20Q: Preschool Hearing Screening is Essential for Early Identification of Childhood Hearing Loss

In the United States, universal newborn hearing screening (UNHS) has been a reality for almost two decades. The emergence of UNHS can be traced back to a convergence in the 1980s of multiple distinct developments. Advances in hearing screening technology were one of the obvious requirements for UNHS. Automated auditory brainstem response (ABR) and otoacoustic emission (OAE) devices permitted relatively cost-effective hearing screening of large numbers of infants with reliance on non-audiology personnel. Subsequent clinical trials with the two new types of technology confirmed acceptable performance, including sensitivity, specificity, failure rates, and false positive rates. Research began to confirm the benefits of early intervention for permanent hearing loss. In combination, these developments plus legislative efforts contributed in the late 1990s to the all-important American Academy of Pediatrics endorsement of UNHS and establishment of benchmarks for UNHS programs (American Academy of Pediatrics, 1999).

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Teleaudiology 101

One main goal of telehealth is to improve access to specialty care, especially in rural areas, or other areas that are not easily accessible. Someone who needs care may live a great distance away from the nearest hospital or clinic. In addition to distances challenges, there may be access-related challenges. For example, it is 30 miles from the south side of Chicago to the north side, but the trip could take you 90 minutes due to traffic. In addition to improving access, we want to reduce the time spent in travel, for both the patient and for the clinician. Another benefit of telehealth is to reduce the amount of time patients have to take off of work, which will ultimately reduce travel expenses.

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Targeted Peripheral Nerve-directed Onabotulinumtoxin A Injection for Effective Long-term Therapy for Migraine Headache

Background: Onabotulinumtoxin A (BOTOX) is an FDA-approved treatment for chronic migraine headaches (MHs) that involves on-label, high-dose administration across 31 anatomic sites. Anatomically specific peripheral nerve trigger sites have been identified that contribute to MH pathogenesis and are amenable to both BOTOX injection and surgical decompression. These sites do not always correlate with the on-label FDA-approved injection pattern, but represent a more targeted approach. The efficacy of peripheral nerve–directed BOTOX injection as an independent long-term therapeutic option has not been investigated. Methods: The technique for peripheral nerve–directed therapeutic long-term BOTOX injection is described. A retrospective review was subsequently completed for 223 patients with MH. Sixty-six patients elected to proceed with diagnostic BOTOX injections. Of these, 24 continued long-term therapeutic BOTOX injections, whereas 42 matriculated to surgery. Outcomes were tracked. Results: Initial outcomes included significant improvement in migraine headache index (MHI) (53.5 ± 83.0, P

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Keratoacanthoma-Like Growths of Incontinentia Pigmenti Successfully Treated with Intralesional Methotrexate

Abstract

We report the case of a 17-year-old girl with incontinentia pigmenti who developed multiple large hyperkeratotic tumors within Blaschkoid hyperpigmented patches on her left leg. Biopsy demonstrated an endoexophytic nodule with irregular invaginations of keratinizing squamous epithelium and a central keratin-filled crater, consistent with keratoacanthoma-like lesions of incontinentia pigmenti. The tumors were successfully treated with intralesional methotrexate.

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Deep Granuloma Annulare Mimicking Inflamed Cysts in a Teenager

Abstract

We describe deep granuloma annulare (DGA) of the forehead mimicking inflamed cysts. Reactive inflammation and sterile purulent drainage may be an underrecognized feature of DGA.

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Neprilysin inhibitors: A new hope to halt the diabetic cardiovascular and renal complications?

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Vajir Malek, Anil Bhanudas Gaikwad
Diabetes is an enormous and ever-growing calamity and a global public health threat of the 21st century. Besides insulin and oral hypoglycaemic drugs, blockage of the renin-angiotensin system (RAS) denotes a key pharmacotherapy for the management of cardiovascular (CVD) and chronic kidney diseases (CKD), which are the leading causes of disability and death among diabetic patients. Neprilysin (NEP) inhibition, auxiliary to RAS blockage increases the bioavailability of natriuretic peptides and benefits the cardio-renal system. Omapatrilat, a dual angiotensin-converting enzyme (ACE) and NEP inhibitor has been reported to show superior anti-hypertensive, anti-atherosclerotic, insulin-sensitizing, cardiovascular and renoprotective effects to ACE inhibitors in experimental animal models for diabetes. In clinical trials on hypertensive subjects Omapatrilat increased the risk of angioedema due to which its further development as anti-hypertensive drug was hampered. This event prompted the development of angiotensin receptor neprilysin inhibitors (ARNi). The first representative of ARNi, LCZ696 (Sacubitril/ Valsartan) halted cardiovascular and renal functional decline and hence protected against CKD and CVD. Recently, LCZ696 was approved by U.S. Food and Drug Administration for the treatment of heart failure. This concise review intends to summarise the currently available reports on NEPi as a therapeutic intervention to treat CVD and CKD associated with diabetes.

Graphical abstract

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Antibacterial, antifungal and antimycobacterial compounds from cyanobacteria

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Shasank S. Swain, Sudhir K. Paidesetty, Rabindra N. Padhy
Infections from multidrug resistant (MDR) pathogenic bacteria, fungi and Mycobacterium tuberculosis remain progressively intractable. The search of effective antimicrobials from other possible non-conventional sources against MDR pathogenic bacteria, fungi and mycobacteria is call of the day. This review considers 121 cyanobacterial compounds or cyano-compounds with antimicrobial activities. Chemical structures of cyano-compounds were retrieved from ChemSpider and PubChem databases and were visualized by the software ChemDraw Ultra. Chemical information on cyano-compounds pertaining to Lipinski rules of five was assessed. The reviewed cyano-compounds belong to the following chemical classes (with examples): alkaloids (ambiguine isonitriles and 12-epi-hapalindole E isonitrile), aromatic compounds (benzoic acid and cyanobacterin), cyclic depsipeptides (cryptophycin 52 and lyngbyabellin A), cyclic peptides (calophycin and tenuecyclamides), cyclic undecapeptides (kawaguchipeptins and lyngbyazothrin A), cyclophane (carbamidocyclophane), extracellular pigment (nostocine A), fatty acids (alpha-dimorphecolic acid and majusculonic acid), linear peptides (muscoride A), lipopeptides (fischerellins and scytonemin A), nucleosides (tolytoxin and tubercidin), phenols (ambigols and 4-4′-hydroxybiphenyl), macrolides (scytophycin A and tolytoxin), polyketides (malyngolide and nostocyclyne), polyphenyl ethers (crossbyanol A), porphinoids (tolyporphin J) and terpenoids (noscomin and scytoscalarol). Cyanobacteria appear to be a diverse source of compounds with antimicrobial activity. Further attention is required to elucidate whether those could be applied as pharmaceuticals.

Graphical abstract

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Preparation of pure tungsten via various rolling methods and their influence on macro-texture and mechanical properties

Publication date: 15 July 2017
Source:Materials & Design, Volume 126
Author(s): Xiaoxin Zhang, Qingzhi Yan, Shaoting Lang, Yijia Wang, Changchun Ge
It's necessary to investigate the texture characteristics of tungsten (W) to improve the functional properties and structural performance simultaneously. Rolling route is an important factor influencing texture evolution of metal. Thus W billets were deformed via unidirectional rolling (UNR), cross rolling (CRR) and clock rolling (CLR) respectively to figure out the effect of strain path on the evolution of microstructures, macro-textures and mechanical properties. The results indicated that the unidirectional rolled pure W exhibited moderate dynamic recrystallization level, pronounced θ-fiber texture and weak γ-fiber texture. Besides, the unidirectional rolled sample showed lower bending strength compared to the cross and clock rolled samples. Crack-tips and high texture level resulted in the low bending strength of the unidirectional rolled pure W. Summarily, to obtain more low crystallographic index texture components and high bending strength simultaneously, W can be deformed via UNR with moderate deformation degree but not CRR and CLR.

Graphical abstract

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Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

Publication date: Available online 11 April 2017
Source:Immunity
Author(s): Frederick Arce Vargas, Andrew J.S. Furness, Isabelle Solomon, Kroopa Joshi, Leila Mekkaoui, Marta H. Lesko, Enrique Miranda Rota, Rony Dahan, Andrew Georgiou, Anna Sledzinska, Assma Ben Aissa, Dafne Franz, Mariana Werner Sunderland, Yien Ning Sophia Wong, Jake Y. Henry, Tim O'Brien, David Nicol, Ben Challacombe, Stephen A. Beers, Samra Turajlic, Martin Gore, James Larkin, Charles Swanton, Kerry A. Chester, Martin Pule, Jeffrey V. Ravetch, Teresa Marafioti, Karl S. Peggs, Sergio A. Quezada
CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology.

Graphical abstract

Teaser

Anti-CD25 antibodies have displayed only modest therapeutic activity against established tumors. Arce Vargas et al. demonstrate that existing anti-CD25 antibodies fail to deplete intra-tumoral Treg cells due to upregulation of FcγRIIb within tumors. Fc-optimized anti-CD25 mediates effective depletion of tumor-infiltrating Treg cells and synergizes with PD-1 blockade to promote tumor eradication.


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NAIP-NLRC4 Inflammasomes Coordinate Intestinal Epithelial Cell Expulsion with Eicosanoid and IL-18 Release via Activation of Caspase-1 and -8

Publication date: Available online 11 April 2017
Source:Immunity
Author(s): Isabella Rauch, Katherine A. Deets, Daisy X. Ji, Jakob von Moltke, Jeannette L. Tenthorey, Angus Y. Lee, Naomi H. Philip, Janelle S. Ayres, Igor E. Brodsky, Karsten Gronert, Russell E. Vance
Intestinal epithelial cells (IECs) form a critical barrier against pathogen invasion. By generation of mice in which inflammasome expression is restricted to IECs, we describe a coordinated epithelium-intrinsic inflammasome response in vivo. This response was sufficient to protect against Salmonella tissue invasion and involved a previously reported IEC expulsion that was coordinated with lipid mediator and cytokine production and lytic IEC death. Excessive inflammasome activation in IECs was sufficient to result in diarrhea and pathology. Experiments with IEC organoids demonstrated that IEC expulsion did not require other cell types. IEC expulsion was accompanied by a major actin rearrangement in neighboring cells that maintained epithelium integrity but did not absolutely require Caspase-1 or Gasdermin D. Analysis of Casp1^–/–Casp8^–/– mice revealed a functional Caspase-8 inflammasome in vivo. Thus, a coordinated IEC-intrinsic, Caspase-1 and -8 inflammasome response plays a key role in intestinal immune defense and pathology.

Graphical abstract

Teaser

Rauch et al. show that selective activation of the NLRC4 inflammasome in intestinal epithelial cells leads to a coordinated response that includes cell expulsion and eicosanoid and cytokine release. This is not fully dependent on Caspase-1, as cell expulsion can also be caused by Caspase-8 activated by NLRC4.


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Polycomb Repressive Complex 2-Mediated Chromatin Repression Guides Effector CD8+ T Cell Terminal Differentiation and Loss of Multipotency

Publication date: Available online 11 April 2017
Source:Immunity
Author(s): Simon M. Gray, Robert A. Amezquita, Tianxia Guan, Steven H. Kleinstein, Susan M. Kaech
Understanding immunological memory formation depends on elucidating how multipotent memory precursor (MP) cells maintain developmental plasticity and longevity to provide long-term immunity while other effector cells develop into terminally differentiated effector (TE) cells with limited survival. Profiling active (H3K27ac) and repressed (H3K27me3) chromatin in naive, MP, and TE CD8⁺ T cells during viral infection revealed increased H3K27me3 deposition at numerous pro-memory and pro-survival genes in TE relative to MP cells, indicative of fate restriction, but permissive chromatin at both pro-memory and pro-effector genes in MP cells, indicative of multipotency. Polycomb repressive complex 2 deficiency impaired clonal expansion and TE cell differentiation, but minimally impacted CD8⁺ memory T cell maturation. Abundant H3K27me3 deposition at pro-memory genes occurred late during TE cell development, probably from diminished transcription factor FOXO1 expression. These results outline a temporal model for loss of memory cell potential through selective epigenetic silencing of pro-memory genes in effector T cells.

Graphical abstract

Teaser

Cytotoxic CD8⁺ T cells either terminally differentiate and die or form a rapidly responding population of memory T cells after pathogen clearance. Gray et al. define a temporal model for how effector T cells lose memory cell potential through selective epigenetic silencing of pro-memory genes.


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Tyrosine Kinase SYK Licenses MyD88 Adaptor Protein to Instigate IL-1α-Mediated Inflammatory Disease

Publication date: Available online 11 April 2017
Source:Immunity
Author(s): Prajwal Gurung, Gaofeng Fan, John R. Lukens, Peter Vogel, Nicholas K. Tonks, Thirumala-Devi Kanneganti
Mice carrying a hypomorphic point mutation in the Ptpn6 gene (Ptpn6^spin mice) develop an inflammatory skin disease that resembles neutrophilic dermatosis in humans. Here, we demonstrated that interleukin-1α (IL-1α) signaling through IL-1R and MyD88 in both stromal and immune cells drive inflammation in Ptpn6^spin mice. We further identified SYK as a critical kinase that phosphorylates MyD88, promoted MyD88-dependent signaling and mediates dermatosis in Ptpn6^spin mice. Our studies further demonstrated that SHP1 encoded by Ptpn6 binds and suppresses SYK activation to inhibit MyD88 phosphorylation. Downstream of SHP1 and SYK-dependent counterregulation of MyD88 tyrosine phosphorylation, we have demonstrated that the scaffolding function of receptor interacting protein kinase 1 (RIPK1) and tumor growth factor-β activated kinase 1 (TAK1)-mediating signaling were required to spur inflammatory disease. Overall, these studies identify SHP1 and SYK crosstalk as a critical regulator of MyD88 post-translational modifications and IL-1-driven inflammation.

Graphical abstract

Teaser

Skin inflammation observed in a mouse model of neutrophilic dermatosis (Ptpn6^spin mice) is instigated by RIPK1 and IL-1α signaling axes, independently of IL-1β and inflammasomes. In this issue, Gurung et al. elucidate the molecular mechanisms underlying RIPK1 and IL-1α mediated inflammatory disease in Ptpn6^spin mice. SHP1 regulates activation of spleen tyrosine kinase (SYK), which phosphorylates MyD88, to regulate inflammation.


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Lathyrol and epoxylathyrol derivatives: modulation of Cdr1p and Mdr1p drug-efflux transporters of Candida albicans in Saccharomyces cerevisiae model

Publication date: Available online 16 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Andreia Mónico, Shweta Nim, Noélia Duarte, Manpreet Kaur Rawal, Rajendra Prasad, Attilio Di Pietro, Maria-José U. Ferreira
Macrocyclic diterpenes were previously found to be able to modulate the efflux pump activity of Candida albicans multidrug transporters. Most of these compounds were jatrophanes, but only a few number of lathyrane-type diterpenes was evaluated. Therefore, the aim of this study was to evaluate the ability of nineteen structurally-related lathyrane diterpenes (1-19) to overcome the drug-efflux activity of Cdr1p and Mdr1p transporters of C. albicans, and get some insights on their structure-activity relationships. The transport assay was performed by monitoring Nile Red (NR) efflux in a Saccharomyces cerevisiae strain overexpressing the referred efflux pumps from C. albicans. Moreover, a chemosensitization assay was performed in order to evaluate the type of interaction between the inhibitory compounds and the antifungal drug fluconazole. Compounds 1-13 were previously isolated from Euphorbia boetica or obtained by derivatization, and compounds 14-19 were prepared by chemical transformations of compound 4. In the transport assays, compounds 14-19 revealed the strongest inhibitory activity of the Cdr1p efflux pump, ranging from 65 to 85%. Concerning Mdr1p efflux pump, the most active compounds were 1, 3, 6, 8, and 12 (75 to 85%). When used in combination with fluconazole, epoxyboetirane K (2) and euphoboetirane N (18) revealed synergistic effects in the AD-CDR1 yeast strain, overexpressing the Cdr1p transporter, through their ability to reduce the effective concentration of the antifungal drug by 23- and 52 fold, respectively.

Graphical abstract

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Sugar, perceived healthfulness, and satiety: When does a sugary preload lead people to eat more?

Publication date: 1 July 2017
Source:Appetite, Volume 114
Author(s): Naomi Mandel, Daniel Brannon
In this research, we examine the interplay between physiological and psychological factors that determine whether the sugar level of a preload increases or decreases consumption on a subsequent snack-eating task. In study 1, participants who drank a high-sugar protein shake (which they believed to be healthy) consumed more subsequent snacks than participants who drank a low-sugar protein shake. Study 2 replicated these findings, but only when the shake was labeled as "healthy." When the shake was labeled as "indulgent," the effect was mitigated.



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A dataset of multi-contrast population-averaged brain MRI atlases of a Parkinson's disease cohort

Publication date: Available online 15 April 2017
Source:Data in Brief
Author(s): Yiming Xiao, Vladimir Fonov, M. Mallar Chakravarty, Silvain Beriault, Fahd Al Subaie, Abbas Sadikot, G. Bruce Pike, Gilles Bertrand, D. Louis Collins
Parkinson's disease (PD) is a neurodegenerative disease that primarily affects the motor functions of the patients. Research and surgical treatment of PD (e.g., deep brain stimulation) often require human brain atlases for structural identification or as references for anatomical normalization. However, two pitfalls exist for many current atlases used for PD. First, most atlases do not represent the disease-specific anatomy as they are based on healthy young subjects. Second, subcortical structures, such as the subthalamic nucleus (STN) used in deep brain stimulation procedures, are often not well visualized. The dataset described in this Data in Brief is a population-averaged atlas that was made with 3T MRI scans of 25 PD patients, and contains 5 image contrasts: T1w (FLASH & MPRAGE), T2⁎w, T1–T2⁎ fusion, phase, and an R2⁎ map. While the T1w, T2⁎w, and T1–T2⁎ fusion templates provide excellent anatomical details for both cortical and sub-cortical structures, the phase and R2⁎ map contain bio-chemical features. Probabilistic tissue maps of whiter matter, grey matter, and cerebrospinal fluid are provided for the atlas. We also manually segmented eight subcortical structures: caudate nucleus, putamen, globus pallidus internus and externus (GPi & GPe), thalamus, STN, substantia nigra (SN), and the red nucleus (RN). Lastly, a co-registered histology-derived digitized atlas containing 123 anatomical structures is included. The dataset is made freely available at the MNI data repository accessible through the link http://ift.tt/2pFF1DR.



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Data on the effect of in vivo knockdown using artificial ErbB3 miRNA on Remak bundle structure

Publication date: Available online 15 April 2017
Source:Data in Brief
Author(s): Yuki Miyamoto, Tomohiro Torii, Kazuko Kawahara, Masashi Inoue, Takako Morimoto, Masahiro Yamamoto, Junji Yamauchi
Mature Schwann cells, the peripheral nervous system (PNS) glial cells, have two major roles for neuronal axons [1]. For large diameter axons, Schwann cells form myelin sheaths with multiple layers. For small diameter axons, they form Remak bundle composed only of single layer of the Schwann cell plasma membrane. In the PNS, ErbB3 forms a dimer with ErbB2 on the Schwann cell plasma membrane. ErbB3 plays a key role in myelination by myelinating Schwann cells, that is to say, its role in myelin thickness. Herein we provide the data regarding the effect of in vivo knockdown of ErbB3 on the thickness between an axon and a neighboring axon in Remak bundle, which is formed by non-myelinating Schwann cells. Since ErbB3 knockout mice are embryonically lethal, Schwann cell lineage-specific transgenic mice transcribing ErbB3 shRNA with an artificial miRNA backbone were generated and used in these experiments [2].



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[Data on anti-insulation detection via Point of Thermal Inflexion (PTI) in 1248 cases; 13 climates, four occupancy profiles, six wall configurations and four insulation levels]

Publication date: Available online 15 April 2017
Source:Data in Brief
Author(s): Yasin M. Idris, Masayuki Mae
The data in this article are the simulation results of 1248 cases that were carried out to detect anti-insulation behaviour in the article titled "Anti-insulation mitigation by altering the envelope layers' configuration" (Y. Idris and M. Mae, 2017) [1]. These cases are generated by a matrix of 13 climates, 6 envelope layer configurations, 4 occupancy profiles and 4 levels of insulation thickness. The data are concerned with the annual cooling and heating loads of these cases. In addition, the data include the Point of Thermal Inflexion (PTI) values and their anti-insulation pattern, when PTI is found. The PTI values are compiled in a single summary file and supplied as well. All These data are shared via this article where they can be reused in different ways, but mainly for serving researchers that intend to approach anti-insulation behaviour from different points of view.



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Path to Illness Intrusiveness: What Symptoms Impact the Life of People Living with Multiple Sclerosis?

Publication date: Available online 15 April 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Vanessa Bouchard, Pierre Duquette, Nancy E. Mayo
ObjectiveTo determine the direct and indirect effects of physical, emotional, and cognitive impairments on illness intrusiveness in people with MS.DesignSecondary analysis of a cross sectional data set collected in 2008 to identify gender differences in people living with MS.SettingThree MS clinics in the Greater Montréal region, Canada.ParticipantsA random sample of 135 women and 48 men diagnosed with Multiple Sclerosis after 1995 recruited and evaluated in 2008.InterventionsNot applicableMain OutcomeIllness IntrusivenessMeasure(s)Illness intrusiveness rating scale (updated version using Rasch Analysis)ResultsPath analysis yielded a model that was significant (Non-normed fit index (NNFI):0.9913; Normed fit index (NFI):0.9846) with adequate fit of the data to the model (goodness of fit index: 0.9781; χ2: 21.41; p=0.2084). The model explained 55% of the variance of illness intrusiveness. Only emotional and physical aspects were represented in the model as no cognitive impairment stayed following variable reduction. The model showed the complete mediation effect of fatigue on the physical function variables.ConclusionsThis project brings new evidence towards the conceptualization of illness intrusiveness as a construct allowing future interventions that wish to target illness intrusiveness or disease impact to be designed. It also presented statistical evidence of the importance of treating fatigue not only as a symptom but also as a consequence of other impairments.



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Vitamins C and D

Publication date: Available online 15 April 2017
Source:Clinical Therapeutics
Author(s): Richard I. Shader




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Genetic predisposition to obesity affects behavioural traits including food reward and anxiety-like behaviour in rats

Publication date: 15 June 2017
Source:Behavioural Brain Research SreeTestContent1, Volume 328
Author(s): Heike Vogel, Maria Kraemer, Cristina Rabasa, Kaisa Askevik, Roger A.H. Adan, Suzanne L. Dickson
Here we sought to define behavioural traits linked to anxiety, reward, and exploration in different strains of rats commonly used in obesity research. We hypothesized that genetic variance may contribute not only to their metabolic phenotype (that is well documented) but also to the expression of these behavioural traits. Rat strains that differ in their susceptibility to develop an obese phenotype (Sprague-Dawley, Obese Prone, Obese Resistant, and Zucker rats) were exposed to a number of behavioural tests starting at the age of 8 weeks. We found a similar phenotype in the obesity susceptible models, Obese Prone and Zucker rats, with a lower locomotor activity, exploratory activity, and higher level of anxiety-like behaviour in comparison to the leaner Obese Resistant strain. We did not find evidence that rat strains with a genetic predisposition to obesity differed in their ability to experience reward from chocolate (in a condition place preference task). However, Zucker rats show higher motivated behaviour for sucrose compared to Obese Resistant rats when the effort required to obtain palatable food is relatively low.Together our data demonstrate that rat strains that differ in their genetic predisposition to develop obesity also differ in their performance in behavioural tests linked to anxiety, exploration, and reward and that these differences are independent of body weight. We conclude that genetic variations which determine body weight and the aforementioned behaviours co-exist but that future studies are required to identify whether (and which) common genes are involved.



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Coil optimisation for transcranial magnetic stimulation in realistic head geometry

Publication date: Available online 15 April 2017
Source:Brain Stimulation
Author(s): Lari M. Koponen, Jaakko O. Nieminen, Tuomas P. Mutanen, Matti Stenroos, Risto J. Ilmoniemi
BackgroundTranscranial magnetic stimulation (TMS) allows focal, non-invasive stimulation of the cortex. A TMS pulse is inherently weakly coupled to the cortex; thus, magnetic stimulation requires both high current and high voltage to reach sufficient intensity. These requirements limit, for example, the maximum repetition rate and the maximum number of consecutive pulses with the same coil due to the rise of its temperature.ObjectiveTo develop methods to optimise, design, and manufacture energy-efficient TMS coils in realistic head geometry with an arbitrary overall coil shape.MethodsWe derive a semi-analytical integration scheme for computing the magnetic field energy of an arbitrary surface current distribution, compute the electric field induced by this distribution with a boundary element method, and optimise a TMS coil for focal stimulation. Additionally, we introduce a method for manufacturing such a coil by using Litz wire and a coil former machined from polyvinyl chloride.ResultsWe designed, manufactured, and validated an optimised TMS coil and applied it to brain stimulation. Our simulations indicate that this coil requires less than half the power of a commercial figure-of-eight coil, with a 41 % reduction due to the optimised winding geometry and a partial contribution due to our thinner coil former and reduced conductor height. With the optimised coil, the resting motor threshold of abductor pollicis brevis was reached with the capacitor voltage below 600 V and peak current below 3000 A.ConclusionThe described method allows designing practical TMS coils that have considerably higher efficiency than conventional figure-of-eight coils.



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Is There an Accurate Pre-operative Criterion for Dialysis Access Artery or Vein diameter?

Publication date: Available online 15 April 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): K.M. Cook, F.T. Padberg




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Commentary on “Five Year Natural History of Screening Detected Sub-Aneurysms and Abdominal Aortic Aneurysms in 70 Year Old Women and Systematic Review of Repair Rate in Women”

Publication date: Available online 15 April 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): R. Hultgren




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Peroral endoscopic myotomy compared with pneumatic dilation for newly diagnosed achalasia.

Related Articles

Peroral endoscopic myotomy compared with pneumatic dilation for newly diagnosed achalasia.

Surg Endosc. 2017 Apr 14;:

Authors: Meng F, Li P, Wang Y, Ji M, Wu Y, Yu L, Niu Y, Lv F, Li W, Li W, Zhai H, Wu S, Zhang S

Abstract
BACKGROUND: This study retrospectively compared the safety and efficacy of two endoscopic techniques for treating newly diagnosed achalasia, pneumatic dilation (PD), and peroral endoscopic myotomy (POEM).
METHODS: Demographics, clinical and manometric data, and outcomes were collected from the medical records of patients who received POEM or PD as the primary therapy for achalasia at our hospital from January 2012 to August 2015.
RESULTS: Of 72 patients, 32 and 40 received POEM and PD, respectively. The two groups had similar preoperative features. On short-term follow-up, improvements in high-resolution esophageal manometry and barium esophagogram parameters were similar. For PD, the success rates at 3, 6, 12, 24, and 36 months were 95, 88, 75, 72, and 60%, respectively. For POEM, these were 96, 96, 96, 93, and 93% (P = 0.013, log-rank test). On subgroup analysis, the success rate was higher with POEM than that with PD in all 3 manometric subtypes, but only that of type III was statistically significant. POEM required significantly longer operative time and hospitalization than did PD (P < 0.001). Four POEM patients experienced subcutaneous emphysema. The rate of gastroesophageal reflux was higher in patients treated by POEM (18.8%) than that in PD (10%; P = 0.286).
CONCLUSIONS: In the intermediate term, the remission rate of symptoms associated with POEM therapy was better than that with PD for newly diagnosed achalasia, especially in patients with type III achalasia. The short-term outcomes of the two therapies were similar.

PMID: 28411346 [PubMed - as supplied by publisher]

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Intraplacental Choriocarcinoma: Rare or Underdiagnosed? Report of 2 Cases Diagnosed after an Incomplete Miscarriage and a Preterm Spontaneous Vaginal Delivery

Intraplacental choriocarcinoma is a rare malignant tumor diagnosed after an abortion, an ectopic pregnancy, or a term or preterm pregnancy or following the diagnosis of a hydatidiform mole. During pregnancy, it may be more common than reported, as most patients are asymptomatic and placental choriocarcinomas are usually inconspicuous macroscopically and are often mistaken for an infarct. Based upon a case study methodology, we describe 2 cases of intraplacental choriocarcinoma: the first case was identified in the product of a uterine curettage following an incomplete miscarriage and the second in one of the placentas of a bichorionic twin pregnancy. Maternal investigation did not reveal evidence of metastatic disease and neither did the infants' one in the second case. The two cases underwent maternal surveillance with serum hCG and remained disease-free until the present. In conclusion, intraplacental choriocarcinoma is easily underdiagnosed but with current treatment, even in the presence of metastasis, the prognosis is excellent. A routine microscopic examination of all the placentas and products of miscarriage can increase the real incidence of this entity and consequently improve its management.

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Animal models for neuropsychiatric disorders: prospects for circuit intervention

Publication date: August 2017
Source:Current Opinion in Neurobiology, Volume 45
Author(s): Tobias Kaiser, Yang Zhou, Guoping Feng
Monogenic animal models for psychiatric diseases have enabled researchers to dissect the relationship between certain candidate genes, neural circuit abnormalities, and behavioral phenotypes along development. Early reports of phenotypic reversal after genetic restoration in mouse models sparked hope that genetic defects do not damage circuits irreversibly in early-onset disorders. However, further studies have suggested that only some circuits exhibit this plasticity, while many others require proper gene function during development. This review focuses on what we have learned from a few evolutionarily conserved circuit–phenotype relationships and their developmental windows to illustrate their importance when considering intervention strategies.



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Successful implantation and immediate activation of Vagus Nerve Stimulation (VNS) during pregnancy in a patient with intractable epilepsy: A case illustration and review of the literature.

Related Articles

Successful implantation and immediate activation of Vagus Nerve Stimulation (VNS) during pregnancy in a patient with intractable epilepsy: A case illustration and review of the literature.

J Clin Neurosci. 2017 Apr 11;:

Authors: Jazebi N, Moghimi N, Lall R, Osadebey E, Ortega-Barnett J, Masel T

Abstract
While Vagus Nerve Stimulation (VNS) is proven to be a safe and effective adjunctive therapy in the general population with medically intractable seizures, little is published about its implantation during pregnancy. Here we illustrate the case of a 21year old primigravid woman with medically refractory seizures who underwent safe and successful VNS implantation and immediate activation of the device in her 32nd week of pregnancy, resulting in dramatically improved seizure control and subsequent delivery of a healthy baby.

PMID: 28410885 [PubMed - as supplied by publisher]

http://ift.tt/2plTzMg

Aged patients with metastatic castration resistant prostate cancer: Should we treat with chemotherapy?

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Aged patients with metastatic castration resistant prostate cancer: Should we treat with chemotherapy?

Cancer Treat Rev. 2017 Apr 03;55:173-180

Authors: Climent MÁ, Torregrosa MD, Vázquez S, Gironés R, Arranz JA

Abstract
Prostate cancer largely affects aged men and as life expectancy continues to increase, it is likely to be a growing burden requiring an adequate management. Aging is a heterogeneous process, thus, to assess the individual state of health when making decisions is essential. Comprehensive geriatric assessment allows a detailed evaluation of the state of health of a specific subject and can modify the therapeutic decision. It is still not commonly used because it is time consuming. Chemotherapy should be administered equally in aged well-fit patients as in the general population as per the SIOG (International society of geriatric oncology) recommendations for geriatric evaluation and treatment in prostate cancer patients. Chemotherapy with docetaxel or cabazitaxel is expected to have an efficacy and toxicity similar to younger patients and they might be considered treatment options for these patients among others. In vulnerable or frail patients, weekly or biweekly docetaxel regimens are acceptable treatment options.

PMID: 28411479 [PubMed - as supplied by publisher]

http://ift.tt/2plEudG

Long term cognitive functioning and psychological well being in surgically treated Low Grade Glioma patients.

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Long term cognitive functioning and psychological well being in surgically treated Low Grade Glioma patients.

World Neurosurg. 2017 Apr 11;:

Authors: Campanella F, Palese A, Del Missier F, Moreale R, Ius T, Shallice T, Fabbro F, Skrap M

Abstract
OBJECTIVE: The aim of this work is to provide an in-depth investigation of the impact of Low Grade Gliomas (LGG) and their surgery on patients' cognitive and emotional functioning and well-being, carried out via a comprehensive and multiple-measure psychological and neuropsychological assessment.
PATIENTS AND METHODS: Fifty surgically treated LGG patients were evaluated 40 months after surgery on their functioning over six different cognitive domains, three core affective/emotional aspects, and three different psychological well-being measures to obtain a clearer picture of the long-term impact of illness and surgery on their psychological and relational world. Close relatives were also involved to obtain an independent measure of the psychological dimensions investigated.
RESULTS: Cognitive status was very satisfactory with only mild Short Term Memory difficulties. The affective and well-being profile was characterized by mild signs of depression, good satisfaction with life and psychological well-being and a good personality development with patients perceiving themselves as stronger and better persons after illness. However patients reported higher emotional reactivity and psychological well-being measures were negatively affected by Epileptic Burden. Well-being was related to positive affective/emotional functioning and unrelated to cognitive functioning. Good agreement between patients and relatives was found.
CONCLUSION: In the long term, patients operated for LGG showed good cognitive functioning, with no significant long-term cognitive sequelae for the extensive surgical approach. Psychologically, patients appear to experience a deep psychological change and maturation, closely resembling that of the so-called Post-Traumatic Growth which, to our knowledge, is for the first time described and quantified in LGG patients.

PMID: 28411105 [PubMed - as supplied by publisher]

http://ift.tt/2pm2BJr

Determinants of social competence in pediatric brain tumor survivors who participated in an intervention study.

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Determinants of social competence in pediatric brain tumor survivors who participated in an intervention study.

Support Care Cancer. 2017 Apr 14;:

Authors: Barrera M, Atenafu EG, Schulte F, Bartels U, Sung L, Janzen L, Chung J, Cataudella D, Hancock K, Saleh A, Strother D, McConnell D, Downie A, Hukin J, Zelcer S

Abstract
PURPOSE: This prospective study describes disease/treatment, personal characteristics, and social/family contextual variables as risk and resilience factors that predict social competence in pediatric brain tumor survivors (PBTS).
METHODS: Ninety-one PBTS (51% male, mean age 11.21 years, off-treatment, attending a regular classroom >50% of the time) participated. PBTS and their primary caregivers (proxy) completed the Social Skills Rating System (SSRS) to assess social competence at baseline, 2, and 8 months follow-up. At baseline, medical information (e.g., tumor type and location, cranial irradiation therapy (CIT)), personal characteristics (e.g., child's age and gender, intelligence, executive function, attention, and memory), and social/family factors (family income and ethnicity) were obtained.
RESULTS: Using mixed model multivariable analyses with a longitudinal component, tumor type (medulloblastoma) (p < 0.01) and poor executive function, specifically, emotional control, were the best predictors of low total and assertion self-reported SSRS scores (p < 0.02). Receiving CIT was associated with low proxy-reported assertion (p = 0.035), and cooperation score (p = 0.02). Poor emotional control was associated with low proxy-reported total (p = 0.032), assertion (p = 0.023), and self-control scores (p = 0.007). Being non-White was associated with low proxy-reported total (p = 0.016), self-control (p = 0.040), responsibility (p = 0.035), and cooperation scores (p = 0.002). There were no significant changes over time.
CONCLUSIONS: This study supports a multifactorial model of insult and non-insult factors (medical, personal, and social context) as determinants of social competence in PBTS. Data from both informants identify determinants of social competence. These factors need to be considered in future interventions to help children better improve their social competence.

PMID: 28411324 [PubMed - as supplied by publisher]

http://ift.tt/2ppmhcr

Practice patterns for the prophylaxis and treatment of acute radiation dermatitis in the United States.

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Practice patterns for the prophylaxis and treatment of acute radiation dermatitis in the United States.

Support Care Cancer. 2017 Apr 14;:

Authors: Lucey P, Zouzias C, Franco L, Chennupati SK, Kalnicki S, McLellan BN

Abstract
PURPOSE: Due to the inconclusive evidence for available treatment options, management of radiation dermatitis (RD) varies among practitioners. This study defines and reviews the current treatment patterns for RD in the USA, providing guidance for practicing physicians as well as directions for future research.
METHODS: An online survey of 21 questions was emailed to all 5626 members of the 2013 American Society for Radiation Oncology (ASTRO) directory, which included radiation oncologists, residents, fellows, physician assistants, nurse practitioners, registered nurses and other care providers. The questions were designed to evaluate demographics of responders, their training and comfort in the management RD, and their patterns of care regarding prophylaxis and treatment of RD. Data was analyzed using simple summary and descriptive statistics.
RESULTS: Out of the 5626 emails sent, we were left with 709 physician respondents for our analysis, or a response rate of 12.9%. Although 84.7% of physicians felt that RD had a moderate or large impact on patients' quality of life during cancer treatment, only 30.1% received special training or specific instructional courses in treating RD during their medical training in residency or fellowship. Eighty-nine percent of surveyed physicians rely on observational and/or anecdotal findings to guide treatment decisions, and 51.4% reported using evidence-based treatments.
CONCLUSION: The results of our study show that there is great variability in the topical agents and dressings used in practice by radiation oncologists to prevent and treat RD. This information may be useful to other practitioners to develop their own personal recommendations and can guide further research into strategies to prevent and treat radiation dermatitis.

PMID: 28411323 [PubMed - as supplied by publisher]

http://ift.tt/2pphl7y

State of the art thoracic ultrasound: intervention and therapeutics.

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State of the art thoracic ultrasound: intervention and therapeutics.

Thorax. 2017 Apr 14;:

Authors: Corcoran JP, Tazi-Mezalek R, Maldonado F, Yarmus LB, Annema JT, Koegelenberg CFN, St Noble V, Rahman NM

Abstract
The use of thoracic ultrasound outside the radiology department and in everyday clinical practice is becoming increasingly common, having been incorporated into standards of care for many specialties. For the majority of practitioners, their experience of, and exposure to, thoracic ultrasound will be in its use as an adjunct to pleural and thoracic interventions, owing to the widely recognised benefits for patient safety and risk reduction. However, as clinicians become increasingly familiar with the capabilities of thoracic ultrasound, new directions for its use are being sought which might enhance practice and patient care. This article reviews the ways in which the advent of thoracic ultrasound is changing the approach to the investigation and treatment of respiratory disease from an interventional perspective. This will include the impact of thoracic ultrasound on areas including patient safety, diagnostic and therapeutic procedures, and outcome prediction; and will also consider potential future research and clinical directions.

PMID: 28411248 [PubMed - as supplied by publisher]

http://ift.tt/2ppouEI

Current and Future Role of Genetic Screening in Gynecologic Malignancies.

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Current and Future Role of Genetic Screening in Gynecologic Malignancies.

Am J Obstet Gynecol. 2017 Apr 11;:

Authors: Ring KL, Garcia C, Thomas MH, Modesitt SC

Abstract
The world of hereditary cancers has seen an exponential growth in recent years. While Hereditary Breast and Ovarian Cancer and Lynch syndrome account for the majority of mutations encountered by gynecologists, newly identified deleterious genetic mutations continue to be unearthed with their associated risks of malignancies. However, these advances in genetic cancer predispositions then force practitioners and their patients to confront the uncertainties of these less commonly identified mutations and the fact that there is limited evidence to guide them in expected cancer risk and appropriate risk reduction strategies. Given the speed of information, it is imperative to involve cancer genetics experts when counseling these patients. In addition, coordination of screening and care in conjunction with specialty high risk clinics, if available, allows for patients to have centralized management for multiple cancer risks under the guidance of physicians with experience counseling these patients. The objective of this review is to present the current literature regarding genetic mutations associated with gynecologic malignancies as well to propose screening and risk reduction options for these high risk patients.

PMID: 28411145 [PubMed - as supplied by publisher]

http://ift.tt/2ppzqT5

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors.

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Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors.

Immunity. 2017 Apr 06;:

Authors: Arce Vargas F, Furness AJS, Solomon I, Joshi K, Mekkaoui L, Lesko MH, Miranda Rota E, Dahan R, Georgiou A, Sledzinska A, Ben Aissa A, Franz D, Werner Sunderland M, Wong YNS, Henry JY, O'Brien T, Nicol D, Challacombe B, Beers SA, Melanoma TRACERx Consortium, Renal TRACERx Consortium, Lung TRACERx Consortium, Turajlic S, Gore M, Larkin J, Swanton C, Chester KA, Pule M, Ravetch JV, Marafioti T, Peggs KS, Quezada SA

Abstract
CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology.

PMID: 28410988 [PubMed - as supplied by publisher]

http://ift.tt/2pprrp2

Epo reprograms the epigenome of erythroid cells.

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Epo reprograms the epigenome of erythroid cells.

Exp Hematol. 2017 Apr 11;:

Authors: Perreault AA, Benton ML, Koury MJ, Brandt SJ, Venters BJ

Abstract
The hormone erythropoietin (Epo) is required for erythropoiesis, yet its molecular mechanism of action remains poorly understood, particularly in regards to chromatin dynamics. To investigate how Epo modulates the erythroid epigenome, we performed epigenetic profiling using an ex vivo murine cell system that undergoes synchronous erythroid maturation in response to Epo stimulation. Our findings define the repertoire of Epo-modulated enhancers, illuminating a new facet of Epo signaling. First, a large number of enhancers rapidly responded to Epo stimulation, revealing a cis-regulatory network of Epo-responsive enhancers. In contrast, most of the other identified enhancers remained in an active acetylated state during Epo signaling, suggesting that most erythroid enhancers are established at an earlier precursor stage. Second, we identified several hundred super enhancers that were linked to key erythroid genes, such as TAL1, BCL11A, and MIR144/451. Third, experimental and computational validation demonstrated that many predicted enhancer regions were occupied by Tal1 and enriched with DNA binding motifs for Gata1, Klf1, Tal1/E-box and Stat5. Additionally, many of these cis-regulatory regions were evolutionarily conserved and displayed correlated enhancer:promoter acetylation. Together, these findings define a cis-regulatory enhancer network for Epo signaling during erythropoiesis, and provide the framework for future studies involving the interplay of epigenetics and Epo signaling.

PMID: 28410882 [PubMed - as supplied by publisher]

http://ift.tt/2oAfTz1

Quantifying Health Utilities in Patients Undergoing Stereotactic Body Radiation Treatment for Liver Metastases for Use in Future Economic Evaluations.

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Quantifying Health Utilities in Patients Undergoing Stereotactic Body Radiation Treatment for Liver Metastases for Use in Future Economic Evaluations.

Clin Oncol (R Coll Radiol). 2017 Apr 12;:

Authors: Warren B, Munoz-Schuffenegger P, Chan KKW, Chu W, Helou J, Erler D, Chung H

Abstract
AIM: Stereotactic body radiation therapy (SBRT) is increasingly used as an option for those with liver metastases. In order to facilitate future economic impact of health technologies, health utility scores may be used. The EuroQOL-5D-3L (EQ-5D) preference-based healthy utility instrument was used to evaluate the impact of treatment with SBRT on health utility scores.
MATERIALS AND METHODS: Between August 2013 and October 2014, 31 patients treated with 3-5 fractions of SBRT for liver metastases were enrolled in this study. The EQ-5D instrument was administered at baseline, during and up to 6 months post-SBRT.
RESULTS: Mean EQ-5D score at baseline was 0.857, which remained stable across the entire study time period. Transient increases in difficulties with mobility (9.7% reported at baseline to 16.1% on the last day of treatment) and usual activities (3.2% reported at baseline to 34.5% on day two) were found during the course of treatment; these returned to baseline levels subsequently. The mean visual analogue score at baseline was 65.8 and remained unchanged throughout treatment and follow-up.
CONCLUSIONS: The stability of health utility scores and problems reported by patients undergoing treatment indicate that SBRT for liver metastases does not impart a significant adverse effect on quality of life. These results may be used for future economic evaluation of SBRT.

PMID: 28410779 [PubMed - as supplied by publisher]

http://ift.tt/2oCYMOW

Discovery of novel 2-substituted-4-(2-fluorophenoxy) pyridine derivatives possessing pyrazolone and triazole moieties as dual c-Met/VEGFR-2 receptor tyrosine kinase inhibitors.

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Discovery of novel 2-substituted-4-(2-fluorophenoxy) pyridine derivatives possessing pyrazolone and triazole moieties as dual c-Met/VEGFR-2 receptor tyrosine kinase inhibitors.

Bioorg Chem. 2017 Apr 08;72:116-122

Authors: Gu W, Dai Y, Qiang H, Shi W, Liao C, Zhao F, Huang W, Qian H

Abstract
In our efforts to develop novel dual c-Met/VEGFR-2 inhibitors as potential anticancer agents, a series of 2-substituted-4-(2-fluorophenoxy) pyridine derivatives bearing pyrazolone scaffold were designed and synthesized. The cell proliferation assay in vitro demonstrated that most target compounds had inhibition potency on both c-Met and VEGFR-2, especially compound 9h, 12b and 12d. Based on the further enzyme assay in vitro, compound 12d was considered as the most promising one, the IC50 values of which were 0.11μM and 0.19μM for c-Met and VEGFR-2, respectively. Further molecular docking studies suggested a common mode of interaction at the ATP-binding site of c-Met and VEGFR-2, indicating that 12d was a potential compound for cancer therapy deserving further study.

PMID: 28411406 [PubMed - as supplied by publisher]

http://ift.tt/2nR4jlT

Rectus femoris muscle necrosis: An underrated donor-site complication of free anterolateral thigh flap.

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Rectus femoris muscle necrosis: An underrated donor-site complication of free anterolateral thigh flap.

J Plast Reconstr Aesthet Surg. 2017 Apr 07;:

Authors: Maruccia M, Di Taranto G, Nicoli F, Ciudad P, Giudice G, Chen HC

PMID: 28410985 [PubMed - as supplied by publisher]

http://ift.tt/2nR5vpG

A systematic review of complications associated with direct implants vs. tissue expanders following Wise pattern skin-sparing mastectomy.

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A systematic review of complications associated with direct implants vs. tissue expanders following Wise pattern skin-sparing mastectomy.

J Plast Reconstr Aesthet Surg. 2017 Mar 14;:

Authors: Corban J, Shash H, Safran T, Sheppard-Jones N, Fouda-Neel O

Abstract
INTRODUCTION: With proven oncological safety and improved aesthetic outcomes, the Type IV or "Wise pattern" skin-sparing mastectomy (SSM) is a procedure that is being performed with increasing frequency. Unfortunately, it is also associated with an increased risk of complications. The purpose of this investigation was to determine the complications associated with direct-to-implant and two-step tissue-expander breast reconstruction following Wise pattern SSM.
METHODS: Systematic electronic searches were performed using PubMed, MEDLINE, and Embase databases. Search terms used were those for studies reporting complications following breast reconstruction using direct-to-implant and two-step tissue-expander approaches following Wise pattern SSM. Included studies were graded for their risk of bias. Pooled descriptive statistics on overall complication rates, skin flap necrosis, delayed wound healing, hematoma, and infections were performed for both procedures. Other complications specific to each procedure were also reported.
RESULTS: A total of 16 articles met the inclusion criteria for this investigation, representing 561 direct-to-implant or two-step breast reconstruction procedures. For direct-to-implant reconstructions, the pooled complication rate was 30%, while for those using tissue expansion, it was 20.3%. Rates of skin flap necrosis (9.70%, 4.69%), delayed wound healing (2.77%, 0.78%), infection (2.54%, 3.91%), seroma (1.15%, 4.68%), and hematoma (0.92%, 0.78%) were calculated for direct-to-implant procedures and two-step tissue expansion, respectively.
CONCLUSION: Following Wise pattern SSM, direct-to-implant reconstruction appears to be associated with an increased rate of overall complications and skin flap necrosis. Modification of the procedure through the placement of a de-epithelialized dermal flap may help limit delays in wound healing and infection. Future investigations that report complication rates for SSM should present data that are segregated according to the type of procedure and the method of reconstruction.

PMID: 28410984 [PubMed - as supplied by publisher]

http://ift.tt/2nR1IbD

Primary adrenal non-Hodgkin lymphoma: a case report and review of the literature.

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Primary adrenal non-Hodgkin lymphoma: a case report and review of the literature.

J Med Case Rep. 2017 Apr 15;11(1):108

Authors: Ram N, Rashid O, Farooq S, Ulhaq I, Islam N

Abstract
BACKGROUND: Lymphomas are cancers that arise from the white blood cells and have been traditionally divided into two large subtypes: Hodgkin and non-Hodgkin lymphoma. B-cell lymphoma is the most common subtype of non-Hodgkin lymphoma; almost 85% of patients with lymphoma have this variant. Lymphomas can potentially arise from any lymphoid tissue located in the body; however, primary adrenal non-Hodgkin lymphoma is extremely rare. We report the history, examination findings, and laboratory results of a 50-year-old man diagnosed with a primary left adrenal diffuse large B-cell lymphoma.
CASE PRESENTATION: A 50-year-old Pakistani man presented to our hospital with progressively increasing pain and fullness in the left upper quadrant of his abdomen, generalized weakness, easy fatigability, and decreased appetite of 1.5 months' duration. On examination, he had a blood pressure of 140/80 mmHg with no postural drop, a pulse rate of 106 beats/minute, and no fever. His past medical history was significant for pulmonary tuberculosis 2 years earlier, for which he received antituberculous therapy. Computed tomography revealed a heterogeneous enhancing soft tissue density mass in the left adrenal gland. It measured 7.1 × 5.6 × 9.5 cm. Further laboratory workup revealed the following levels: sodium 135 mEq/L, potassium 4.5 mEq/L, lactate dehydrogenase 905 IU/L, renin 364 IU/ml, aldosterone 5.79 ng/dl, dehydroepiandrosterone sulfate 79.20 μg/dl, urinary vanillylmandelic acid 6.4 mg/24 hours, and a low-dose overnight dexamethasone suppression test result of 3.20 μg/dl. The patient underwent left adrenalectomy. Histopathological test results showed a diffuse large B-cell lymphoma. Immunohistochemical stains were strongly positive for CD20 and negative for CD3, CD5, CD10, and cyclin D1. The patient's Ki-67 (Mib-1) index was approximately 80%. He received a total of six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (rituximab was not given, owing to financial constraints) and was routinely followed pre- and postchemotherapy at our hematology clinic with complete blood count and serum lactate dehydrogenase evaluations. The patient responded to chemotherapy and is currently doing well.
CONCLUSIONS: Primary adrenal lymphoma is an extremely rare but rapidly progressive disease. It generally carries a poor prognosis, partly because an optimal treatment protocol has not yet been established. Further studies with larger sample sizes are needed to establish the best treatment option and increase overall survival.

PMID: 28410600 [PubMed - in process]

http://ift.tt/2ppyYnR

Endovascular repair of a ruptured thoracic aortic dissection with a right sided aortic arch: A case report.

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Endovascular repair of a ruptured thoracic aortic dissection with a right sided aortic arch: A case report.

Int J Surg Case Rep. 2017 Mar 28;34:139-143

Authors: Irvan JL, Elmore JR, Flora SL, Ryer EJ

Abstract
BACKGROUND: Emergency treatment of complex aortic pathology is challenging in the setting of a right-sided aortic arch. We report the successful treatment of a ruptured thoracic aortic aneurysm (TAA) in the setting of a Stanford type B aortic dissection (TBAD) and right-sided aortic arch.
PRESENTATION OF CASE: The patient is a 66-year-old male with chronic kidney disease (CKD) admitted with right sided chest pain and hypotension. Computed tomography angiography (CTA) revealed a 5cm ruptured TAA in the setting of a TBAD and right-sided aortic arch. The TBAD began just distal to the right common carotid artery and involved the origin of the left subclavian artery (SCA). Using a totally percutaneous approach, a conformable Gore(®) TAG(®) thoracic endoprosthesis was placed in proximal descending thoracic aorta covering the left SCA. Aside from progression of his pre-existing CKD, the patient had an uneventful recovery. CTA one-month post-procedure revealed a type IB endoleak with degeneration of the distal descending thoracic aorta. To exclude the endoleak, the repair was extended distally using a Medtronic Valiant(®) thoracic stent graft. The left subclavian artery was subsequently coil embolized to treat an additional retrograde endoleak. The patient has done well with no further evidence of endoleak or aneurysm expansion.
CONCLUSION: Right-sided aortic arch presents challenges in the emergency setting. CTA and post-processing reconstructions are very helpful. While the endoleaks prompted additional interventions, the end result was excellent. This case displays the importance of careful attention to detail and follow-up in these complicated patients.

PMID: 28411526 [PubMed - as supplied by publisher]

http://ift.tt/2ozXTot

Different influence of antipsychotics on the balance between pro- and anti-inflammatory cytokines depends on glia activation: An in vitro study.

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Different influence of antipsychotics on the balance between pro- and anti-inflammatory cytokines depends on glia activation: An in vitro study.

Cytokine. 2017 Apr 11;:

Authors: Obuchowicz E, Bielecka-Wajdman AM, Paul-Samojedny M, Nowacka M

Abstract
The microglial hypothesis of schizophrenia suggests that its neuropathology is closely associated with neuroinflammation manifested, inter alia, by an increased expression of cytokines. However, clinical investigations imply that schizophrenia is a heterogeneous disease and in some groups of patients the activated inflammatory process does not contribute to the disease-associated impairment of brain function. Clinical studies revealed also an equivocal impact of antipsychotics on peripheral and CSF cytokines, whereas experimental research performed on the stimulated glia cultures showed their inhibitory effect on pro-inflammatory cytokine levels. In the present study, the effect of chlorpromazine, haloperidol and risperidone (0.5, 5 or 10μM) on production of pro-inflammatory cytokines IL-1β and TNF-α and anti-inflammatory IL-10 was investigated in the unstimulated and lipopolysaccharide-stimulated primary rat mixed glial cell cultures. In the unstimulated cultures, haloperidol at all applied concentrations, risperidone at 5, 10μM and chlorpromazine at 10μM increased IL-10 levels in the culture supernatants without a significant influence on IL-1β or TNF-α levels, and all drugs applied at 10μM induced a robust increase in IL-10 mRNA expression. Under strong inflammatory activation, haloperidol and risperidone at all concentrations reduced production of both pro-inflammatory cytokines, without adverse effects on IL-10 expression when used at 10μM. Chlorpromazine at all concentrations diminished the production of three cytokines and did not induce anti-inflammatory effect. These results suggest that dependently on glia activation antipsychotics via different mechanisms may induce anti-inflammatory effect and that this activity is not common for all drugs under conditions of strong glia activation.

PMID: 28411046 [PubMed - as supplied by publisher]

http://ift.tt/2ozXUJ3

Lipid correlates of antidepressant response to omega-3 polyunsaturated fatty acid supplementation: A pilot study.

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Lipid correlates of antidepressant response to omega-3 polyunsaturated fatty acid supplementation: A pilot study.

Prostaglandins Leukot Essent Fatty Acids. 2017 Apr;119:38-44

Authors: Ganança L, Galfalvy HC, Oquendo MA, Hezghia A, Cooper TB, Mann JJ, Sublette ME

Abstract
Low omega-3 polyunsaturated fatty acid (PUFA) levels are seen in major depression. We examined effects of six weeks of fish oil supplementation on clinical characteristics in 16 patients with symptomatic major depressive disorder, and tested plasma phospholipid levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) as correlates of clinical response. Depression symptoms improved after supplementation (p=0.007). The reduction in depression severity was not predicted by baseline PUFA levels but did exhibit a relationship with endpoint PUFAs, correlating negatively with DHA as a percentage of plasma phospholipids (DHA%; R(2)=0.60, p=0.004), adjusting for endpoint EPA%; and correlating positively with endpoint EPA% (R(2)=0.58, p=0.007), adjusting for endpoint DHA%. Thus, the higher the proportion of DHA to EPA, the greater the reduction in depression severity (r=-0.43, p=0.097). Five patients showed a decrease of >50% on the 17-item Hamilton Depression Rating Scale and a final score <7 and were thus not only responders but met standard criteria for remission, and were distinguished from non-responders by higher levels of DHA% (p=0.03). This pilot study suggests that post-supplementation DHA% levels may be a necessary target for antidepressant response to fish oil, and that this may depend to some extent on the efficacy of EPA conversion to DHA.

PMID: 28410668 [PubMed - in process]

http://ift.tt/2oAdyEa

Frontotemporal Dementia.

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Frontotemporal Dementia.

Neurol Clin. 2017 May;35(2):339-374

Authors: Olney NT, Spina S, Miller BL

Abstract
Frontotemporal dementia (FTD) is a heterogeneous disorder with distinct clinical phenotypes associated with multiple neuropathologic entities. Presently, the term FTD encompasses clinical disorders that include changes in behavior, language, executive control, and often motor symptoms. The core FTD spectrum disorders include behavioral variant FTD, nonfluent/agrammatic variant primary progressive aphasia, and semantic variant PPA. Related FTD disorders include frontotemporal dementia with motor neuron disease, progressive supranuclear palsy syndrome, and corticobasal syndrome. In this article, the authors discuss the clinical presentation, diagnostic criteria, neuropathology, genetics, and treatments of these disorders.

PMID: 28410663 [PubMed - in process]

http://ift.tt/2oAaDvb

Mitochondrial "power" drives tamoxifen resistance: NQO1 and GCLC are new therapeutic targets in breast cancer.

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Mitochondrial "power" drives tamoxifen resistance: NQO1 and GCLC are new therapeutic targets in breast cancer.

Oncotarget. 2017 Mar 02;8(12):20309-20327

Authors: Fiorillo M, Sotgia F, Sisci D, Cappello AR, Lisanti MP

Abstract
Here, we identified two new molecular targets, which are functionally sufficient to metabolically confer the tamoxifen-resistance phenotype in human breast cancer cells. Briefly, ~20 proteins were first selected as potential candidates, based on unbiased proteomics analysis, using tamoxifen-resistant cell lines. Then, the cDNAs of the most promising candidates were systematically transduced into MCF-7 cells. Remarkably, NQO1 and GCLC were both functionally sufficient to autonomously confer a tamoxifen-resistant metabolic phenotype, characterized by i) increased mitochondrial biogenesis, ii) increased ATP production and iii) reduced glutathione levels. Thus, we speculate that pharmacological inhibition of NQO1 and GCLC may be new therapeutic strategies for overcoming tamoxifen-resistance in breast cancer patients. In direct support of this notion, we demonstrate that treatment with a known NQO1 inhibitor (dicoumarol) is indeed sufficient to revert the tamoxifen-resistance phenotype. As such, these findings could have important translational significance for the prevention of tumor recurrence in ER(+) breast cancers, which is due to an endocrine resistance phenotype. Importantly, we also show here that NQO1 has significant prognostic value as a biomarker for the prediction of tumor recurrence. More specifically, higher levels of NQO1 mRNA strongly predict patient relapse in high-risk ER(+) breast cancer patients receiving endocrine therapy (mostly tamoxifen; H.R. > 2.15; p = 0.007).

PMID: 28411284 [PubMed - in process]

http://ift.tt/2p7jxn6

Systematic functional perturbations uncover a prognostic genetic network driving human breast cancer.

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Systematic functional perturbations uncover a prognostic genetic network driving human breast cancer.

Oncotarget. 2017 Mar 15;8(13):20572-20587

Authors: Gallenne T, Ross KN, Visser NL, Salony, Desmet CJ, Wittner BS, Wessels LFA, Ramaswamy S, Peeper DS

Abstract
Prognostic classifiers conceivably comprise biomarker genes that functionally contribute to the oncogenic and metastatic properties of cancer, but this has not been investigated systematically. The transcription factor Fra-1 not only has an essential role in breast cancer, but also drives the expression of a highly prognostic gene set. Here, we systematically perturbed the function of 31 individual Fra-1-dependent poor-prognosis genes and examined their impact on breast cancer growth in vivo. We find that stable shRNA depletion of each of nine individual signature genes strongly inhibits breast cancer growth and aggressiveness. Several factors within this nine-gene set regulate each other's expression, suggesting that together they form a network. The nine-gene set is regulated by estrogen, ERBB2 and EGF signaling, all established breast cancer factors. We also uncover three transcription factors, MYC, E2F1 and TP53, which act alongside Fra-1 at the core of this network. ChIP-Seq analysis reveals that a substantial number of genes are bound, and regulated, by all four transcription factors. The nine-gene set retains significant prognostic power and includes several potential therapeutic targets, including the bifunctional enzyme PAICS, which catalyzes purine biosynthesis. Depletion of PAICS largely cancelled breast cancer expansion, exemplifying a prognostic gene with breast cancer activity. Our data uncover a core genetic and prognostic network driving human breast cancer. We propose that pharmacological inhibition of components within this network, such as PAICS, may be used in conjunction with the Fra-1 prognostic classifier towards personalized management of poor prognosis breast cancer.

PMID: 28411283 [PubMed - in process]

http://ift.tt/2p7loIB

Rapid Induction Therapy with Oral Tacrolimus in Elderly Patients with Refractory Ulcerative Colitis Can Easily Lead to Elevated Tacrolimus Concentrations in Blood: A Report of 5 Cases.

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Rapid Induction Therapy with Oral Tacrolimus in Elderly Patients with Refractory Ulcerative Colitis Can Easily Lead to Elevated Tacrolimus Concentrations in Blood: A Report of 5 Cases.

Am J Case Rep. 2017 Apr 15;18:405-409

Authors: Kawamura H, Matsumoto S, Nakamura N, Miyatani H, Mashima H

Abstract
BACKGROUND Tacrolimus is reportedly effective for the treatment of refractory ulcerative colitis (UC). At our hospital, there has been an increase in the number of patients, including elderly patients, with refractory UC treated with tacrolimus. Here, we review the data from 5 patients with elderly-onset UC treated with tacrolimus as remission induction therapy. CASE REPORT The subjects were 5 patients ≥65 years of age with refractory UC who had received oral tacrolimus as remission induction therapy between 2009 and 2014 (3 men and 2 women; median age at onset, 75 years). At the start of the tacrolimus treatment, the median duration of disease was 3 months, and the type of UC was total colitis in 4 cases, and left-sided colitis in 1 case. The drugs used concomitantly at the start of tacrolimus treatment were mesalazine (5 cases) and an immunomodulator drug (1 case). Standard induction therapy (0.05 mg/kg/day) was used in 2 patients and rapid induction therapy (0.1 mg/kg/day) was used in the remaining 3 patients. One week after the start of treatment, the blood trough concentrations of tacrolimus were over the target level of 15 mg/mL in 4 patients. The clinical activity index values on day 0 and day 14 were 10.6±2.1 and 7.6±3.4, respectively. The ulcerative colitis endoscopic index of severity in the remaining 3 patients, after excluding the 2 patients who required colectomy within 14 days after the start of tacrolimus therapy, was 7.3±1.0 before the start of the tacrolimus treatment, improving to 4.5±0.5 on day 14. Subsequently, 1 of these 3 patients was also judged to need surgery due to symptom exacerbation, while complete remission was maintained in the other 2 patients. CONCLUSIONS In elderly-onset refractory UC patients, tacrolimus appears to be effective as remission induction therapy. However, since tacrolimus concentrations in the blood can rise easily in elderly patients, frequent monitoring of the drug concentrations and dosage adjustments are necessary.

PMID: 28411286 [PubMed - in process]

http://ift.tt/2ppz0fi

Response: Letter to the Editor.

Response: Letter to the Editor.

Int J Pediatr Otorhinolaryngol. 2017 Apr 06;:

Authors: Sztano B, Rovo L

PMID: 28410847 [PubMed - as supplied by publisher]

http://ift.tt/2oMkSyM

CD4(+) T cells support establishment of RSV-specific IgG and IgA antibody secreting cells in the upper and lower murine respiratory tract following RSV infection.

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CD4(+) T cells support establishment of RSV-specific IgG and IgA antibody secreting cells in the upper and lower murine respiratory tract following RSV infection.

Vaccine. 2017 Apr 11;:

Authors: Sealy RE, Surman SL, Hurwitz JL

Abstract
The RSV vaccine field suffered a major set-back when children were vaccinated with a formalin-inactivated RSV vaccine (FI-RSV). Unexpectedly, the vaccinated children fared worse than unvaccinated children when they were naturally infected with RSV. Mouse models were then developed that implicated the CD4(+) T helper cell population as a contributor to adverse events. Today, the T cell is viewed with much caution in the RSV field, and its induction by vaccination is sometimes discouraged. Here we re-emphasize the beneficial role of the CD4(+) T cell. Experiments were performed with RSV-infected nude mice that received CD4(+) T cells by adoptive transfer. Data demonstrated that CD4(+) T cells were necessary for the induction of mucosal and systemic RSV-specific antibodies, for the establishment of RSV-specific IgG and IgA antibody secreting cells in the upper and lower respiratory tract, and for RSV clearance.

PMID: 28410812 [PubMed - as supplied by publisher]

http://ift.tt/2pls71o

Cone beam computed tomography incidental findings of the cervical spine and clivus: retrospective analysis and review of the literature.

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Cone beam computed tomography incidental findings of the cervical spine and clivus: retrospective analysis and review of the literature.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Mar 19;:

Authors: Alsufyani NA

Abstract
OBJECTIVE: The aim of this study was to analyze and describe incidental findings in the cervical spine (C-spine) and the clivus encountered in cone beam computed tomography (CBCT) imaging. The wide range of possible anatomic variants and pathoses is discussed in the context of the medical and dental literature to clarify their radiographic appearance and clinical implications as a guide for the oral and maxillofacial radiologist.
STUDY DESIGN: A retrospective analysis of radiographic reports was conducted based on CBCT images from 2 oral and maxillofacial imaging centers. Reports documenting incidental findings in the C-spine or the clivus were selected. Data on patient age and sex were collected, and each incidental finding was categorized as degenerative, congenital, or developmental/pathologic. Each finding is discussed with clinical importance and is pictorially presented.
RESULTS: From a total of 7689 CBCT reports, there were 732 incidental findings (9.5%) in the C-spine or the clivus. Most findings were in the C-spine (92.3%), were degenerative in nature (78.7%), and occurred in females in their sixth decade. Logistic regression analysis showed that the odds of presenting with a degenerative incidental finding in the C-spine or the clivus did not differ based on sex but were 5.5 times (95% confidence interval, 3.77-8.04) higher if the patient was aged 50 years or older.
CONCLUSIONS: This review is the largest and the first to characterize incidental findings in the C-spine and the clivus. Such findings were reported in 9.5% of radiographic reports. Several presented as uncommon congenital variants that are not usually spotlighted during oral and maxillofacial radiology training.

PMID: 28411008 [PubMed - as supplied by publisher]

http://ift.tt/2oMH4Jl

Influence of lip retraction on the cone beam computed tomography assessment of bone and gingival tissues of the anterior maxilla.

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Influence of lip retraction on the cone beam computed tomography assessment of bone and gingival tissues of the anterior maxilla.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Feb 20;:

Authors: Silva JNN, Andrade PF, Sotto-Maior BS, Souza Picorelli Assis NM, Pires Carvalho AC, Devito KL

Abstract
OBJECTIVE: To evaluate the influence of lip retraction on cone beam computed tomography (CBCT) assessment of bone and gingival tissues on the labial surface of the anterior maxilla.
STUDY DESIGN: A retrospective study was conducted using measurements of bone and gingival tissues collected from 120 maxillary incisors. The thicknesses of the bone and gingival tissues of different regions were measured on CBCT images, with and without a lip retractor. The thicknesses of the gingival tissues obtained from CBCT were correlated with measurements performed by clinical probing.
RESULTS: The thickness of bone in the more cervical region presented a higher mean value for exams performed with a lip retractor (P = .021). The thickness of bone found a significant correlation with the thickness of the gingiva (P ≤ .020) with a lip retractor in CBCT exams. The thickness of the gingival tissue obtained from CBCT scans with lip retraction found significant correlations with those obtained clinically (P ≤ .001).
CONCLUSIONS: The use of lip retractors is a simple and reliable practice that allows the measurement of gingival tissues on CBCT images. This practice can exempt a patient from an invasive clinical procedure for measuring the thickness of the gingival tissue for implant cases of the anterior segment.

PMID: 28411007 [PubMed - as supplied by publisher]

http://ift.tt/2oMn5u2

The efficacy of minocycline mouth rinses on the symptoms associated with recurrent aphthous stomatitis: a randomized, double-blind, crossover study assessing different doses of oral rinse.

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The efficacy of minocycline mouth rinses on the symptoms associated with recurrent aphthous stomatitis: a randomized, double-blind, crossover study assessing different doses of oral rinse.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Feb 28;:

Authors: Yarom N, Zelig K, Epstein JB, Gorsky M

Abstract
OBJECTIVE: The aim of the study was to assess the efficacy of 2 different concentrations of minocycline mouthwashes on the symptoms of recurrent aphthous stomatitis (RAS).
STUDY DESIGN: The 2-year study was designed as a randomized, double-blind, crossover study. Healthy patients with frequent RAS episodes received 2 sealed and computer-randomized marked kits containing minocycline mouthwashes (0.2% and 0.5% solution). The patients were asked to use 1 of the kits on the first episode of RAS, starting with the first onset of prodromal symptoms, until the symptoms resolved or up to a maximum of 10 days (whichever came first). The patients were asked to use their second kit during a subsequent episode.
RESULTS: A total of 14 patients (8 males, 6 females) completed the 2 arms of the study. The mean intensity of pain was significantly lower when the 0.5% solution was used compared with the 0.2% solution (P = .027). The difference reached the level of statistical significance as soon as the end of the second day of use (P = .032). Only minor and temporary adverse reactions were documented.
CONCLUSIONS: We found that 0.5% minocycline mouth rinse was more effective than the 0.2% concentration, which had been suggested by our group in previous studies for the management of RAS.

PMID: 28411006 [PubMed - as supplied by publisher]

http://ift.tt/2oMAemQ

Bacterial and histopathological findings in deep head and neck infections: a retrospective analysis.

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Bacterial and histopathological findings in deep head and neck infections: a retrospective analysis.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Feb 20;:

Authors: Cordesmeyer R, Kauffmann P, Markus T, Sömmer C, Eiffert H, Bremmer F, Laskawi R

Abstract
OBJECTIVES: Deep neck infections are among the most dangerous acute diseases in the head and neck region. This analysis gives an overview of the bacterial and histopathologic findings of deep neck infections.
STUDY DESIGN: From January 2002 to December 2012, 63 patients were diagnosed with and treated for deep neck infections at the University Medical Center Göttingen. Bacterial and histopathologic examinations were made, and the occurrence of bacterial pathogens and histopathologic findings were analyzed.
RESULTS: The most commonly isolated aerobic gram-positive pathogen was Streptococcus viridans (26.7%); Staphylococcus epidermidis and Staphylococcus aureus were each found in 16.7% of infections. The most commonly isolated aerobic gram-negative pathogens were Escherichia coli, Klebsiella oxytoca, and Haemophilus influenzae. In 1.6% of patients, a malignant cancer was detected.
CONCLUSION: For clear diagnosis and effective therapy, a bacteriologic investigation of deep neck infections is essential because of the heterogeneous spectrum of the detected bacteria. In contrast to Asia, where Klebsiella pneumoniae is the most common pathogen, in South Lower Saxony, Germany, we discovered a dominating spectrum of aerobic gram-positive cocci. Biopsy obtained from an abscess cavity for histologic examination should always be part of the diagnostic process in order to exclude a malignant process.

PMID: 28411005 [PubMed - as supplied by publisher]

http://ift.tt/2oMvaPp

Firm, dome-shaped mass of lower lip.

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Firm, dome-shaped mass of lower lip.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Mar 01;:

Authors: Upadhyaya JD, Cohen DM, Islam MN, Bhattacharyya I

PMID: 28411004 [PubMed - as supplied by publisher]

http://ift.tt/2ojk2FO

Bryne's grading system predicts poor disease-specific survival of oral squamous cell carcinoma: a comparative study among different histologic grading systems.

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Bryne's grading system predicts poor disease-specific survival of oral squamous cell carcinoma: a comparative study among different histologic grading systems.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Feb 28;:

Authors: Wagner VP, Webber LP, Curra M, Klein IP, Meurer L, Carrad VC, Martins MD

Abstract
OBJECTIVES: The aim of this study was to access the prognostic value of 4 histopathologic grading systems of oral squamous cell carcinoma (OSCC): The World Health Organization (WHO), Anneroth, Bryne (1989), and Bryne (1992).
STUDY DESIGN: Eighty-five cases of OSCC diagnosed between 1996 and 2010 at the Clinics Hospital of Porto Alegre (Porto Alegre, Brazil) were included. Slides stained with hematoxylin and eosin were obtained, and a histologic grade was assigned on the basis of the consensus of 3 expert oral pathologists, who were blinded to the clinicopathologic factors. Each system was correlated with proliferative labeling index, accessed through Ki67 immunostaining, clinicopathologic factors, patient outcome (alive or deceased), and survival time.
RESULTS: The increase in Bryne (1992) histologic grades was accompanied by an increase in proliferative labeling index. Moreover, this system was the only one associated with patient outcome (P = .01) and survival. Bryne (1992) grading system grade III tumors were associated with poor disease-specific survival according to univariate and multivariate cox regression analyses and the log-rank test (P < .05). The other systems evaluated presented no association with patients' outcome or survival.
CONCLUSIONS: The Bryne (1992) grading system is more effective in predicting survival in OSCC compared with the systems proposed by the WHO, Anneroth, or Bryne (1989).

PMID: 28411003 [PubMed - as supplied by publisher]

http://ift.tt/2ojk40o

Clinical prognostic markers in stage IIIC melanoma.

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Clinical prognostic markers in stage IIIC melanoma.

J Surg Oncol. 2017 Apr 15;:

Authors: Madu MF, Schopman JHH, Berger DMS, Klop WMC, Jóźwiak K, Wouters MWJM, van der Hage JA, van Akkooi ACJ

Abstract
BACKGROUND: Although the EORTC 18071-trial has shown a clear survival benefit for adjuvant ipilimumab, accurately selecting patients for this toxic adjuvant therapy is important. We aimed to identify prognostic factors for death and disease recurrence in AJCC stage IIIC melanoma patients.
PATIENTS AND METHODS: Retrospective analysis of patients who underwent lymph node dissection (LND) for stage IIIC melanoma in our institution between 2000 and 2016. Baseline characteristics, melanoma-specific survival (MSS), and disease-free survival (DFS) were assessed, and prognostic factors for recurrence and survival were analyzed using uni- and multivariable analysis.
RESULTS: A total of 205 patients were included. Median follow-up was 20 months (interquartile range 11-43 months), median MSS was 28 months, and median DFS was 11 months. Five-year MSS was 33% and 5-year DFS was 23%. N3 (≥4 involved lymph nodes) and extracapsular extension (ECE) carried an increased risk of disease recurrence after LND and death by melanoma. Patients with both N3 and ECE had virtually no long-term survival.
CONCLUSIONS: Although survival for patients with stage IIIC is poor in general, patients with both N3 disease and ECE constitute the group with the worst prognosis and should be considered for adjuvant therapy with ipilimumab or any other future effective adjuvant therapy (study).

PMID: 28411392 [PubMed - as supplied by publisher]

http://ift.tt/2oMFZRE

Prophylactic dissection of level V in primary mucosal SCC in the clinically N positive neck: A systematic review.

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Prophylactic dissection of level V in primary mucosal SCC in the clinically N positive neck: A systematic review.

Laryngoscope. 2017 Apr 14;:

Authors: McLean T, Kerr SJ, Giddings CEB

Abstract
OBJECTIVE: To review the evidence for level V dissection in the management of previously untreated mucosal squamous cell carcinoma (SCC) of the head and neck presenting with nodal metastasis when level V is clinically uninvolved.
DATA SOURCE: The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) were used to conduct a systematic review of the current literature, including all English language articles published after 1990. A literature search was performed on November 29, 2015, of Medline, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Library.
REVIEW METHODS: The search yielded a total of 270 papers. Strict inclusion and exclusion criteria were applied, leaving 20 eligible papers. Overall prevalence was calculated using random effect meta-analysis.
RESULTS: The overall prevalence of level V occult disease in the node (N)-positive neck, irrespective of subsite, was 2.56% (95% confidence interval 1.29-3.84) (2,368 patients and 2,533 necks). The prevalence of occult level V metastasis was up to 7.7% for oral cavity and 8.3% for oropharyngeal tumors. Five studies reported regional recurrence rates over variable time periods. There is exceedingly limited data on outcomes, such as spinal accessory nerve function, quality of life, and perioperative complications.
CONCLUSION: Mucosal head and neck SCC presenting with nodal metastasis but with level V clinically uninvolved has a low prevalence of occult level V disease. Routine dissection of level V does not appear to be warranted; however, a definitive conclusion is unable to be drawn due to limited data on morbidity and oncological outcomes. Laryngoscope, 2017.

PMID: 28411387 [PubMed - as supplied by publisher]

http://ift.tt/2oMCydv

Nomograms to estimate long-term overall survival and tongue cancer-specific survival of patients with tongue squamous cell carcinoma.

Related Articles

Nomograms to estimate long-term overall survival and tongue cancer-specific survival of patients with tongue squamous cell carcinoma.

Cancer Med. 2017 Apr 14;:

Authors: Li Y, Zhao Z, Liu X, Ju J, Chai J, Ni Q, Ma C, Gao T, Sun M

Abstract
The aim of this study was to construct nomograms to predict long-term overall survival (OS) and tongue cancer-specific survival (TCSS) of tongue squamous cell carcinoma (TSCC) patients based on clinical and tumor characteristics. Clinical, tumor, and treatment characteristics of 12,674 patients diagnosed with TSCC between 2004 and 2013 were collected from the Surveillance, Epidemiology, and End Results database. These patients were then divided into surgery and nonsurgery cohorts, and nomograms were developed for each of these groups. The step-down method and cumulative incidence function were used for model selection to determine the significant prognostic factors associated with OS and TCSS. These prognostic variables were incorporated into nomograms. An external cohort was used to validate the surgery nomograms. Seven variables were used to create the surgery nomograms for OS and TCSS, which had c-indexes of 0.709 and 0.728, respectively; for the external validation cohort, the c-indexes were 0.691 and 0.711, respectively. Nine variables were used to create the nonsurgery nomograms for OS and TCSS, which had c-indexes of 0.750 and 0.754, respectively. The calibration curves of the 5- and 8-year surgery and nonsurgery nomograms showed excellent agreement between the probabilities and observed values. By incorporating clinicopathological and host characteristics in patients, we are the first to establish nomograms that accurately predict prognosis for individual patients with TSCC. These nomograms ought to provide more personalized and reliable prognostic information, and improve clinical decision-making for TSCC patients.

PMID: 28411370 [PubMed - as supplied by publisher]

http://ift.tt/2oMCMl0

MicroRNA expression profiling of Xp11 renal cell carcinoma.

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MicroRNA expression profiling of Xp11 renal cell carcinoma.

Hum Pathol. 2017 Apr 11;:

Authors: Marchionni L, Hayashi M, Guida E, Ooki A, Munari E, Jabboure FJ, Dinalankara W, Raza A, Netto GJ, Hoque MO, Argani P

Abstract
Renal cell carcinomas (RCCs) with Xp11 translocation (Xp11 RCC) constitute a distinctive molecular subtype characterized by chromosomal translocations involving the Xp11.2 locus, resulting in gene fusions between the TFE3 transcription factor with a second gene (usually ASPSCR1, PRCC, NONO, or SFPQ). RCCs with Xp11 translocations comprise up to 1-4% of adult cases, frequently displaying papillary architecture with epithelioid clear cells. In order to better understand the biology of this molecularly distinct tumor subtype, we analyze the miRNA expression profiles of Xp11 Renal cell carcinoma (RCC) compared to normal renal parenchyma using microarray and quantitative reverse transcription polymerase chain reaction (RT-PCR). We further compare Xp11 RCC with other RCC histologic subtypes using publically available datasets, identifying common and distinctive microRNA (miRNA) signatures along with the associated signaling pathways and biological processes. Overall, Xp11 RCC more closely resemble clear cell rather than papillary RCC. Further, among the most differentially expressed miRNAs specific for Xp11 RCC, we identify miR-148a-3p, miR-221-3p, miR-185-5p, miR-196b-5p, and miR-642a-5p to be up-regulated, while miR-133b and miR-658 were down-regulated. Finally, Xp11 RCC is most strongly associated with microRNA expression profiles modulating DNA damage responses, cell cycle progression and apoptosis, and the Hedgehog signaling pathway. In summary, we describe here for the first time the miRNA expression profiles of a molecularly distinct type of renal cancer associated with Xp11.2 translocations involving the TFE3 gene. Our results might help understanding the molecular underpinning of Xp11 RCC, assisting in developing targeted treatments for this disease.

PMID: 28411178 [PubMed - as supplied by publisher]

http://ift.tt/2oMCN8y

Bacterial and histopathological findings in deep head and neck infections: a retrospective analysis.

Related Articles

Bacterial and histopathological findings in deep head and neck infections: a retrospective analysis.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Feb 20;:

Authors: Cordesmeyer R, Kauffmann P, Markus T, Sömmer C, Eiffert H, Bremmer F, Laskawi R

Abstract
OBJECTIVES: Deep neck infections are among the most dangerous acute diseases in the head and neck region. This analysis gives an overview of the bacterial and histopathologic findings of deep neck infections.
STUDY DESIGN: From January 2002 to December 2012, 63 patients were diagnosed with and treated for deep neck infections at the University Medical Center Göttingen. Bacterial and histopathologic examinations were made, and the occurrence of bacterial pathogens and histopathologic findings were analyzed.
RESULTS: The most commonly isolated aerobic gram-positive pathogen was Streptococcus viridans (26.7%); Staphylococcus epidermidis and Staphylococcus aureus were each found in 16.7% of infections. The most commonly isolated aerobic gram-negative pathogens were Escherichia coli, Klebsiella oxytoca, and Haemophilus influenzae. In 1.6% of patients, a malignant cancer was detected.
CONCLUSION: For clear diagnosis and effective therapy, a bacteriologic investigation of deep neck infections is essential because of the heterogeneous spectrum of the detected bacteria. In contrast to Asia, where Klebsiella pneumoniae is the most common pathogen, in South Lower Saxony, Germany, we discovered a dominating spectrum of aerobic gram-positive cocci. Biopsy obtained from an abscess cavity for histologic examination should always be part of the diagnostic process in order to exclude a malignant process.

PMID: 28411005 [PubMed - as supplied by publisher]

http://ift.tt/2oMvaPp

Spontaneous cerebrospinal fluid fistula in the clivus.

Related Articles

Spontaneous cerebrospinal fluid fistula in the clivus.

Eur Ann Otorhinolaryngol Head Neck Dis. 2017 Apr 11;:

Authors: Codina Aroca A, Gras Cabrerizo JR, De Juan Delago M, Massegur Solench H

Abstract
INTRODUCTION: Spontaneous cerebrospinal fluid (CSF) fistulas are infrequent and only 10 cases in the literature have been located in the clivus. We describe two new cases of CSF fistulas in this site and review the literature.
CASE REPORT: The first patient was a 52-year-old woman referred to our centre for intermittent rhinorrhea that had been diagnosed after an episode of meningitis. The second case was a 69-year-old man who was visited for rhinorrhea of one-year duration; he also developed meningitis during the preoperative study. In both cases, the spontaneous CSF fistula was diagnosed by beta-2-transferrin testing, CT scan and MRI. We performed an endonasal endoscopic transsphenoidal approach and used free grafts and vascularized flaps to close the clival defect. Treatment was successful in both cases.
DISCUSSION: The physiopathology of spontaneous CSF fistulas remains unknown. Possible explanations given to date in this location are pulsatility of the basilar artery, repeated Valsalva maneuvers and Marfan's disease, the two latter also related to CSF fistulas in other locations. Closure of a CSF leak towards the nasal cavity is mandatory due to potential complications. Our results support the endoscopic transsphenoidal approach using free grafts and/or pediculated flaps as a good alternative to open surgery.

PMID: 28410953 [PubMed - as supplied by publisher]

http://ift.tt/2oMkTmk

Response: Letter to the Editor.

Related Articles

Response: Letter to the Editor.

Int J Pediatr Otorhinolaryngol. 2017 Apr 06;:

Authors: Sztano B, Rovo L

PMID: 28410847 [PubMed - as supplied by publisher]

http://ift.tt/2oMkSyM

Dual-energy imaging method to improve the image quality and the accuracy of dose calculation for cone-beam computed tomography.

Related Articles

Dual-energy imaging method to improve the image quality and the accuracy of dose calculation for cone-beam computed tomography.

Phys Med. 2017 Apr;36:110-118

Authors: Men K, Dai J, Chen X, Li M, Zhang K, Huang P

Abstract
PURPOSE: To improve the image quality and accuracy of dose calculation for cone-beam computed tomography (CT) images through implementation of a dual-energy cone-beam computed tomography method (DE-CBCT), and evaluate the improvement quantitatively.
METHODS: Two sets of CBCT projections were acquired using the X-ray volumetric imaging (XVI) system on a Synergy (Elekta, Stockholm, Sweden) system with 120kV (high) and 70kV (low) X-rays, respectively. Then, the electron density relative to water (relative electron density (RED)) of each voxel was calculated using a projection-based dual-energy decomposition method. As a comparison, single-energy cone-beam computed tomography (SE-CBCT) was used to calculate RED with the Hounsfield unit-RED calibration curve generated by a CIRS phantom scan with identical imaging parameters. The imaging dose was measured with a dosimetry phantom. The image quality was evaluated quantitatively using a Catphan 503 phantom with the evaluation indices of the reproducibility of the RED values, high-contrast resolution (MTF50%), uniformity, and signal-to-noise ratio (SNR). Dose calculation of two simulated volumetric-modulated arc therapy plans using an Eclipse treatment-planning system (Varian Medical Systems, Palo Alto, CA, USA) was performed on an Alderson Rando Head and Neck (H&N) phantom and a Pelvis phantom. Fan-beam planning CT images for the H&N and Pelvis phantom were set as the reference. A global three-dimensional gamma analysis was used to compare dose distributions with the reference. The average gamma values for targets and OAR were analyzed with paired t-tests between DE-CBCT and SE-CBCT.
RESULTS: In two scans (H&N scan and body scan), the imaging dose of DE-CBCT increased by 1.0% and decreased by 1.3%. It had a better reproducibility of the RED values (mean bias: 0.03 and 0.07) compared with SE-CBCT (mean bias: 0.13 and 0.16). It also improved the image uniformity (57.5% and 30.1%) and SNR (9.7% and 2.3%), but did not affect the MTF50%. Gamma analyses of the 3D dose distribution with criteria of 1%/1mm showed a pass rate of 99.0-100% and 85.3-97.6% for DE-CBCT and 73.5-99.1% and 80.4-92.7% for SE-CBCT. The average gamma values were reduced significantly by DE-CBCT (p< 0.05). Gamma index maps showed that matching of the dose distribution between CBCT-based and reference was improved by DE-CBCT.
CONCLUSIONS: DE-CBCT can achieve both better image quality and higher accuracy of dose calculation, and could be applied to adaptive radiotherapy.

PMID: 28410679 [PubMed - in process]

http://ift.tt/2oMyWrV