Development of nonsteroidal glucocorticoid receptor modulators based on N-benzyl-N-(4-phenoxyphenyl)benzenesulfonamide scaffold

Publication date: Available online 29 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Hiromasa Yoshioka, Ayumi Yamada, Yuko Nishiyama, Hiroyuki Kagechika, Yuichi Hashimoto, Shinya Fujii
N-Benzyl-N-(4-phenoxyphenyl)benzenesulfonamide derivatives were developed as a novel class of nonsteroidal glucocorticoid receptor (GR) modulators, which are promising drug candidates for treating immune-related disorders. Focusing on the similarity of the GR and progesterone receptor (PR) ligand-binding domain (LBD) structures, we adopted our recently developed PR antagonist 10 as a lead compound and synthesized a series of derivatives. We found that the N-(4-phenoxyphenyl)benzenesulfonamide skeleton serves as a versatile scaffold for GR antagonists. Among them, 4-cyano derivative 14m was the most potent, with an IC50 value of 1.43 μM for GR. This compound showed good selectivity for GR; it retained relatively weak antagonistic activity toward PR (IC50 for PR: 8.00 μM; 250-fold less potent than 10), but showed no activity toward AR, ERα or ERβ. Interestingly, the 4-amino derivative 15a exhibited transrepression activity toward NF-κB in addition to GR-antagonistic activity, whereas 14m did not. The structure-activity relationship for transrepression was different from that for GR-antagonistic activity. Computational docking simulations suggested that 15a might bind to the ligand-binding pocket of GR in a different manner from 14m. These findings open up new possibilities for developing novel nonsteroidal GR modulators with distinctive activity profiles.

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Exploration of pyrrole derivatives to find an effective potassium-competitive acid blocker with moderately long-lasting suppression of gastric acid secretion

Publication date: Available online 27 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Haruyuki Nishida, Ikuo Fujimori, Yasuyoshi Arikawa, Keizo Hirase, Koji Ono, Kazuo Nakai, Nobuhiro Inatomi, Yasunobu Hori, Jun Matsukawa, Yasushi Fujioka, Akio Imanishi, Hideo Fukui, Fumio Itoh
With the aim to discover a novel excellent potassium-competitive acid blocker (P-CAB) that could perfectly overcome the limitations of proton pump inhibitors (PPIs), we tested various approaches based on pyrrole derivative 1 as a lead compound. As part of a comprehensive approach to identify a new effective drug, we tried to optimize the duration of action of the pyrrole derivative. Among the compounds synthesized, fluoropyrrole derivative 20j, which has a 2-F-3-Py group at position 5, fluorine atom at position 4, and a 4-Me-2-Py sulfonyl group at the first position of the pyrrole ring, showed potent gastric acid-suppressive action and moderate duration of action in animal models. On the basis of structural properties including a slightly larger Clog P value (1.95), larger log D value (0.48) at pH 7.4, and fairly similar pKa value (8.73) compared to those of the previously optimized compound 2a, compound 20j was assumed to undergo rapid transfer to the stomach and have a moderate retention time there after single administration. Therefore, compound 20j was selected as a new promising P-CAB with moderately long duration of action.

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Development of molecular tools based on the dopamine D3 receptor ligand FAUC 329 showing inhibiting effects on drug and food maintained behavior

Publication date: Available online 29 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Anne Stößel, Regine Brox, Nirupam Purkayastha, Harald Hübner, Carsten Hocke, Olaf Prante, Peter Gmeiner
Dopamine D3 receptor-mediated networks have been associated with a wide range of neuropsychiatric diseases, drug addiction and food maintained behavior, which makes D3 a highly promising biological target. The previously described dopamine D3 receptor ligand FAUC 329 (1) showed protective effects against dopamine depletion in a MPTP mouse model of Parkinson's disease. We used the radioligand [¹⁸F]2, a [¹⁸F]fluoroethoxy substituted analog of the lead compound 1 as a molecular tool for visualization of D3-rich brain regions including the islands of Calleja. Furthermore, structural modifications are reported leading to the pyrimidylpiperazine derivatives 3 and 9 displaying superior subtype selectivity and preference over serotonergic receptors. Evaluation of the lead compound 1 on cocaine-seeking behavior in non-human primates showed a substantial reduction in cocaine self-administration behavior and food intake.

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Derivatives of caffeic acid, a natural antioxidant, as the basis for the discovery of novel nonpeptidic neurotrophic agents

Publication date: Available online 27 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Fatemeh Moosavi, Razieh Hosseini, Hamid Rajaian, Tiago Silva, Diogo Magalhães e Silva, Luciano Saso, Najmeh Edraki, Ramin Miri, Fernanda Borges, Omidreza Firuzi
Neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease, threaten the lives of millions of people and the number of affected patients is constantly growing with the increase of the aging population. Small molecule neurotrophic agents represent promising therapeutics for the pharmacological management of neurodegenerative diseases. In this study, a series of caffeic acid amide analogues with variable alkyl chain lengths, including ACAF3 (C3), ACAF4 (C4), ACAF6 (C6), ACAF8 (C8) and ACAF12 (C12) were synthesized and their neurotrophic activity was examined by different methods in PC12 neuronal cells. We found that all caffeic acid amide derivatives significantly increased survival in PC12 neuronal cells in serum-deprived conditions at 25 μM, as measured by the MTT assay. ACAF4, ACAF6 and ACAF8 at 5 µM also significantly enhanced the effect of nerve growth factor (NGF) in inducing neurite outgrowth, a sign of neuronal differentiation. The neurotrophic effects of amide derivatives did not seem to be mediated by direct activation of tropomyosin receptor kinase A (TrkA) receptor, since K252a, a potent TrkA antagonist, did not block the neuronal survival enhancement effect. Similarly, the active compounds did not activate TrkA as measured by immunoblotting with anti-phosphoTrkA antibody. We also examined the effect of amide derivatives on signaling pathways involved in survival and differentiation by immunoblotting. ACAF4 and ACAF12 induced ERK1/2 phosphorylation in PC12 cells at 5 and 25 µM, while ACAF12 was also able to significantly increase AKT phosphorylation at 5 and 25 µM. Molecular docking studies indicated that compared to the parental compound caffeic acid, ACAF12 exhibited higher binding energy with phosphoinositide 3-kinase (PI3K) as a possible molecular target. Based on Lipinski's rule of five, all of the compounds obeyed3 molecular descriptors (HBD, HBA and MM) in drug-likeness test. Taken together, these findings show for the first time that caffeic amides possess strong neurotrophic effects exerted via modulation of ERK1/2 and AKT signaling pathways presumably by activation of PI3K and thus represent promising agents for the discovery of neurotrophic compounds for management of neurodegenerative diseases.

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Medicinal chemistry of antischistosomal drugs: Praziquantel and Oxamniquine

Publication date: Available online 27 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Vinícius Barros Ribeiro da Silva, Bruna Rafaella Koresch Leiva Campos, Jamerson Ferreira de Oliveira, Jean-Luc Decout, Maria do Carmo Alves de Lima
Neglected tropical diseases (NTDs) are a group of diseases that, besides prevailing in poverty conditions, contribute to the maintenance of social inequality, being a strong barrier to a country development. Schistosomiasis, a NTD, is a tropical and subtropical disease caused by the trematode Schistosoma mansoni (Africa, Middle East, Caribbean, Brazil, Venezuela, Suriname), japonicum (China, Indonesia, the Philippines), mekongi (several districts of Cambodia and the Lao People's Democratic Republic), intercalatum and guianensis (areas of tropical rainforests in Central Africa) and hematobium (Middle East Africa, Corsica, France) whose adult forms inhabit the mesenteric vessels of the host, while the intermediate forms are found in the aquatic gastropod snails of the genus Biomphalaria. Currently, Praziquantel (PZQ) is the first line drug chosen for the treatment of schistosomiasis according to the World Health Organization (WHO) Model List of Essential Medicines, 2015. PZQ chemotherapy is considered to be the most important development for decades in the treatment of schistosomiasis. Beside the PZQ, Oxamniquine (OXA) has been first described in 1969 and launched in Brazil by Pfizer under the name of Mansil® for oral administration. It has a lower cost when compared to PZQ, being active in the intestinal and hepatosplenic infections caused exclusively by S. mansoni, single species in Brazil. Both PZQ and OXA have limitations, as low efficacy in the treatment of acute schistosomiasis, low activity against S. mansoni in immature stages and resistance or tolerance, which is the reason why further research are still necessary for the development of a second generation of antischistosomal drugs. For the development of new PZQ analogs, three main strategies can be adopted: (a) synthesis and evaluation of PZQ analogues; (b) rational design of new pharmacophores; (c) discovery of new active compounds from screening programs on a large scale. Such (b) approache is difficult as the target of PZQ still unknown, the synthesis of new active analogues is possible from delineation of structure-activity relationships for PZQ. Thus, we proposed for a review article an accurate analysis of PZQ and OXA medicinal properties and uses, focusing on the pharmacochemical aspects of both drugs through 178 bibliographic references. The mechanisms of action will be discussed, with the latest information available in the literature (for the first time in the case of the Oxamniquine). Cases of resistance are also discussed. As both drugs are available as a racemic mixture the biological impact of their stereochemistry to activity and side effects are reviewed. The results obtained for the combination of PZQ and artemisinine derivatives against immature worms are also introduced in the discussion. Using the information about more than 200 PZQ new derivatives synthetized during almost 35 years since its discovery, a deep Structure-Activity Relationship (SAR) is also proposed in this study.

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Striatal dopaminergic modulation of reinforcement learning predicts reward—Oriented behavior in daily life

Publication date: Available online 29 April 2017
Source:Biological Psychology
Author(s): Zuzana Kasanova, Jenny Ceccarini, Michael J Frank, Thérèse van Amelsvoort, Jan Booij, Alexander Heinzel, Felix Mottaghy, Inez Myin-Germeys
Much human behavior is driven by rewards. Preclinical neurophysiological and clinical positron emission tomography (PET) studies have implicated striatal phasic dopamine (DA) release as a primary modulator of reward processing. However, the relationship between experimental reward-induced striatal DA release and responsiveness to naturalistic rewards, and therefore functional relevance of these findings, has been elusive.We therefore combined, for the first time, a DA D2/3 receptor [¹⁸F]fallypride PET during a probabilistic reinforcement learning (RL) task with a six day ecological momentary assessments (EMA) of reward-related behavior in the everyday life of 16 healthy volunteers. We detected significant reward-induced DA release in the bilateral putamen, caudate nucleus and ventral striatum, the extent of which was associated with better behavioral performance on the RL task across all regions. Furthermore, individual variability in the extent of reward-induced DA release in the right caudate nucleus and ventral striatum modulated the tendency to be actively engaged in a behavior if the active engagement was previously deemed enjoyable. This study suggests a link between striatal reward-related DA release and ecologically relevant reward-oriented behavior, suggesting an avenue for the inquiry into the DAergic basis of optimal and impaired motivational drive.



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Accuracy of a computed tomography scanning procedure to manufacture digital models

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Amir M. Darroudi, Anne Marie Kuijpers-Jagtman, Edwin M. Ongkosuwito, Christiaan Maarten Suttorp, Ewald M. Bronkhorst, K. Hero Breuning
IntroductionAccurate articulation of the digital dental casts is crucial in orthodontic diagnosis and treatment planning. We aimed to determine the accuracy of manufacturing digital dental casts from computed tomography scanning of plaster casts regarding linear dimensions and interarch relationships and to test whether eventual differences in interarch relationships between plaster and digital casts would affect orthodontic diagnostics.MethodsPlaster casts with the wax bites of 2 patients were used to create digital dental casts with a computed tomography scanner. This was repeated 4 times with a 1-week interval. Linear distances were measured on plaster and digital models twice by 2 observers. Next, the 4 digital models of each patient were scored twice by 5 observers for interarch variables.ResultsDigital vs plaster measurements showed high Pearson correlation coefficients (>0.954), whereas the mean difference was small (<0.1 mm) and not significant. The interarch scorings, however, showed significant differences for all variables, except overjet for model 1.ConclusionsWe found substantial interarch inaccuracies of the digital models. These inaccuracies are probably due to a lack of built-in "collision control" in the software and manual articulation of the digital models by a human operator.



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Editorial Board

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5





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Information for readers

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5





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Cytotoxic outcomes of orthodontic bands with and without silver solder in different cell lineages

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Letícia Spinelli Jacoby, Valnês da Silva Rodrigues Junior, Maria Martha Campos, Luciane Macedo de Menezes
IntroductionThe safety of orthodontic materials is a matter of high interest. In this study, we aimed to assess the in-vitro cytotoxicity of orthodontic band extracts, with and without silver solder, by comparing the viability outcomes of the HaCat keratinocytes, the fibroblastic cell lineages HGF and MRC-5, and the kidney epithelial Vero cells.MethodsSterilized orthodontic bands with and without silver solder joints were added to culture media (6 cm²/mL) and incubated for 24 hours at 37°C under continuous agitation. Subsequently, the cell cultures were exposed to the obtained extracts for 24 hours, and an assay was performed to evaluate the cell viability. Copper strip extracts were used as positive control devices.ResultsThe extracts from orthodontic bands with silver solder joints significantly reduced the viability of the HaCat, MRC-5, and Vero cell lines, whereas the viability of HGF was not altered by this material. Conversely, the extracts of orthodontic bands without silver solder did not significantly modify the viability index of all evaluated cell lines.ConclusionsExcept for HGF fibroblasts, all tested cell lines showed decreased viability percentages after exposure to extracts of orthodontic bands containing silver solder joints. These data show the relevance of testing the toxicity of orthodontic devices in different cell lines.



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Aristotle on generosity

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Rolf G. Behrents




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Understanding masticatory function in unilateral crossbites

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Tore L. Hansson




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ABO certification a valuable learning experience—not a marketing tool

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Warren D. Woods




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A challenge that is surmountable: Rethinking American Board of Orthodontics certification

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Alan J. Borislow




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Table of Contents

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5





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Rethinking American Board of Orthodontics certification

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Robert E. Williams




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Nonsurgical correction using miniscrew-assisted vertical control of a severe high angle with mandibular retrusion and gummy smile in an adult

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Xue-Dong Wang, Jie-Ni Zhang, Da-Wei Liu, Fei-fei Lei, Wei-tao Liu, Yang Song, Yan-Heng Zhou
Orthodontic treatment in adult patients with a skeletal discrepancy can be challenging. In this case report, we achieved both sagittal and vertical control by combining the classic sliding mechanics straight-wire technique with miniscrew anchorage. We treated a 21-year-old Chinese woman with a severe high mandibular plane angle, a retrusive chin, and a gummy smile. Her diagnosis included a skeletal Class II skull base with a mild anterior open bite, a protrusive maxilla, and a backwardly rotated mandible. This case underscores the importance of anchorage control in both the sagittal and vertical directions. First, we used miniscrews in the maxillary and mandibular buccal segments to obtain rigid anchorage. Next, we achieved good anterior and posterior vertical control with miniscrews in the maxillary anterior labial and posterior buccolingual segments. Intrusion of the maxillary molars contributed to deepening of the anterior overbite and counterclockwise rotation of the mandibular plane, which, in turn, improved the facial profile. Intrusion of the maxillary incisors contributed to correction of the gummy smile. After 1 year of retention, the patient had a stable, well-aligned dentition with ideal intercuspation and an improved facial contour. Our results thus suggest that placement of miniscrews in the anterior and posterior regions of the maxilla is effective for camouflaging a high-angle skeletal Class II defect. This technique requires minimal patient compliance and is particularly useful for correction of a high angle in an adult with a gummy smile.



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Serum and urine insulin-like growth factor-1 as biochemical growth maturity indicators

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Siddharth Mehta




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Logistic regression: Part 2

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Nikolaos Pandis




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Authors’ response

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Mohita Sinha, Tulika Tripathi, Priyank Rai, Santosh Kumar Gupta




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Feasibility of yttria-stabilized zirconia

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Sharanya Sabrish




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Authors’ response

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Matthew Stout, Brian Cook, Dwayne Arola, Hanson Fong, Ariel Raigrodski, Anne-Marie Bollen




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Correction

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5





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Your brother's gatekeeper

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Peter M. Greco




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Addition of ammonium-based methacrylates to an experimental dental adhesive for bonding metal brackets: Carious lesion development and bond strength after cariogenic challenge

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Patrícia Layane de Menezes Macedo Nascimento, Carine Tais Welter Meereis, Tamires Timm Maske, Fabrício Aulo Ogliari, Maximiliano Sérgio Cenci, Carmem Sílvia Pfeifer, André Luis Faria-e-Silva
IntroductionIn this study, we evaluated the caries inhibition and shear bond strength achieved with the addition of the antibacterial monomer [2-(Methacryloyloxy)ethyl] trimethylammonium chloride (MADQUAT) to an adhesive used to bond orthodontic brackets.MethodsExperimental adhesives were formulated with addition of 0% (control), 5%, or 10% MADQUAT followed by measurement of the degree of conversion. These adhesives were used to lute brackets to the enamel of premolars (n = 30). Biofilm from a microcosm model was cultivated in half of the specimens under cariogenic challenge for 5 days. The brackets were subjected to a shear bond strength test followed by measurement of the internal hardness of the enamel around the brackets to calculate the integrated mineral loss.ResultsThe addition of MADQUAT slightly increased the degree of conversion. Adhesive containing 10% MADQUAT significantly reduced the integrated mineral loss around the bracket but also resulted in the lowest values of bond strength. No effects on bond strength and integrated mineral loss were observed with the addition of 5% MADQUAT to the adhesive. The cariogenic challenge did not affect the bond strength and the failure mode.ConclusionsMADQUAT was effective to reduce the integrated mineral loss only when added to the adhesive at a concentration of 10% despite the reduction of bond strength.



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Evaluation of objective structured clinical examination for advanced orthodontic education 12 years after introduction

Publication date: May 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 151, Issue 5
Author(s): Henry W. Fields, Do-Gyoon Kim, Minjeong Jeon, Allen R. Firestone, Zongyang Sun, Shiva Shanker, Ana M. Mercado, Toru Deguchi, Katherine W.L. Vig
IntroductionAdvanced education programs in orthodontics must ensure student competency in clinical skills. An objective structure clinical examination has been used in 1 program for over a decade. The results were analyzed cross-sectionally and longitudinally to provide insights regarding the achievement of competency, student growth, question difficulty, question discrimination, and question predictive ability.MethodsIn this study, we analyzed 218 (82 first-year, 68 second-year, and 68 third-year classes) scores of each station from 85 orthodontic students. The grades originated from 13 stations and were collected anonymously for 12 consecutive years during the first 2 decades of the 2000s. The stations tested knowledge and skills regarding dental relationships, analyzing a cephalometric tracing, performing a diagnostic skill, identifying cephalometric points, bracket placement, placing first-order and second-order bends, forming a loop, placing accentuated third-order bends, identifying problems and planning mixed dentition treatment, identifying problems and planning adolescent dentition treatment, identifying problems and planning nongrowing skeletal treatment, superimposing cephalometric tracings, and interpreting cephalometric superimpositions. Results were evaluated using multivariate analysis of variance, chi-square tests, and latent growth analysis.ResultsThe multivariate analysis of variance showed that all stations except 3 (analyzing a cephalometric tracing, forming a loop, and identifying cephalometric points) had significantly lower mean scores for the first-year student class than the second- and third-year classes (P <0.028); scores between the second- and third-year student classes were not significantly different (P >0.108). The chi-square analysis of the distribution of the number of noncompetent item responses decreased from the first to the second years (P <0.0003), from the second to the third years (P <0.0042), and from the first to the third years (P <0.00003). The latent growth analysis showed a wide range of difficulty and discrimination between questions. It also showed continuous growth for some areas and the ability of 6 questions to predict competency at greater than the 80% level.ConclusionsObjective structure clinical examinations can provide a method of evaluating student performance and curriculum impact over time, but cross-sectional and longitudinal analyses of the results may not be complementary. Significant learning appears to occur during all years of a 3-year program. Valuable questions were both easy and difficult, discriminating and not discriminating, and came from all domains: diagnostic, technical, and evaluation/synthesis.



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Vaccine allergy

Publication date: Available online 27 April 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Philip Hei Li, Annette Wagner, Ryszard Rutkowski, Krzysztof Rutkowski




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Risk of obstructive sleep apnea in African American patients with chronic rhinosinusitis

Publication date: Available online 27 April 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Jessica W. Hui, Jason Ong, James J. Herdegen, Hajwa Kim, Christopher D. Codispoti, Vahid Kalantari, Mary C. Tobin, Robert P. Schleimer, Pete S. Batra, Phillip S. LoSavio, Mahboobeh Mahdavinia
BackgroundIt is widely known that patients with chronic rhinosinusitis (CRS) commonly experience sleep disruption. Many of these patients have the associated diagnosis of obstructive sleep apnea (OSA). However, little is known about the risk factors for developing OSA in the CRS population.ObjectiveTo identify the risk factors for OSA in CRS to determine who should be screened for OSA among patients with CRS.MethodsWe evaluated a large cohort of patients with confirmed diagnostic criteria for CRS. Patient medical records were reviewed to identify those with OSA confirmed by overnight polysomnography. Records were further reviewed for demographic information (age, sex, race, and ethnicity), body mass index, and medical history, including the presence of nasal polyps, asthma, aspirin-exacerbated respiratory disease, allergic rhinitis, and eczema. The number of endoscopic sinus operations, duration of CRS, presence of subjective smell loss, and computed tomography Lund-Mackay score were also ascertained.ResultsA total of 916 patients with CRS were included in the study. Implementation of a multivariable regression model for identifying adjusted risk factors revealed that African American patients had a significantly higher risk for OSA than white patients, with an adjusted odds ratio of 1.98 (95% confidence interval, 1.19–3.29). Furthermore, patients with CRS without nasal polyps were at higher risk for OSA, with an odds ratio of 1.63 (95% confidence interval, 1.02–2.61) compared with patients with CRS with nasal polyps.ConclusionAfrican American patients with CRS were at higher risk for OSA compared with white patients, and this patient group needs to be screened for OSA.



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Systemic reaction to timothy grass pollen sublingual immunotherapy

Publication date: Available online 27 April 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Anita Wasan, Anil Nanda




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Hypothyroidism in Carcinoma of the Tongue with Adjuvant Treatment.

Related Articles

Hypothyroidism in Carcinoma of the Tongue with Adjuvant Treatment.

Rambam Maimonides Med J. 2017 Mar 29;:

Authors: Kumari S, Gondi J, Nemade H, Chandra Sekhara Rao LM, Gudipudi D, Rao TS

Abstract
OBJECTIVE: The objective of this study was to evaluate the incidence of hypothyroidism with adjuvant treatment in oral tongue carcinoma patients treated primarily with surgery.
MATERIALS AND METHODS: A retrospective review was carried out to analyze hypothyroidism incidence and its relation to adjuvant treatment (radiation/radio-chemotherapy) in oral tongue carcinoma after the primary surgical ablation and neck dissection. Hypothyroidism was analyzed in relation with dose of radiation, gender, and adjuvant treatment modality.
RESULTS: The study analyzed the patients who were treated between January 2012 and June 2015. Among 705 patients with carcinoma of the tongue treated primarily with wide local excision and neck dissection, 383 received adjuvant treatment. A total of 215 patients received radiation, and 168 received concurrent radio-chemotherapy. Of 378 patients, 78 developed hypothyroidism during follow-up: 27 patients received concurrent radio-chemotherapy, and the remaining 51 received only radiation. Lower neck received 40-48 Gy in 2 patients, 50 Gy in 74 patients, and 60-70 Gy and concurrent radio-chemotherapy in 27 patients. Median follow-up was 32 months. Hypothyroidism occurred in 21.5% of patients with squamous cell carcinoma of the oral tongue. The minimum period to develop hypothyroidism was 3 months in this study. Gender and adjuvant treatment were not found to be significant for the incidence of hypothyroidism.
CONCLUSIONS: A significant number of patients with carcinoma of the tongue who receive adjuvant treatment will develop hypothyroidism, hence frequent monitoring of thyroid function is advised during follow-up.

PMID: 28448252 [PubMed - as supplied by publisher]

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Cariogenic properties of Streptococcus mutans clinical isolates with sortase defects

Publication date: September 2017
Source:Archives of Oral Biology, Volume 81
Author(s): Jinthana Lapirattanakul, Yukiko Takashima, Pornpen Tantivitayakul, Thaniya Maudcheingka, Pattarawadee Leelataweewud, Kazuhiko Nakano, Michiyo Matsumoto-Nakano
ObjectiveIn Streptococcus mutans, a Gram-positive pathogen of dental caries, several surface proteins are anchored by the activity of sortase enzyme. Although various reports have shown that constructed S. mutans mutants deficient of sortase as well as laboratory reference strains with a sortase gene mutation have low cariogenic potential, no known studies have investigated clinical isolates with sortase defects. Here, we examined the cariogenic properties of S. mutans clinical isolates with sortase defects as well as caries status in humans harboring such defective isolates.DesignSortase-defective clinical isolates were evaluated for biofilm formation, sucrose-dependent adhesion, stress-induced dextran-dependent aggregation, acid production, and acid tolerance. Additionally, caries indices of subjects possessing such defective isolates were determined.ResultsOur in vitro results indicated that biofilm with a lower quantity was formed by sortase-defective as compared to non-defective isolates. Moreover, impairments of sucrose-dependent adhesion and stress-induced dextran-dependent aggregation were found among the isolates with defects, whereas no alterations were seen in regard to acid production or tolerance. Furthermore, glucan-binding protein C, a surface protein anchored by sortase activity, was predominantly detected in culture supernatants of all sortase-defective S. mutans isolates. Although the sortase-defective isolates showed lower cariogenic potential because of a reduction in some cariogenic properties, deft/DMFT indices revealed that all subjects harboring those isolates had caries experience.ConclusionsOur findings suggest the impairment of cariogenic properties in S. mutans clinical isolates with sortase defects, though the detection of these defective isolates seemed not to imply low caries risk in the subjects harboring them.



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The effects of fluoride, strontium, theobromine and their combinations on caries lesion rehardening and fluoridation

Publication date: August 2017
Source:Archives of Oral Biology, Volume 80
Author(s): Frank Lippert
ObjectiveThe aim was to investigate the effects of fluoride, strontium, theobromine and their combinations on caries lesion rehardening and fluoridation (EFU) under pH cycling conditions.DesignHuman enamel specimens were demineralized at 37°C for 24h using a pH 5.0 solution containing 50mM lactic acid and 0.2% Carbopol 907 which was 50% saturated with respect to hydroxyapatite. Lesions were assigned to nine treatment groups (n=16) based on Knoop surface microhardness indentation length.Treatmentaqueous solutions were: placebo, 11.9mM sodium fluoride (F), 23.8mM sodium fluoride (2×F), 1.1mM strontium chloride hexahydrate (Sr), 1.1mM F theobromine, Sr+theobromine, F+Sr, F+theobromine, F+Sr+theobromine. Lesions were pH cycled for 5d (daily protocol: 3×1min-treatment; 2×60min-demineralization; 4×60min & overnight-artificial saliva). Knoop indentation length was measured again and%surface microhardness recovery (%SMHr) calculated. EFU was determined using the acid-etch technique. Data were analysed using ANOVA.ResultsModel showed fluoride dose-response for both variables (2×F>F>placebo). For%SMHr, F+Sr+/−theobromine resulted in more rehardening than F, however less than 2×F. F+theobromine was similar to F. For EFU, F+Sr was inferior to F, F+theobromine and F+Sr+theobromine which were similar and inferior to 2×F. In absence of fluoride, Sr, theobromine or Sr+theobromine were virtually indistinguishable from placebo and inferior to F.ConclusionsIt can be concluded that a) strontium aids rehardening but not EFU and only in presence of fluoride; b) theobromine does not appear to offer any anti-caries benefits in this model; c) there are no synergistic effects between strontium and theobromine in the presence or absence of fluoride.



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Insufficient sleep is prevalent among migraineurs: a population-based study

Sleep disorder and sleep complaints are common in subjects with migraine. Although the association between sleep disorders and migraine has been reported, the association between perceived insufficient sleep a...

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Lymphoepithelioma-like carcinoma of the upper urinary tract

Abstract

In this report, we summarized the clinicopathologic features of ten cases of lymphoepithelioma-like carcinoma (LELC) of the upper urinary tract (ureter n = 6; renal pelvis n = 4), a rare variant of urothelial cancer characterized by a malignant epithelial component densely infiltrated by lymphoid cells. The initial diagnosis was made on radical nephrectomy in five cases, nephroureterectomy in three cases, and ureterectomy in two others. Four patients had pathologic stage T1 (n = 2) or T2 (n = 2) tumors, and six patients had stage pT3 disease. Microscopically, all tumors contained pure (n = 3) or predominant (n = 7) LELC, which composed 60 to 80% of the entire tumor. Non-LELC tumor component was adenocarcinoma (n = 2), spindle cell carcinoma (n = 1), or high-grade conventional urothelial carcinoma (n = 4). The LELC component was characterized by indistinct cytoplasmic borders and a syncytial growth pattern. Immunohistochemical staining showed LELC to be positive for cytokeratin AE1/AE3, CK7, CK34ßE12 (rare cells), CK5/6 (rare cells), and CK20 (rare cells); rare cells were p40 positive. GATA 3 was positive in all cases in a variable proportion of cells (20–80%). Lymphoid markers showed a polyclonal proliferation of predominant T cells admixed with B cells. In situ hybridization for the HPV genome was negative in all ten cases. Survival analysis showed no differences between LELC and conventional upper urinary tract urothelial carcinoma, pT classification being the only significant prognostic parameter. Morphologic recognition and distinction from other (non-)neoplastic lesions with prominent lymphoid stroma are critical for its clinical management.

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Chemotherapy and tyrosine-kinase inhibitors for medullary thryoid cancer

Publication date: Available online 28 April 2017
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Julien Hadoux, Martin Schlumberger
Medullary thyroid cancer (MTC) represents 3% of all clinical thyroid cancers and arises from thyroid C cells that produce calcitonin. Locally advanced or metastatic MTC requires a careful work-up including measurement of serum calcitonin and carcinoembryonic antigen, determination of their doubling time and comprehensive imaging to determine the extent of the disease, its aggressiveness, and the need for treatment.Cytotoxic chemotherapy can control tumor burden in some patients with response rates of around 20% in old series. For the last 10 years, systemic therapy for MTC patients with large tumor burden and documented progression of the disease has involved the use of tyrosine kinase inhibitors targeting VEGFR and ret. Progression-free survival benefits have been demonstrated for both vandetanib and cabozantinib, as compared to placebo. Although these molecules are effective, they also have specific toxicity profiles which require a thorough clinical management in specialized centres. In the present review, we describe the work-up and treatment modalities of patients with advanced or metastatic medullary thyroid cancer with a focus on chemotherapy and targeted therapy results.



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rFSH in medically assisted procreation: Evidence for ovarian follicular hyperplasia and interest of mass spectrometry to measure 17-hydroxyprogesterone and Δ4-androstenedione in serum.

Publication date: Available online 28 April 2017
Source:Molecular and Cellular Endocrinology
Author(s): M.C. Menet, M.L. Hebert-Schuster, N. Lahlou, L. Marcellin, M.C. Leguy, V. Gayet, E. Guibourdenche
Ovarian monitoring requires the determination of serum estradiol and progesterone levels. We investigated whole follicular steroidogenesis under rFSH in medically assisted procreation (MAP: 26 IVF, 24 ICSI) compared to 11 controls (IUI). Estrone, estradiol, Δ4-androstenedione, testosterone, progesterone and 17-hydroxyprogesterone were measured by immunoassay and mass spectrometry except for estrogens.At the start of a spontaneous or induced cycle, steroids levels fluctuated within normal ranges: estradiol (314–585 pmol/L), estrone (165–379 pmol/L) testosterone (1.3–1.6 nmol/L), Δ4-androstenedione (4.5–5.6 nmol/L), 17-hydroxyprogesterone (2.1–2.2 nmol/L) and progesterone (1.8–1.9 nmol/L). 17-hydroxyprogesterone, Δ 4-androstenedione and estradiol predominated. Then estradiol and oestrone levels rise, but less markedly for oestrone in IUI. In MAP, rFSH injections induce a sharp increase in estrogens associated with a rise in 17-hydroxyprogesterone and Δ4-androstenedione levels, disrupting oestrogen/androgen ratios. rFSH stimulation induces an ovarian hyperplasia and Δ4pathway which could become abnormal. Determining 17-hydroxyprogesterone and Δ4-androstenedione levels with LC-MS/MS may therefore be useful in managing recurrent MAP failures.

Graphical abstract

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Vitamin D endocrinology on the cross-road between immunity and metabolism

Publication date: Available online 28 April 2017
Source:Molecular and Cellular Endocrinology
Author(s): An-Sofie Vanherwegen, Conny Gysemans, Chantal Mathieu
The effects of vitamin D on the immune function have been recognized for more than a quarter of a century. However, our understanding of the multifactorial nature of the effects of vitamin D at the cellular, molecular and metabolic level in different immune subsets of the innate and adaptive system has dramatically progressed during the last decades. In this review, we summarize the main metabolic pathways preferentially used in different subsets of T cells, B cells, macrophages and dendritic cells as well as the immunomodulatory effects of vitamin D on these cells. We will highlight the metabolic reprogramming happening in vitamin D-conditioned tolerogenic dendritic cells. A better knowledge of the dynamics of metabolic states in immune subsets and their possible roles in inflammation and autoimmunity may advance the development of novel immunotherapies. Likewise, the implications of effects of vitamin D on immunometabolism may progress our insights in the nature of immune responses in health and disease.



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Absence of Gim proteins, but not GimC complex, alter stress-induced transcription

Publication date: Available online 28 April 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Ana Fátima Amorim, Dora Pinto, Laurent Kuras, Lisete Fernandes
Saccharomyces cerevisiae GimC (mammalian Prefoldin) is a hexameric (Gim1–6) cytoplasmic complex involved in the folding pathway of actin/tubulin. In contrast to a shared role in GimC complex, we show that absence of individual Gim proteins results in distinct stress responses. No concomitant alteration in F-actin integrity was observed. Transcription of stress responsive genes is altered in gim2Δ, gim3Δ and gim6Δ mutants: TRX2 gene is induced in these mutants but with a profile diverging from type cells, whereas CTT1 and HSP26 fail to be induced. Remaining gimΔ mutants display stress transcript abundance comparable to wild type cells. No alteration in the nuclear localization of the transcriptional activators for TRX2 (Yap1) and CTT1/HSP26 (Msn2) was observed in gim2Δ. In accordance with TRX2 induction, RNA polymerase II occupancy at TRX2 discriminates the wild type from gim2Δ and gim6Δ. In contrast, RNA polymerase II occupancy at CTT1 is similar in wild type and gim2Δ, but higher in gim6Δ. The absence of active RNA polymerase II at CTT1 in gim2Δ, but not in wild type and gim1Δ, explains the respective CTT1 transcript outputs. Altogether our results put forward the need of Gim2, Gim3 and Gim6 in oxidative and osmotic stress activated transcription; others Gim proteins are dispensable. Consequently, the participation of Gim proteins in activated-transcription is independent from the GimC complex.

Graphical abstract

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Ehmt2/G9a controls placental vascular maturation by activating the Notch pathway [RESEARCH ARTICLE]

Lijun Chi, Abdalla Ahmed, Anna R. Roy, Sandra Vuong, Lindsay S. Cahill, Laura Caporiccio, John G. Sled, Isabella Caniggia, Michael D. Wilson, and Paul Delgado-Olguin

Defective fetoplacental vascular maturation causes intrauterine growth restriction (IUGR). A transcriptional switch initiates placental maturation where blood vessels elongate. However, cellular mechanisms and regulatory pathways involved are unknown. We show that the histone methyltransferase Ehmt2, also known as G9a, activates the Notch pathway to promote placental vascular maturation. Placental vasculature from embryos with G9a-deficient endothelial progenitor cells failed to expand due to decreased endothelial cell proliferation and increased trophoblast proliferation. Moreover, G9a deficiency altered the transcriptional switch initiating placental maturation and caused downregulation of Notch pathway effectors including Rbpj. Importantly, Notch pathway activation in G9a-deficient endothelial progenitors extended embryonic life and rescued placental vascular expansion. Thus, G9a activates the Notch pathway to balance endothelial cell and trophoblast proliferation and coordinates the transcriptional switch controlling placental vascular maturation. Accordingly, G9A and RBPJ were downregulated in human placentae from IUGR-affected pregnancies, suggesting that G9a is an important regulator in placental diseases caused by defective vascular maturation.

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Lmx1b-targeted cis-regulatory modules involved in limb dorsalization [RESEARCH ARTICLE]

Endika Haro, Billy A. Watson, Jennifer M. Feenstra, Luke Tegeler, Charmaine U. Pira, Subburaman Mohan, and Kerby C. Oberg

Lmx1b is a homeodomain transcription factor responsible for limb dorsalization. Despite striking double-ventral (loss-of-function) and double-dorsal (gain-of-function) limb phenotypes, no direct gene targets in the limb have been confirmed. To determine direct targets, we performed a chromatin immunoprecipitation against Lmx1b at E12.5 followed by next generation sequencing (ChIP-seq). Nearly 84% (n=617) of the Lmx1b-bound genomic intervals (LBIs) identified overlap with chromatin regulatory marks indicative of potential cis-regulatory modules (PCRMs). In addition, 73 LBIs mapped to known CRMs active during limb development. We compared Lmx1b-bound PCRMs to genes differentially expressed by Lmx1b and found 292 PCRMs within 1 Mb of 254 Lmx1b-regulated genes. Gene ontologic analysis suggests that Lmx1b targets extracellular matrix production, bone/joint formation, axonal guidance, vascular development, cell proliferation and cell movement. We validated the functional activity of a PCRM associated with joint-related Gdf5 that provides a mechanism for Lmx1b-mediated joint modification and a PCRM associated with Lmx1b that suggests a role in autoregulation. This is the first report to describe genome-wide Lmx1b binding during limb development, directly linking Lmx1b to targets that accomplish limb dorsalization.

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Negative regulation of Endothelin signaling by SIX1 is required for proper maxillary development [RESEARCH ARTICLE]

Andre L. P. Tavares, Timothy C. Cox, Robert M. Maxson, Heide L. Ford, and David E. Clouthier

Jaw morphogenesis is a complex event mediated by inductive signals that establish and maintain the distinct developmental domains required for formation of hinged jaws, the defining feature of gnathostomes. The mandibular portion of pharyngeal arch one is patterned dorsally by JAGGED-NOTCH signaling and ventrally by Endothelin receptor-A (EDNRA) signaling. Loss of EDNRA signaling disrupts normal ventral gene expression, the result of which is homeotic transformation of the mandible into a maxilla-like structure. However, loss of JAGGED-NOTCH signaling does not result in significant changes in maxillary development. Here we show that the transcription factor SIX1 regulates dorsal arch development not only by inducing dorsal Jag1 expression but also by inhibiting Endothelin1 (Edn1) expression in the pharyngeal endoderm of the dorsal arch, thus preventing dorsal EDNRA signaling. In the absence of SIX1, but not JAG1, aberrant EDNRA signaling in the dorsal domain results in partial duplication of the mandible. Together, our results illustrate that SIX1 is the central mediator of dorsal mandibular arch identity, thus ensuring separation of bone development between the upper and lower jaws.

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microRNA172 plays a critical role in wheat spike morphology and grain threshability [RESEARCH ARTICLE]

Juan Manuel Debernardi, Huiqiong Lin, Justin D. Faris, and Jorge Dubcovsky

Wheat domestication from wild species involved mutations in the Q gene. The q allele (wild wheats) is associated with elongated spikes and hulled grains, whereas the mutant Q allele (domesticated wheats) confers subcompact spikes and free-threshing grains. Previous studies showed that Q encodes an AP2-like transcription factor, but the causal polymorphism of the domestication traits remained unclear. Here we show that the interaction between microRNA172 (miR172) and the Q allele is reduced by an SNP in the miRNA binding site. The inhibition of miR172 activity by a miRNA target mimic resulted in compact spikes and transition from glumes to florets in distal spikelets. By contrast, overexpression of miR172 was sufficient to induce elongated spikes and non-free-threshing grains, similar to those observed in three Q loss-of-function mutations. These lines showed transitions from florets to glumes in the basal spikelets. These localized homeotic changes were associated with opposing miR172/ Q gradients along the spike. We propose that the selection of a nucleotide change at the miR172 binding site contributed to subcompact spikes and free-threshing grains during wheat domestication.

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ChIP-seq analysis of genomic binding regions of five major transcription factors in mouse epiblast stem cells that highlights a central role for ZIC2 [TECHNIQUES AND RESOURCES ARTICLE]

Kazunari Matsuda, Tomoyuki Mikami, Shinya Oki, Hideaki Iida, Munazah Andrabi, Jeremy M. Boss, Katsushi Yamaguchi, Shuji Shigenobu, and Hisato Kondoh

To obtain an insight into the transcription factor (TF)-dependent regulation of epiblast stem cells (EpiSCs), we performed ChIP-seq analysis of the genomic binding regions in EpiSCs of five major TFs, ZIC2, OTX2, SOX2, POU5F1, and POU3F1, using biotinylated TFs, identifying the following new features: (1) The genomic domains of megabase scale rich in ZIC2 peaks and genes, and those rich in POU3F1 but sparse in genes alternate in EpiSCs, reflecting the clustering of regulatory regions that act in short- and long-ranges, which involve binding of ZIC2 and POU3F1, respectively. (2) The enhancers bound by ZIC2 and OTX2 prominently regulate TF genes in EpiSCs. (3) The binding sites for SOX2 and POU5F1 in mouse embryonic stem cells (ESCs) and EpiSCs are divergent, reflecting the shift of major-acting TFs from SOX2/POU5F1 in ESCs to OTX2/ZIC2 in EpiSCs. (4) This shift in the major-acting TFs appears to be primed by binding of ZIC2 in ESCs at relevant genomic positions that later function as enhancers following the disengagement of SOX2/POU5F1from the major regulatory functions and subsequent binding by OTX2.

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New alleles of the wheat domestication gene Q reveal multiple roles in growth and reproductive development [RESEARCH REPORT]

Julian R. Greenwood, E. Jean Finnegan, Nobuyoshi Watanabe, Ben Trevaskis, and Steve M. Swain

The advantages of free threshing in wheat led to the selection of the domesticated Q allele which is now present in almost all modern wheat varieties. Q and the pre-domestication allele, q, encode an AP2 transcription factor with the domesticated allele conferring a free threshing character and a subcompact (i.e. partially compact) inflorescence (spike). We demonstrate that mutations in the miR172-binding site of the Q gene are sufficient to increase transcript levels via a reduction in miRNA dependent degradation, consistent with the conclusion that a SNP in the miRNA-binding site of Q relative to q was essential in defining the modern Q allele. We also describe novel gain- and loss-of-function alleles of Q and use these to define new roles for this gene in spike development. Q is required for the suppression of 'sham ramification' and increased Q expression can lead to the formation of ectopic florets and spikelets (specialized inflorescence branches that bear florets and grains) resulting in a deviation from the canonical spike and spikelet structures of domesticated wheat.

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Reinforcing nanomedicine using graphene family nanomaterials

Publication date: Available online 28 April 2017
Source:Journal of Controlled Release
Author(s): Jumana Abdul Jaleel, S. Sruthi, K. Pramod
Graphene is an allotrope of carbon which consists of single layered sp² hybridized carbon arranged in honey comb lattice. The fascinating properties such as ultrahigh surface area, high electrical and thermal conductivity and optical property made graphene a major point of research interest. Apart from their application in the field such as nanoelectronics, energy storage, engineering of nanocomposite materials, transistors, sensors, diodes, catalysis; they are also investigated in the field of nanomedicine. This review mainly focus on the applications of graphene in nanomedicine including drug delivery, cancer therapy, cellular imaging, gene therapy, photodynamic and photothermal therapy, antimicrobial activity, biosensing and tissue engineering, along with a short description of their unique physicochemical, biological properties and safety profile.

Graphical abstract

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Adaptation of the vertical vestibulo-ocular reflex in cats during low-frequency vertical rotation

Publication date: Available online 28 April 2017
Source:Auris Nasus Larynx
Author(s): Hiroaki Fushiki, Motoyoshi Maruyama, Hideo Shojaku
ObjectiveWe examined plastic changes in the vestibulo-ocular reflex (VOR) during low-frequency vertical head rotation, a condition under which otolith inputs from the vestibular system are essential for VOR generation.MethodsFor adaptive conditioning of the vertical VOR, 0.02Hz sinusoidal pitch rotation for one hour about the earth's horizontal axis was synchronized with out-of-phase vertical visual stimulation from a random dot pattern.ResultsA vertical VOR was well evoked when the upright animal rotated around the earth-horizontal axis (EHA) at low frequency due to the changing gravity stimulus and dynamic stimulation of the otoliths. After adaptive conditioning, the amplitude of the vertical VOR increased by an average of 32.1%.ConclusionOur observations showing plasticity in the otolithic contribution to the VOR may provide a new strategy for visual-vestibular mismatch training in patients with otolithic disorders. This low-frequency vertical head rotation protocol also provides a model for investigating the mechanisms underlying the adaptation of VORs mediated by otolith activation.



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The acceptability and tolerability of nasal douching in children with allergic rhinitis: a systematic review

Allergic rhinitis (AR) is a significant issue in children. Treatment options include allergen avoidance, pharmacotherapy and immunotherapy. The use of nasal saline douching (NSD) in children has recently gained acceptability. However, there is limited data regarding the acceptability and tolerability of NSD in children with AR.

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The effect of terrain on entheseal changes in the lower limbs

Abstract

One of the main factors involved in entheseal changes (EC) aetiology may be related to the physiological limits of biomechanical loading fixed during bone development, such that higher load during childhood and the adolescent growth spurt leads to a lower frequency of EC during adulthood. In this sense, it is possible that ECs may be related to overloading beyond an individual's normal physiological limits as established during childhood and adolescence.

This meta-analysis tested this aetiological possibility by studying the influence of terrain on the entheses of the lower extremities. The hypothesis is that individuals who inhabited rugged terrain have lower EC than those living in flat terrain. This is because biomechanical loads associated with rugged terrain will lead to a higher normal capacity (defined during skeletal development) mitigating the probability of overloading compared to those living in flat terrain who will therefore have a higher frequency of ECs. To test this, papers reporting EC frequencies in the lower limbs were analysed alongside the local terrain. Terrain was defined into two categories: flat or rugged based on altimetry profile, i.e. the average elevation gains and losses along four specific paths (North-South, East-West, Northwest-Southeast, Southwest-Northeast). Odds ratios were calculated to compare rugged and flat terrain.

The overall results are consistent with the hypothesis that overloading is a factor in EC aetiology. However, when the analysis is conducted by sex and side, this general trend does not always occur. Limitations such as the lack of standardized age ranges could be affecting the outcome, i.e. older individuals have a higher frequency of ECs. The findings of this analysis suggest that the theoretical assumptions associated with the cause of ECs require further testing and evaluation.

http://ift.tt/2oHlsiD

17beta-hydroxysteroid dehydrogenase type 5 is negatively correlated to apoptosis inhibitor GRP78 and tumor-secreted protein PGK1, and modulates breast cancer cell viability and proliferation

Publication date: Available online 27 April 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Dan Xu, Juliette A. Aka, Ruixuan Wang, Sheng-Xiang Lin
17beta-hydroxysteroid dehydrogenase type 5 (17β-HSD5) is an important enzyme associated with sex steroid metabolism in hormone-dependent cancer. However, reports on its expression and its prognostic value in breast cancer are inconsistent. Here, we demonstrate the impact of 17β-HSD5 expression modulation on the proteome of estrogen receptor-positive (ER+) breast cancer cells. RNA interference technique (siRNA) was used to knock down 17β-HSD5 gene expression in the ER+ breast cancer cell line MCF-7 and the proteome of the 17β-HSD5-knockdown cells was compared to that of MCF-7 cells using two-dimensional (2-D) gel electrophoresis followed by mass spectrometry analysis. Ingenuity pathway analysis (IPA) was additionally used to assess functional enrichment analyses of the proteomic dataset, including protein network and canonical pathways. Our proteomic analysis revealed only four differentially expressed protein spots (fold change>2, p<0.05) between the two cell lines. The four spots were up-regulated in 17β-HSD5-knockdown MCF-7 cells, and comprised 21 proteins involved in two networks and in functions that include apoptosis inhibition, regulation of cell growth and differentiation, signal transduction and tumor metastasis. Among the proteins are nucleoside diphosphate kinase A (NME1), 78 kDa glucose-regulated protein (GRP78) and phosphoglycerate kinase 1 (PGK1). We also showed that expression of 17β-HSD5 and that of the apoptosis inhibitor GRP78 are strongly but negatively correlated. Consistent with their opposite regulation, GRP78 knockdown decreased MCF-7 cell viability whereas 17β-HSD5 knockdown or inhibition increased cell viability and proliferation. Besides, IPA analysis revealed that ubiquitination pathway is significantly affected by 17β-HSD5 knockdown. Furthermore, IPA predicted the proto-oncogene c-Myc as an upstream regulator linked to the tumor-secreted protein PGK1. The latter is over-expressed in invasive ductal breast carcinoma as compared with normal breast tissue and its expression increased following 17β-HSD5 knockdown. Our present results indicate a 17β-HSD5 role in down-regulating breast cancer development. We thus propose that 17β-HSD5 may not be a potent target for breast cancer treatment but its low expression could represent a poor prognosis factor.



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Deep Image Mining for Diabetic Retinopathy Screening

Publication date: Available online 28 April 2017
Source:Medical Image Analysis
Author(s): Gwenolé Quellec, Katia Charrière, Yassine Boudi, Béatrice Cochener, Mathieu Lamard
Deep learning is quickly becoming the leading methodology for medical image analysis. Given a large medical archive, where each image is associated with a diagnosis, efficient pathology detectors or classifiers can be trained with virtually no expert knowledge about the target pathologies. However, deep learning algorithms, including the popular ConvNets, are black boxes: little is known about the local patterns analyzed by ConvNets to make a decision at the image level. A solution is proposed in this paper to create heatmaps showing which pixels in images play a role in the image-level predictions. In other words, a ConvNet trained for image-level classification can be used to detect lesions as well. A generalization of the backpropagation method is proposed in order to train ConvNets that produce high-quality heatmaps. The proposed solution is applied to diabetic retinopathy (DR) screening in a dataset of almost 90,000 fundus photographs from the 2015 Kaggle Diabetic Retinopathy competition and a private dataset of almost 110,000 photographs (e-ophtha). For the task of detecting referable DR, very good detection performance was achieved: Az=0.954 in Kaggle's dataset and Az=0.949 in e-ophtha. Performance was also evaluated at the image level and at the lesion level in the DiaretDB1 dataset, where four types of lesions are manually segmented: microaneurysms, hemorrhages, exudates and cotton-wool spots. For the task of detecting images containing these four lesion types, the proposed detector, which was trained to detect referable DR, outperforms recent algorithms trained to detect those lesions specifically, with pixel-level supervision. At the lesion level, the proposed detector outperforms heatmap generation algorithms for ConvNets. This detector is part of the Messidor® system for mobile eye pathology screening. Because it does not rely on expert knowledge or manual segmentation for detecting relevant patterns, the proposed solution is a promising image mining tool, which has the potential to discover new biomarkers in images.

Graphical abstract

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Slice-to-volume medical image registration: a survey

Publication date: Available online 28 April 2017
Source:Medical Image Analysis
Author(s): Enzo Ferrante, Nikos Paragios
During the last decades, the research community of medical imaging has witnessed continuous advances in image registration methods, which pushed the limits of the state-of-the-art and enabled the development of novel medical procedures. A particular type of image registration problem, known as slice-to-volume registration, played a fundamental role in areas like image guided surgeries and volumetric image reconstruction. However, to date, and despite the extensive literature available on this topic, no survey has been written to discuss this challenging problem. This paper introduces the first comprehensive survey of the literature about slice-to-volume registration, presenting a categorical study of the algorithms according to an ad-hoc taxonomy and analyzing advantages and disadvantages of every category. We draw some general conclusions from this analysis and present our perspectives on the future of the field.

Graphical abstract

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Continuous Representations of Brain Connectivity using Spatial Point Processes

Publication date: Available online 28 April 2017
Source:Medical Image Analysis
Author(s): Daniel Moyer, Boris A. Gutman, Joshua Faskowitz, Neda Jahanshad, Paul M. Thompson
We present a continuous model for structural brain connectivity based on the Poisson point process. The model treats each streamline curve in a tractography as an observed event in connectome space, here the product space of the gray matter/white matter interfaces. We approximate the model parameter via kernel density estimation. To deal with the heavy computational burden, we develop a fast parameter estimation method by pre-computing associated Legendre products of the data, leveraging properties of the spherical heat kernel. We show how our approach can be used to assess the quality of cortical parcellations with respect to connectivity. We further present empirical results that suggest that "discrete" connectomes derived from our model have substantially higher test-retest reliability compared to standard methods. In this, the expanded form of this paper for journal publication, we also explore parcellation free analysis techniques that avoid the use of explicit partitions of the cortical surface altogether. We provide an analysis of sex effects on our proposed continuous representation, demonstrating the utility of this approach.

Graphical abstract

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Adaptation of the vertical vestibulo-ocular reflex in cats during low-frequency vertical rotation

We examined plastic changes in the vestibulo-ocular reflex (VOR) during low-frequency vertical head rotation, a condition under which otolith inputs from the vestibular system are essential for VOR generation.

http://ift.tt/2oHbXzZ

Adaptation of the vertical vestibulo-ocular reflex in cats during low-frequency vertical rotation

We examined plastic changes in the vestibulo-ocular reflex (VOR) during low-frequency vertical head rotation, a condition under which otolith inputs from the vestibular system are essential for VOR generation.

http://ift.tt/2oHbXzZ

Influence of cement type and ceramic primer on retention of polymer-infiltrated ceramic crowns to a one-piece zirconia implant

Publication date: Available online 28 April 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Nadja Rohr, Stefan Brunner, Sabrina Märtin, Jens Fischer
Statement of problemThe best procedure for cementing a restoration to zirconia implants has not yet been established.PurposeThe purpose of this in vitro study was to measure the retention of polymer-infiltrated ceramic crowns to zirconia 1-piece implants using a wide range of cements. The effect of ceramic primer treatment on the retention force was also recorded. The retention results were correlated with the shear bond strength of the cement to zirconia and the indirect tensile strength of the cements to better understand the retention mechanism.Material and methodsThe retention test was performed using 100 polymer-infiltrated ceramic crowns (Vita Enamic) and zirconia implants (ceramic.implant CI) The crowns were cemented with either temporary cement (Harvard Implant semipermanent, Temp Bond), glass-ionomer cement (Ketac Cem), self-adhesive cement (Perma Cem 2.0, RelyX Unicem Automix 2, Panavia SA), or adhesive cement (Multilink Implant, Multilink Automix, Vita Adiva F-Cem, RelyX Ultimate, Panavia F 2.0, Panavia V5 or Panavia 21) (n=5). Additionally ceramic primer was applied on the intaglio crown surface and implant abutment before cementation for all adhesive cements (Multilink Implant, Multilink Automix: Monobond plus; RelyX Ultimate Scotchbond Universal; Vita Adiva F-Cem: Vita Adiva Zr-Prime; Panavia F2.0, Panavia V5: Clearfil Ceramic Primer) and 1 self-adhesive cement containing 10-methacryloyloxydecyl dihydrogen phosphate (MDP) (Panavia SA: Clearfil Ceramic Primer). Crown debond fracture patterns were recorded. Shear bond strength was determined for the respective cement groups to polished zirconia (n=6). The diametral tensile strength of the cements was measured (n=10). Statistical analysis was performed using 1-way or 2-way analysis of variance followed by the Fisher LSD test (α=.05) within each test parameter.ResultsAdhesive and self-adhesive resin cements had shear bond strength values of 0.0 to 5.3 MPa and revealed similar retention forces. Cements containing MDP demonstrated shear bond strength values above 5.3 MPa and displayed increased retention. The highest retention values were recorded for Panavia F 2.0 (318 ±28 N) and Panavia 21 (605 ±82 N). All other adhesive and self-adhesive resin cements attained retention values between 222 ±16 N (Multilink Automix) and 270 ±26 N (Panavia SA), which were significantly higher (P<.05) than glass-ionomer (Ketac Cem: 196 ±34 N) or temporary cement (Harvard Implant semipermanent: 43 ±6 N, Temp Bond: 127 ±13 N). Application of manufacturer-specific ceramic primer increased crown retention significantly only for Panavia SA.ConclusionsProducts containing MDP provided a high chemical bond to zirconia. Self-adhesive and adhesive resin cements with low chemical bonding capabilities to zirconia provided retention force values within a small range (220 to 290 N).



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Influence of laser irradiation on the push-out bond strength between a glass fiber post and root dentin

Publication date: Available online 28 April 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Karla G.F. Gomes, Natália S. Faria, Walter R. Neto, Vivian Colucci, Erica A. Gomes
Statement of problemA major issue related to the failure of endodontically treated teeth restored with an intraradicular post is gradual debonding of the glass fiber post, resin cement, and dentin.PurposeThe purpose of this in vitro study was to evaluate the influence of laser irradiation on the push-out bond strength of glass fiber posts to radicular dentin.Material and methodsThirty-two mandibular bovine incisors were endodontically treated and divided into 4 groups according to the surface treatment of the post: silane control (GC); irradiation with Er:YAG (GYAG); irradiation with Er,Cr:YSGG (GCR); and 980-nm diode laser (GDI) application. After surface treatment, the glass fiber posts were cemented with dual adhesive resin cement. To evaluate bond strength, the specimens were subjected to a push-out test at a crosshead speed of 0.5 mm/min using a universal testing machine. Failure mode was analyzed using stereomicroscopy. The surface morphology was evaluated qualitatively after surface treatment by using confocal laser microscopy. The push-out test data (MPa) were analyzed using a linear mixed effects model and the Bonferroni test (α=.05).ResultsAt the cervical third, no significant differences were observed between the GC and GCR groups (P=1.00), and both of the groups exhibited higher bond strength. At the middle and apical thirds, the GCR group revealed higher bond strength, which was significantly different from that observed in all other groups (P<.05). No statistical differences were observed among the other tested protocols (GC, GYAG, and GDI groups; P=1.00). Adhesive failure was predominant in all groups.ConclusionsIrradiation with Er,Cr:YSGG improved the bond strength of the cement-post-dentin interfaces.



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Synthesis of vegetable-oil based polymer by terpolymerization of epoxidized soybean oil, propylene oxide and carbon dioxide

Publication date: 15 November 2017
Source:Science of The Total Environment, Volume 598
Author(s): Farra Wahida Shaarani, Jordi J. Bou
Although carbon dioxide (CO2) is well known as one of the major green-house gases, it is also an economical C1 resource. Thus, CO2 has been regarded as an appealing starting material for the synthesis of polymers, like polycarbonates by the reaction with epoxides. Herein the reaction between natural epoxidized soybean oil (ESO), propylene oxide (PO) and CO2 under high pressure (4.0MPa) with the presence of Co-Zn double metal cyanide (Co-Zn DMC) catalyst was studied. Temperature and reaction time were varied accordingly and the products obtained were characterized by FTIR, GPC and ¹H NMR. The results obtained indicate the formation of polycarbonates in the samples collected with yields vary from 60 to 85%. The number average molecular weight (Mn) of the resultant polymer prepared at reaction temperature of 80°C and reaction time of 6h can reach up to 6498g/mol.

Graphical abstract

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Chemical contaminants (trace metals, persistent organic pollutants) in albacore tuna from western Indian and south-eastern Atlantic Oceans: Trophic influence and potential as tracers of populations

Publication date: 15 October 2017
Source:Science of The Total Environment, Volumes 596–597
Author(s): Tiphaine Chouvelon, Christophe Brach-Papa, Dominique Auger, Nathalie Bodin, Sandrine Bruzac, Sylvette Crochet, Maxime Degroote, Stephanie J. Hollanda, Clarisse Hubert, Joël Knoery, Catherine Munschy, Alexis Puech, Emmanuelle Rozuel, Bastien Thomas, Wendy West, Jérôme Bourjea, Natacha Nikolic
Albacore tuna (Thunnus alalunga) is a highly commercial fish species harvested in the world's Oceans. Identifying the potential links between populations is one of the key tools that can improve the current management across fisheries areas. In addition to characterising populations' contamination state, chemical compounds can help refine foraging areas, individual flows and populations' structure, especially when combined with other intrinsic biogeochemical (trophic) markers such as carbon and nitrogen stable isotopes. This study investigated the bioaccumulation of seven selected trace metals – chromium, nickel, copper (Cu), zinc (Zn), cadmium (Cd), mercury (Hg) and lead – in the muscle of 443 albacore tunas, collected over two seasons and/or years in the western Indian Ocean (WIO: Reunion Island and Seychelles) and in the south-eastern Atlantic Ocean (SEAO: South Africa). The main factor that explained metal concentration variability was the geographic origin of fish, rather than the size and the sex of individuals, or the season/year of sampling. The elements Cu, Zn, Cd and Hg indicated a segregation of the geographic groups most clearly. For similar sized-individuals, tunas from SEAO had significantly higher concentrations in Cu, Zn and Cd, but lower Hg concentrations than those from WIO. Information inferred from the analysis of trophic markers (δ¹³C, δ¹⁵N) and selected persistent organic pollutants, as well as information on stomach contents, corroborated the geographical differences obtained by trace metals. It also highlighted the influence of trophic ecology on metal bioaccumulation. Finally, this study evidenced the potential of metals and chemical contaminants in general as tracers, by segregating groups of individuals using different food webs or habitats, to better understand spatial connectivity at the population scale. Limited flows of individuals between the SEAO and the WIO are suggested. Albacore as predatory fish also provided some information on environmental and food web chemical contamination in the different study areas.

Graphical abstract

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A new highly selective chemosensor for the detection of iron ion in aqueous medium based on click generated triazole

Publication date: October 2017
Source:Sensors and Actuators B: Chemical, Volume 249
Author(s): Kiramat Shah, Noor ul Ain, Farid Ahmed, Itrat Anis, Muhammad Raza Shah
A new click generated triazole based chemosensor 5 was designed and synthesized, that exhibits excellent selectivity for Fe⁺³ ion over a wide range of tested metal ions e.g. NH4⁺, Li⁺, Na⁺, K⁺, Cu⁺, Ag⁺, Ca⁺², Ni⁺², Co⁺², Cd⁺², Mg⁺², Cu⁺², Zn⁺², Pb⁺², Hg⁺², In⁺³, La⁺³and Y⁺³ in an aqueous medium without any remarkable interference. With Fe⁺³, the sensor 5 showed enhancement in absorption intensity at wavelength of 262nm. The sensor forms a host-guest complex in 1:1 stoichiometry with the detection limit down to 3.21μM. The interaction was also confirmed by FT-IR, ¹H NMR and FAB showing the Sensor 5–Fe⁺³ adduct at 495. Further, the sensor was successfully utilized to detect Fe⁺³ in human blood plasma and laboratory tap water as well.



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Synthesis, spectral, thermal and optical properties of Schiff-base complexes derived from 2(E)-2-((z)-4-hydroxypent-3-en-2-ylideneamino)-5-guanidinopentanoic acid and acetylacetone

Publication date: 5 September 2017
Source:Journal of Molecular Structure, Volume 1143
Author(s): Nasser Mohammed Hosny, Mostafa A. Hussien, Fatima M. Radwan, Nagwa Nawar
New metal complexes derived from the in situ reaction of Cu(II), Co(II), Ni(II) and Zn(II) acetates with the Schiff-base ligand (H2L) resulted from the condensation of 2-amino-5-guanidinopentanoic acid (arginine) and acetylacetone have been synthesized. The resulting complexes have been characterized by, elemental analyses, ES-MS, IR, Raman spectra, UV–Vis., ¹HNMR, ESR, thermal analyses (TGA and DTG) and magnetic measurements. The results showed that, The Schiff-base ligand acts as bi-negative tridentate coordinating via azomethine nitrogen, enolic carbonyl oxygen and carboxylate oxygen after displacement of hydrogen. The thermodynamic parameters E^∗, ΔH, ΔG and ΔS of the isolated complexes have been calculated. The optical band gap (Eg) values of Cu, Co, Ni and Zn were found to be 3.3, 3.4, 3.7 and 4.3 eV, respectively, arising from direct transitions. Optical band gap measurements indicate the semi-conductivity nature of these complexes.

Graphical abstract

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Fixation of fractures of the condylar head of the mandible with a new magnesium-alloy biodegradable cannulated headless bone screw

It is difficult to fix fractures of the condylar head of the mandible. Several techniques have been described which show satisfactory outcomes, but stability can be questionable, and some can cause irritation of the soft tissues. We describe a technique and first results of treating such fractures with resorbable magnesium-based headless bone screws (Magnezix® 2.7mm CS; Syntellix AG, Hanover, Germany).

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Long-term therapeutic effects of dextrose prolotherapy in patients with hypermobility of the temporomandibular joint: a single-arm study with 1-4 years’ follow up

The aim was to analyse the short-term and long-term therapeutic efficacy of dextrose prolotherapy for dislocation or subluxation (hypermobility) of the temporomandibular joint (TMJ). Sixty-one patients with symptomatic hypermobility of the TMJ were included in this single-arm prospective study, in which they were each given four sessions of intra-articular and pericapsular injections six weeks apart. Each injection comprised 10% dextrose/mepivacaine solution 3ml. Clinical outcomes including severity of pain on movement according to the numerical rating scale (NRS), maximal interincisal opening, clicking, and frequency of locking were measured before treatment (T1), during treatment (T2) (just before the third session of injections), at the short-term follow-up (T3) (three months after treatment), and at the long-term follow-up (T4) (1-4 years after treatment).

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The Effect of a Vocal Loading Test on Cough and Phonation in Patients With Chronic Cough

Talking is a significant trigger for cough in patients with chronic cough; however, the stimulus required to trigger cough has not been quantified. The aim of this study was to examine the effect of a vocal loading task on phonation and cough behavior in patients with chronic cough and identify change following therapy.

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Singing Lessons for Respiratory Health: A Literature Review

Several studies have explored the role of music and singing as a treatment for respiratory symptoms. The objective of this paper was to review the current body of literature in regard to the use of singing as both a physiological and a psychological therapy for respiratory disease and assess the role the singing teacher might play in this treatment.

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Corrigendum to “Prevalence and predictors of obstructive sleep apnea in young children with Down syndrome” [Sleep Med 27–28 (2016) 99–106]

The authors regret that the following text was omitted from the Acknowledgements section: We acknowledge the support of the Southampton NIHR Wellcome Trust Clinical Research Facility. The authors would like to apologise for any inconvenience caused.

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A rare complication of tonsillitis: septic arthritis of the temporomandibular joint

Septic arthritis of the temporomandibular joint (TMJ) is a rarely seen clinical condition. Such an infection may be encountered following infections in the head and neck region, with direct or haematogenous spread to the joint. This article presents the case of a patient with tonsillitis leading to septic arthritis of the TMJ and reports the results of a review of the literature.

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Multi-center machine learning in imaging psychiatry: A meta-model approach

Publication date: 15 July 2017
Source:NeuroImage, Volume 155
Author(s): Petr Dluhoš, Daniel Schwarz, Wiepke Cahn, Neeltje van Haren, René Kahn, Filip Španiel, Jiří Horáček, Tomáš Kašpárek, Hugo Schnack
One of the biggest problems in automated diagnosis of psychiatric disorders from medical images is the lack of sufficiently large samples for training. Sample size is especially important in the case of highly heterogeneous disorders such as schizophrenia, where machine learning models built on relatively low numbers of subjects may suffer from poor generalizability. Via multicenter studies and consortium initiatives researchers have tried to solve this problem by combining data sets from multiple sites. The necessary sharing of (raw) data is, however, often hindered by legal and ethical issues. Moreover, in the case of very large samples, the computational complexity might become too large. The solution to this problem could be distributed learning. In this paper we investigated the possibility to create a meta-model by combining support vector machines (SVM) classifiers trained on the local datasets, without the need for sharing medical images or any other personal data. Validation was done in a 4-center setup comprising of 480 first-episode schizophrenia patients and healthy controls in total. We built SVM models to separate patients from controls based on three different kinds of imaging features derived from structural MRI scans, and compared models built on the joint multicenter data to the meta-models. The results showed that the combined meta-model had high similarity to the model built on all data pooled together and comparable classification performance on all three imaging features. Both similarity and performance was superior to that of the local models. We conclude that combining models is thus a viable alternative that facilitates data sharing and creating bigger and more informative models.

Graphical abstract

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Analysis of chronic myofascial pain in the upper trapezius muscle of breast cancer survivors and women with neck pain

Publication date: Available online 28 April 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Almir Vieira Dibai-Filho, Rinaldo Roberto de Jesus Guirro, Vânia Tie Koga Ferreira, Alessandra Kelly de Oliveira, Ana Maria de Almeida, Elaine Caldeira de Oliveira Guirro
Myofascial trigger points are present in dysfunctioning muscles and are associated with several diseases. However, the scientific literature has not established whether myofascial trigger points from different underlying diseases have the same clinical characteristics. Thus, the objective of the present study was to compare the intensity of myofascial pain, catastrophizing, and the pressure pain threshold at myofascial trigger points among breast cancer survivors and women with neck pain. This was a cross-sectional study that included women over 18 years old complaining of myofascial pain in the upper trapezius muscle region for more than 90 days, equally divided into breast cancer survivors (n = 30) and those with neck pain (n = 30). For inclusion, the presence of a bilateral, active, and centrally located mean distance from C7 to acromion in the upper trapezius was mandatory. The measures of assessment were: pain intensity, catastrophizing, and the pressure pain threshold at the myofascial trigger points. A significant difference was observed only when comparing pain intensity (p < 0.001) between the breast cancer survivors (median score: 8.00 points, first quartile: 7.00 points, third quartile: 8.75 points) and women with neck pain (median score: 2.50 points, first quartile: 2.00 points, third quartile: 4.00 points). No significant difference was found between groups in catastrophizing and pressure pain threshold. The conclusion of this study was that breast cancer survivors have a higher intensity of myofascial pain in the upper trapezius muscle when compared to patients with neck pain, which indicates the need for evaluation and a specific intervention for the myofascial dysfunction of these women.



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Acute electromyographic responses of deep thoracic paraspinal muscles to spinal manual therapy interventions. An experimental, randomized cross-over study

Publication date: Available online 28 April 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Gary Fryer, Michael Bird, Barry Robbins, Jane C. Johnson
This single group, randomized, cross-over study explored whether manual therapy alters motor tone of deep thoracic back muscles by examining resting electromyographic activity (EMG) after 2 types of manual therapy and a sham control intervention. Twenty-two participants with thoracic spinal pain (15 females, 7 males, mean age 28.1±6.4 years) had dual fine-wire, intramuscular electrodes inserted into deep transversospinalis muscles at a thoracic level where tissues appeared abnormal to palpation (AbP) and at 2 sites above and below normal and non-tender to palpation (NT). A surface electrode was on the contralateral paraspinal mass at the level of AbP. EMG signals were recorded for resting prone, two 3-second free neck extension efforts, two 3-second resisted maximal voluntary isometric contractions (MVIC), and resting prone before the intervention. Randomized spinal manipulation, counterstrain, or sham manipulation was delivered and EMG re-measured. Participants returned 1 and 2 weeks later for the remaining 2 treatments. Reductions in resting EMG followed counterstrain in AbP (median decrease 3.3%, P=.01) and NT sites (median decrease 1.0%, P=.05) and for the surface electrode site (median decrease 2.0%, P=.009). Reduction in EMG following counterstrain during free neck extension was found for the surface electrode site (median decrease 2.7%, P<.01). Spinal manipulation produced no change in EMG, whereas counterstrain technique produced small significant reductions in paraspinal muscle activity during prone resting and free neck extension conditions. The clinical relevance of these changes is unclear.



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Reply

Truly, the described clinical scenario1 had its origins in 1999 with the discovery and ongoing characterization of IL-18 binding protein (IL-18BP) by Novick et al.2 We are grateful for their correspondence detailing the salient properties of this molecule.3 Regrettably, our original article was unable to include such details due to space limitations and the need to provide sufficient detail on the clinical scenario presented. We obviously agree that this molecule is well suited to the task of therapeutically blocking IL-18.

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IL-18 binding protein reverses the life-threatening hyperinflammation of a baby with the NLRC4 mutation

We read with excitement the article titled "Life-threatening NLRC4-associated hyperinflammation successfully treated with Interleukin-18 inhibition" by Canna et al.1 We congratulate the authors for this outstanding diagnostic and therapeutic triumph. This article also represents translation from the bench of a unique protein, the IL-18 binding protein (IL-18BP),2 into a targeted therapy drug that saved the life of this child. IL-18BP was an unexpected discovery and we believe that a short description of its unique features3,4 is useful to scientists and essential to clinicians and therefore should have been included in the publication of Canna et al.

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Integrated, exposure-based treatment for PTSD and comorbid substance use disorders: Predictors of treatment dropout

Publication date: October 2017
Source:Addictive Behaviors, Volume 73
Author(s): Derek D. Szafranski, Alexandra Snead, Nicholas P. Allan, Daniel F. Gros, Therese Killeen, Julianne Flanagan, Irene Pericot-Valverde, Sudie E. Back
High rates of comorbid posttraumatic stress disorder (PTSD) and substance use disorders (SUD) have been noted in veteran populations. Fortunately, there are a number of evidence-based psychotherapies designed to address comorbid PTSD and SUD. However, treatments targeting PTSD and SUD simultaneously often report high dropout rates. To date, only one study has examined predictors of dropout from PTSD/SUD treatment. To address this gap in the literature, this study aimed to 1) examine when in the course of treatment dropout occurred, and 2) identify predictors of dropout from a concurrent treatment for PTSD and SUD. Participants were 51 male and female veterans diagnosed with current PTSD and SUD. All participants completed at least one session of a cognitive-behavioral treatment (COPE) designed to simultaneously address PTSD and SUD symptoms. Of the 51 participants, 22 (43.1%) dropped out of treatment prior to completing the full 12 session COPE protocol. Results indicated that the majority of dropout (55%) occurred after session 6, with the largest amount of dropout occurring between sessions 9 and 10. Results also indicated a marginally significant relationship between greater baseline PTSD symptom severity and premature dropout. These findings highlight inconsistencies related to timing and predictors of dropout, as well as the dearth of information noted about treatment dropout within PTSD and SUD literature. Suggestions for procedural changes, such as implementing continual symptom assessments during treatment and increasing dialog between provider and patient about dropout were made with the hopes of increasing consistency of findings and eventually reducing treatment dropout.



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Ultrasound-guided fine-needle aspiration of hyperenhancing lesion suspicious for pancreatic neuroendocrine tumor in the tail of pancreas-potential pitfalls

Kinda Hayek, Tatyana Kalinicheva, Vinod B Shidham

CytoJournal 2017 14(1):8-8



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Cytomorphologic features distinguishing Bethesda category IV thyroid lesions from parathyroid

Simon Sung, Anjali Saqi, Elizabeth M Margolskee, John P Crapanzano

CytoJournal 2017 14(1):10-10

Background: Thyroid follicular cells share similar cytomorphological features with parathyroid. Without a clinical suspicion, the distinction between a thyroid neoplasm and an intrathyroidal parathyroid can be challenging. The aim of this study was to assess the distinguishing cytomorphological features of parathyroid (including intrathyroidal) and Bethesda category IV (Beth-IV) thyroid follicular lesions, which carry a 15%–30% risk of malignancy and are often followed up with surgical resection. Methods: A search was performed to identify "parathyroid" diagnoses in parathyroid/thyroid-designated fine-needle aspirations (FNAs) and Beth-IV thyroid FNAs (follicular and Hurthle cell), all with diagnostic confirmation through surgical pathology, immunocytochemical stains, Afirma® analysis, and/or clinical correlation. Unique cytomorphologic features were scored (0-3) or noted as present versus absent. Statistical analysis was performed using R 3.3.1 software. Results: We identified five FNA cases with clinical suspicion of parathyroid neoplasm, hyperthyroidism, or thyroid lesion that had an eventual final diagnosis of the parathyroid lesion (all female; age 20–69 years) and 12 Beth-IV diagnoses (11 female, 1 male; age 13–64 years). The following cytomorphologic features are useful distinguishing features (P value): overall pattern (0.001), single cells (0.001), cell size compared to red blood cell (0.01), nuclear irregularity (0.001), presence of nucleoli (0.001), nuclear-to-cytoplasmic ratio (0.007), and nuclear chromatin quality (0.028). Conclusions: There are cytomorphologic features that distinguish Beth-IV thyroid lesions and (intrathyroidal) parathyroid. These features can aid in rendering correct diagnoses and appropriate management.

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Indian visceral leishmaniasis with extensive lymphadenopathy – An unusual presentation: A case report with literature review

Poojan Agarwal, Vijay Kumar, Manju Kaushal, Manju Kumari, Arvind Chaudhary

CytoJournal 2017 14(1):9-9

Visceral leishmaniasis (VL), also known as kala-azar, is a life-threatening systemic disease caused by the obligate intracellular protozoan, Leishmania, and transmitted to humans by the female phlebotomine sand fly (Phlebotomus argentipes). The disease is fatal, if left untreated. We report a case of a patient clinically suspected of disseminated tuberculosis, but fine needle aspiration cytology of cervical and axillary lymph nodes yielded a diagnosis of leishmaniasis. Diagnosis of VL was challenging as the disease closely mimicked tuberculosis in the setting of extensive lymphadenopathy including conglomerate of mesenteric lymph nodes, on and off fever, and granulomatous lymphadenitis on aspiration. Bone marrow examination was further performed. A detailed workup revealed patient to be severely immunocompromised and newly diagnosed human immunodeficiency virus (HIV) positive. Worldwide, India has the largest number of VL cases, accounting for 40%–50% of world's disease burden and the second largest HIV-infected population, accounting for approximately 10% of the global disease burden. HIV increases the risk of developing VL by 100–2320 times in endemic areas and concurrently VL promotes the clinical progression of HIV disease. Co-infection with HIV alters the body's immune response to leishmaniasis thus leading to unusual presentations. This case highlights the diagnostic problem in the aforesaid setting. Moreover, co-infection with HIV in VL can be a potential source of drug resistance. An early diagnosis and intensified treatment is the key to patient management.

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Innate Immune Gene Transcript Level Associated with the Infection of Macrophages with Ectromelia Virus in Two Different Mouse Strains

Viral Immunology , Vol. 0, No. 0.


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High Rate of Hepatitis B Virus Surface Antigenemia Among People Living with HIV/AIDS in Kakuri, Kaduna State, North West Nigeria

Viral Immunology , Vol. 0, No. 0.


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Verbal working memory and reading abilities among students with visual impairment

Publication date: May 2017
Source:Research in Developmental Disabilities, Volume 64
Author(s): Vassilios Argyropoulos, Elvira Masoura, Thomai K. Tsiakali, Magda Nikolaraizi, Christina Lappa
AimThis study investigated the relationship between working memory (WM) and reading abilities among students with visual impairment (VI). Seventy-five students with VI (visually impairment and blindness), aged 10–15 years old participated in the study, of whom 44 were visually impaired and 31 were blind.MethodsThe participants' reading ability was assessed with the standardized reading ability battery Test-A (Padeliadu & Antoniou, 2008) and their verbal working memory ability was assessed with the listening recall task from the Working Memory Test Battery for Children (Pickering et al., 2001).Results-Implications: Data analysis indicated a strong correlation between verbal WM and decoding, reading comprehension and overall reading ability among the participants with VI, while no correlation was found between reading fluency and verbal WM. The present study points out the important role of verbal WM in reading among students who are VI and carries implications for the education of those individuals.



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Development and Validation of Two Measures of Emotional Contrast Avoidance: The Contrast Avoidance Questionnaires

Publication date: Available online 28 April 2017
Source:Journal of Anxiety Disorders
Author(s): Sandra J. Llera, Michelle G. Newman
The Contrast Avoidance (CA) model (Newman & Llera, 2011) proposed that individuals with generalized anxiety disorder (GAD) fear sharp emotional shifts (or contrasts), such as the shift from a pleasant or neutral state to one of sudden distress following a negative event. Further, the model suggests that chronic worry is employed by those with GAD to sustain negative emotionality as a means to avoid sudden shifts into negativity. The model has received empirical support; however, no validated measure exists to assess CA tendencies. In this paper we developed and tested two measures of CA: one focusing on worry, and another examining broader mechanisms of CA that could be used test whether CA is applicable to other disorders. In Study 1, Part 1, we used 3 samples of participants (each N=410) to perform item reduction, exploratory factor analysis, and confirmatory factor analysis. In Study 1, Part 2, we performed tests of construct validity. In Study 2, we used a new sample (N=126) to determine test-retest reliability. All data point to the strong psychometric properties of the CA questionnaires and their relationship to GAD. Both measures distinguished between participants reporting clinical levels of GAD symptoms and nonanxious controls, demonstrating their utility as complementary measures of CA tendencies.



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A Review of Sociocultural Factors that may Underlie Differences in African American and European American Anxiety

Publication date: Available online 27 April 2017
Source:Journal of Anxiety Disorders
Author(s): Patricia D. Hopkins, Natalie J. Shook
Preliminary evidence indicates there may be differences in the prevalence and severity of anxiety in African Americans and European Americans. A number of sociocultural risk and protective factors have been suggested to contribute to these group differences, such as salience of physical illnesses, discrimination, stigma toward mental illness, religiosity, and ethnic identity. In this paper, the literature concerning each of these factors is reviewed. Overall, the strongest evidence was found for ethnic identity and stigma toward mental illness as factors underlying group differences in anxiety. Ethnic identity and stigma toward mental illness consistently differed by racial group and were associated with anxiety in African Americans. Ethnic identity may buffer against the negative consequences of anxiety, reducing prevalence rates in African Americans. Stigma toward mental illness may decrease African Americans willingness to report anxiety symptoms, reducing overall prevalence rates but increasing the severity of treated cases. The research regarding discrimination, salience of physical illnesses, and religiosity was less clear. Much more research is required, but the findings of this review suggest that future studies should put particular emphasis on stigma toward mental illness and ethnic identity as important factors in understanding African American anxiety outcomes.



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Predictors of clinician use of exposure therapy in community mental health settings

Publication date: Available online 27 April 2017
Source:Journal of Anxiety Disorders
Author(s): Emily M. Becker-Haimes, Kelsie Okamura, Courtney Benjamin Wolk, Ronnie Rubin, Arthur C. Evans, Rinad S. Beidas
Exposure therapy is recognized as the key component of cognitive-behavioral treatment for anxiety. However, exposure is the least used evidence-based treatment in community mental health settings and is the most challenging technique for clinicians to adopt within the context of effectiveness and implementation trials. Little work has examined clinician and organizational characteristics that predict use of exposure, which is important for identifying implementation strategies that may increase its use. In a large sample of community health clinicians (N=335) across 31 clinical practice sites, this study characterized clinician and organizational predictors of exposure use and relaxation for anxiety. Mixed effects regression analyses indicated that both clinician attitudes and an organization's implementation climate may be important levers for interventions seeking to increase clinician exposure use. Greater clinician use of relaxation strategies was also associated with less exposure use. Results point to important implications for implementing cognitive-behavioral therapy for anxiety, including de-emphasizing relaxation and attending to organizational climate.



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The 14th Hoyt Lecture: Ischemic Optic Neuropathy: The Evolving Profile, 1966-2015: Response.

No abstract available

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