Head and Neck Diseases by Alexandros G.Sfakianakis: 02/15/17

Τετάρτη 15 Φεβρουαρίου 2017

The Chronic Otitis Media Benefit Inventory (COMBI): Development and Validation of a Dynamic Quality of Life Questionnaire for Chronic Ear Disease.

Objective: This study introduces a change-oriented short-form health-related quality of life questionnaire suited to symptoms of adult chronic middle ear disease and its consequences, and describes its properties. Study Design: Two-centre prospective correlational study primarily for instrument development. Setting: Two otology secondary care centers in England. Patients: Fifty-two consecutive adult patients with active chronic otitis media undergoing surgery. Methods: The 12 items for the chronic otitis media benefit inventory (COMBI) were appraised chiefly for internal consistency of resulting score and for factor structure (exploratory factor analysis). Results: The internal consistency of the COMBI was high within our cohort of patients, with a Cronbach's alpha value of 0.907. The three-factor solution from factor analysis explaining 73.6% of the variance was readily interpretable in terms of the intended item content: changes in hearing, ear symptoms, and daily activities plus healthcare uptake. Conclusions: The COMBI has suitable properties for the dynamic assessment of active chronic otitis media. Initial psychometric appraisal confirms its suitability for early adoption to acquire more comprehensive large-sample information with it and on it, for future refinement and application. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Pneumatocele of the Tympanic Membrane.

No abstract available

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Fisetin inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice

Publication date: April 2017
Source:International Immunopharmacology, Volume 45
Author(s): Wenhao Zheng, Zhenhua Feng, Shengban You, Hui Zhang, Zhenyu Tao, Quan Wang, Hua Chen, Yaosen Wu
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. Fisetin, a polyphenol extracted from fruits and vegetables, has been reported to have anti-inflammatory effects. Our study aimed to investigate the effect of fisetin on OA both in vitro and in vivo. In vitro, chondrocytes were pretreated with fisetin alone or fisetin combined with sirtinol (an inhibitor of SIRT1) for 2h before IL-1β stimulation. Production of NO, PGE2, TNF-α and IL-6 were evaluated by the Griess reaction and ELISAs. The mRNA (COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5, Sox-9, aggrecan and collagen-II) and protein expression (COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5 and SIRT1) were measured by qRT-PCR and Western blot respectively. Immunofluorescence was used to assess the expression of collagen-II and SIRT1. SIRT1 activity was quantified with SIRT1 fluorometric assay kit. The in vivo effect of fisetin was evaluated by gavage in mice OA models induced by destabilization of the medial meniscus (DMM). We found that fisetin inhibited IL-1β-induced expression of NO, PGE2, TNF-α, IL-6, COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5. Besides, fisetin remarkably decreased IL-1β-induced degradation of Sox-9, aggrecan and collagen-II. Furthermore, fisetin significantly inhibited IL-1β-induced SIRT1 decrease and inactivation. However, the inhibitory effect of fisetin was obvious abolished by sirtinol, suggesting that fisetin exerts anti-inflammatory effects through activating SIRT1. In vivo, fisetin-treated mice exhibited less cartilage destruction and lower OARSI scores. Moreover, fisetin reduced subchondral bone plate thickness and alleviated synovitis. Taken together, these findings indicate that fisetin may be a potential agent in the treatment of OA.

Graphical abstract

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Role of MRI in differentiating benign from malignant breast lesions using dynamic contrast enhanced MRI and diffusion weighted MRI

Publication date: Available online 15 February 2017
Source:Alexandria Journal of Medicine
Author(s): Mohamed Ahmed Youssef, Hanan Mohamed Saleh Elahwal, Mohamed Morsi Alwageeh, Sally Elbially Attya
ObjectiveTo evaluate the role of MRI in differentiation of benign from malignant breast lesions using dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted MRI (DW-MRI).Patients and methodsThe study included 33 female patients with clinically suspicious breast lesions detected by mammography and/or breast ultrasound. Cases were referred from general surgery departments in Tanta university hospital. The patients underwent full history taking and clinical examination, full field digital mammography and US, for those patients cases diagnosed on sonomammography as BI-RADS 3 & 4 were selected for MRI examination.ResultsQuantitative analysis of DWI was done for the 33 breast lesions and their ADC values are recorded at 3 different b-values (250, 600, and 1000). Seventeen lesions showed facilitated diffusion, proved to be benign and 10 lesions showed restricted diffusion, 9 lesions of them proved to be malignant and one proved to be benign. There are 6 lesions showed mixed restricted and facilitated diffusion proved to be malignant.ConclusionDWI improves the diagnostic ability of the DCE-MRI of the breast. It is a better method for detecting breast lesions than either T1- or T2-weighted imaging, but it is better to be performed in conjunction with contrast enhanced MRI.

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Aminoazobenzene in tattoo: another case of allergic contact dermatitis

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Regression of cutaneous xerosis with emollient treatment in sub-Saharan African patients

Abstract

Emollients have proven effective in improving cutaneous xerosis in various populations; however, no clinical data are available for African patients. The observational study "Xerafrica" was conducted by dermatologists in seven sub-Saharan countries to assess the evolution of xerosis after an 8-week treatment with an emollient. Patients were children above 3 years or adults. Secondary objectives were to assess pruritus, improvement in symptoms, quality of life, satisfaction, and tolerance. An analysis of 185 patients was made. After 8 weeks of emollient treatment, the relative reduction of the "Scaling Roughness Redness Cracks" (SRRC) score was −83.9% and −80.4% in children and adults, respectively. The effect was significantly stronger when topical steroids were co-prescribed with the emollient and in patients with co-dermatosis. To a lesser extent, the effect of emollient was also observed at week 4. Similarly, pruritus and quality of life strongly improved during follow-up. Skin lesions improved in almost all patients, with a high level of satisfaction noted by both dermatologists and patients. The "Xerafrica" study addressed, for the first time, the treatment of xerosis by emollients in an African population. In this specific context, the emollient markedly reduced xerosis as soon as 4 weeks and resolved it almost totally by 8 weeks. The study confirms, under real-life conditions, the efficacy and tolerability of an emollient in improving xerosis.

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In vivo instability of platensimycin and platencin: Synthesis and biological evaluation of urea- and carbamate-platensimycin

Publication date: Available online 16 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Liao-Bin Dong, Jeffrey D. Rudolf, Li Lin, Claudia Ruiz, Michael D. Cameron, Ben Shen
Platensimycin (PTM) and platencin (PTN), two natural products and promising drug leads that target bacterial and mammalian fatty acid synthases, are known to have unfavorable pharmacokinetic properties. It is not clear, however, what the metabolic fates of PTM and PTN are and no efforts have been reported to address this key roadblock in the development of these compounds as viable drug options. Here we describe the pharmacokinetics of PTM and PTN, and reveal rapid renal clearance as the primary metabolic liability with three additional sites of chemical liability: (i) amide hydrolysis, (ii) glucuronidation, and (iii) oxidation. We determined that hydrolysis is a viable clearance mechanism in vivo and synthesized two PTM analogues to address in vivo hydrolysis. Urea- and carbamate-PTM analogues showed no detectable hydrolysis in vivo, at the expense of antibacterial activity, with no further improvement in systemic exposure. The antibacterial sulfur-containing analogues PTM D1 and PTM ML14 showed significant decreases in renal clearance. These studies set the stage for continued generation of PTM and PTN analogues in an effort to improve their pharmacokinetics while retaining or improving their biological activities.

Graphical abstract

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Synthesis and anti-inflammatory activity of isoquebecol

Publication date: Available online 16 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Sébastien Cardinal, Pierre-Alexandre Paquet-Côté, Jabrane Azelmat, Corinne Bouchard, Daniel Grenier, Normand Voyer
We report here the synthesis of isoquebecol, an unprecedented constitutional isomer of quebecol, a polyphenolic compound discovered in maple syrup. The methodology used to prepare isoquebecol involves, as key steps, the formation of a dibromoalkene from an α-ketoester precursor, followed by a double Suzuki-Miyaura reaction. The anti-inflammatory activity of isoquebecol was studied on macrophage cells by monitoring its ability to inhibit LPS-induced IL-6 secretion. Results show that this new compound has an improved bioactivity over that of its natural isomer. Precursors and derivatives of quebecol, isoquebecol and model analog 2,3,3-triphenylpropanol were also prepared and tested in this study. Comparison between the three series of compounds led to establishing new SARs concerning the aryl ring substitution pattern on the triarylpropanol scaffold and substructure functionalization.

Graphical abstract

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Design and synthesis of novel, potent and selective hypoxanthine analogs as adenosine A1 receptor antagonists and their biological evaluation

Publication date: Available online 16 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Summon Koul, Vidya Ramdas, Dinesh A. Barawkar, Yogesh B. Waman, Neela Prasad, Santosh Kumar Madadi, Yogesh D. Shejul, Rajesh Bonagiri, Sujay Basu, Suraj Menon, Srinivasa B. Reddy, Sandhya Chaturvedi, Srinivas Rao Chennamaneni, Gaurav Bedse, Rhishikesh Thakare, Jayasagar Gundu, Sumit Chaudhary, Siddhartha De, Ashwinkumar V. Meru, Venkata Palle, Anita Chugh, Kasim A. Mookhtiar
Multipronged approach was used to synthesize a library of diverse C-8 cyclopentyl hypoxanthine analogs from a common intermediate III. Several potent and selective compounds were identified and evaluated for pharmacokinetic (PK) properties in Wistar rats. One of the compounds 14 with acceptable PK parameters was selected for testing in in-vivo primary acute diuresis model. The compound demonstrated significant diuretic activity in this model.

Graphical abstract

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Iminosugar-based ceramide mimicry for the design of new CERT START domain ligands

Publication date: Available online 14 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Cécile Santos, Fabien Stauffert, Stéphanie Ballereau, Cécile Dehoux, Frédéric Rodriguez, Anne Bodlenner, Philippe Compain, Yves Génisson
The enigmatical dichotomy between the two CERT/GPBP protein isoforms, their vast panel of biological implications and the scarcity of known antagonist series call for new ligand chemotypes identification. We report the design of iminosugar-based ceramide mimics for the development of new START domain ligands potentially targeting either protein isoforms. Strategic choice of i) an iminoxylitol core structure and ii) the positioning of two dodecyl residues led to an extent of protein binding comparable to that of the natural cargo lipid ceramide or the archetypical inhibitor HPA-12. Molecular docking study evidenced a possible mode of protein binding fully coherent with the one observed in crystalline co-structures of known ligands. The present study thus paves the way for cellular CERT inhibition activity studies en route to the development of pharmacological tools aiming at deciphering the respective function and therapeutic potential of the two CERT/GPBP protein isoforms.

Graphical abstract

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Multifunctional thioxanthone derivatives with acetylcholinesterase, monoamine oxidases and β-amyloid aggregation inhibitory activities as potential agents against Alzheimer’s disease

Publication date: Available online 14 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Li Luo, Yan Li, Xiaoming Qiang, Zhongcheng Cao, Rui Xu, Xia Yang, Ganyuan Xiao, Qing Song, Zhenghuai Tan, Yong Deng
A series of 1-hydroxyl-3-aminoalkoxy-thioxanthone derivatives were designed, synthesized and evaluated as potential multifunctional agents against Alzheimer's disease (AD). The results indicated that most of these compounds exhibited good AChE and MAOs inhibitory activities, significant inhibition of self- and Cu²⁺-induced Aβ1-42 aggregation, and moderate to good antioxidant activities. Specifically, compound 9e displayed high inhibitory potency toward AChE (IC50 = 0.59 ± 0.02 μM), MAO-A and MAO-B (IC50 = 1.01 ± 0.02 μM and 0.90 ± 0.01 μM respectively), excellent efficiency to block both self- and Cu²⁺-induced Aβ1-42 aggregation (74.8 ± 1.2% and 87.7 ± 1.9% at 25 μM, respectively), good metal-chelating property and a low toxicity in SH-SY5Y cells. Furthermore, kinetic and molecular modeling studies revealed that compound 9e binds simultaneously to the catalytic active site and peripheral anionic site of AChE, and could penetrate the BBB. Collectively, these results suggested that 9e might be a potential multifunctional agent for further development in the treatment of AD.

Graphical abstract

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Synthesis of 1,3,5-trisubstituted pyrazolines as potential antimalarial and antimicrobial agents

Publication date: Available online 14 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Vikash K Mishra, Mitali Mishra, Varsha Kashaw, Sushil K Kashaw
A series of novel 1,3,5-trisubstituted pyrazolines derivatives have been synthesized from chalcones and nicotinic acid hydrazide in two steps. In first step, chalcones were prepared by treatment of 4-hydroxy acetophenone with different substituted benzaldehyde by Claisen-Schimidt Condensation. In second step, various pyrazoline derivatives were prepared by reflux reaction of chalcones with nicotinic acid hydrazide in ethanolic solution. Compounds were confirmed by elemental analyses, IR, ¹H NMR and ¹³C NMR spectral data and were evaluated for antimalarial and antibacterial activity. Compounds 5n (IC50=0.022 μM for MRC-2 and IC50=0.192 μM for RKL-9) displayed better antiplasmodial activity than the chloroquine (CQ) against chloroquine-sensitive (MRC-2) and chloroquine-resistant (RKL-9) P. falciparum strains. The in vitro cytotoxicity study conducted on the human HepG2 cell line (>30μM) and selectivity index (100-220) indicate that this series presents an interesting selective antiplasmodial profile. Further, in vitro heme crystallization inhibition assay showed compound 5e inhibited formation of β-hematin more efficiently than CQ. In addition, antibacterial and antifungal evaluations were conducted, compounds 5c, 5i and 5j displayed better antibacterial activity against S. aureus, B. subtilis, E. coli and P. aeruginosa than ciproafloxacin. Antifungal activity of compound 5l against A. niger (MIC-3.25μg/ml) and C. albicans(MIC-6.5μg/ml) was found to be better than the standard drug fluconazole.

Graphical abstract

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"Arch Plast Surg"[jour]; +19 new citations

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Paediatric nasopharyngeal cytology: a new diagnostic opportunity?

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Paediatric nasopharyngeal cytology: a new diagnostic opportunity?

Eur J Clin Microbiol Infect Dis. 2016 Jul;35(7):1097-9

Authors: Torretta S, Marchisio P, Colombo MR, Rosazza C, Pignataro L

Abstract
The purpose of this investigation was to describe the first application of nasopharyngeal cytology (NPC), a new cytological technique to collect cellular material from the nasopharyngeal surface non-invasively in children with chronic adenoiditis associated with recurrent acute otitis media and/or otitis media with effusion. Cellular material was collected transorally using an extra-thin flexible wire nasopharyngeal swab and then examined under a light microscope. The diagnostic accuracy of NPC in detecting the presence of allergy and pathogens (compared to microbiological evaluation of nasopharyngeal aspirates, NPAs) was assessed. NPC was performed on 121 children (mean age 69.4 ± 15.5 months). Inflammatory cells and pathogens were detected in 61.1 % and 44.2 % of patients, respectively. The specificity of nasopharyngeal eosinophils in detecting allergy was good (91.9 %), as was the specificity of mast cells, but the sensitivities were less. The NPAs revealed bacterial colonisation in 84.7 % of the patients, and Streptococcus pneumoniae was the most frequently isolated (60.0 %). NPC revealed the presence of bacteria in 94.9 % of patients, including bacillary species in 33.9 %. NPC was highly sensitive in detecting pathogens (96.0 %). Its specificity in detecting bacillary species was fairly good (75.0 %), but the corresponding values of the specificity of NPC in detecting pathogens and its sensitivity in detecting bacillary species were poor. Our findings suggest the need for more structured studies that can test the real effectiveness and usefulness of NPC in defining nasopharyngeal cytological patterns in children with chronic nasopharyngeal diseases by comparing it with established diagnostic techniques.

PMID: 27039342 [PubMed - indexed for MEDLINE]

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American Cancer Society Head and Neck Cancer Survivorship Care Guideline.

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American Cancer Society Head and Neck Cancer Survivorship Care Guideline.

CA Cancer J Clin. 2016 05;66(3):203-39

Authors: Cohen EE, LaMonte SJ, Erb NL, Beckman KL, Sadeghi N, Hutcheson KA, Stubblefield MD, Abbott DM, Fisher PS, Stein KD, Lyman GH, Pratt-Chapman ML

Abstract
Answer questions and earn CME/CNE The American Cancer Society Head and Neck Cancer Survivorship Care Guideline was developed to assist primary care clinicians and other health practitioners with the care of head and neck cancer survivors, including monitoring for recurrence, screening for second primary cancers, assessment and management of long-term and late effects, health promotion, and care coordination. A systematic review of the literature was conducted using PubMed through April 2015, and a multidisciplinary expert workgroup with expertise in primary care, dentistry, surgical oncology, medical oncology, radiation oncology, clinical psychology, speech-language pathology, physical medicine and rehabilitation, the patient perspective, and nursing was assembled. While the guideline is based on a systematic review of the current literature, most evidence is not sufficient to warrant a strong recommendation. Therefore, recommendations should be viewed as consensus-based management strategies for assisting patients with physical and psychosocial effects of head and neck cancer and its treatment. CA Cancer J Clin 2016;66:203-239. © 2016 American Cancer Society.

PMID: 27002678 [PubMed - indexed for MEDLINE]

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Decellularized human colorectal cancer matrices polarize macrophages towards an anti-inflammatory phenotype promoting cancer cell invasion via CCL18

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): M.L. Pinto, E. Rios, A.C. Silva, S.C. Neves, H.R. Caires, A.T. Pinto, C. Durães, F.A. Carvalho, A.P. Cardoso, N.C. Santos, C.C. Barrias, D.S. Nascimento, P. Pinto-do-Ó, M.A. Barbosa, F. Carneiro, M.J. Oliveira
Macrophages are frequently identified in solid tumors, playing important roles in cancer progression. Their remarkable plasticity makes them very sensitive to environmental factors, including the extracellular matrix (ECM). In the present work, we investigated the impact of human colorectal tumor matrices on macrophage polarization and on macrophage-mediated cancer cell invasion. Accordingly, we developed an innovative 3D-organotypic model, based on the decellularization of normal and tumor tissues derived from colorectal cancer patients' surgical resections. Extensive characterization of these scaffolds revealed that DNA and other cell constituents were efficiently removed, while native tissue characteristics, namely major ECM components, architecture and mechanical properties, were preserved. Notably, normal and tumor decellularized matrices distinctly promoted macrophage polarization, with macrophages in tumor matrices differentiating towards an anti-inflammatory M2-like phenotype (higher IL-10, TGF-β and CCL18 and lower CCR7 and TNF expression). Matrigel invasion assays revealed that tumor ECM-educated macrophages efficiently stimulated cancer cell invasion through a mechanism involving CCL18. Notably, the high expression of this chemokine at the invasive front of human colorectal tumors correlated with advanced tumor staging. Our approach evidences that normal and tumor decellularized matrices constitute excellent scaffolds when trying to recreate complex microenvironments to understand basic mechanisms of disease or therapeutic resistance.

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Exploring deformable particles in vascular-targeted drug delivery: Softer is only sometimes better

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): Margaret B. Fish, Catherine A. Fromen, Genesis Lopez-Cazares, Alexander W. Golinski, Timothy F. Scott, Reheman Adili, Michael Holinstat, Omolola Eniola-Adefeso
The ability of vascular-targeted drug carriers (VTCs) to localize and bind to a targeted, diseased endothelium determines their overall clinical utility. Here, we investigate how particle modulus and size determine adhesion of VTCs to the vascular wall under physiological blood flow conditions. In general, deformable microparticles (MPs) outperformed nanoparticles (NPs) in all experimental conditions tested. Our results indicate that MP modulus enhances particle adhesion in a shear-dependent manner. In low shear human blood flow profiles in vitro, low modulus particles showed favorable adhesion, while at high shear, rigid particles showed superior adhesion. This was confirmed in vivo by studying particle adhesion under venous shear profiles in a mouse model of mesenteric inflammation, where MP adhesion was 127% greater (p < 0.0001) for low modulus particles compared to more rigid ones. Mechanistically, we establish that particle collisions with leukocytes drive these trends, rather than differences in particle deformation, localization, or detachment. Overall, this work demonstrates the importance of VTC modulus as a design parameter for enhanced VTC interaction with vascular walls, and thus, contributes important knowledge for development of successful clinical theranostics with applications for many diseases.

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Tracking Training-Related Plasticity by Combining fMRI and DTI: The Right Hemisphere Ventral Stream Mediates Musical Syntax Processing

<span class="paragraphSection"><div class="boxTitle">Abstract</div>As a functional homolog for left-hemispheric syntax processing in language, neuroimaging studies evidenced involvement of right prefrontal regions in musical syntax processing, of which underlying white matter connectivity remains unexplored so far. In the current experiment, we investigated the underlying pathway architecture in subjects with 3 levels of musical expertise. Employing diffusion tensor imaging tractography, departing from seeds from our previous functional magnetic resonance imaging study on music syntax processing in the same participants, we identified a pathway in the right ventral stream that connects the middle temporal lobe with the inferior frontal cortex via the extreme capsule, and corresponds to the left hemisphere ventral stream, classically attributed to syntax processing in language comprehension. Additional morphometric consistency analyses allowed dissociating tract core from more dispersed fiber portions. Musical expertise related to higher tract consistency of the right ventral stream pathway. Specifically, tract consistency in this pathway predicted the sensitivity for musical syntax violations. We conclude that enduring musical practice sculpts ventral stream architecture. Our results suggest that training-related pathway plasticity facilitates the right hemisphere ventral stream information transfer, supporting an improved sound-to-meaning mapping in music.</span>

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Geometric Navigation of Axons in a Cerebral Pathway: Comparing dMRI with Tract Tracing and Immunohistochemistry

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Brain fiber pathways are presumed to follow smooth curves but recent high angular resolution diffusion MRI (dMRI) suggests that instead they follow 3 primary axes often nearly orthogonal. To investigate this, we analyzed axon pathways under monkey primary motor cortex with (1) dMRI tractography, (2) axon tract tracing, and (3) axon immunohistochemistry. dMRI tractography shows the predicted crossings of axons in mediolateral and dorsoventral orientations and does not show axon turns in this region. Axons labeled with tract tracer in the motor cortex dispersed in the centrum semiovale by microscopically sharp axonal turns and/or branches (radii ≤15 µm) into 2 sharply defined orientations, mediolateral and dorsoventral. Nearby sections processed with SMI-32 antibody to label projection axons and SMI-312 antibody to label all axons revealed axon distributions parallel to the tracer axons. All 3 histological methods confirmed preponderant axon distributions parallel with dMRI axes with few axons (<20%) following smooth curves or diagonal orientations. These findings indicate that axons navigate deep white matter via microscopic sharp turns and branches between primary axes. They support dMRI observations of primary fiber axes, as well as the prediction that fiber crossings include navigational events not yet directly resolved by dMRI. New methods will be needed to incorporate coherent microscopic navigation into dMRI of connectivity.</span>

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Neuronal Activation After Prolonged Immobilization: Do the Same or Different Neurons Respond to a Novel Stressor?

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Despite extensive research on the impact of emotional stressors on brain function using immediate-early genes (e.g., c-<span style="font-style:italic;">fos</span>), there are still important questions that remain unanswered such as the reason for the progressive decline of c-<span style="font-style:italic;">fos</span> expression in response to prolonged stress and the neuronal populations activated by different stressors. This study tackles these 2 questions by evaluating c-<span style="font-style:italic;">fos</span> expression in response to 2 different emotional stressors applied sequentially, and performing a fluorescent double labeling of c-Fos protein and c-<span style="font-style:italic;">fos</span> mRNA on stress-related brain areas. Results were complemented with the assessment of the hypothalamic–pituitary–adrenal axis activation. We showed that the progressive decline of c-<span style="font-style:italic;">fos</span> expression could be related to 2 differing mechanisms involving either transcriptional repression or changes in stimulatory inputs. Moreover, the neuronal populations that respond to the different stressors appear to be predominantly separated in high-level processing areas (e.g., medial prefrontal cortex). However, in low-hierarchy areas (e.g., paraventricular nucleus of the hypothalamus) neuronal populations appear to respond unspecifically. The data suggest that the distinct physiological and behavioral consequences of emotional stressors, and their implication in the development of psychopathologies, are likely to be closely associated with neuronal populations specifically activated by each stressor.</span>

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Decellularized human colorectal cancer matrices polarize macrophages towards an anti-inflammatory phenotype promoting cancer cell invasion via CCL18

Exploring deformable particles in vascular-targeted drug delivery: Softer is only sometimes better

Precocious glucocorticoid exposure reduces skeletal muscle satellite cells in the fetal rat

Perinatal skeletal muscle growth rates are a function of protein and myonuclear accretion. Precocious exposure of the fetus to glucocorticoids (GLC) in utero impairs muscle growth. Reduced muscle protein synthesis rates contribute to this response, but the consequences for myonuclear hyperplasia are unknown. To test the hypothesis that blunting of Pax7+ muscle progenitor cell proliferative activity by GLC in vivo also contributes to reduced fetal muscle growth, pregnant rats were administered dexamethasone (DEX: 1 mg/L drinking water) from embryonic day (ED) 13 to ED21. Their responses were compared to pair-fed (PF) and ad libitum-fed controls (CON). Bromodeoxyuridine (BrdU) was administered before delivery to measure myonuclear accretion. Fetal hind limb and diaphragm muscles were collected at term and analyzed for myofiber cross-sectional area (CSA), total and BrdU+ myonuclei, Pax7+ nuclei, MyoD and myogenin protein and mRNA abundance and myosin heavy chain (MyHC) isoform composition. Mean fiber CSA, myonuclei/myofiber and Pax7+ nuclei/myofiber ratios were reduced in DEX compared to those in CON and PF muscles; CSA/myonucleus, BrdU+/total myonuclei and BrdU+ myonuclei/Pax7+ nuclei were similar among groups. Myogenin abundance was reduced and MyHC-slow was increased in DEX fetuses. The data are consistent with GLC inhibition of muscle progenitor cell proliferation limiting satellite cell and myonuclear accretion. The response of PF-fed compared to CON muscles indicated that decreased food consumption by DEX dams contributed to the smaller myofiber CSA but did not affect Pax7+ nuclear accretion. Thus, the effect on satellite cell reserve and myonuclear number also contributes to the blunting of fetal muscle growth by GLC.

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A Simplified Vocal Profile Analysis Protocol for the Assessment of Voice Quality and Speaker Similarity

A simplified perceptual protocol for the assessment of voice quality (VQ) is attempted based on the Vocal Profile Analysis (VPA) scheme, with the aim of alleviating typical issues associated with the multidimensionality of VQ and enabling an easy quantification of speaker similarity.

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Hematemesis as Initial Presentation in a 10-Week-Old Infant with Eosinophilic Gastroenteritis

Eosinophilic gastroenteritis is a rare condition characterized by eosinophilic inflammation in the gastrointestinal tract resulting in a variety of gastrointestinal symptoms. There is currently a dearth of information on this topic in the pediatric literature, as very few cases have been reported. In this report, we present a case of eosinophilic gastroenteritis in a 10-week-old patient with initial presenting symptom of hematemesis. To our knowledge, this is the youngest case reported in the literature and is unique in its initial presentation.

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Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis

Abstract

Immune checkpoint inhibitors (ICPI), such as ipilimumab [anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody] and nivolumab or pembrolizumab [anti-programmed cell death protein-1 (PD-1) antibodies], improve survival in several cancer types. Since inhibition of CTLA-4 or PD-1 leads to non-selective activation of the immune system, immune-related adverse events (irAEs) are frequent. Enterocolitis is a common irAE, currently managed with corticosteroids and, if necessary, anti-tumor necrosis factor-α therapy. Such a regimen carries a risk of serious side-effects including infections, and may potentially imply impaired antitumor effects. Vedolizumab is an anti-integrin α4β7 antibody with gut-specific immunosuppressive effects, approved for Crohn's disease and ulcerative colitis. We report a case series of seven patients with metastatic melanoma or lung cancer, treated with vedolizumab off-label for ipilimumab- or nivolumab-induced enterocolitis, from June 2014 through October 2016. Clinical, laboratory, endoscopic, and histologic data were analyzed. Patients initially received corticosteroids but were steroid-dependent and/or partially refractory. One patient was administered infliximab but was refractory. The median time from onset of enterocolitis to start of vedolizumab therapy was 79 days. Following vedolizumab therapy, all patients but one experienced steroid-free enterocolitis remission, with normalized fecal calprotectin. This was achieved after a median of 56 days from vedolizumab start, without any vedolizumab-related side-effects noted. The patient in whom vedolizumab was not successful, due to active ulcerative colitis, received vedolizumab prophylactically. This is the first case series to suggest that vedolizumab is an effective and well-tolerated therapeutic for steroid-dependent or partially refractory ICPI-induced enterocolitis. A larger prospective study to evaluate vedolizumab in this indication is warranted.

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Effects of impacted maxillary canines on root resorption of lateral incisors

Abstract

Objectives

The aim of this study was to analyze the amount of root resorption of maxillary lateral incisors by relating the position, location, and angulation of the impacted canine using cone-beam computed tomography (CBCT).

Materials and methods

The study sample consisted of panoramic and CBCT radiographs of 46 patients with a unilateral impacted canine (16 males and 30 females; mean age: 19.53 ± 6.66 and 19.44 ± 5.77 years, respectively). Sector location and canine angulation were measured in panoramics. All tomographs were obtained using CBCT (NewTom 5G, QR, Verona, Italy) and three-dimensional (3D) reconstructions of the maxillary laterals assessed by Mimics 14.01 image analysis software.

Results

Upper lateral incisor volume was smaller on the impacted side (401.95 ± 83.69 mm³) than on the nonimpacted side (433.54 ± 92.6 mm³, P < 0.05). There were no significant differences of lateral root resorption volume when comparing the impacted canines being on the labial or palatal sides (P > 0.05), but impacted canine angulation was significantly steeper on the labial side (70.85°) than on the palatal side (46.09°, P < 0.05). The volume of root resorption of laterals when comparing the various positions of the canine in different sectors or canine angulation in 30^o intervals was not statistically significantly different (P > 0.05).

Conclusions

The impacted canines caused root resorption of lateral incisors. The angulation of the canine was steeper on the labial side than on the palatal side but root resorption of adjacent laterals was not different. There were no statistically significant differences in the amount of root resorption of the laterals when the canine was evaluated according to localization and angulation.

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Retrospective 25-year follow-up of treatment outcomes in Angle Class III patients

Abstract

Objectives

Despite recommendations for early treatment of hereditary Angle Class III syndrome, late pubertal growth may cause a relapse requiring surgical intervention. This study was performed to identify predictors of successful Class III treatment.

Materials and methods

Thirty-eight Class III patients treated with a chincup were retrospectively analyzed. Data were collected from the data archive, cephalograms, and casts, including pretreatment (T0) and posttreatment (T1) data, as well as long-term follow-up data collected approximately 25 years after treatment (T2). Each patient was assigned to a success or a failure group. Data were analyzed based on time (T0, T1, T2), deviations from normal (Class I), and prognathism types (true mandibular prognathism, maxillary retrognathism, combined pro- and retrognathism).

Results

Compared to Class I normal values, the data obtained in both groups yielded 11 significant parameters. The success group showed values closer to normal at all times (T0, T1, T2) and vertical parameters decreased from T0 to T2. The failure group showed higher values for vertical and horizontal mandibular growth, as well as dentally more protrusion of the lower anterior teeth and more negative overjet at all times. In adittion, total gonial and upper gonial angle were higher at T0 and T1. A prognostic score—yet to be evaluated in clinical practice—was developed from the results. The failure group showed greater amounts of horizontal development during the years between T1 and T2. Treatment of true mandibular prognathism achieved better outcomes in female patients. Cases of maxillary retrognathism were treated very successfully without gender difference. Failure was clearly more prevalent, again without gender difference, among the patients with combined mandibular prognathism and maxillary retrognathism. Crossbite situations were observed in 44% of cases at T0. Even though this finding had been resolved by T1, it relapsed in 16% of the cases by T2.

Conclusion

The failure rate increased in cases of combined mandibular prognathism and maxillary retrognathism. Precisely in these combined Class III situations, it should be useful to apply the diagnostic and prognostic parameters identified in the present study and to provide the patients with specific information about the increased risk of failure.

http://ift.tt/2kyNyWs

Nonsyndromic oligodontia

Abstract

Objectives

The literature suggests an association between phenotype and causative mutation in nonsyndromic oligodontia. Thus, the present study was designed to verify this hypothesis in a consecutive cohort of patients.

Methods

All patients with nonsyndromic oligodontia who had been treated at the study center (Department of Orthodontics, University of Giessen, Germany) over the period 1986–2013 were contacted. Candidates were included only if at least one more family member had hypo- or oligodontia (i.e., without regard to the number of congenitally missing teeth). A total of 20 patients were included. After evaluating the dental status of each participant, the Tooth Agenesis Code (TAC) was applied. On this basis, a tentative diagnosis was made to predict which gene (MSX1, AXIN2, EDA, or PAX9) was likely to show mutation. Afterwards this hypothesis was confirmed or rejected by analyzing a saliva sample for mutation of the predicted gene. If confirmed, any available family members were also genetically analyzed.

Results

Based on their TAC scores and sums, gene mutations were predicted for MXS1 in 11, AXIN2 in 3, EDA in 6, and PAX9 in none of the patients. The evaluation of MSX1 yielded variants in 4 of 11 cases, all of which were classified as nonpathogenic since they were not considered as functional mutations. The evaluation of EDA yielded a pathogenic exon-7 mutation in 2 of 6 patients, both being brothers with different TAC scores; the same mutation, which represents a novel missense mutation, was also found in other members of the same family. The evaluation of AXIN2 yielded variants in 3 of 3 cases, all of which were classified as nonpathogenic.

Conclusions

Our findings obtained in consecutive patients with nonsyndromic oligodontia did not reveal any clinically relevant associations between oligodontia phenotype (based on TAC) and causative mutations for nonsyndromic oligodontia.

http://ift.tt/2lkyQ9l

Novel germline mutation (Leu512Met) in the thyrotropin receptor gene (TSHR) leading to sporadic non-autoimmune hyperthyroidism

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print

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Adiposity Indexes as Phenotype-Specific Markers of Preclinical Metabolic Alterations and Cardiovascular Risk in Polycystic Ovary Syndrome: A Cross-Sectional Study

02-2016-0096-endo_10-1055-s-0042-119524-

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-119524

Polycystic ovary syndrome (PCOS) is a common condition in women of reproductive age. 2 PCOS phenotypes (classic and ovulatory) are currently recognized as the most prevalent, with important differences in terms of cardiometabolic features. We studied the performance of different adiposity indexes to predict preclinical metabolic alterations and cardiovascular risk in 234 women with PCOS (173 with classic and 61 with ovulatory PCOS) and 129 controls. Performance of waist circumference, waist-to-height ratio, conicity index, lipid accumulation product, and visceral adiposity index was assessed based on HOMA-IR ≥ 3.8 as reference standard for screening preclinical metabolic alterations and cardiovascular risk factors in each group. Lipid accumulation product had the best accuracy for classic PCOS, and visceral adiposity index had the best accuracy for ovulatory PCOS. By applying the cutoff point of lipid accumulation product<34, we identified a subgroup of patients without cardiometabolic alterations (P<0.05) in the group with classic PCOS, a population at higher risk for hypertension, dyslipidemia, and impaired glucose tolerance. In ovulatory PCOS, visceral adiposity index ≥ 1.32 was capable of detecting women with significantly higher blood pressure and less favorable glycemic and lipid variables as compared to ovulatory PCOS with lower visceral adiposity index (P<0.05). These results suggest LAP ≥ 34 as the best marker for classic PCOS, and VAI ≥ 1.32 for ovulatory PCOS women. Both indexes can be easily calculated with measures obtained in routine clinical practice and may be useful to detect cardiometabolic risk and secure early interventions.
[...]

Article in Thieme eJournals:
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Heart Rate and Oxygen Uptake Kinetics in Type 2 Diabetes Patients – A Pilot Study on the Influence of Cardiovascular Medication on Regulatory Processes

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-119526

The aim of this pilot study was to investigate whether there are differences in heart rate and oxygen uptake kinetics in type 2 diabetes patients, considering their cardiovascular medication. It was hypothesized that cardiovascular medication would affect heart rate and oxygen uptake kinetics and that this could be detected using a standardized exercise test. 18 subjects were tested for maximal oxygen uptake. Kinetics were measured in a single test session with standardized, randomized moderate-intensity work rate changes. Time series analysis was used to estimate kinetics. Greater maxima in cross-correlation functions indicate faster kinetics. 6 patients did not take any cardiovascular medication, 6 subjects took peripherally acting medication and 6 patients were treated with centrally acting medication. Maximum oxygen uptake was not significantly different between groups. Significant main effects were identified regarding differences in muscular oxygen uptake kinetics and heart rate kinetics. Muscular oxygen uptake kinetics were significantly faster than heart rate kinetics in the group with no cardiovascular medication (maximum in cross-correlation function of muscular oxygen uptake vs. heart rate; 0.32±0.08 vs. 0.25±0.06; p=0.001) and in the group taking peripherally acting medication (0.34±0.05 vs. 0.28±0.05; p=0.009) but not in the patients taking centrally acting medication (0.28±0.05 vs. 0.30±0.07; n.s.). It can be concluded that regulatory processes for the achievement of a similar maximal oxygen uptake are different between the groups. The used standardized test provided plausible results for heart rate and oxygen uptake kinetics in a single measurement session in this patient group.
[...]

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Hypogonadotropic Hypogonadism in Non-Functioning Pituitary Adenomas: Impact of Intervention

10-2016-0416-endo_10-1055-s-0042-124355-

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-124355

To determine the prevalence of hypogonadotropic hypogonadism (HH) among patients with non-functioning pituitary adenomas (NFPA) and the post-surgery outcome on pituitary gonadotropins secretion (PGS); to determine the prevalence of erectile dysfunction (ED) on male patients with NFPA, to evaluate the impact of testosterone replacement therapy (TRT) in those with HH. Retrospective evaluation of gonadal function in 109 NFPA patients (45 males), with a mean age of 51.8 years, diagnosed on the last 10 years. ED questionnaire applied to 34 male patients. Male patients with NFPA were significantly older (males 58.1±15.8 vs. females 47.4±16.94; p=0.001). Most patients had macroadenomas (67%; p=0.001) and only a minority were incidentalomas (19%; p<0.001). Prevalence of HH was 40% (60% on males, 25% on females; p<0.001). Surgery was performed in 54% of all patients (71% of males, 42% of females; p<0.003). After intervention, 14% became HH, 69% maintained previous function and 17% improved. On the questionnaire, 76% reported having ED, 54% of which had HH and 21% were under TRT. Of the patients under TRT, 79% still had ED. Median age of patients with ED was significantly higher [with ED 65 vs. without 49 years; p=0.012). There was no BMI difference between patients with or without TRT (28.0 vs. 27.4 Kg/m2). NFPA was more frequent in older rather than younger patients. Males were older, had more HH and surgery. There was no significant improvement of pituitary function with surgery (17%) and 13% became iatrogenic HH. TRT had a low efficacy to improve ED in these patients.
[...]

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Add on Exenatide Treatment is Beneficial in Poorly Controlled Obese Type 2 Diabetics under Intensive Insulin Regimens

08-2016-0321-dia_10-1055-s-0042-120708-1

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-120708

Background: Intensive insulin treatment is bothersome in obese patients with type 2 diabetes mellitus. High insulin dosages further increase weight gain and the risk of hypoglycemia. Glucagon like peptide-1 receptor agonists decrease the insulin need, cause weight loss and reduce the risk of hypoglycemia. There is limited data about the effect of exenatide on obese diabetics under intensive insulin regimens. Methods: This retrospective case series report the clinical outcomes of 23 obese (13 morbidly obese) patients with uncontrolled type 2 diabetes mellitus (Age=59±10.44 years, body mass index 41.1±6.8 kg/m2, HbA1c 9.9±1.5%), under high dose (94.1±39.6 unit) intensive insulin. Exenatide twice daily was added for a mean follow-up period of 11.22±7.01 (3–30) months. Intensive insulin regimens were continued in 7 patients while the others were switched to basal insulin during the follow-up. Results: During the follow-up, mean HbA1c levels of the patients significantly improved (p=0.019), along with the significant decrease in body mass index and the total insulin need (p<0.001 for both). Baseline insulin dosages were significantly higher in the intensive regimen group (p=0.013) while other demographical and clinical characteristics were similar. No significant difference was present between the groups regarding the alterations of HbA1c, body mass index and the reduction in total insulin dosages. Conclusion: Add on exenatide appears to be a rational treatment modality in uncontrolled obese patients with type 2 diabetes mellitus despite intensive insulin regimens. Further prospective randomized studies with longer follow-up periods are recommended.
[...]

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Editorial Board

Publication date: 23 February 2017
Source:Journal of Proteomics, Volume 155

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Quantitative proteomic analysis of human testis reveals system-wide molecular and cellular pathways associated with non-obstructive azoospermia

Publication date: Available online 15 February 2017
Source:Journal of Proteomics
Author(s): Mehdi Alikhani, Mehdi Mirzaei, Marjan Sabbaghian, Pouria Parsamatin, Razieh Karamzadeh, Samane Adib, Niloofar Sodeifi, Mohammad Ali Sadighi Gilani, Masoud Zabet-Moghaddam, Lindsay Parker, Yunqi Wo, Vivek Gupta, Paul A. Haynes, Hamid Gourabi, Hossein Baharvand, Ghasem Hosseini Salekdeh
Male infertility accounts for half of the infertility problems experienced by couples. Azoospermia, having no measurable level of sperm in seminal fluid, is one of the known conditions resulting in male infertility. In order to elucidate the complex molecular mechanisms causing male azoospermia, label-free quantitative shotgun proteomics was carried out on testicular tissue specimens from patients with obstructive azoospermia and non-obstructive azoospermia, including maturation arrest (MA) and Sertoli cell only syndrome (SCOS). The abundance of 520 proteins was significantly changed across three groups of samples. We were able to identify several functional biological pathways enriched in azoospermia samples and confirm selected differentially abundant proteins, using multiple histological methods. The results revealed that cell cycle and proteolysis, and RNA splicing were the most significant biological processes impaired by the substantial suppression of proteins related to the aforementioned categories in SCOS tissues. In the MA patient testes, generation of precursor metabolites and energy as well as oxidation-reduction were the most significantly altered processes. Novel candidate proteins identified in this study include key transcription factors, many of which have not previously been shown to be associated with azoospermia. Our findings, can provide substantial insights into the molecular regulation of spermatogenesis and human reproduction.SignificanceThe obtained data showed a drastic suppression of proteins involved in spliceosome, cell cycle and proteasome proteins, as well as energy and metabolic production in Sertoli cell only syndrome testis tissue and to a lesser extent in maturation arrest samples. Moreover, we identified new transcription factors that are highly down-regulated in SCOS and MA patients, thus helping to understand the molecular complexity of spermatogenesis in male infertility. Our findings provide novel candidate protein targets associated with SCOS or MA azoospermia.

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Impact of Continuous Two-Team Approach in Autologous Breast Reconstruction

J reconstr Microsurg
DOI: 10.1055/s-0037-1598199

Background Autologous breast reconstruction has been noted in the literature to provide superior aesthetic outcomes and patient satisfaction. Additionally, free perforator flap tissue transfer has the potential for lower abdominal donor site morbidity. However, it has been noted that the percentage of women who are undergoing autologous breast reconstruction in the United States is decreasing. Factors related to the technical difficulty, prolonged operative times, and decreasing reimbursement have been implicated as the causes. Methods A retrospective review of electronic medical records over a 5-year period was performed with evaluation of 77 autologous breast reconstructions at a single institution. Patient demographics, comorbidities, number of surgeons involved, operative times, length of stay, and postoperative complications were measured. Wilcoxon rank-sum, Pearson's chi-squared, and proportional odds likelihood ratio tests were performed to compare continuous, categorical, and ordinal outcomes, respectively. Propensity score weighting was used to adjust for presurgical covariates and laterality. Results Operative time and length of stay were both significantly lower in the two- versus the single-microsurgeon groups in the unadjusted setting. When covariates and laterality were adjusted for, operative times still remained significantly shorter in the two-microsurgeon group; there were no differences in complications. Conclusion Based on our findings, we propose that the two-microsurgeon approach can be utilized in more time-consuming microsurgical cases, such as autologous breast reconstruction, to safely decrease operative times and potentially alleviate surgeon fatigue, reduce operative costs, and thus increase overall surgeon productivity.
[...]

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Ventricular Geometry From Non-contrast Non-ECG-gated CT Scans

Publication date: Available online 15 February 2017
Source:Academic Radiology
Author(s): Farbod N. Rahaghi, Gonzalo Vegas-Sanchez-Ferrero, Jasleen K. Minhas, Carolyn E. Come, Isaac De La Bruere, James M. Wells, Germán González, Surya P. Bhatt, Brett E. Fenster, Alejandro A. Diaz, Puja Kohli, James C. Ross, David A. Lynch, Mark T. Dransfield, Russel P. Bowler, Maria J. Ledesma-Carbayo, Raúl San José Estépar, George R. Washko
Rationale and ObjectivesImaging-based assessment of cardiovascular structure and function provides clinically relevant information in smokers. Non-cardiac-gated thoracic computed tomographic (CT) scanning is increasingly leveraged for clinical care and lung cancer screening. We sought to determine if more comprehensive measures of ventricular geometry could be obtained from CT using an atlas-based surface model of the heart.Materials and MethodsSubcohorts of 24 subjects with cardiac magnetic resonance imaging (MRI) and 262 subjects with echocardiography were identified from COPDGene, a longitudinal observational study of smokers. A surface model of the heart was manually initialized, and then automatically optimized to fit the epicardium for each CT. Estimates of right and left ventricular (RV and LV) volume and free-wall curvature were then calculated and compared to structural and functional metrics obtained from MRI and echocardiograms.ResultsCT measures of RV dimension and curvature correlated with similar measures obtained using MRI. RV and LV volume obtained from CT inversely correlated with echocardiogram-based estimates of RV systolic pressure using tricuspid regurgitation jet velocity and LV ejection fraction respectively. Patients with evidence of RV or LV dysfunction on echocardiogram had larger RV and LV dimensions on CT. Logistic regression models based on demographics and ventricular measures from CT had an area under the curve of >0.7 for the prediction of elevated right ventricular systolic pressure and ventricular failure.ConclusionsThese data suggest that non-cardiac-gated, non-contrast-enhanced thoracic CT scanning may provide insight into cardiac structure and function in smokers.

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Sun-protective behaviors in patients with cutaneous hyperpigmentation: A cross-sectional study

Disorders of hyperpigmentation are seen commonly in clinical practice. Despite numerous studies investigating sun-protective habits among healthy persons, little is known about these behaviors within patient populations with hyperpigmentation disorders.

http://ift.tt/2lSVHpo

The Vitiligo Working Group recommendations for narrowband ultraviolet B light phototherapy treatment of vitiligo

Treatment of vitiligo with narrowband ultraviolet B light (NBUVB) is an important component of the current standard of care. However, there are no consistent guidelines regarding the dosing and administration of NBUVB in vitiligo, reflected by varied treatment practices around the world.

http://ift.tt/2krMLvd

NLRP6: A Multifaceted Innate Immune Sensor

Publication date: Available online 15 February 2017
Source:Trends in Immunology
Author(s): Maayan Levy, Hagit Shapiro, Christoph A. Thaiss, Eran Elinav
NLRP6, a member of the nucleotide-binding domain, leucine-rich repeat-containing (NLR) innate immune receptor family, regulates inflammation and host defense against microorganisms. Similar to other NLRs, NLRP6 not only participates in inflammasome formation, but is also involved in nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling regulation and facilitation of gastrointestinal antiviral effector functions. Additionally, NLRP6 contributes to the regulation of mucus secretion and antimicrobial peptide production, thereby impacting intestinal microbial colonization and associated microbiome-related infectious, autoinflammatory, metabolic, and neoplastic diseases. However, several of the mechanisms attributed to the functions of NLRP6 remain debatable, leaving open questions as to the relevant molecular mechanisms and interacting partners, and putative human relevance. We herein discuss recent findings related to NLRP6 activity, while highlighting outstanding questions and future perspectives in elucidating its roles in health and disease.

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Clinical Features and Current Optimal Management of Natural Killer/T-Cell Lymphoma

Publication date: Available online 30 January 2017
Source:Hematology/Oncology Clinics of North America
Author(s): Shinichi Makita, Kensei Tobinai

Teaser

Extranodal natural killer/T-cell lymphoma, nasal type (ENKL) is a rare subtype of non-Hodgkin lymphoma, and its treatment outcome was previously poor. Novel treatment strategies have improved the outcomes of ENKL remarkably in the last decade. Nowadays, patients with localized nasal ENKL are recommended treatment with concurrent chemoradiotherapy, and their 5-year overall survival rate is approximately 70%. In patients with advanced or relapsed/refractory disease, the efficacy of l-asparaginase-containing therapy has been confirmed. However, there still remain unmet needs in the treatment of ENKL. Continued efforts should be made to further improvements in the treatment of ENKL.

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Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment

Infection with human papillomavirus (HPV) is the primary cause of oropharyngeal squamous cell cancer (OPC) in the United States [1]. Following treatment, HPV-driven oropharyngeal cancer (HPV-OPC) has good survival, with a 5-year survival rate of 82% [2–4]. While recurrence risk remains low among HPV-OPC [5–7], current standard of care surveillance includes intensive post-therapy monitoring that could include physical exam, fiberoptic examinations, and radiologic imaging procedures. These procedures are associated with significant time, resources, and additional costs.

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Viruserkrankungen in der Dermatologie

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Salicylsäure-Öle zur Anwendung auf der Kopfhaut

http://ift.tt/2kLTpbR

Neues zu Früherkennung und Screening

Das Hautkrebsscreening ist seit seiner Einführung in der Diskussion und auch weiterhin Gegenstand von Untersuchungen. So kamen auch im vergangenen Jahr Gegner und Fürsprecher zu Wort, zudem gibt es neue Kosten-Nutzen-Bewertungen, alternative Screeningmethoden und Ansätze, die Eigenuntersuchung zu verbessern.

http://ift.tt/2lSqrXL

Highlights der „Kultveranstaltung“

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Weiterhin ungebremster Zuwachs der Neuinfektionsrate

Ist die Zunahme der Syphilisinfektionen einer gefährlichen Sorglosigkeit geschuldet oder einer Rückkehr zur Normalität? Aktuelle Publikationen gehen von ersterem aus. Die Neuinfektionen sollten trotz neu erprobter Therapieregime und einer möglichen Therapieintensivierung leitliniengerecht behandelt werden.

http://ift.tt/2lS4ZSX

Inhaltsverzeichnis

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Derma Update 2016 – ein Rückblick in Bildern

http://ift.tt/2lS8gRR

Neues zu In-vitro-Diagnostik, Autoinjektoren und Kounis-Syndrom

Warum funktioniert die SIT mit Bienengift schlechter als bei Wespengift? Was ist die ideale Nadellänge für einen Adrenalinautoinjektor? Wie stellt man sicher, dass man ein Kounis-Syndrom nicht übersieht? Diese und weitere Fragen wurden im Rahmen des aktuellen Derma Updates diskutiert.

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Rund um die Psoriasis

Psoriasispatienten leiden in den seltensten Fällen allein an ihrer Grunderkrankung. Betroffene sind sowohl für somatische als auch psychische Komorbidität anfällig. Durch die Beachtung psychischer Begleiterkrankungen und deren Behandlung durch die entsprechenden Fachkollegen könnten Haut, Gelenke und Psyche gleichermaßen positiv beeinflusst werden.

http://ift.tt/2lMBl5y

Atopische Dermatitis: Was ist in der Pipeline?

In den letzten Jahren wurden mehrere neue Systemtherapien für die Psoriasis zugelassen. Bei der atopischen Dermatitis – einer anderen dermatologischen Volkskrankheit – nehmen Neuentwicklungen auch an Fahrt auf. Zahlreiche Angriffspunkte werden untersucht, darunter der Histamin-4-Rezeptor und diverse Interleukinrezeptoren. Auch zur Immunadsorption und zur Stammzelltherapie gibt es aktuelle Studiendaten.

http://ift.tt/2lS9sF4

Besondere Lokalisationen

Pigmentierte Läsionen präsentieren sich in besonderen Lokalisationen wie zum Beispiel der Mukosa oft untypisch. Ob in solchen Fällen die Auflichtmikroskopie zur Diagnosesicherung überhaupt dienlich ist, war lange strittig, zumal es ob der Seltenheit von Schleimhautmelanomen nur wenig valides Datenmaterial gab. Erst in den letzten Jahren wurden neue, wichtige Erkenntnisse gewonnen.

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Malignomrisiko erfordert enges Monitoring

Zusammenfassung

Die Therapieoptionen der zur Gruppe der inflammatorischen Myopathien zählenden Dermatomyositis sind nach wie vor nicht zufriedenstellend. Dafür wurde in den letzten Jahren die Diagnostik verfeinert: Unter anderem ermöglichen neue Biomarker eine Verlaufsüberwachung oder eine Zuordnung zu Erkrankungsgruppen. Weiterhin bleibt aufgrund der Tumorassoziation eine engmaschige Überwachung notwendig.

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Effect of food on the bioavailability of palbociclib

Abstract

Purpose

This phase I study estimated the effect of food on bioavailability of palbociclib (IBRANCE^®), and a selective inhibitor of cyclin-dependent kinase 4/6 approved for oncology indications has pH-dependent solubility and high permeability.

Methods

In this randomized, four-sequence, four-period crossover study, 28 healthy volunteers received a single 125-mg dose of palbociclib (free-base capsule) following an overnight fast or (1) after a high-fat/-calorie meal, (2) after a low-fat/-calorie meal, and (3) between two moderate-fat/standard-calorie meals. Pharmacokinetic samples were collected predose and serially ≤144 h postdose; palbociclib concentrations were measured using validated high-performance liquid chromatography tandem mass spectrometry. Pharmacokinetic data were analyzed using a noncompartmental approach based on a mixed-effects model.

Results

Median time to maximum concentration was 8 h for all conditions. Exposure (AUC_inf and C _max) increased slightly in the fed versus fasted conditions; ratios (90% CIs) of the adjusted geometric mean relative to the fasted condition ranged from 111.8 (104.3–119.9%) to 120.6% (112.6–129.1%) for AUC_inf and from 124.0 (108.4–141.9%) to 137.8% (120.6–157.5%) for C _max due mainly to three subjects with significantly lower exposure (low liers) in the fasted condition. Pharmacokinetic variability was reduced in the fed (AUC_inf, 23–27%; C _max, 21–24%) versus fasted (AUC_inf, 39%; C _max, 73%) conditions. In a supplemental analysis excluding the three low liers, food intake did not affect palbociclib exposure.

Conclusions

Food intake modestly increased palbociclib exposure while greatly reducing pharmacokinetic variability. For subjects with normal absorption, food intake did not affect palbociclib exposure. Thus, palbociclib should be administered with food.

Trial registration

ClinicalTrials.gov: NCT01904747.

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Accumulation of alpha-fluoro-beta-alanine and fluoro mono acetate in a patient with 5-fluorouracil-associated hyperammonemia

Abstract

Purpose

High-dose 5-fluorouracil (5-FU) containing chemotherapy occasionally causes hyperammonemia and can be lethal. However, the mechanism of 5FU-associated hyperammonemia has not been known. The aim of this study was to reveal the pharmacokinetics of 5-FU-associated hyperammonemia in a recurrent colorectal cancer patient with end-stage renal disease (ESRD).

Methods

We experienced a case of hyperammonemia during mFOLFOX6 plus bevacizumab therapy for recurrent colorectal cancer. He was a dialyzed patient due to diabetic nephropathy and was registered to prospective blood sampling for pharmacokinetics analysis during chemotherapy. Blood concentrations of 5-FU and its catabolites were determined by inductively coupled plasma-mass spectrometry.

Results

The patient developed hyperammonemia encephalopathy 41 h after the initiation of continuous 5-FU infusion (on the third day). Before onset of hyperammonemia encephalopathy, serum alpha-fluoro-beta-alanine (FBAL, 59.2 µg/ml) and fluoro mono acetate (FMA, 905.8 ng/ml) were gradually increased. After hemodialysis for hyperammonemia, FBAL and FMA were collaterally decreased and his symptom was improved. Other intermediate catabolites of 5-FU, dihydrofluorouracil, and alpha-fluoro-beta-ureidopropionic acid were not changed.

Conclusion

We found increases of serum FBAL and FMA under the condition of hyperammonemia in the patient with ESRD during mFOLFOX6 plus bevacizumab therapy. This research supported the hypothesis that impairment of tricarboxylic acid (TCA) cycle by FMA would cause 5-FU-associated hyperammonemia.

http://ift.tt/2kU8PNs

Application of magnetic susceptibility in assessment of heavy metal contamination of Saxonian soil (Germany) caused by industrial dust deposition

Publication date: 1 June 2017
Source:Geoderma, Volume 295
Author(s): Marzena Rachwał, Kati Kardel, Tadeusz Magiera, Oliver Bens
Magnetic susceptibility is used worldwide as a measure of concentration of (ferri)magnetic minerals in soil, sediment and dust. In soils, these minerals are of various origins: air-derived particulate pollution, parent rocks or pedogenesis. Human activity causes different changes in the content of magnetic minerals as well as their spatial and vertical distribution in soil profiles. Magnetic minerals are characterised by an affinity to other elements occurring in the soil, e.g. heavy metals. Therefore magnetic susceptibility has been widely applied as approximation of soil contamination by heavy metals.The archival soil samples collected from different soil horizons in the territory of the Free State of Saxony (Germany) were subjected to magnetic susceptibility measurements using Bartington MS2B. Additionally, samples were chemically analysed in order to determine the content of Fe, Mn, Ni, Cu, Zn, Cd, Pb and As using a method of atomic absorption spectroscopy (AAS). The contamination factor (CF) and geoaccumulation index (Igeo) were applied for assessment of soil contamination with particular potentially toxic elements (PTE), while the more general pollution load index (PLI) was used for comparison between different geographic sites.Values of magnetic susceptibility varied from 16.6 to 1382×10⁻⁸m³kg⁻¹ in organic soil horizons and from 0.1 to 1580×10⁻⁸m³kg⁻¹ in deeper layers. Significant and relatively high correlation coefficients between soil magnetic susceptibility and the content of some heavy metals indicated that they were of the similar origin as (ferri)magnetic minerals occurring in soil (viz. industrial pollution, parent rocks or pedogenic processes). PLI distribution over the entire area of Saxony corresponds well with the magnetic susceptibility distribution, especially in the organic soil horizon. The indices qualify the northeastern part of Saxony as extremely or heavily polluted in the organic soil horizon (under forests) with decreasing contamination in deeper layers, being classified as non-polluted to moderately polluted. However, the prevailing Saxony area is characterised by low and moderate contamination by potentially toxic elements, such as heavy metals.

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Clinical markers of asthma and IgE assessed in parents before conception predicts asthma and hay fever in the offspring

Abstract

Background

Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans.

Objective

We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs after birth, with offspring asthma and hay fever.

Methods

The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991-1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions.

Results

Offspring asthma with hay fever was more strongly associated with parental BHR and specific IgE measured before conception than after birth (BHR: aRRR=2.96 [95% CI: 1.92, 4.57] and 1.40[1.03, 1.91], respectively; specific IgEs: 3.08[2.13, 4.45] and 1.83[1.45, 2.31], respectively). This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth.

Conclusion & Clinical Relevance

Parental BHR and specific IgE were associated with offspring asthma and hay fever, with the strongest associations observed with before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hay fever.

http://ift.tt/2krnW2h

Clinical markers of asthma and IgE assessed in parents before conception predicts asthma and hay fever in the offspring

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http://ift.tt/2krnW2h

Impact of Hormonal Contraception and Weight Loss on HDL-C efflux and Lipoprotein Particles in Women with Polycystic Ovary Syndrome

Abstract

Objective

To study the effects of oral contraceptive pills (OCP), the first line treatment for PCOS, on HDL-C function (reverse cholesterol efflux capacity) and lipoprotein particles measured by NMR spectroscopy.

Design

Secondary analysis of a randomized controlled trial (OWL-PCOS) of OCP or Lifestyle (intensive lifestyle modification) or Combined (OCP+Lifestyle) treatment for 16 weeks.

Patients

87 overweight/obese women with PCOS at two academic centers.

Measurements

Change in HDL-C efflux capacity and lipoprotein particles.

Results

HDL-C efflux capacity increased significantly at 16 weeks in the OCP group (0.11; 95% CI 0.03, 0.18, p=0.008) but not in the Lifestyle (p=0.39) or Combined group (p=0.18). After adjusting for HDL-C and TG levels, there was significant mean change in efflux in the Combined group (0.09; 95% CI 0.01, 0.15; p=0.01). Change in HDL-C efflux correlated inversely with change in serum testosterone (r_s = -0.21; p=0.05). In contrast, OCP use induced an atherogenic LDL-C profile with increase in small (p=0.006) and large LDL-particles (p=0.002). Change in small LDL-particles correlated with change in serum testosterone (r_s = -0.31, p=0.009) and insulin sensitivity index (r_s = -0.31, p=0.02). Both Lifestyle and Combined groups did not show significant changes in the atherogenic LDL-particles.

Conclusions

OCP use is associated with improved HDL-C function and a concomitant atherogenic LDL-C profile. Combination of a Lifestyle program with OCP use improved HDL-C function and mitigated adverse effects of OCP on lipoproteins. Our study provides evidence for use of OCP in overweight/obese women with PCOS when combined with Lifestyle changes.

http://ift.tt/2kU4kT5

Spectrum of Disease Associated with Partial Lipodystrophy (PL): Lessons from a Trial Cohort

Abstract

Context

Partial lipodystrophy (PL) is associated with metabolic co-morbidities but may go undiagnosed as the disease spectrum is not fully described.

Objective

Define disease spectrum in PL using genetic, clinical (historical, morphometric) and laboratory characteristics.

Design

Cross-sectional evaluation.

Participants

23 patients (22 with familial, one acquired, 78.3% female, aged 12-64 years) with PL and non-alcoholic fatty liver disease (NAFLD).

Measurements

Genetic, clinical and laboratory characteristics, body composition indices, liver fat content by MRI, histopathological and immunofluorescence examinations of liver biopsies.

Results

7 patients displayed heterozygous pathogenic variants in LMNA. Two related patients had a heterozygous, likely pathogenic novel variant of POLD1 (NM002691.3: c.3199 G>A; p.E1067K). Most patients had high ratios (>1.5) of %fat trunk to %fat legs (FMR) when compared to reference normals. Liver fat quantified using MR Dixon method was high (11.3+6.3%) and correlated positively with hemoglobin A1c and triglycerides while leg fat by dual-energy X-ray absorptiometry (DEXA) correlated negatively with triglycerides. In addition to known metabolic comorbidities; chronic pain (78.3%), hypertension (56.5%) and mood disorders (52.2%) were highly prevalent. Mean NAFLD Activity Score (NAS) score was 5±1 and 78.3% had fibrosis. LMNA-immunofluorescence staining from select patients (including one with the novel POLD1 variant) showed a high degree of nuclear atypia and disorganization.

Conclusions

PL is a complex multi-system disorder. Metabolic parameters correlate negatively with extremity fat and positively with liver fat. DEXA-based FMR may prove useful as a diagnostic tool. Nuclear disorganization and atypia may be a common biomarker even in the absence of pathogenic variants in LMNA.

http://ift.tt/2lQCllY

Funktionell-ästhetische Chirurgie der Nase

http://ift.tt/2lMrkW0

Buccal Films as a Dressing for the Treatment of Aphthous Lesions

Abstract

Background

Buccal flexible films in the form of solid, thin, mucoadhesive patches can be used as dressings separating aphthous lesions from the environment of the oral cavity, which can in turn shorten the treatment period and reduce the pain perception.

Methods

The clinical study was performed on 36 volunteers suffering from aphthous lesions. The first group was treated using standard means - by application of an oral gel containing cholin salicylas (Mundisal) on the aphthous lesion. The second group was treated with the same preparation, however, the lesion was covered with a mucoadhesive film following the application of the gel. The criteria for statistical evaluation were the size of lesions in relation to the length of the treatment and the subjective perception of the treatment results.

Results And Conclusions

The application of buccal films covering aphthous lesions during the treatment significantly increased the rate of healing when compared with the standard methods of treatment. While the pain improvement was statistically significant as soon as Day 3 in the experimental group, it was only apparent on Day 5 in the control group, and the number of successfully treated patients (pain perception improving to VAS 2 or less) was at all time points higher in the experimental group than in the control group. The results imply that the use of buccal films for treatment of aphthous lesions is very promising and can lead to a significant reduction of the duration of patients' discomfort.

http://ift.tt/2lRVEua

Funktionell-ästhetische Chirurgie der Nase

http://ift.tt/2lMrkW0

Thyroid dysfunction in children with autism spectrum disorder is associated with folate receptor alpha autoimmune disorder

Abstract

Folate receptor α (FRα) autoantibodies (FRAAs) are prevalent in Autism Spectrum Disorder (ASD). FRAAs disrupt folate transport across the blood-brain barrier by binding to the FRα. Thyroid dysfunction is frequently found in children with ASD. We measured blocking and binding FRAAs and thyroid stimulating hormone (TSH), free T4 (FT4), total T3 (TT3), reverse T3 (rT3), thyroid releasing hormone (TRH) and other metabolites in 87 children with ASD, 84 of whom also underwent behavior and cognition testing and in 42 of whom FRAAs, TSH and FT4 were measured at two time points. To better understand the significance of the FRα in relation to thyroid development, we examined FRα expression on prenatal and postnatal thyroid. TSH, TT3 and rT3 were above the normal range in 7%, 33% and 51% of the participants and TRH was below the normal range in 13% of the participants. FT4 was rarely outside the normal range. TSH concentration was positively and the FT4/TSH, TT3/TSH and rT3/TSH ratios were inversely related to blocking FRAA titers. On repeated measurements, change in TSH and FT4/TSH ratio were found to correspond to change in blocking FRAA titers. TSH and the FT4/TSH, TT3/TSH and rT3/TSH ratios were related to irritability on the Aberrant Behavior Checklist and several scales of the Social Responsiveness Scale (SRS), while TT3 was associated with SRS subscales and TRH were related to Vineland Adaptive Behavior Scale subscales. The thyroid showed significant FRα expression during the early prenatal period but expression decreased significantly in later gestation and postnatal thyroid tissue. This study suggests that thyroid dysfunction in ASD may be related to the blocking FRAA. The high expression of FRα in the early fetal thyroid suggests that fetal and neonatal exposure to maternal FRAAs could affect the development of the thyroid and may contribute to the pathology in ASD.

http://ift.tt/2kLeZNu

One-Year Swallowing Outcomes in Patients Treated with Prophylactic Gabapentin During Radiation-Based Treatment for Oropharyngeal Cancer

Abstract

Recent investigations by our study team have demonstrated patients using gabapentin for pain management during chemoradiotherapy (CRT) do well maintaining swallowing during treatment with less need for narcotic pain medication, PEG dependence, weight loss, and short-term swallowing morbidity. The purpose of this investigation was to characterize the long-term swallowing function of these patients 1-year following treatment. Sequential patients receiving CRT for oropharyngeal cancer and concurrent gabapentin were evaluated 1-year following treatment for swallowing outcomes. Functional Oral Intake Scores (FOIS) were utilized to assess diet level. The MD Anderson Dysphagia Inventory (MDADI) was chosen to evaluate patient perception of swallowing function. Videofluoroscopic swallowing studies were completed approximately 1 year after treatment to assess physiologic outcomes as well as Penetration Aspiration Scores (PAS). Data from 26 consecutive participants were available for analysis. The majority of patients had advanced stage disease (Stage 3–4). No patients had a PEG tube 1-year following treatment, and the mean FOIS score was 6.83. Pharyngeal deficits were infrequent with reduced pharyngeal constriction and prominence/early closure of cricopharyngeus predominating. Mean PAS score was 1.5, indicating that the majority of patients had either no laryngeal penetration/aspiration, or transient penetration that was fully cleared. Mean MDADI score was 85.52, indicating that, in general, patients perceived their swallowing to be minimally impaired. Patients receiving gabapentin pain management as part of a comprehensive dysphagia prevention protocol during CRT have excellent long-term swallowing outcomes as reflected in diet levels, physiologic functioning, and patient-perceived quality of life.

http://ift.tt/2krag7C

Skull 5 from Dmanisi: Descriptive anatomy, comparative studies, and evolutionary significance

Publication date: March 2017
Source:Journal of Human Evolution, Volume 104
Author(s): G. Philip Rightmire, Marcia S. Ponce de León, David Lordkipanidze, Ann Margvelashvili, Christoph P.E. Zollikofer
A fifth hominin skull (cranium D4500 and mandible D2600) from Dmanisi is massively constructed, with a large face and a very small brain. Traits documented for the first time in a basal member of the Homo clade include the uniquely low ratio of endocranial volume to basicranial width, reduced vertex height, angular vault profile, smooth nasal sill coupled with a long and sloping maxillary clivus, elongated palate, and tall mandibular corpus. The convex clivus and receding symphysis of skull 5 produce a muzzle-like form similar to that of Australopithecus afarensis. While the Dmanisi cranium is very robust, differing from OH 13, OH 24, and KNM-ER 1813, it resembles Homo habilis specimens in the "squared off" outline of its maxilla in facial view, maxillary sulcus, rounded and receding zygomatic arch, and flexed zygomaticoalveolar pillar. These characters distinguish early Homo from species of Australopithecus and Paranthropus. Skull 5 is unlike Homo rudolfensis cranium KNM-ER 1470. Although it appears generally primitive, skull 5 possesses a bar-like supraorbital torus, elongated temporal squama, occipital transverse torus, and petrotympanic traits considered to be derived for Homo erectus. As a group, the Dmanisi crania and mandibles display substantial anatomical and metric variation. A key question is whether the fossils document age-related growth and sex dimorphism within a single population, or whether two (or more) distinct taxa may be present at the site. We use the coefficient of variation to compare Dmanisi with Paranthropus boisei, H. erectus, and recent Homo sapiens, finding few signals that the Dmanisi sample is excessively variable in comparison to these reference taxa. Using cranial measurements and principal components analysis, we explore the proposal that the Dmanisi skulls can be grouped within a regionally diverse hypodigm for H. erectus. Our results provide only weak support for this hypothesis. Finally, we consider all available morphological and paleobiological evidence in an attempt to clarify the phyletic relationship of Dmanisi to Homo species evolving >2.0 to 1.0 Ma.

http://ift.tt/2lkBfkA

Identification of candidate miRNA biomarkers for pancreatic ductal adenocarcinoma by weighted gene co-expression network analysis

Abstract

Purpose

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal prognosis which is, among others, due to a lack of suitable biomarkers and therapeutic targets. Previously, basic gene expression analysis methods have been used for their identification, but recently new algorithms have been developed allowing more comprehensive data analyses. Among them, weighted gene co-expression network analysis (WGCNA) has already been applied to several cancer types with promising results.

Methods

We applied WGCNA to miRNA expression data from PDAC patients. Specifically, we processed microarray-based expression data of 2555 miRNAs in serum from 100 PDAC patients and 150 healthy subjects. We identified network modules of co-expressed miRNAs in the healthy subject dataset and verified their preservation in the PDAC dataset. In the non-preserved modules, we selected key miRNAs and carried out functional enrichment analyses of their experimentally known target genes. Finally, we tested their prognostic significance using overall survival analyses.

Results

Through WGCNA we identified several miRNAs that discriminate healthy subjects from PDAC patients and that, therefore, may play critical roles in PDAC development. At a functional level, we found that they regulate p53, FoxO and ErbB associated cellular signalling pathways, as well as cell cycle progression and various genes known to be involved in PDAC development. Some miRNAs were also found to serve as novel prognostic biomarkers, whereas others have previously already been proposed as such, thereby validating the WGCNA approach. In addition, we found that these novel data may explain at least some of our previous PDAC gene expression analysis results.

Conclusions

We identified several miRNAs critical for PDAC development using WGCNA. These miRNAs may serve as biomarkers for PDAC diagnosis/prognosis and patient stratification, and as putative novel therapeutic targets.

http://ift.tt/2kz3iZw

Effects of impacted maxillary canines on root resorption of lateral incisors

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Materials and methods

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http://ift.tt/2lkDhks

Retrospective 25-year follow-up of treatment outcomes in Angle Class III patients

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http://ift.tt/2kyNyWs

Nonsyndromic oligodontia

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http://ift.tt/2lkyQ9l

Low prevalence of human papillomavirus in head and neck squamous cell carcinoma in the northwest region of the Philippines

by Pia Marie Albano, Dana Holzinger, Christianne Salvador, Jose Orosa III, Sheryl Racelis, Modesty Leaño, Danilo Sanchez Jr, Lara Mae Angeles, Gordana Halec, Markus Schmitt, John Donnie Ramos, Michael Pawlita

Background

Geographic heterogeneity of human papillomavirus (HPV) involvement in head and neck squamous cell carcinoma (HNSCC) has been observed over the last few years. This trend has not been evaluated in the Philippines. Hence, this study aims to provide for the first time a data on the prevalence of HPV in HNSCC in the northwestern region of the Philippines.

Methods

Two hundred one (201) biopsy samples (179 formalin fixed paraffin embedded and 22 fresh frozen) from 163 Filipino HNSCC cases (oral cavity = 88; larynx = 60; oropharynx = 15) diagnosed between 2003 to 2013 were initially included in this study. HPV DNA was detected by two methods: (1) BSGP5+/6+-PCR/ multiplex human papillomavirus genotyping and (2) TaqMan probes-based real-time qPCR. Presence of HPV type-specific transcripts were also analyzed by reverse transcription-PCR with subsequent hybridization to oligonucleotide probes coupled to Luminex beads. Co-amplification of the β-globin and ubiquitin C genes served as internal positive controls for DNA and RNA analyses, respectively.

Results and conclusions

Of the 163, 82 (50.3%) cases had at least one tissue sample that was valid for molecular analysis. Only two of the DNA valid cases (2.4%) were HPV DNA-positive (HPV11 and HPV33). All HPV mRNA assays rendered negative results except for HPV11 transcripts. Results of this study may indicate that there is probably very low prevalence of HPV-associated HNSCC among Filipino adults living in a rural region of the Philippines. This study could serve as a benchmark for designing follow-up studies that would assess possible changes in trends of HNSCC among Filipinos in different ethnic regions of the country, especially urban areas in which the population is expected to adapt Western style sexual behavior. A prospective sampling of fresh frozen tissue is also highly recommended to ensure better molecular analyses.

http://ift.tt/2lQ9zS8

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Τετάρτη 15 Φεβρουαρίου 2017

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