Παρασκευή, 30 Σεπτεμβρίου 2016

IJERPH, Vol. 13, Pages 971: Spatial Distribution Balance Analysis of Hospitals in Wuhan

The spatial distribution pattern of hospitals in Wuhan indicates a core in the central urban areas and a sparse distribution in the suburbs, particularly at the center of suburbs. This study aims to improve the gravity and Huff models to analyze healthcare accessibility and resources. Results indicate that healthcare accessibility in central urban areas is better than in the suburbs, where it increasingly worsens for the suburbs. A shortage of healthcare resources is observed in large-scale and high-class hospitals in central urban areas, whereas the resources of some hospitals in the suburbs are redundant. This study proposes the multi-criteria evaluation (MCE) analysis model for the location assessment in constructing new hospitals, which can effectively ameliorate healthcare accessibility in suburban areas. This study presents implications for the planning of urban healthcare facilities.

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About Diode Laser Stapedotomy.

About Diode Laser Stapedotomy.

Otolaryngol Head Neck Surg. 2016 Oct;155(4):719

Authors: Poletti AM

PMID: 27683356 [PubMed - in process]



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Highlights from the Current Issue: October 2016.

Highlights from the Current Issue: October 2016.

Otolaryngol Head Neck Surg. 2016 Oct;155(4):545-6

Authors: Krouse JH

PMID: 27683355 [PubMed - in process]



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Efficacy of Perioperative Lumbar Drainage following Endonasal Endoscopic Cerebrospinal Fluid Leak Repair: A Meta-analysis.

Efficacy of Perioperative Lumbar Drainage following Endonasal Endoscopic Cerebrospinal Fluid Leak Repair: A Meta-analysis.

Otolaryngol Head Neck Surg. 2016 Sep 27;

Authors: Ahmed OH, Marcus S, Tauber JR, Wang B, Fang Y, Lebowitz RA

Abstract
OBJECTIVE: Perioperative lumbar drain (LD) use in the setting of endoscopic cerebrospinal fluid (CSF) leak repair is a well-established practice. However, recent data suggest that LDs may not provide significant benefit and may thus confer unnecessary risk. To examine this, we conducted a meta-analysis to investigate the effect of LDs on postoperative CSF leak recurrence following endoscopic repair of CSF rhinorrhea.
DATA SOURCES: A comprehensive search was performed with the following databases: Ovid MEDLINE (1947 to November 2015), EMBASE (1974 to November 2015), Cochrane Review, and PubMed (1990 to November 2015).
REVIEW METHOD: A meta-analysis was performed according to PRISMA guidelines.
RESULTS: A total of 1314 nonduplicate studies were identified in our search. Twelve articles comprising 508 cases met inclusion criteria. Overall, use of LDs was not associated with significantly lower postoperative CSF leak recurrence rates following endoscopic repair of CSF rhinorrhea (odds ratio: 0.89, 95% confidence interval: 0.40-1.95) as compared with cases performed without LDs. Subgroup analysis of only CSF leaks associated with anterior skull base resections (6 studies, 153 cases) also demonstrated that lumbar drainage did not significantly affect rates of successful repair (odds ratio: 2.67, 95% confidence interval: 0.64-11.10).
CONCLUSIONS: There is insufficient evidence to support that adjunctive lumbar drainage significantly reduces postoperative CSF leak recurrence in patients undergoing endoscopic CSF leak repair. Subgroup analysis examining only those patients whose CSF leaks were associated with anterior skull base resections demonstrated similar results. More level 1 and 2 studies are needed to further investigate the efficacy of LDs, particularly in the setting of patients at high risk for CSF leak recurrence.

PMID: 27677601 [PubMed - as supplied by publisher]



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Effect of Preoperative Counseling on Hospital Length of Stay and Readmissions after Total Laryngectomy.

Effect of Preoperative Counseling on Hospital Length of Stay and Readmissions after Total Laryngectomy.

Otolaryngol Head Neck Surg. 2016 Sep 27;

Authors: Shenson JA, Craig JN, Rohde SL

Abstract
OBJECTIVE: Total laryngectomy (TL) is a high-cost procedure with patients at risk for significant postoperative health care use. Face-to-face preoperative counseling provided by speech-language pathologists is a relatively inexpensive intervention that may improve care quality and decrease costs. We evaluated if preoperative counseling for patients undergoing TL was associated with differences in length of stay (LOS), use of the emergency department (ED), or unplanned readmissions within 30 days of discharge. A secondary analysis identified predictors of these 3 outcomes.
STUDY DESIGN: Case series with chart review.
SETTING: Academic medical center in the United States.
SUBJECTS AND METHODS: Patients were included if they underwent TL from 2011 to 2015. Patient demographics and comorbidities, surgical characteristics, and perioperative care data were retrieved and analyzed for 116 patients. Univariate and multivariate models were constructed for 3 outcomes.
RESULTS: LOS was significantly lower for patients receiving counseling (-3.0 days, P = .02). No differences were observed in rates of 30-day ED visits or unplanned readmissions. Care provided by high-volume surgeons was associated with decreased LOS (P = .005), while having postoperative complications increased LOS (P < .001). High rates of ED visits (12.1%) and readmissions (20.6%) were observed. Discharge to inpatient rehabilitation and the patient's home distance from the institution were predictors of ED visits. TL as salvage therapy and occurrence of postoperative complications were risk factors for readmission.
CONCLUSION: Preoperative counseling was associated with marked reduction in LOS following TL without increased readmissions, which suggests that it may promote safe, earlier patient readiness for discharge.

PMID: 27677600 [PubMed - as supplied by publisher]



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Practice Patterns of Sleep Otolaryngologists at Training Institutions in the United States.

Practice Patterns of Sleep Otolaryngologists at Training Institutions in the United States.

Otolaryngol Head Neck Surg. 2016 Sep 27;

Authors: Lam AS, Wise SK, Dedhia RC

Abstract
OBJECTIVE: To assess the practice characteristics of adult sleep otolaryngologists within US otolaryngology residency training programs.
STUDY DESIGN: Cross-sectional online survey.
SETTING: Otolaryngology residency training programs.
SUBJECTS AND METHODS: Program directors from 106 otolaryngology training programs in the United States were contacted. Program directors were instructed to forward a survey to otolaryngologists within the institution who provided Accreditation Council for Graduate Medical Education (ACGME) Otolaryngology Milestone Project feedback in "sleep-disordered breathing." The survey assessed demographics, nonsurgical practices, and surgical/procedural practices of adult sleep otolaryngologists. Data were collected and analyzed.
RESULTS: Forty-six surveys met inclusion criteria, representing 40 of 106 (38%) programs. Ninety-three percent of respondents reported that residents gained a significant portion of their sleep medicine training from themselves (ie, the respondents), yet only 36% of respondents spent ≥50% of their time on sleep medicine/surgery. Forty-one percent reported being board certified in sleep, with 18% having completed an ACGME fellowship in sleep medicine. Respondents with board certification were more likely to spend greater portions of their practice on sleep medicine/surgery, χ(2)(3, n = 44) = 23.161 (P < .001), treat non-obstructive sleep apnea sleep disorders (13 of 18 vs 1 of 26, P < .001), interpret polysomnograms (13 of 17 vs 1 of 15, P < .001), and perform drug-induced sleep endoscopy, χ(2)(1, n = 43) = 5.43, (P = .02). A similar pattern was seen with stratification by ACGME sleep medicine fellowship.
CONCLUSION: This study highlights the variance in practice patterns among sleep otolaryngologists who instruct residents. Board certification and fellowship training in sleep medicine significantly influence breadth of trainee exposure to this field. The highly disparate trainee experiences to sleep otolaryngology across US programs require attention.

PMID: 27677599 [PubMed - as supplied by publisher]



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Performance Assessment for Mastoidectomy: State of the Art Review.

Performance Assessment for Mastoidectomy: State of the Art Review.

Otolaryngol Head Neck Surg. 2016 Sep 27;

Authors: Sethia R, Kerwin TF, Wiet GJ

Abstract
OBJECTIVE: The aim of this report is to provide a review of the current literature for assessment of performance for mastoidectomy, to identify the current assessment tools available in the literature, and to summarize the evidence for their validity.
DATA SOURCES: The MEDLINE database was accessed via PubMed.
REVIEW METHODS: Inclusion criteria consisted of English-language published articles that reported use of a mastoidectomy performance assessment tool. Studies ranged from 2007 to November 2015 and were divided into 2 groups: intraoperative assessments and those performed with simulation (cadaveric laboratory or virtual reality). Studies that contained specific reliability analyses were also highlighted. For each publication, validity evidence data were analyzed and interpreted according to conceptual definitions provided in a recent systematic review on the modern framework of validity evidence.
CONCLUSIONS: Twenty-three studies were identified that met our inclusion criteria for review, including 4 intraoperative objective assessment studies, 5 cadaveric studies, 10 virtual reality simulation studies, and 4 that used both cadaveric assessment and virtual reality.
IMPLICATIONS FOR PRACTICE: A review of the literature revealed a wide variety of mastoidectomy assessment tools and varying levels of reliability and validity evidence. The assessment tool developed at Johns Hopkins possesses the most validity evidence of those reviewed. However, a number of agreed-on specific metrics could be integrated into a standardized assessment instrument to be used nationally. A universally agreed-on assessment tool will provide a means for developing standardized benchmarks for performing mastoid surgery.

PMID: 27677598 [PubMed - as supplied by publisher]



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Why Participate in Peer Review as a Journal Manuscript Reviewer: What's in It for You?

Why Participate in Peer Review as a Journal Manuscript Reviewer: What's in It for You?

Otolaryngol Head Neck Surg. 2016 Sep 27;

Authors: Pytynia KB

Abstract
The peer review process for scientific journals relies on the efforts of volunteer reviewers. Reviewers are selected due to their expertise in their fields. With so many demands on professional time, the benefits of participating in peer review may not be obvious. However, reviewers benefit by exposure to the latest developments in their fields, facilitating their keeping up-to-date with the latest publications. Tenure committees look favorably on participation in peer review, and invitations to review underscore that the reviewer is a respected subject matter expert. Contacts made during the peer review process can lead to long-lasting collaboration. Continuing medical education credit can be obtained through various mechanisms. Overall, participating in peer review is an important part of career development and should be viewed as a critical component of advancement.

PMID: 27677597 [PubMed - as supplied by publisher]



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Collagen and α-Tubulin of Mouse Tympanic Membrane Fibroblasts Treated with Quinolones and Aminoglycosides.

Collagen and α-Tubulin of Mouse Tympanic Membrane Fibroblasts Treated with Quinolones and Aminoglycosides.

Otolaryngol Head Neck Surg. 2016 Sep 27;

Authors: Milne-Davies BA, Antonelli PJ, Orobello NC, Dirain CO

Abstract
OBJECTIVE: To assess collagen and α-tubulin levels of mouse tympanic membrane fibroblasts treated with quinolone and aminoglycoside antibiotics at concentrations found in eardrops.
STUDY DESIGN: Prospective controlled cell culture study.
SETTING: Academic tertiary medical center.
SUBJECTS: Mouse tympanic membrane fibroblasts.
METHODS: In experiment 1, fibroblasts were treated with the following for 24 or 48 hours: phosphate-buffered saline (negative control), dilute hydrochloric acid (positive control), 0.5% gatifloxacin, or commercially available 0.3% ciprofloxacin, 0.3% ciprofloxacin + 0.1% dexamethasone, 0.3% ofloxacin, 0.5% moxifloxacin, 0.3% gentamicin, or 3.5 mg/mL of neomycin + polymyxin B sulfate + hydrocortisone. In experiment 2, cells were treated with the pure form of gatifloxacin, gentamicin, ofloxacin, or ciprofloxacin. Cells were observed with phase-contrast microscope until harvested. Proteins were extracted for Western blotting with antibodies against collagen α1 type I (collagen 1A1) and α-tubulin, and for densitometry to quantify levels.
RESULTS: Collagen and tubulin levels in fibroblasts treated with ofloxacin, moxifloxacin, gatifloxacin, or gentamicin for 24 hours were not different from the saline control. Fibroblasts treated with neomycin + polymyxin B + hydrocortisone, ciprofloxacin + dexamethasone, or ciprofloxacin for 24 hours had lower collagen 1A1 and α-tubulin levels (all P < .001) than the negative control. After 48 hours, fibroblasts treated with neomycin + polymyxin B sulfate + hydrocortisone, ciprofloxacin + dexamethasone, ciprofloxacin, or moxifloxacin had lower collagen 1A1 (P ≤ .007) and α-tubulin (P < .0001; except ciprofloxacin, P = .033) as compared with control. In experiment 2, only cells treated with ciprofloxacin had lower collagen 1A1 and α-tubulin levels and cell viability (all P < .0001) than control. Cytotoxicity assay and phase-contrast images mirrored the protein findings.
CONCLUSION: The adverse impact of topical antibiotic exposure on tympanic membrane collagen and tubulin protein levels is drug specific. This may be important for selection of ototopical therapy.

PMID: 27677596 [PubMed - as supplied by publisher]



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Is the hypothalamic–pituitary–adrenal axis disrupted in type 2 diabetes mellitus?



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Only 1 week to go until #ESMO16. Register for the event here: https://t.co/63ebdOlWm2

Only 1 week to go until #ESMO16. Register for the event here: https://t.co/63ebdOlWm2

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Nearly 50% of eligible patients in 9 developing countries have unmet need for radiation therapy… https://t.co/ZvaWPrVLOw

Nearly 50% of eligible patients in 9 developing countries have unmet need for radiation therapy… https://t.co/ZvaWPrVLOw

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Endangered giraffes threatened by Uganda’s oil drilling bid

Plans to drill for oil in one of the last remaining habitats of the highly endangered Rothschild’s giraffe could further threaten this neglected animal

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Rosetta’s final landing spot on comet revealed in new image

The latest image - taken from 8.9km above its surface - shows the spacecraft is on track to impact its target in the Ma'at region of the comet, which is littered with boulders

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Feedback: Investigators on the scent of missing Sardinian blood

Plus Bank of America in existential crisis, UKIP calls for closer ties to the sun, giving smartphones a sense of humour, and more

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IJMS, Vol. 17, Pages 1662: Investigation of Self-Assembly Processes for Chitosan-Based Coagulant-Flocculant Systems: A Mini-Review

The presence of contaminants in wastewater poses significant challenges to water treatment processes and environmental remediation. The use of coagulation-flocculation represents a facile and efficient way of removing charged particles from water. The formation of stable colloidal flocs is necessary for floc aggregation and, hence, their subsequent removal. Aggregation occurs when these flocs form extended networks through the self-assembly of polyelectrolytes, such as the amine-based polysaccharide (chitosan), which form polymer “bridges” in a floc network. The aim of this overview is to evaluate how the self-assembly process of chitosan and its derivatives is influenced by factors related to the morphology of chitosan (flocculant) and the role of the solution conditions in the flocculation properties of chitosan and its modified forms. Chitosan has been used alone or in conjunction with a salt, such as aluminum sulphate, as an aid for the removal of various waterborne contaminants. Modified chitosan relates to grafted anionic or cationic groups onto the C-6 hydroxyl group or the amine group at C-2 on the glucosamine monomer of chitosan. By varying the parameters, such as molecular weight and the degree of deacetylation of chitosan, pH, reaction and settling time, dosage and temperature, self-assembly can be further investigated. This mini-review places an emphasis on the molecular-level details of the flocculation and the self-assembly processes for the marine-based biopolymer, chitosan.

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IJMS, Vol. 17, Pages 1646: Construction and Characterization of a Cellulolytic Consortium Enriched from the Hindgut of Holotrichia parallela Larvae

Degradation of rice straw by cooperative microbial activities is at present the most attractive alternative to fuels and provides a basis for biomass conversion. The use of microbial consortia in the biodegradation of lignocelluloses could reduce problems such as incomplete synergistic enzymes, end-product inhibition, and so on. In this study, a cellulolytic microbial consortium was enriched from the hindgut of Holotrichia parallela larvae via continuous subcultivation (20 subcultures in total) under static conditions. The degradation ratio for rice straw was about 83.1% after three days of cultivation, indicating its strong cellulolytic activity. The diversity analysis results showed that the bacterial diversity and richness decreased during the consortium enrichment process, and the consortium enrichment process could lead to a significant enrichment of phyla Proteobacteria and Spirochaetes, classes Clostridia, Epsilonproteobacteria, and Betaproteobacteria, and genera Arcobacter, Treponema, Comamonas, and Clostridium. Some of these are well known as typical cellulolytic and hemicellulolytic microorganisms. Our results revealed that the microbial consortium identified herein is a potential candidate for use in the degradation of waste lignocellulosic biomass and further highlights the hindgut of the larvae as a reservoir of extensive and specific cellulolytic and hemicellulolytic microbes.

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OTULIN deficiency causes auto-inflammatory syndrome

cr2016113f1th.jpg



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Cathepsin S contributes to microglia-mediated olfactory dysfunction through the regulation of Cx3cl1–Cx3cr1 axis in a Niemann–Pick disease type C1 model

Microglia can aggravate olfactory dysfunction by mediating neuronal death in the olfactory bulb (OB) of a murine model of Niemann–Pick disease type C1 (NPC1), a fatal neurodegenerative disorder accompanied by lipid trafficking defects. In this study, we focused on the crosstalk between neurons and microglia to elucidate the mechanisms underlying extensive microgliosis in the NPC1-affected brain. Microglia in the OB of NPC1 mice strongly expressed CX3C chemokine receptor 1 (Cx3cr1), a specific receptor for the neural chemokine C-X3-C motif ligand 1 (Cx3cl1). In addition, a high level of Cx3cl1 was detected in NPC1 mouse-derived CSF due to enhanced catalytic activity of Cathepsin S (Ctss), which is responsible for Cx3cl1 secretion. Notably, nasal delivery of Cx3cl1 neutralizing antibody or Ctss inhibitor could inhibit the Cx3cl1–Cx3cr1 interaction and support neuronal survival through the suppression of microglial activation, leading to an improvement in the olfactory function in NPC1 mice. Relevant in vitro experiments revealed that intracellular cholesterol accumulation could act as a strong inducer of abnormal Ctss activation and, in turn, stimulated the Cx3cl1–Cx3cr1 axis in microglia via p38 mitogen-activated protein kinase signaling. Our data address the significance of Cx3cl1–Cx3cr1 interaction in the development of microglial neurotoxicity and suggest that Ctss is a key upstream regulator. Therefore, this study contributes to a better understanding of the crosstalk between neurons and microglia in the development of the neurodegeneration and provides a new perspective for the management of olfactory deficits and other microglia-dependent neuropathies. GLIA 2016

Thumbnail image of graphical abstract

Main Points

  • Enhanced crosstalk between neuron and microglia via Cx3cl1–Cx3cr1 interaction contributes to the olfactory loss in NPC1 mice.
  • Disturbed cholesterol homeostasis induces P38 MAPK activation and microglial Cathepsin S maturation.


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Transcriptomic regulations in oligodendroglial and microglial cells related to brain damage following fetal growth restriction

Fetal growth restriction (FGR) is a major complication of human pregnancy, frequently resulting from placental vascular diseases and prenatal malnutrition, and is associated with adverse neurocognitive outcomes throughout life. However, the mechanisms linking poor fetal growth and neurocognitive impairment are unclear. Here, we aimed to correlate changes in gene expression induced by FGR in rats and abnormal cerebral white matter maturation, brain microstructure, and cortical connectivity in vivo. We investigated a model of FGR induced by low-protein-diet malnutrition between embryonic day 0 and birth using an interdisciplinary approach combining advanced brain imaging, in vivo connectivity, microarray analysis of sorted oligodendroglial and microglial cells and histology. We show that myelination and brain function are both significantly altered in our model of FGR. These alterations, detected first in the white matter on magnetic resonance imaging significantly reduced cortical connectivity as assessed by ultrafast ultrasound imaging. Fetal growth retardation was found associated with white matter dysmaturation as shown by the immunohistochemical profiles and microarrays analyses. Strikingly, transcriptomic and gene network analyses reveal not only a myelination deficit in growth-restricted pups, but also the extensive deregulation of genes controlling neuroinflammation and the cell cycle in both oligodendrocytes and microglia. Our findings shed new light on the cellular and gene regulatory mechanisms mediating brain structural and functional defects in malnutrition-induced FGR, and suggest, for the first time, a neuroinflammatory basis for the poor neurocognitive outcome observed in growth-restricted human infants. GLIA 2016

Thumbnail image of graphical abstract
  • FGR induced by low-protein-diet in rat significantly alters myelination, and brain microstructure and function.
  • Transcriptomic analyses reveal deregulation of genes controlling neuroinflammation in oligodendrocytes and microglia.


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The risk of myocardial infarction with aromatase inhibitors relative to tamoxifen in post-menopausal women with early stage breast cancer

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Publication date: November 2016
Source:European Journal of Cancer, Volume 68
Author(s): Husam Abdel-Qadir, Eitan Amir, Hadas D. Fischer, Longdi Fu, Peter C. Austin, Paula J. Harvey, Paula A. Rochon, Douglas S. Lee, Geoffrey M. Anderson
BackgroundAromatase inhibitors (AIs) may increase cardiovascular risk relative to tamoxifen in post-menopausal women with breast cancer. This risk has not been well-quantified outside of clinical trials.MethodsObservational population-based cohort study of women aged >55 years diagnosed with stage I–III breast cancer between 2005 and 2010. Women treated with AIs or tamoxifen were followed to March 2012. The primary outcome was hospitalisation for myocardial infarction (MI). Cause-specific hazards were compared using tamoxifen as the reference group. Inverse probability of treatment weighting using the propensity score was used to reduce confounding due to measured baseline covariates. Results were confirmed using two cause-specific hazards models. Subgroup analyses included women aged ≥66 years, those with prior ischaemic heart disease, and a ‘lower-risk group’ aged <74 years with stage I–II cancer and no prior ischaemic heart disease.ResultsIn 7409 aromatase inhibitor-treated and 1941 tamoxifen-treated women, the median age was 71 versus 74 years, respectively (p < 0.001). Baseline prevalence of ischaemic heart disease was similar (17.0% versus 16.9%, p = 0.96). Over a mean of 1184 d of follow-up, there were 123 hospitalisations for MI; the cause-specific hazard was higher with AIs (hazard ratio 2.02; 95% confidence interval 1.16–3.53 in the weighted sample). We observed comparable patterns within pre-defined subgroups and when adjusted using cause-specific hazards models.ConclusionAromatase inhibitors are associated with a higher risk of MI compared with tamoxifen. This risk should be accounted for when managing aromatase inhibitor-treated women.



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Molecular Epidemiology of Human Metapneumovirus in Riyadh Province, Saudi Arabia

Human metapneumovirus (HMPV) is an important cause of respiratory tract illness in children. Two HMPV subgroups, A and B, and four genotypes, A1, A2, B1 and B2, have been identified. Concurrent circulation of the different genotypes in yearly epidemics has been recorded globally, but not in Saudi Arabia. The current report was designed to study HMPV epidemiology in Saudi children and to analyze the genetic diversity and circulation patterns. Nasopharyngeal aspirates (n = 174) were collected from hospitalized children in Riyadh (2008-2009). The screening of samples using real-time RT-PCR identified 19 HMPV strains. The majority of the strains belonged to subgroup B, while all strains of subgroup A were members of genotype A2. In 2008, only subgroup B was recognized, whereas in 2009 both subgroups were identified to be cocirculating at similar rates. The full-length attachment (G) gene and a partial sequence of the fusion (F) gene of positive samples were sequenced. The G gene showed a high degree of genetic diversity and exhibited a variable number of positively selected sites in different lineages. In contrast, the F gene demonstrated an extensive genetic stability with a higher tendency toward purifying selection. This is the first report on HMPV genotype circulation in Saudi Arabia; however, the exact circulation kinetics requires further retrospective and prospective study.
J Mol Microbiol Biotechnol 2016;26:414-421

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Low cancer symptom awareness linked to lower chance of survival

In regions where cancer survival is poorer, people on average have lower awareness of cancer symptoms, according to new findings published in the British Journal of Cancer. Researchers also found that general awareness of cancer symptoms varies greatly...

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Blood pressure drug may boost effectiveness of lung cancer treatment

A blood pressure drug may make a type of lung cancer treatment more effective, suggests a new study. The early-stage research, conducted on human cells in the lab and on mice, was led by scientists from Imperial College London and Fudan University in...

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Weekly cisplatin with radiotherapy for locally advanced head and neck squamous cell carcinoma.

Weekly cisplatin with radiotherapy for locally advanced head and neck squamous cell carcinoma.

J BUON. 2016 Jul-Aug;21(4):979-988

Authors: Sautois B, Schroeder H, Martin M, Piret P, Demez P, Bouchain O, Mutijima E, Moreau P

Abstract
PURPOSE: Although commonly used for the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC) concomitant radio-chemotherapy (RT-CT) with weekly cisplatin has not been definitely studied. We conducted a single centre retrospective study with the aim to evaluate efficacy and acute toxicity of definitive concomitant RT-CT with 40 mg/m(2) weekly cisplatin in patients with locally advanced HNSCC with a particular emphasis on RT modality (conventional or accelerated) and dose of cisplatin delivered.
METHODS: One hundred and twelve consecutive patients were included. They were given cisplatin 40 mg/m(2))week concomitantly with conventionally fractionated (CFRT) (N=33) or accelerated (ART) (N=79) RT.
RESULTS: RT was delivered according to the treatment plan in 104 patients and full dose was given to 107 patients. A median cumulative cisplatin dose of 240 mg/m(2) was administered to patients treated with CFRT and of 200 mg/m(2) to those treated with ART. Overall complete response rate was 81.3%. With a median follow up of 38.4 months, median overall survival (OS) was 75 months, not influenced by RT type or cisplatin dose received. The most clinically significant grade 3 or 4 acute toxicities were stomatitis (35.7%), neutropenia (25%), anemia (12.5%) and acute kidney injury (5.4%).
CONCLUSIONS: Our study shows that a median cumulative dose of 200 mg/m(2) cisplatin can be safely administered using a weekly regimen to patients treated with concomitant RT (CFRT or ART). Efficacy results and toxicity compare favorably with those described with triweekly cisplatin RT-CT, suggesting that a randomized comparison should be undertaken.

PMID: 27685923 [PubMed - as supplied by publisher]



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Cbl-b regulates the sensitivity of cetuximab through ubiquitin-proteasome system in human gastric cancer cells.

Cbl-b regulates the sensitivity of cetuximab through ubiquitin-proteasome system in human gastric cancer cells.

J BUON. 2016 Jul-Aug;21(4):867-873

Authors: Yu P, Fan Y, Qu X, Zhang J, Song N, Liu J, Liu Y

Abstract
PURPOSE: Cetuximab is a monoclonal antibody against epidermal growth factor receptor (EGFR) and is approved for clinical use in combination with chemotherapy in patients affected by colorectal cancer (CRC), non small cell lung cancer (NSCLC), and head and neck cancer. Compared with these cancers, gastric cancer is relatively resistant to cetuximab and its regulatory mechanism is still unclear.
METHODS: In this study, we assessed whether the ubiquitin- proteasome pathway is involved in regulating cetuximab-induced cells apoptosis in MGC803 and BGC823 gastric cancer cell lines.
RESULTS: The casitas B lineage lymphoma-b (Cbl-b), a kind of E3 ubiquitin ligase, was involved in this process. Specific silenced Cbl-b expression increased the expression of EGFR.
CONCLUSIONS: Our findings lead to a better understanding of the mechanism of cetuximab action, and suggests that Cbl-b increases the sensitivity of cetuximab in gastric cancer cells.

PMID: 27685907 [PubMed - as supplied by publisher]



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Critical Airway Compromise due to a Massive Vagal Schwannoma.

Critical Airway Compromise due to a Massive Vagal Schwannoma.

Ir Med J. 2016;109(5):408

Authors: McDermott AM, Sadadcharam M, Manning BJ, Sheahan P

Abstract
We describe the case of a 37-year-old man with a slowly enlarging neck lump and compressive symptoms. He presented to a separate institution 10 years prior where an observational approach was advocated. Following preoperative investigations and embolization, an 11cm vagal schwannoma was excised and vagus nerve was sacrificed. Although conservative management is appropriate for a select patient population, surgical excision is treatment of choice for cervical neurogenic tumours and paraganglionomas and must be considered in young patients or rapidly expanding tumours to avoid compressive symptoms, as in this case.

PMID: 27685879 [PubMed - as supplied by publisher]



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Classifying and Standardizing Panfacial Trauma With a New Bony Facial Trauma Score.

Classifying and Standardizing Panfacial Trauma With a New Bony Facial Trauma Score.

JAMA Facial Plast Surg. 2016 Sep 29;

Authors: Casale GG, Fishero BA, Park SS, Sochor M, Heltzel SB, Christophel JJ

Abstract
Importance: The practice of facial trauma surgery would benefit from a useful quantitative scale that measures the extent of injury.
Objective: To develop a facial trauma scale that incorporates only reducible fractures and is able to be reliably communicated to health care professionals.
Design and Setting: A cadaveric tissue study was conducted from October 1 to 3, 2014. Ten cadaveric heads were subjected to various degrees of facial trauma by dropping a fixed mass onto each head. The heads were then imaged with fine-cut computed tomography. A Bony Facial Trauma Scale (BFTS) for grading facial trauma was developed based only on clinically relevant (reducible) fractures. The traumatized cadaveric heads were then scored using this scale as well as 3 existing scoring systems. Regression analysis was used to determine correlation between degree of incursion of the fixed mass on the cadaveric heads and trauma severity as rated by the scoring systems. Statistical analysis was performed to determine correlation of the scores obtained using the BFTS with those of the 3 existing scoring systems. Scores obtained using the BFTS were not correlated with dentition (95% CI, -0.087 to 1.053; P = .08; measured as absolute number of teeth) or age of the cadaveric donor (95% CI, -0.068 to 0.944; P = .08).
Main Outcome Measures: Facial trauma scores.
Results: Among all 10 cadaveric specimens (9 male donors and 1 female donor; age range, 41-87 years; mean age, 57.2 years), the facial trauma scores obtained using the BFTS correlated with depth of penetration of the mass into the face (odds ratio, 4.071; 95% CI, 1.676-6.448) P = .007) when controlling for presence of dentition and age. The BFTS scores also correlated with scores obtained using 3 existing facial trauma models (Facial Fracture Severity Scale, rs = 0.920; Craniofacial Disruption Score, rs = 0.945; and ZS Score, rs = 0.902; P < .001 for all 3 models). In addition, the BFTS was found to have excellent interrater reliability (0.908; P = .001), which was similar to the interrater reliability of the other 3 tested trauma scales. Scores obtained using the BFTS were not correlated with dentition (odds ratio, .482; 95% CI, -0.087 to 1.053; P = .08; measured as absolute number of teeth) or age of the cadaveric donor (odds ratio, .436; 95% CI, -0.068 to 0.944; P = .08).
Conclusions and Relevance: Facial trauma severity as measured by the BFTS correlated with depth of penetration of the fixed mass into the face. In this study, the BFTS was clinically relevant, had high fidelity in communicating the fractures sustained in facial trauma, and correlated well with previously validated models.
Level of Evidence: NA.

PMID: 27685864 [PubMed - as supplied by publisher]



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Site-specific methylation patterns of the GAL and GALR1/2 genes in head and neck cancer: Potential utility as biomarkers for prognosis.

Site-specific methylation patterns of the GAL and GALR1/2 genes in head and neck cancer: Potential utility as biomarkers for prognosis.

Mol Carcinog. 2016 Sep 29;

Authors: Misawa K, Mochizuki D, Endo S, Mima M, Misawa Y, Imai A, Shinmura K, Kanazawa T, Carey TE, Mineta H

Abstract
BACKGROUND: The aim of this study was to evaluate the prognostic value of the promoter methylation status of galanin (GAL) and galanin receptor 1/2 (GALR1/2) by assessing their association with disease-free survival and known prognostic factors in head and neck cancer.
METHODS: We generated methylation profiles of GAL and GALR1/2 in tumor samples obtained from 202 patients with head and neck squamous cell carcinoma (HNSCC); these included 43 hypopharynx, 42 larynx, 59 oral cavity, and 58 oropharynx tumor samples. CpG island hypermethylation status of the 3 genes was analyzed using quantitative methylation-specific PCR (Q-MSP). In order to determine the prognostic value of the methylation status of these genes, the associations between methylation index and various clinical characteristics, especially tumor site, were assessed for tumors from patients with HNSCC.
RESULTS: The methylation index was positively correlated with female gender (P = 0.008) and disease recurrence (P = 0.01) in oral cancer and human papillomavirus (HPV)-positive (P = 0.004) status and disease recurrence (P = 0.005) in oropharyngeal cancer. Among patients with oral and oropharyngeal cancer, promoter hypermethylation of GAL, GALR1, or GALR2 was statistically correlated with a decrease in disease-free survival (log-rank test, P = 0.036 and P = 0.042, respectively). Furthermore, methylation of GAL, GALR1, or GALR2 exhibited the highest association with poor survival (log-rank test, P = 0.018) in patients with HPV-negative oropharyngeal cancers.
CONCLUSIONS: As such, GAL and GALR1/2 methylation status may serve as an important site-specific biomarker for prediction of clinical outcome in patients with HNSCC. This article is protected by copyright. All rights reserved.

PMID: 27685843 [PubMed - as supplied by publisher]



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Inhibition of phosphodiesterase 3, 4, and 5 induces endolymphatic hydrops in mouse inner ear, as evaluated with repeated 9.4T MRI.

Inhibition of phosphodiesterase 3, 4, and 5 induces endolymphatic hydrops in mouse inner ear, as evaluated with repeated 9.4T MRI.

Acta Otolaryngol. 2016 Aug 15;:1-8

Authors: Degerman E, In 't Zandt R, Pålbrink A, Eliasson L, Cayé-Thomasen P, Magnusson M

Abstract
CONCLUSION: The data indicate important roles for phosphodiesterase (PDE) 3, 4, 5, and related cAMP and cGMP pools in the regulation of inner ear fluid homeostasis. Thus, dysfunction of these enzymes might contribute to pathologies of the inner ear.
OBJECTIVE: The mechanisms underlying endolymphatic hydrops, a hallmark of inner ear dysfunction, are not known in detail; however, altered balance in cAMP and cGMP signaling systems appears to be involved. Key components of these systems are PDEs, enzymes that modulate the amplitude, duration, termination, and specificity of cAMP and cGMP signaling.
METHOD: To evaluate the role of PDE3, 4, and 5 and associated cAMP and cGMP pools in inner ear function, the effect of cilostamide (PDE3 inhibitor), rolipram (PDE4 inhibitor), and sildenafil (PDE5 inhibitor), administrated via mini-osmotic pumps, on mouse inner ear fluid homeostasis was evaluated using 9.4T in vivo MRI in combination with intraperitoneally administered Gadolinium contrast. Also, using human saccule as a model, the expression of PDEs and related signaling molecules and targets was studied using immunohistochemistry.
RESULTS: PDE3, PDE4, as well as PDE5 inhibitors resulted in the development of endolymphatic hydrops. Furthermore, PDE3B, PDE4D, and some related signaling components were shown to be expressed in the human saccule.

PMID: 27685753 [PubMed - as supplied by publisher]



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miR-612 suppresses stem cell-like property of hepatocellular carcinoma cells by modulating Sp1/Nanog signaling.

miR-612 suppresses stem cell-like property of hepatocellular carcinoma cells by modulating Sp1/Nanog signaling.

Cell Death Dis. 2016;7(9):e2377

Authors: Liu Y, Liu DL, Dong LL, Wen D, Shi DM, Zhou J, Fan J, Wu WZ

Abstract
In our previous study we found that miR-612 negatively regulated stem cell-like property and tumor metastasis of hepatocellular carcinoma cells (HCC). In this study, we try to elucidate underlying mechanism of the regulation, and find that miR-612 inversely modulate the mRNA and protein level of epithelial cell adhesion molecule as well as CD133, negatively regulate the numbers and sizes of tumor spheres, directly inhibit the protein level of Sp1, and subsequently reduce transcription activity of Nanog. Of importance, the higher levels of Sp1 and Nanog in biopsies are the more unfavorable prognoses of HCC patients are found after tumor resection. Taken together, miR-612 has a suppressive role on HCC stemness via Sp1/Nanog signaling pathway.

PMID: 27685621 [PubMed - as supplied by publisher]



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Expression and purification of EPHA2 tyrosine kinase domain for crystallographic and NMR studies.

Expression and purification of EPHA2 tyrosine kinase domain for crystallographic and NMR studies.

Chembiochem. 2016 Sep 29;

Authors: Gande SL, Saxena K, Sreeramulu S, Linhard V, Kudlinzki D, Heinzlmeir S, Reichert AJ, Skerra A, Kuster B, Schwalbe H

Abstract
The receptor tyrosine kinase EPHA2 is overexpressed in several cancer entities (breast, head and neck, non-small cell lung cancer). Small molecule-based inhibition of the activity of the EPHA2 kinase domain (KD) has been seen as an important strategy for achieving therapeutic intervention. However, obtaining structural information by protein crystallography or by NMR spectroscopy aiding drug discovery, has been severely hampered due to the lack of pure and homogeneous protein. Here different fragments of the EPHA2 KD were expressed and purified from both bacterial (Escherichia coli BL21 (DE3) cells) and insect cells (Spodoptera frugiperda, Sf9 cells). [1H,15N]-HSQCs were used to determine the proper folding and homogeneity of all the constructs. E. coli expressed and purified protein constructs though well-folded were unstable and did not crystallize. However, the construct (D596-G900) produced in Sf9 cells yielded in a homogenous, well-folded and crystallized readily, resulting in eleven new EPHA2-ligand co-crystal structures. We have also established a strategy for selective and uniform 15N amino acid labeling of the EPHA2 KD in Sf9 cells for investigating dynamics and EPHA2-drug interactions by NMR.

PMID: 27685543 [PubMed - as supplied by publisher]



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Dermoscopy of small size basal cell carcinoma: a case-control study.

Dermoscopy of small size basal cell carcinoma: a case-control study.

J Eur Acad Dermatol Venereol. 2016 Sep 29;

Authors: Longo C, Specchio F, Ribero S, Coco V, Kyrgidis A, Moscarella E, Ragazzi M, Peris K, Argenziano G

Abstract
BACKGROUND: Several dermoscopic criteria for diagnosing BCC have been identified over the last years with the aim to help recognition of the tumour among others entities. However, few literature data are available regarding the identification of specific diagnostic criteria of small size BCCs OBJECTIVES: the aims of this study were 1) to investigate whether small size BCCs (<5 mm) are typified by specific dermoscopic criteria compared to larger BCCs (>5 mm) in a consecutive cohort of excised lesions and 2) to explore whether small BCCs belong to distinct histologic subtype METHODS: Histopathologically proven BCCs with a full set of clinical and dermoscopic images were retrieved in order to have a case-control study of small (<5mm in size) and large (>5mm in size) tumors.
RESULTS: Our study population included 87 small-size BCCs (cases) and an equal number of larger BCCs (controls). Small BCC were more frequent in younger patients (mean age 59.19 +/- 13.7 years) than controls (68.18 +/- 14.8 years) (p<0.001). Furthermore, Small BCCs were more frequently present on head and neck area (60%) compared to large BCCs (40%) (p=0.006). At univariate logistic regression, predictors of small BCC (Fig 1 and Table 2) were multiple blue grey dots (OR 1.319519; 95% CI 0.591-2.942) and large blue-gray ovoid nests (OR 1.506518; 95% CI 0.703-3.227). Interestingly, small BCCs were associated with a crude 3.5-fold higher odd of being nodular (OR 3.486; 95% CI 1.860-6.532).
CONCLUSIONS: Dermoscopy is as a reliable tool for the diagnosis of small BCC that could be regarded as a "miniaturized" BCC. According to our findings, the detection of a small nodule on the head-neck region dermoscopically typified by blue-grey ovoid nests and multiple blue grey dots is strongly suggestive of small BCC. This article is protected by copyright. All rights reserved.

PMID: 27685248 [PubMed - as supplied by publisher]



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Is the dose distribution distorted in IMRT and RapidArc treatment when patient plans are swapped across beam-matched machines?

Is the dose distribution distorted in IMRT and RapidArc treatment when patient plans are swapped across beam-matched machines?

J Appl Clin Med Phys. 2016;17(5):6104

Authors: Chockkalingam K, Radha CA, Subramani V, Subramani V, Gunasekaran MK

Abstract
The purpose of this study is to evaluate the degree of dose distribution distortion in advanced treatments like IMRT and RapidArc when patient plans are swapped across dosimetrically equivalent so-called "beam-matched" machines. For this purpose the entire work is divided into two stages. At forefront stage all basic beam properties of 6 MV X-rays like PDD, profiles, output factors, TPR20/10 and MLC transmission of two beam-matched machines - Varian Clinac iX and Varian 600 C/D Unique - are compared and evaluated for differences. At second stage 40 IMRT and RapidArc patient plans from the pool of head and neck (H&N) and pelvis sites are selected for the study. The plans are swapped across the machines for dose recalculation and the DVHs of target and critical organs are evaluated for dose differences. Following this, the accuracy of the beam-matching at the TPS level for treatments like IMRT and RapidArc are compared. On PDD, profile (central 80%) and output factor comparison between the two machines, a maxi-mum percentage disagreement value of -2.39%, -2.0% and -2.78%, respectively, has been observed. The maximum dose difference observed at volumes in IMRT and RapidArc treatments for H&N dose prescription of 69.3 Gy/33 fractions is 0.88 Gy and 0.82 Gy, respectively. Similarly, for pelvis, with a dose prescription of 50 Gy/25 fractions, a maximum dose difference of 0.55 Gy and 0.53 Gy is observed at volumes in IMRT and RapidArc treatments, respectively. Overall results of the swapped plans between two machines' 6 MV X-rays are well within the limits of accepted clinical tolerance.

PMID: 27685106 [PubMed - as supplied by publisher]



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Pedunculated carcinoma ex pleomorphic adenoma of the nasal cavity: A unique case report.

Pedunculated carcinoma ex pleomorphic adenoma of the nasal cavity: A unique case report.

Medicine (Baltimore). 2016 Sep;95(39):e5004

Authors: Liao PW, Chen YL, Chen JW

Abstract
BACKGROUND: A carcinoma ex pleomorphic adenoma (CXPA) is an epithelial malignancy arising in or from a benign pleomorphic salivary adenoma. The parotid gland is the most common location of CXPAs. Minor salivary gland CXPAs of the nasal cavity are exceedingly rare, with only 6 documented in the literature.
METHODS AND RESULT: We present a 7th case: an unusual pedunculated intranasal CXPA, which had a favorable outcome after a wide endoscopic excision and the longest follow-up period reported to date. The clinical features, immunohistochemical characteristics, treatment choices, and disease outcomes of the intranasal CXPAs reported in previous studies are also reviewed.
CONCLUSION: This case demonstrates the importance of considering the possibility of CXPA in the differential diagnosis of minor salivary gland malignancies in the nasal cavity.

PMID: 27684860 [PubMed - as supplied by publisher]



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3-Dimensional shear wave elastography of breast lesions: Added value of color patterns with emphasis on crater sign of coronal plane.

3-Dimensional shear wave elastography of breast lesions: Added value of color patterns with emphasis on crater sign of coronal plane.

Medicine (Baltimore). 2016 Sep;95(39):e4877

Authors: Chen YL, Chang C, Zeng W, Wang F, Chen JJ, Qu N

Abstract
Color patterns of 3-dimensional (3D) shear wave elastography (SWE) is a promising method in differentiating tumoral nodules recently. This study was to evaluate the diagnostic accuracy of color patterns of 3D SWE in breast lesions, with special emphasis on coronal planes.A total of 198 consecutive women with 198 breast lesions (125 malignant and 73 benign) were included, who underwent conventional ultrasound (US), 3D B-mode, and 3D SWE before surgical excision. SWE color patterns of Views A (transverse), T (sagittal), and C (coronal) were determined. Sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) were calculated.Distribution of SWE color patterns was significantly different between malignant and benign lesions (P = 0.001). In malignant lesions, "Stiff Rim" was significantly more frequent in View C (crater sign, 60.8%) than in View A (51.2%, P = 0.013) and View T (54.1%, P = 0.035). AUC for combination of "Crater Sign" and conventional US was significantly higher than View A (0.929 vs 0.902, P = 0.004) and View T (0.929 vs 0.907, P = 0.009), and specificity significantly increased (90.4% vs 78.1%, P = 0.013) without significant change in sensitivity (85.6% vs 88.0%, P = 0.664) as compared with conventional US.In conclusion, combination of conventional US with 3D SWE color patterns significantly increased diagnostic accuracy, with "Crater Sign" in coronal plane of the highest value.

PMID: 27684820 [PubMed - as supplied by publisher]



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Identification of benign and malignant thyroid nodules by in vivo iodine concentration measurement using single-source dual energy CT: A retrospective diagnostic accuracy study.

Identification of benign and malignant thyroid nodules by in vivo iodine concentration measurement using single-source dual energy CT: A retrospective diagnostic accuracy study.

Medicine (Baltimore). 2016 Sep;95(39):e4816

Authors: Gao SY, Zhang XY, Wei W, Li XT, Li YL, Xu M, Sun YS, Zhang XP

Abstract
This study proposed to determine whether in vivo iodine concentration measurement by single-source dual energy (SSDE) CT can improve differentiation between benign and malignant thyroid nodules. In total, 53 patients presenting with thyroid nodules underwent SSDE CT scanning. Iodine concentrations were measured for each nodule and normal thyroid tissue using the GSI-viewer image analysis software. A total of 26 thyroid nodules were malignant in 26 patients and confirmed by surgery; 33 nodules from 27 patients were benign, with 10 confirmed by surgery and others after follow-up. Iodine concentrations with plain CT were significantly lower in malignant than benign nodules (0.47 ± 0.20 vs 1.17 ± 0.38 mg/mL, P = 0.00). Receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.93; with a cutoff of 0.67, iodine concentration showed 92.3% sensitivity and 88.5% specificity in diagnosing malignancy. Iodine concentration obtained by enhanced and plain CT were significantly higher in malignant than benign nodules (9.05 ± 3.35 vs 3.46 ± 2.24 mg/mL, P = 0.00). ROC curve analysis showed an AUC of 0.93; with a cutoff value of 3.37, iodine concentration displayed 78% sensitivity, 95% specificity in diagnosing malignancy. Combining unenhanced with enhanced iodine concentrations, the diagnostic equation was: Y = -8.641 × unenhanced iodine concentration + 0.663 × iodine concentration. ROC curve showed an AUC of 0.98 (95% CI, 0.94, 1.00). With Y ≥ -2 considered malignancy, diagnostic sensitivity and specificity were 96%, 96.3%, respectively. This study concluded that SSDE CT can detect the differences in iodine uptake and blood supply between benign and malignant thyroid lesions.

PMID: 27684811 [PubMed - as supplied by publisher]



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Neuropsychology in Finland - over 30 years of systematically trained clinical practice.

Neuropsychology in Finland - over 30 years of systematically trained clinical practice.

Clin Neuropsychol. 2016 Aug 10;:1-22

Authors: Hokkanen L, Nybo T, Poutiainen E

Abstract
OBJECTIVE: The aim of this invited paper for a special issue of international practice in The Clinical Neuropsychologist is to provide information on training models, clinical practice, and professional issues within neuropsychology in Finland.
METHOD: Relevant information was gathered via literature searches, a survey by the Neuropsychology Working Group of the Finnish Psychological Association, archives of the Finnish Neuropsychological Society, and personal communication with professionals in Finland.
RESULTS: The roots of Finnish neuropsychology are linked to the early German tradition of experimental psychology. Since the 1970s, it has been strongly influenced by both the psychometric approach in the U.S. and the qualitative approach by Luria. Systematic specialization training program began in Finland in 1983. It was first organized by the Finnish Neuropsychological Society and since 1997 by Finnish universities. At present, around 260 neuropsychologists have completed this training. According to the survey by the Finnish Psychological Association in 2014, 67% of Finnish neuropsychologists work in the public sector, 36% in the private sector, and 28% reported that they had private practice. Work includes assessments for 90% of the respondents, rehabilitation for 74%, and many are involved in teaching and research. Of the respondents, 20% worked both with adults and children, 44% with adults only and 36% with children only. Within test development, pediatric neuropsychology is an especially prominent field.
CONCLUSIONS: A unique blend of approaches and a solid systematic training tradition has led to a strong position of neuropsychologists as distinguished experts in the Finnish health care system.

PMID: 27684724 [PubMed - as supplied by publisher]



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Potential Interest in Circulating miR-BART17-5p As a Post-Treatment Biomarker for Prediction of Recurrence in Epstein-Barr Virus-Related Nasopharyngeal Carcinoma.

Potential Interest in Circulating miR-BART17-5p As a Post-Treatment Biomarker for Prediction of Recurrence in Epstein-Barr Virus-Related Nasopharyngeal Carcinoma.

PLoS One. 2016;11(9):e0163609

Authors: Hirai N, Wakisaka N, Kondo S, Aga M, Moriyama-Kita M, Ueno T, Nakanishi Y, Endo K, Sugimoto H, Murono S, Sato H, Yoshizaki T

Abstract
OBJECTIVES: Epstein-Barr virus (EBV)-related micoRNAs (miRNAs), BamHI-A rightward transcripts (BART)-miRNAs, are released in a stable form from viable cells, which are abundant in patients with EBV-positive nasopharyngeal carcinoma (NPC). We estimated copy numbers of circulating miR-BART2-5p, miR-BART17-5p, and miR-BART18-5p as well as BamHI-W DNA as biomarkers.
MATERIALS AND METHODS: Serums from 31 EBV-positive (confirmed by in situ hybridization for EBV-encoded small RNAs) NPC patients and 40 non-NPC controls were analyzed. Among the 31 NPC patients, serums at the initial diagnosis and three months after treatment were obtained from 20 patients, and serums only at three months after treatment were obtained from 11 patients.
RESULTS: The sensitivity/specificity of circulating BamHI-W DNA, miR-BART2-5p, miR-BART17-5p, and miR-BART18-5p for the diagnosis of NPC before treatment were 100 / 100, 85 / 85, 60 / 95, and 25 / 100%, respectively. For BamHI-W DNA, NPC patients with stage IV disease had significantly higher copy numbers than those with I-III. Copy numbers decreased significantly post-treatment. In contrast, copy numbers of the three BART-miRNAs showed no significant correlation with the clinical stage at diagnosis or any significant post-treatment change. After treatment, BamHI-W DNA and miR-BART17-5p were detected in 5 and 6 cases out of 11 patients with recurrent or residual tumors, respectively. However, BamHI-W DNA and miR-BART17-5p were absent in all 20 patients without relapse or residual tumors.
CONCLUSION: The copy number of circulating BamHI-W DNA is a more useful biomarker for the initial diagnosis of NPC than the three BART-miRNAs examined. Post-treatment detection of miR-BART17-5p is a potential biomarker of a poor prognosis.

PMID: 27684719 [PubMed - as supplied by publisher]



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Sensory Topography of Oral Structures.

Sensory Topography of Oral Structures.

JAMA Otolaryngol Head Neck Surg. 2016 Sep 29;

Authors: Bearelly S, Cheung SW

Abstract
Importance: Sensory function in the oral cavity and oropharynx is integral to effective deglutition and speech production. The main hurdle to evaluation of tactile consequences of upper aerodigestive tract diseases and treatments is access to a reliable clinical tool. We propose a rapid and reliable procedure to determine tactile thresholds using buckling monofilaments to advance care.
Objective: To develop novel sensory testing monofilaments and map tactile thresholds of oral cavity and oropharyngeal structures.
Design, Setting, and Participants: A prospective cross-sectional study of 37 healthy adults (12 men, 25 women), specifically without a medical history of head and neck surgery, radiation, or chemotherapy, was carried out in an academic tertiary medical center to capture normative data on tactile sensory function in oral structures.
Interventions: Cheung-Bearelly monofilaments were constructed by securing nylon monofilament sutures (2-0 through 9-0) in the lumen of 5-French ureteral catheters, exposing 20 mm for tapping action.
Main Outcomes and Measures: Buckling force consistency was evaluated for 3 lots of each suture size. Sensory thresholds of 4 oral cavity and 2 oropharyngeal subsites in healthy participants (n = 37) were determined by classical signal detection methodology (d-prime ≥1). In 21 participants, test-retest reliability of sensory thresholds was evaluated. Separately in 16 participants, sensory thresholds determined by a modified staircase method were cross-validated with those obtained by classical signal detection.
Results: Buckling forces of successive suture sizes were distinct (P < .001), consistent (Cronbach α, 0.99), and logarithmically related (r = 0.99, P < .001). Test-retest reliability of sensory threshold determination was high (Cronbach α, >0.7). The lower lip, anterior tongue, and buccal mucosa were more sensitive than the soft palate, posterior tongue, and posterior pharyngeal wall (P < .001). Threshold determination by classical signal detection and modified staircase methods were highly correlated (r = 0.93, P < .001). Growth of perceptual intensity was logarithmically proportional to stimulus strength (P < .01).
Conclusions and Relevance: Topography of normal oral cavity and oropharyngeal tactile sensation is organized in accordance to decreasing sensitivity along the anteroposterior trajectory and growth of perceptual intensity at all subsites is log-linear. Cheung-Bearelly monofilaments are accessible, disposable, and consistent esthesiometers. This novel clinical tool is deployable for quantitative sensory function assessment of oral cavity and oropharyngeal structures.

PMID: 27684535 [PubMed - as supplied by publisher]



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Device Life of the Tracheoesophageal Voice Prosthesis Revisited.

Device Life of the Tracheoesophageal Voice Prosthesis Revisited.

JAMA Otolaryngol Head Neck Surg. 2016 Sep 29;

Authors: Lewin JS, Baumgart LM, Barrow MP, Hutcheson KA

Abstract
Importance: Voice prosthesis (VP) device life is a limiting factor of tracheoesophageal (TE) voice restoration that drives patient satisfaction, health care costs, and overall burden. Historic data suggest that TE VPs have an average device life of generally 3 to 6 months, but these data are typically derived from small samples using only 1 or 2 devices.
Objective: To reexamine current device life in a large, contemporary cancer hospital in the United States that uses a wide assortment of VPs.
Design, Setting, and Participants: This retrospective observational study included 390 laryngectomized patients with a tracheoesophageal puncture (TEP) who had VP management at MD Anderson Cancer Center between July 1, 2003, and December 31, 2013.
Main Outcomes and Measures: Tracheoesophageal voice-related outcomes were: (1) device life duration to VP removal, and (2) treatment-related and prosthetic-related factors influencing device failure. Primary independent variables included treatment history (extent of surgery and radiation history), VP type (indwelling vs nonindwelling, size, specialty features), and reason for removal (leakage, complication, other). Duration was examined using Kaplan-Meier analysis. Disease, treatment, and patient-specific factors were analyzed as predictors of duration.
Results: Overall, 3648 VPs were placed in the 390 patients (median [range] age, 62 [34-92] years). Indwelling prostheses accounted for more than half (56%) of the devices placed (55%, 20-Fr diameter; 33%, 8-mm length). More than two-thirds (69%) of prostheses were removed because of leakage, while the rest were removed for other reasons. Median device life was 61 days for all prostheses. Indwelling and nonindwelling VPs had median device lives of 70 and 38 days, respectively. There was no significant difference between specialty prostheses compared with standard devices (median duration, 61 vs 70 days, respectively). The Provox ActiValve (Atos Medical) had the longest life. Neither radiation therapy nor extent of surgery had a meaningful impact on device life.
Conclusions and Relevance: Our data suggest that VP duration demonstrates a lower durability than historically reported. This may reflect the intensification of treatment regimens that complicate TEP management in an era of organ preservation; however, further investigation is needed.

PMID: 27684464 [PubMed - as supplied by publisher]



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Prosthetic Voice Rehabilitation Following Laryngectomy: It's the Archer Not the Arrow.

Prosthetic Voice Rehabilitation Following Laryngectomy: It's the Archer Not the Arrow.

JAMA Otolaryngol Head Neck Surg. 2016 Sep 29;

Authors: Abemayor E

PMID: 27684361 [PubMed - as supplied by publisher]



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A Young Man With Hypercalcemia.

A Young Man With Hypercalcemia.

JAMA Otolaryngol Head Neck Surg. 2016 Sep 29;

Authors: Yousif J, Birkeland AC, Spector ME

PMID: 27684299 [PubMed - as supplied by publisher]



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Facial reanimation using hypoglossal-facial nerve anastomosis after schwannoma removal.

Facial reanimation using hypoglossal-facial nerve anastomosis after schwannoma removal.

Acta Otolaryngol. 2016 Aug 12;:1-7

Authors: Han JH, Suh MJ, Kim JW, Cho HS, Moon IS

Abstract
CONCLUSION: In this series, the split type hypoglossal-facial nerve anastomosis resulted in more favorable outcomes in terms of both facial function and tongue atrophy.
OBJECTIVE: This study compared surgical techniques for hypoglossal-facial nerve anastomosis after schwannoma removal and evaluated which technique achieves better facial outcomes and less tongue morbidity.
METHOD: This study included 14 patients who underwent hypoglossal-facial nerve anastomosis after schwannoma removal and were followed for more than 1 year. Three surgical techniques were performed: end-to-end, end-to-side, and split anastomoses. Facial palsy and tongue atrophy after anastomosis were evaluated using the scales suggested by House-Brackmann and Martins, respectively. Tumor volume and the time to surgery were also evaluated, and the effects on facial outcomes were analyzed.
RESULTS: Overall, nine of 14 (64.3%) patients had favorable facial outcomes, and eight of 14 (57.1%) had favorable tongue outcomes. Regarding facial palsy, five of seven (71.4%) end-to-end, three of four (75%) split, and only one of three (33.3%) end-to-side patients had favorable facial function. Regarding tongue atrophy, all three (100%) end-to-side, three of four (75%) split, and two of seven (28.6%) end-to-end patients had favorable tongue outcomes. The effects of tumor volume and time to surgery on facial outcome were not significant.

PMID: 27684271 [PubMed - as supplied by publisher]



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IJERPH, Vol. 13, Pages 972: Universal Stress Proteins as New Targets for Environmental and Therapeutic Interventions of Schistosomiasis

In spite of various control measures and eradication methods that have been in progress, schistosomiasis still prevails as one of the most prevalent debilitating parasitic diseases, typically affecting the poor and the underprivileged that are predominantly concentrated in sub-Saharan Africa. The parasitic schistosome blood fluke responsible for causing the disease completes its complex developmental cycle in two hosts: humans and freshwater snails, where they physically undergo gross modifications to endure the different conditions associated with each host. Just like any other organism, the worm possesses mechanisms that help them respond to environmental insults. It has been hypothesized that a special class of proteins known as Universal Stress Proteins (USPs) are up-regulated during sudden environmental changes, thus assisting the worm to tolerate the unfavourable conditions associated with its developmental cycle. The position of praziquantel as the drug of choice against all schistosome infections has been deemed vulnerable due to mounting concerns over drug pressure and so the need for alternative treatment is now a matter of urgency. Therefore, this review seeks to explore the associations and possible roles of USPs in schistosomiasis as well as the functioning of these proteins in the schistosomulae stage in order to develop new therapeutic interventions against this disease.

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IJMS, Vol. 17, Pages 1665: Detection and Characterization of Circulating Tumor Associated Cells in Metastatic Breast Cancer

The availability of blood-based diagnostic testing using a non-invasive technique holds promise for real-time monitoring of disease progression and treatment selection. Circulating tumor cells (CTCs) have been used as a prognostic biomarker for the metastatic breast cancer (MBC). The molecular characterization of CTCs is fundamental to the phenotypic identification of malignant cells and description of the relevant genetic alterations that may change according to disease progression and therapy resistance. However, the molecular characterization of CTCs remains a challenge because of the rarity and heterogeneity of CTCs and technological difficulties in the enrichment, isolation and molecular characterization of CTCs. In this pilot study, we evaluated circulating tumor associated cells in one blood draw by size exclusion technology and cytological analysis. Among 30 prospectively enrolled MBC patients, CTCs, circulating tumor cell clusters (CTC clusters), CTCs of epithelial–mesenchymal transition (EMT) and cancer associated macrophage-like cells (CAMLs) were detected and analyzed. For molecular characterization of CTCs, size-exclusion method for CTC enrichment was tested in combination with DEPArray™ technology, which allows the recovery of single CTCs or pools of CTCs as a pure CTC sample for mutation analysis. Genomic mutations of TP53 and ESR1 were analyzed by targeted sequencing on isolated 7 CTCs from a patient with MBC. The results of genomic analysis showed heterozygous TP53 R248W mutation from one single CTC and pools of three CTCs, and homozygous TP53 R248W mutation from one single CTC and pools of two CTCs. Wild-type ESR1 was detected in the same isolated CTCs. The results of this study reveal that size-exclusion method can be used to enrich and identify circulating tumor associated cells, and enriched CTCs were characterized for genetic alterations in MBC patients, respectively.

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IJMS, Vol. 17, Pages 1667: Internet-Supported Physical Exercise Training for Persons with Multiple Sclerosis—A Randomised, Controlled Study

Physical exercise is effective in improving functional outcomes in persons with multiple sclerosis (pwMS). We evaluated the feasibility and effectiveness of internet-based exercise training (e-training) for pwMS on health-related quality of life (HrQoL). Secondary outcomes were muscle strength, aerobic capacity, lung function, physical activity, and fatigue. This is a randomised, controlled trial with a wait-list control group. Data were collected at baseline, after three and six months, and analysed using a hybrid linear model. One-hundred twenty-six pwMS participated in the home-based aerobic (1×/week) and strength training (2×/week) intervention that was supervised and documented via an internet-platform. The intervention group received e-training for six months, and the control group received e-training after a three months waiting period. Significant differences between the groups were only observed for muscle strength (knee flexion (effect size ES = 0.3, p = 0.003), knee extension (ES = 0.24, p = 0.015)), peak expiratory flow (ES = 0.2, p = 0.039), and sports activity (ES = 0.33, p = 0.001) after three months. E-training had no effect on HrQoL but did on muscle strength, lung function, and physical activity. It is a promising and feasible approach to facilitate large-scale, yet individual, training support.

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IJMS, Vol. 17, Pages 1666: Disease Activity and Conversion into Multiple Sclerosis after Optic Neuritis Is Treated with Erythropoietin

Changes in cerebral lesion load by magnetic resonance imaging (MRI) in patients from a double-blind, placebo-controlled, phase II study on erythropoietin in clinically isolated optic neuritis (ClinicalTrials.gov, NCT00355095) were analyzed. Therefore, patients with acute optic neuritis were assigned to receive either 33,000 IU of recombinant human erythropoietin (IV) daily for three days, or a placebo, as an add-on to methylprednisolone. Of 35 patients, we investigated changes in cerebral lesion load in MRIs obtained at baseline and at weeks 4, 8, and 16. In 5 of the 35 patients, we found conversion into multiple sclerosis (MS) based on MRI progression only. These five patients had received the placebo. Another five patients showed MRI progression together with relapses. Three of these patients had received erythropoietin, and two the placebo. Yet, analyzing the change in absolute numbers of periventricular, juxtacortical, and infratentorial lesions including gadolinium-enhancing lesions, there were no significant differences between the groups. Although effective in terms of retinal nerve fiber layer protection, erythropoietin treatment of acute isolated optic neuritis did not influence further evolution of MRI lesions in the brain when comparing absolute numbers. However, early conversion from clinically isolated syndrome to MS assessed by MRI activity seemed to occur more frequently in the placebo-treated group.

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IJMS, Vol. 17, Pages 1661: Dimerization of the Vacuolar Receptors AtRMR1 and -2 from Arabidopsis thaliana Contributes to Their Localization in the trans-Golgi Network

In Arabidopsis thaliana, different types of vacuolar receptors were discovered. The AtVSR (Vacuolar Sorting Receptor) receptors are well known to be involved in the traffic to lytic vacuole (LV), while few evidences demonstrate the involvement of the receptors from AtRMR family (Receptor Membrane RING-H2) in the traffic to the protein storage vacuole (PSV). In this study we focused on the localization of two members of AtRMR family, AtRMR1 and -2, and on the possible interaction between these two receptors in the plant secretory pathway. Our experiments with agroinfiltrated Nicotiana benthamiana leaves demonstrated that AtRMR1 was localized in the endoplasmic reticulum (ER), while AtRMR2 was targeted to the trans-Golgi network (TGN) due to the presence of a cytosolic 23-amino acid sequence linker. The fusion of this linker to an equivalent position in AtRMR1 targeted this receptor to the TGN, instead of the ER. By using a Bimolecular Fluorescent Complementation (BiFC) technique and experiments of co-localization, we demonstrated that AtRMR2 can make homodimers, and can also interact with AtRMR1 forming heterodimers that locate to the TGN. Such interaction studies strongly suggest that the transmembrane domain and the few amino acids surrounding it, including the sequence linker, are essential for dimerization. These results suggest a new model of AtRMR trafficking and dimerization in the plant secretory pathway.

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IJMS, Vol. 17, Pages 1669: Implications of Hypoxia in Breast Cancer Metastasis to Bone

Most solid tumors contain regions of hypoxia in which increased cell proliferation promotes increased oxygen consumption and the condition is further exacerbated as cancer cells become localized far from a functional blood vessel, further decreasing the oxygen supply. An important mechanism that promotes cell adaptation to hypoxic conditions is the expression of hypoxia-inducible factors (HIFs). Hypoxia-inducible factors transcriptionally regulate many genes involved in the invasion and metastasis of breast cancer cells. Patients, whose primary tumor biopsies show high HIF expression levels, have a greater risk of metastasis. The current review will highlight the potential role of hypoxia in breast cancer metastasis to the bone by considering the regulation of many steps in the metastatic process that include invasion, migration, margination and extravasation, as well as homing signals and regulation of the bone microenvironment.

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Combining transrectal ultrasound and CT for image-guided adaptive brachytherapy of cervical cancer: Proof of concept

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Publication date: Available online 29 September 2016
Source:Brachytherapy
Author(s): Nicole Nesvacil, Maximilian P. Schmid, Richard Pötter, Gernot Kronreif, Christian Kirisits
PurposeTo investigate the feasibility of a treatment planning workflow for three-dimensional image-guided cervix cancer brachytherapy, combining volumetric transrectal ultrasound (TRUS) for target definition with CT for dose optimization to organs at risk (OARs), for settings with no access to MRI.Methods and MaterialsA workflow for TRUS/CT-based volumetric treatment planning was developed, based on a customized system including ultrasound probe, stepper unit, and software for image volume acquisition. A full TRUS/CT-based workflow was simulated in a clinical case and compared with MR- or CT-only delineation. High-risk clinical target volume was delineated on TRUS, and OARs were delineated on CT. Manually defined tandem/ring applicator positions on TRUS and CT were used as a reference for rigid registration of the image volumes. Treatment plan optimization for TRUS target and CT organ volumes was performed and compared to MRI and CT target contours.ResultsTRUS/CT-based contouring, applicator reconstruction, image fusion, and treatment planning were feasible, and the full workflow could be successfully demonstrated. The TRUS/CT plan fulfilled all clinical planning aims. Dose-volume histogram evaluation of the TRUS/CT-optimized plan (high-risk clinical target volume D90, OARs D2cm³ for) on different image modalities showed good agreement between dose values reported for TRUS/CT and MRI-only reference contours and large deviations for CT-only target parameters.ConclusionsA TRUS/CT-based workflow for full three-dimensional image-guided cervix brachytherapy treatment planning seems feasible and may be clinically comparable to MRI-based treatment planning. Further development to solve challenges with applicator definition in the TRUS volume is required before systematic applicability of this workflow.



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The dosimetric impact of air in vaginal vault brachytherapy

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Publication date: Available online 29 September 2016
Source:Brachytherapy
Author(s): Áine Maxwell, Niluja Thiruthaneeswaran, Gerry Lowe, Rachel Wills, Samadara Sripali, Peter J. Hoskin
PurposeVaginal vault brachytherapy is an adjuvant treatment to reduce risk of local recurrence in endometrial cancer. Axial imaging has demonstrated the presence of air gaps between the surface of a cylindrical applicator and mucosal wall. The impact of these on dosimetry and applicability of the TG-43 formalism in the presence of air has been assessed.Methods and MaterialsThe planning CT scans for a retrospective sample of 82 patients were examined for the presence of air gaps. These were quantified in terms of the radial and longitudinal aspect with reference to the applicator, frequency per patient, and location along the applicator. Monte Carlo calculations and ionization chamber measurements were made in a phantom to estimate the uncertainty of the TG-43 algorithm.ResultsThe overall incidence of air gaps was 91.4%. The most common radial size was between 2 and 3 mm (43.0%) that resulted in an average dose reduction of 14.8%. There is a strong correlation between radial dimension and TG-43 calculated dose reduction. Monte Carlo simulations and phantom measurements indicated that the inhomogeneity resulted in a maximum of 2.4% deviation from doses calculated using TG-43.ConclusionsAir gaps are common. TG-43 formalism is not significantly compromised by the presence of air. However, the presence of the air does produce a displacement of the mucosal surface away from the applicator and this causes a significant dose reduction.



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Good things come in small packages: Overcoming challenges to harness extracellular vesicles for therapeutic delivery

Publication date: 10 November 2016
Source:Journal of Controlled Release, Volume 241
Author(s): Dominique Ingato, Jong Uk Lee, Sang Jun Sim, Young Jik Kwon
Extracellular vesicles (EVs) hold great promise as potential therapeutic carriers. EVs are biologically active, intrinsically transporting cargo between cells. Moreover, they can be loaded with specific cargo for distribution and/or engineered to achieve enhanced uptake. Although studies have already demonstrated therapeutic delivery using EVs, various challenges must be overcome before EV technology is ready for the clinic. Since the properties of EVs are dependent upon their cell of origin and the conditions of their formation, establishing clear characterization practices is essential to ensuring reproducibility and safety. Identifying methods for mass production of EVs is crucial for achieving high EV yields necessary for clinical trials. This review introduces current theory behind EV formation and function, describes the latest methods for characterization and mass production, and discusses future opportunities for extracellular vesicles in therapeutic delivery.

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Functionalized carbon nanotubes: From intracellular uptake and cell-related toxicity to systemic brain delivery

Publication date: Available online 30 September 2016
Source:Journal of Controlled Release
Author(s): Pedro M. Costa, Maxime Bourgognon, Julie T-W Wang, Khuloud T. Al-Jamal
Carbon nanotubes (CNTs) have long been regarded as promising carriers in biomedicine. Due to their high surface area and unique needle-like structure, CNTs are uniquely equipped to carry therapeutic molecules across biological membranes and, therefore, have been widely researched for use in theranostic applications. The attractive properties of the CNTs entice also their use in the brain environment. Cutting edge brain-specific therapies, capable of circumventing the physical and biochemical blockage of the blood-brain barrier, could be a precious tool to tackle brain disorders. With an increasing number of applications and expanding production, the effects of direct and indirect exposure to CNTs on cellular and molecular levels and more globally the general health, must be carefully assessed and limited.In this chapter, we review the most recent trends on the development and application of CNT-based nanotechnologies, with a particular focus on the carrier properties, cell internalisation and processing, and mechanisms involved in cell toxicity. Novel approaches for CNT-based systemic therapeutic brain delivery following intravenous administration are also reviewed. Moreover, we highlight fundamental questions that should be addressed in future research involving CNTs, aiming at achieving its safe introduction into the clinics.

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A New Method for Evaluating Actual Drug Release Kinetics of Nanoparticles inside Dialysis Devices via Numerical Deconvolution

Publication date: Available online 29 September 2016
Source:Journal of Controlled Release
Author(s): Yousheng Zhou, Chunsheng He, Kun Chen, Jieren Ni, Yu Cai, Xiaodi Guo, Xiao Yu Wu
Nanoparticle formulations have found increasing applications in modern therapies. To achieve desired treatment efficacy and safety profiles, drug release kinetics of nanoparticles must be controlled tightly. However, actual drug release kinetics of nanoparticles cannot be readily measured due to technique difficulties, although various methods have been attempted. Among existing experimental approaches, dialysis method is the most widely applied one due to its simplicity and avoidance of separating released drug from the nanoparticles. Yet this method only measures the released drug in the medium outside a dialysis device (the receiver), instead of actual drug release from the nanoparticles inside the dialysis device (the donor). Thus we proposed a new method using numerical deconvolution to evaluate actual drug release kinetics of nanoparticles inside the donor based on experimental release profiles of nanoparticles and free drug solution in the receptor determined by existing dialysis tests. Two computer programs were developed based on two different numerical methods, namely least square criteria with prescribed Weibull function or orthogonal polynomials as input function. The former was used for all analyses in this work while the latter for verifying the reliability of the predictions. Experimental data of drug release from various nanoparticle formulations obtained from different dialysis settings and membrane pore sizes were used to substantiate this approach. The results demonstrated that this method is applicable to a broad range of nanoparticle and microparticle formulations requiring no additional experiments. It is independent of particle formulations, drug release mechanisms, and testing conditions. This new method may also be used, in combination with existing dialysis devices, to develop a standardized method for quality control, in vitro-in vivo correlation, and for development of nanoparticles and other types of dispersion formulations.

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A stabilized peptide ligand for multifunctional glioma targeted drug delivery

Publication date: Available online 29 September 2016
Source:Journal of Controlled Release
Author(s): Man Ying, Qing Shen, Changyou Zhan, Xiaoli Wei, Jie Gao, Cao Xie, Bingxin Yao, Weiyue Lu
Peptide ligands consisting of L-amino acids are subject to proteolysis in vivo. When modified on the surface of nanocarriers, those peptide ligands would readily degrade and the targeting efficacy is significantly attenuated. It has received increasing scrutiny to design stable peptide ligands for targeted drug delivery. Here, we present the design of a stable peptide ligand by the formation of a head-to-tail amide bond as an example. Even though the linear L-peptide A7R (termed LA7R) can bind specifically to vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) that are overexpressed on glioma cells, neovasculature and glioma vasculogenic mimicry (VM), the tumor-homing capacity of LA7R is greatly impaired in vivo due to proteolysis (e.g. in the serum). A cyclic A7R (cA7R) peptide was identified by computer-aided peptide design and synthesized with high yield by combining solid phase peptide synthesis and native chemical ligation. The binding of cA7R to both receptors was theoretically and experimentally assessed. In our simulated model hydrophobic and ionic interactions dominated the binding of LA7R to receptors. It is very interesting that cA7R adopting a different structure from LA7R retained high binding affinities to receptors without affecting the hydrophobic and ionic interactions. After head-to-tail cyclization by the formation of an amide bond, cA7R exhibited exceptional stability in mouse serum. Either cA7R or LA7R was conjugated on the surface of doxorubicin (DOX) loaded liposomes (cA7R–LS/DOX or LA7R–LS/DOX). The results of in vitro cellular assays indicated that cA7R–LS/DOX not only displayed stronger anti-proliferative effect against glioma cells, but also demonstrated to be more efficient in destruction of VM and HUVEC tubes in comparison to LA7R–LS/DOX and plain liposomes (LS/DOX, without peptide conjugation). cA7R conjugation could achieve significantly higher accumulation of liposomes in glioma than did LA7R conjugation, which in turn, cA7R–LS/DOX could substantially suppress subcutaneous tumor growth when compared with other DOX formulations (free DOX, LS/DOX and LA7R–LS/DOX). The designed cyclic A7R exhibited the capability of targeting glioma cells, neovasculature and VM simultaneously in vivo. Considering the ease of synthesis, high binding affinity to receptors and increased stability of cA7R peptide in the present study, the design of head-to-tail cyclized peptides by the formation of amide bond based on computer-aided peptide design presents an alternative method to identify proteolytically stable peptide ligands.

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Electrophysiological assessment of driving pleasure and difficulty using a task-irrelevant probe technique

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Publication date: Available online 29 September 2016
Source:Biological Psychology
Author(s): Yuji Takeda, Kazuya Inoue, Motohiro Kimura, Toshihisa Sato, Chikara Nagai
The amplitude of event-related brain potentials (ERPs) elicited by task-irrelevant auditory probes decreases when more attentional resources are allocated to a visual task. This task-irrelevant probe technique is considered to be useful in assessing the degree of interest in a visual task, as well as task difficulty. The present study examined the amplitude of the N1 and P2 components elicited by task-irrelevant auditory probes during a driving task in a simulated environment. The analysis of ERPs showed that the N1 amplitude decreased when participants drove on the road course that had more frequent and sharper curves, whereas the P2 amplitude decreased when the road contained sharper curves, irrespective of curve frequency. Subjective ratings of driving pleasure and difficulty showed the same variation patterns as the N1 and P2 amplitudes, respectively. These results suggest that use of the task-irrelevant probe technique can assess the degree of driving pleasure and difficulty separately.



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Language Development of Three- to Twelve-Year-Old Twins Compared to Singletons

Objective: The language development of twins tends to lag behind in comparison to that of singletons. The purpose of this study was to compare expressive and receptive language skills of 3- to 12-year-old twins with singletons. Secondly, correlations between language differences between twins and singletons and age were investigated. Patients and Methods: Twenty-four twins with a mean age of 5.1 years participated in the study. The control group consisted of 24 singletons who were matched for gender and age. Language development was investigated using the Clinical Evaluation of Language Fundamentals. Results: Twins scored significantly lower for expressive and receptive language skills compared to singletons. Even when excluding preterm-born children, twins still scored significantly lower for expressive language skills. There was no correlation between age and language differences between twins and their matched singletons. Conclusion: Twins score lower for expressive and receptive language skills compared to singletons, and preterm birth cannot be regarded as the main cause for the language delay. The language delay in twins is rather mild but does not seem to decrease with increasing age.
Folia Phoniatr Logop 2016;68:92-98

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