, Doris Moser, Su Ma, Berit Schneider-Stickler
ObjectivesOral candidiasis is one of the most common human fungal infections. While most cases of the Candida species isolated from the oral cavity are Candida albicans, a large number of candidiasis is attributed to non-albicans Candida species. In this study, we aim to evaluate the in vitro inhibition of supernatants of Lactobacillus gasseri and Lactobacillus rhamnosus on the single and mixed species biofilm of non-albicans Candida species, including Candida tropicalis, Candida krusei and Candida parapsilosis.DesignCell-free supernatants of Lactobacillus gasseri and Lactobacillus rhamnosus were prepared. Single and mixed non-albicans Candida species biofilm were formed in the 96-well microplate and on the surfaces of medical grade silicone. Biomass and cell viability were tested with crystal violet and cell counting kit-8. In order to examine the ability of the supernatant to disrupt pre-formed biofilm, supernatant was added to 24h-old biofilms. Biofilm architecture on silicone was investigated by scanning electron microscopy and confocal laser scanning microscopy was used to examine live/dead organisms within biofilm.ResultsSingle and mixed species biofilms and cell viability of non-albicans Candida biofilms were inhibited by probiotic lactobacilli supernatants. Matrue biofilm formation was disrupted by lactobacilli supernatants added at 24h after biofilm initiation. Examination with confocal laser scanning microscopy and scanning electron microscopy confirmed that lactobacilli supernatants inhibited the mixed biofilms and damaged the cells.ConclusionsOur data elucidate the inhibitory activity of probiotic lactobacilli on non-albicans Candida biofilm, so as to support their utility as an adjunctive therapeutic mode against oral candida infections.



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Colonization of oropharynx and lower respiratory tract in critical patients: Risk of ventilator-associated pneumonia

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Ivany Machado de Carvalho Baptista, Frederico Canato Martinho, Gustavo Giacomelli Nascimento, Carlos Eduardo da Rocha Santos, Renata Falchete do Prado, Marcia Carneiro Valera
ObjectiveTo investigate the microbial diversity existing in oral cavity and respiratory tract samples (from mini-bronchoalveolar lavage (BAL), endotracheal aspirate, and orotracheal tube) of patients on mechanical ventilation by using the checkerboard DNA-DNA hybridisation. Also, the study aimed to evaluate whether the microbial profile in the oral cavity is found in respiratory tract samples, at different periods of mechanical ventilation time (12h, 48h, 96h) in attempt to identification of relationship between VAP (ventilator-associated pneumonia) and bacterial species studied. The last objective was to analyses correlation between blood cultures and VAP.DesignThe samples were collected from ten patients in intensive care unit with medical prescription of orotracheal intubation and mechanical ventilation. Clinical data were tabulated and blood cultures were performed according medical indication. For checkerboard samples collection, chosen sites were the dorsal side of the tongue and gingival sulcus at 12h, 48h, 96h, BAL, at 12h, endotracheal aspirate at 48 and 96h, and orotracheal tube at extubation time, when feasible.ResultsIt was possible to identify the presence of bacterial species in mouth and in the BAL/endotracheal aspirate. The data demonstrated an increase in the quantity of bacterial associated with prolonged use of mechanical ventilation (48 and 96h).ConclusionsBacterial species may migrate rapidly from mouth and upper airways during orotracheal intubation which contributes to the pathogenesis of VAP. There were associations between VAP and Enterococcus faecalis, Fusobacterium periodonticum, Gemella morbillorum, Neisseria mucosa, Propionibacterium acnes, Prevotella melaninogenica, Streptococcus oralis, Streptococcus sanguinis, Treponema denticola, Treponema socransckii, and Veillonella parvula.



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Probiotic intervention influences the salivary levels of Matrix Metalloproteinase (MMP)-9 and Tissue Inhibitor of metalloproteinases (TIMP)-1 in healthy adults

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Heli Jäsberg, Taina Tervahartiala, Timo Sorsa, Eva Söderling, Anna Haukioja
ObjectiveTo study the effect of orally administered Bifidobacterium animalis subsp. lactis BB-12 and Lactobacillus rhamnosus GG on the salivary levels of Matrix Metalloproteinases (MMP)-8, MMP-9 and of Tissue Inhibitor of Metalloproteinases (TIMP)-1 in healthy adults. Furthermore, the correlations between MMP-8, MMP-9 and TIMP-1 and plaque and gingival indices, salivary mutans streptococci and lactobacilli counts, and stimulated saliva secretion rate were analysed.DesignThe salivary samples originated from a randomized controlled trial where healthy student volunteers consumed probiotic or placebo lozenges twice a day for four weeks. The saliva samples were collected and clinical parameters measured at the baseline and at the end of the original study. For this study, the salivary levels of MMP-8, MMP-9 and TIMP-1 were analysed with immunofluorometric assay (IFMA) and enzyme-linked immunosorbent assay (ELISA).ResultsIn the probiotic group (n=29), salivary MMP-9 levels increased (p<0.01) and TIMP-1 levels decreased (p<0.01) significantly during the intervention. Furthermore, MMP-9/TIMP-1 ratio differed significantly from the baseline level (p<0.01). These changes were not observed in the control group (n=31). In the whole data, salivary MMP-9 and gingival index correlated (r=0.260, p<0.05 at baseline and r=0.354, p<0.01 at the end of the study). Intergroup differences or correlations with other clinical parameters were not found. Probiotic consumption did not affect the saliva flow rate.ConclusionsIncreased MMP-9 and decreased TIMP-1 levels in saliva may indicate that probiotics have immunomodulatory effects in the oral cavity. Furthermore, increased salivary MMP-9 levels may be an indication of the defensive potential of matrix metalloproteinases.



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Reactivation of peroxidase activity in human saliva samples by polyphenols

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Jana Gau, Jürgen Arnhold, Jörg Flemmig
ObjectivesThe enzyme lactoperoxidase (LPO), which is released into several body fluids like saliva, is an essential part to maintain the oral bacterial homeostasis by catalysing the oxidation of thiocyanate (SCN⁻) to hypo-thiocyanite (⁻OSCN). The formation of unreactive redox intermediates (like Compound II) leads to a decreased pseudo-halogenating enzyme activity, which is associated with a higher risk for oral infections. According to former studies with bovine LPO selected flavonoids were tested in respect to their potential to reactivate the enzymatic activity in a more physiological, human salivary system.DesignSaliva samples from healthy donors were collected and characterized by using several gel staining methods and immunoblotting. Afterwards kinetic measurements were performed by applying the TNB-assay to evaluate the pseudo-halogenating salivary peroxidase (SAPX) activity. The measurements were performed in the presence of excess H2O2 to simulate pro-inflammatory conditions. Moreover selected flavonoids or an ethanolic extract of Tormentillae rhizoma were applied to test their regenerating effect on the LPO-derived ⁻OSCN production.ResultsDespite the complex protein composition of the collected saliva samples, an SAPX-derived pseudo-halogenating activity could be identified. The ⁻OSCN regenerating effects of the tested polyphenols were completely comparable to previous in vitro experiments with bovine LPO. Thus, we could show that phenolic substances are suitable to regenerate the peroxidase activity in human saliva samples after H2O2-induced inactivation.ConclusionThe studies provide new insights into the effect of pharmaceutical relevant polyphenols on salivary peroxidase activity and thus, suggest this enzyme as a new target for the prevention and therapy of oral inflammatory diseases.



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The Apple Watch can accurately detect hypertension and sleep apnea, a new study suggests

A new study out from health startup Cardiogram and the University of California San Francisco (UCSF) suggests wearables like the Apple Watch, Fitbit and others are able to accurately detect common but serious conditions like hypertension and sleep apnea.

Cardiogram and USCF previously demonstrated the ability for the Apple Watch to detect abnormal heart rhythm with a 97 percent accuracy. This new study shows the Watch can detect sleep apnea with a 90 percent accuracy and hypertension with an 82 percent accuracy.

Read more at: Tech Crunch

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Magnetofection is superior to other chemical transfection methods in a microglial cell line

Publication date: 1 January 2018
Source:Journal of Neuroscience Methods, Volume 293
Author(s): Silke Smolders, Sofie Kessels, Sophie Marie-Thérèse Smolders, Florent Poulhes, Olivier Zelphati, Cedric Sapet, Bert Brône
BackgroundMicroglia, the resident phagocytic cells of the brain, have recently been the subject of intense investigation given their role in pathology and normal brain physiology. In general, phagocytic cells are hard to transfect with plasmid DNA. The BV2 cell line is a murine cell line of microglial origin which is often used to study this cell type in vitro. Unfortunately, this microglial cell line is, like other phagocytic cells, resistant to transfection.New methodMagnetofection is a well-established transfection method that combines DNA with magnetic particles which, under the influence of a magnetic field, ensures a high concentration of particles in proximity of cultured cells. Only recently, Glial-Mag was specifically developed for efficient transfection of microglia and microglial cell lines.ResultsMagnetofection with Glial-Mag yielded a transfection efficiency of 34.95% in BV2 cells, 24h after transfection with an eGFP-expressing plasmid. Efficient gene delivery caused a modest and short-lived cell activation (as measured by IL6 secretion) that ceased by 24h after transfection.Comparison with existing methodsHere we show that Glial-Mag magnetofection of BV2 cells yielded a significantly higher transfection efficiency (34.95%) compared to other chemical transfection methods including calcium-phoshate precipication (0.34%), X-tremeGENE (3.30%) and Lipofectamine 2000 (12.51%).ConclusionTransfection of BV2 cells using Glial-Mag magnetofection is superior compared to other chemical transfection methods and could be considered as the method of choice to chemically transfect microglial cell lines.



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Online detection of amplitude modulation of motor-related EEG desynchronization using a lock-in amplifier: Comparison with a fast Fourier transform, a continuous wavelet transform, and an autoregressive algorithm

Publication date: 1 January 2018
Source:Journal of Neuroscience Methods, Volume 293
Author(s): Kenji Kato, Kensho Takahashi, Nobuaki Mizuguchi, Junichi Ushiba
BackgroundNeurofeedback of event-related desynchronization (ERD) in electroencephalograms (EEG) of the sensorimotor cortex (SM1) using a brain–computer interface (BCI) paradigm is a powerful tool to promote motor recovery from post-stroke hemiplegia. However, the feedback delay attenuates the degree of motor learning and neural plasticity.New methodThe present study aimed to shorten the delay time to estimate amplitude modulation of the motor-imagery-related alpha and beta SM1-ERD using a lock-in amplifier (LIA) algorithm. The delay time was evaluated by calculating the value of the maximal correlation coefficient (MCC) between the time-series trace of ERDs extracted by the online LIA algorithm and those identified by an offline algorithm with the Hilbert transform (HT).ResultsThe MCC and delay values used to estimate the ERDs calculated by the LIA were 0.89±0.032 and 200±9.49ms, respectively.Comparison with Existing Method(s)The delay time and MCC values were significantly improved compared with those calculated by the conventional fast Fourier transformation (FFT), continuous Wavelet transformation (CWT), and autoregressive (AR) algorithms. Moreover, the coefficients of variance of the delay time and MCC values across trials were significantly lower in the LIA compared with the FFT, CWT, and AR algorithms.ConclusionsThese results indicate that the LIA improved the detection delay, accuracy, and stability for estimating amplitude modulation of motor-related SM1-ERD. This would be beneficial for BCI paradigms to facilitate neurorehabilitation in patients with motor deficits.



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Do alerting signals increase the size of the attentional focus?

Abstract

Previous research has shown that the presentation of an auditory alerting signal before a visual target increases the interference from flanking distractors. Recently, it has been suggested that this increase in interference may be due to an expansion of the spatial focus of attention. In five experiments, this hypothesis was tested by using a probe technique dedicated to measuring variations in the size of the attentional focus: In the majority of trials, participants performed a letter discrimination task in which their attention was focused on a central target letter. In a randomly intermixed probe task, the size of the attentional focus was measured by letting participants respond to a probe occurring at varying positions. In all experiments, reaction time (RT) to the probe increased from the most central to more lateral probe positions. This V-shaped probe-RT function, however, was not flattened by the presentation of an alerting signal. Overall, this pattern of results is inconsistent with the hypothesis that alerting signals increase the attentional focus. Instead, it is consistent with nonspatial accounts that attribute the increase in interference to an alerting effect on perceptual processing, which then leads to a detrimental effect at the level of response selection.

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Expanding Smoking Cessation Services at NCI-designated Cancer Centers: An Interview with Dr. Glen Morgan

NCI's Dr. Glen Morgan discusses NCI's Cancer Center Cessation Initiative, including how and why this smoking cessation initiative was developed and its long-term goals.

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Juvenile Nasopharyngeal Angiofibroma: Our Experience in a Tertiary Hospital

Abstract

Nasopharyngeal angiofibroma is a highly vascular tumor seen typically in young adolescent males. It is an uncommon tumor accounting for less than 0.5% of all head and neck tumors. This peculiar tumor is thought to arise from the area of the sphenopalatine foramen and it classically presents with progressive nasal obstruction and epistaxis. This is a retrospective study of angiofibroma treated at our hospital over 3 years. The study discusses about clinical features, management options and the role of embolization in reducing the intra-operative blood loss.

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Worsening Respiratory Distress in a 7-Month-Old Infant

A 7-month-old male presented with noisy breathing; he fed poorly from the bottle with frequent choking, grunting, and irritability; nasopharyngolaryngoscopy showed no laryngomalacia, laryngeal lesions, or cord paralysis. What is your diagnosis?

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Hearing Difficulty in the United States

This survey study analyzes the epidemiologic features and treatment patterns of hearing difficulty in the United States using data from responses from the 2014 National Health Interview Survey.

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Association of Neurocognitive Decline Treated With Radiotherapy or Chemoradiotherapy for Head and Neck Cancer

This prospective, longitudinal study assesses objective neurocognitive function before and after definitive radiation therapy for patients with head and neck cancer.

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First-Generation Deescalation Trials in HPV-Positive Oropharyngeal Cancer

This Viewpoint discusses the limitations of precision medicine in patients with human papillomavirus–positive oropharyngeal cancer.

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Efficacy and Safety of Titanium Miniplates in Septorhinoplasty

This case series evaluates the efficacy and safety of titanium miniplates for cartilaginous graft fixation in patients undergoing septorhinoplasty.

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Hybrid Cartilage-Modifying Otoplasty Technique and Outcomes

This observational study compares preoperative and postoperative measurements of the ears of patients who underwent hybrid cartilage-modifying otoplasty.

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Striatal dopamine in Parkinson's disease: A meta-analysis of imaging studies

Abstract

A meta-analysis of 141 PET and SPECT studies that have investigated striatal presynaptic dopamine function in Parkinson's disease (PD) was performed. Subregional estimates of striatal dopamine metabolism are presented. The aromatic L-amino-acid decarboxylase (AADC) defect appears to be consistently smaller than the dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) defects, suggesting up-regulation of AADC function in PD. The correlation between disease severity and dopamine loss appears linear but the majority of longitudinal studies point to a negative exponential progression pattern of dopamine loss in PD. This article is protected by copyright. All rights reserved.

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