Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Κυριακή 23 Οκτωβρίου 2016

Reply to the letter to the editor concerning: 'Inlay butterfly cartilage tympanoplasty in the treatment of dry central perforated chronic otitis media as an effective and time-saving procedure' by Haksever et al.

Reply to the letter to the editor concerning: 'Inlay butterfly cartilage tympanoplasty in the treatment of dry central perforated chronic otitis media as an effective and time-saving procedure' by Haksever et al.

Eur Arch Otorhinolaryngol. 2016 Oct 21;

Authors: Haksever M, Akduman D, Solmaz F, Gundogdu E

PMID: 27770260 [PubMed - as supplied by publisher]



http://ift.tt/2etR717

A Dog Is a Doctor’s Best Friend: The Use of a Service Dog as a Perioperative Assistant

Service dogs are beneficial in providing assistance to people with multiple types of disabilities and medical disorders including visual impairment, physical disabilities, seizure disorders, diabetes, and mental illness. Some service animals have been trained as a screening tool for cancer. We review a case involving a 6-year-old female with a history of mast cell mediator release and immediate hypersensitivity due to the urticaria pigmentosa variant of cutaneous mastocytosis who underwent a cystourethroscopy. Her service dog, JJ, who would alert to mast cell mediator release, was used throughout the perioperative course as a means of anxiolysis and comfort and to monitor for mast cell mediator release. This case presents an example of a service dog used in a family-care model in the field of anesthesiology and provides a unique example of using a service dog as an additional monitor to alert the care team for impending mast cell mediator release.

http://ift.tt/2eGMzCe

Efficacy of Water Resistance Therapy in Subjects Diagnosed With Behavioral Dysphonia: A Randomized Controlled Trial.

Efficacy of Water Resistance Therapy in Subjects Diagnosed With Behavioral Dysphonia: A Randomized Controlled Trial.

J Voice. 2016 Oct 18;:

Authors: Guzman M, Jara R, Olavarria C, Caceres P, Escuti G, Medina F, Medina L, Madrid S, Muñoz D, Laukkanen AM

Abstract
PURPOSE: The purpose of the present study was to determine the efficacy of water resistance therapy (WRT) in a long-term period of voice treatment in subjects diagnosed with voice disorders.
METHODS: Twenty participants, with behavioral dysphonia, were randomly assigned to one of two treatment groups: (1) voice treatment with WRT, and (2) voice treatment with tube phonation with the distal end in air (TPA). Before and after voice therapy, participants underwent aerodynamic, electroglottographic, acoustic, and auditory-perceptual assessments. The Voice Handicap Index and self-assessment of resonant voice quality were also performed. The treatment included eight voice therapy sessions. For the WRT group, the exercises consisted of a sequence of five phonatory tasks performed with a drinking straw submerged 5 cm into water. For the TPA, the exercises consisted of the same phonatory tasks, and all of them were performed into the same straw but the distal end was in air.
RESULTS: Wilcoxon test showed significant improvements for both groups for Voice Handicap Index (decrease), subglottic pressure (decrease), phonation threshold pressure (decrease), and self-perception of resonant voice quality (increase). Improvement in auditory-perceptual assessment was found only for the TPA group. No significant differences were found for any acoustic or electroglottographic variables. No significant differences were found between WRT and TPA groups for any variable.
CONCLUSIONS: WRT and TPA may improve voice function and self-perceived voice quality in individuals with behavioral dysphonia. No differences between these therapy protocols should be expected.

PMID: 27769697 [PubMed - as supplied by publisher]



http://ift.tt/2eGRNO3

Social Death.

Social Death.

QJM. 2016 Oct 20;:

Authors: Borgstrom E

Abstract
This review will outline various ways in which the notion of 'social death' can be understood, and how they can be related to clinical practice. The idea of social death is used to analytically represent how someone can be identified and treated as if they are ontologically deficient - meaning that they are not seen as being 'fully human.' This impacts on their position within society and how they are interacted with. This review will consider three examples of social death - often distinguished from physical or biological death - that are important for clinical practice: loss of agency and identity; treating people as if they are already dead; and, rituals and bereavement. Recognising that a distinction between social and biological death may not always be helpful, this review will suggest ways in which healthcare practitioners can minimise the likelihood of inadvertently treating someone as 'socially dead'.

PMID: 27770051 [PubMed - as supplied by publisher]



http://ift.tt/2eGuUcA

Guest Editorial: Topics in Death and Dying.

Guest Editorial: Topics in Death and Dying.

QJM. 2016 Oct 20;:

Authors: Emmerich N

PMID: 27770050 [PubMed - as supplied by publisher]



http://ift.tt/2dLNUbV

Treatment decision, death, and the value of life.

Treatment decision, death, and the value of life.

QJM. 2016 Oct 20;:

Authors: Holland S

PMID: 27770049 [PubMed - as supplied by publisher]



http://ift.tt/2eGrrdY

Comprehensive proteome profiling of glioblastoma-derived extracellular vesicles identifies markers for more aggressive disease.

Comprehensive proteome profiling of glioblastoma-derived extracellular vesicles identifies markers for more aggressive disease.

J Neurooncol. 2016 Oct 21;

Authors: Mallawaaratchy DM, Hallal S, Russell B, Ly L, Ebrahimkhani S, Wei H, Christopherson RI, Buckland ME, Kaufman KL

Abstract
Extracellular vesicles (EVs) play key roles in glioblastoma (GBM) biology and represent novel sources of biomarkers that are detectable in the peripheral circulation. Despite this notionally non-invasive approach to assess GBM tumours in situ, a comprehensive GBM EV protein signature has not been described. Here, EVs secreted by six GBM cell lines were isolated and analysed by quantitative high-resolution mass spectrometry. Overall, 844 proteins were identified in the GBM EV proteome, of which 145 proteins were common to EVs secreted by all cell lines examined; included in the curated EV compendium (Vesiclepedia_559; http://ift.tt/WAcpwx ). Levels of 14 EV proteins significantly correlated with cell invasion (invadopodia production; r(2) > 0.5, p < 0.05), including several proteins that interact with molecules responsible for regulating invadopodia formation. Invadopodia, actin-rich membrane protrusions with proteolytic activity, are associated with more aggressive disease and are sites of EV release. Gene levels corresponding to invasion-related EV proteins showed that five genes (annexin A1, actin-related protein 3, integrin-β1, insulin-like growth factor 2 receptor and programmed cell death 6-interacting protein) were significantly higher in GBM tumours compared to normal brain in silico, with common functions relating to actin polymerisation and endosomal sorting. We also show that Cavitron Ultrasonic Surgical Aspirator (CUSA) washings are a novel source of brain tumour-derived EVs, demonstrated by particle tracking analysis, TEM and proteome profiling. Quantitative proteomics corroborated the high levels of proposed invasion-related proteins in EVs enriched from a GBM compared to low-grade astrocytoma tumour. Large-scale clinical follow-up of putative biomarkers, particularly the proposed survival marker annexin A1, is warranted.

PMID: 27770278 [PubMed - as supplied by publisher]



http://ift.tt/2f53UYp

Knowledge gaps and research recommendations for essential tremor.

Knowledge gaps and research recommendations for essential tremor.

Parkinsonism Relat Disord. 2016 Oct 4;:

Authors: Hopfner F, Haubenberger D, Galpern WR, Gwinn K, Van't Veer A, White S, Bhatia K, Adler CH, Eidelberg D, Ondo W, Stebbins GT, Tanner CM, Helmich RC, Lenz FA, Sillitoe RV, Vaillancourt D, Vitek JL, Louis ED, Shill HA, Frosch MP, Foroud T, Kuhlenbäumer G, Singleton A, Testa CM, Hallett M, Elble R, Deuschl G

Abstract
Essential tremor (ET) is a common cause of significant disability, but its etiologies and pathogenesis are poorly understood. Research has been hampered by the variable definition of ET and by non-standardized research approaches. The National Institute of Neurological Disorders and Stroke (USA) invited experts in ET and related fields to discuss current knowledge, controversies, and gaps in our understanding of ET and to develop recommendations for future research. Discussion focused on phenomenology and phenotypes, therapies and clinical trials, pathophysiology, pathology, and genetics. Across all areas, the need for collaborative and coordinated research on a multinational level was expressed. Standardized data collection using common data elements for genetic, clinical, neurophysiological, and pathological studies was recommended. Large cohorts of patients should be studied prospectively to collect bio-samples, characterize the natural history of the clinical syndrome including patient-oriented outcomes, investigate potential etiologies of various phenotypes, and identify pathophysiological mechanisms. In particular, cellular and system-level mechanisms of tremor oscillations should be elucidated because they may yield effective therapeutic targets and biomarkers. A neuropathology consortium was recommended to standardize postmortem analysis and further characterize neuropathological observations in the cerebellum and elsewhere. Furthermore, genome-wide association studies on large patient cohorts (>10,000 patients) may allow the identification of common genes contributing to risk, and whole exome or genome sequencing may enable the identification of genetic risk and causal mutations in cohorts and well-characterized families.

PMID: 27769649 [PubMed - as supplied by publisher]



http://ift.tt/2f53C3G

IMPORTANT ASPECT OF HEALTH CARE ASSOCIATED INFECTIONS IN GEORGIA WITH THE FOCUS ON VENTILATOR-ASSOCIATED PNEUMONIA (REVIEW).

IMPORTANT ASPECT OF HEALTH CARE ASSOCIATED INFECTIONS IN GEORGIA WITH THE FOCUS ON VENTILATOR-ASSOCIATED PNEUMONIA (REVIEW).

Georgian Med News. 2016 Sep;(258):80-84

Authors: Akhvlediani T, Akhvlediani N, Kuchuloria T

Abstract
Health care associated infections are the most frequent adverse event accompanying healthcare delivery worldwide. Of these, respiratory tract infections, including ventilator-associated pneumonia (VAP), have been recognized as the most common infections in acute hospitals. Sparse anecdotal and epidemiologic data from intensive care units (ICU) and infectious diseases physicians, as well as several publications in this field, suggest that the etiology of VAP in Georgia is most likely Klebsiella pneumoniae. This review article discusses the challenges of infection control in the Georgian health care system, with a focus on VAP. We present the most significant risk factors as well as potential strategies to remediate infection control practices and reduce the prevalence of VAP.

PMID: 27770536 [PubMed - in process]



http://ift.tt/2euFvfZ

Measles-Mumps-Rubella vaccine for children with egg allergy: Is admission for inpatient vaccination necessary?

Measles-Mumps-Rubella vaccine for children with egg allergy: Is admission for inpatient vaccination necessary?

Med J Malaysia. 2016 Aug;71(4):157-160

Authors: Tan MS, Teoh EJ, Hor CP, Yeoh AA

Abstract
INTRODUCTION: Children who develop any hypersensitivity reaction to eggs are routinely referred to hospital for Measles-Mumps-Rubella (MMR) vaccination as inpatients to prevent anaphylaxis. We aimed to study the association between hypersensitivity reactions after egg exposure and similar reactions after MMR immunisation; and examine the necessity of hospital admission for vaccination.
METHODS: A prospective observational study was conducted in Paediatric Department in Bukit Mertajam Hospital, Penang, between March and December 2014. Children referred from local polyclinics for inpatient MMR vaccination because of a history of egg allergy were recruited. The children were observed in the ward for post vaccination allergic reactions. Concurrently, a group of children without egg allergy was recruited from those admitted for other illnesses but had recent MMR vaccination at polyclinics. Parents of these children were interviewed and asked if they had observed any reactions post vaccination. In both groups, sociodemographics, medical history and family history of atopy were collected.
RESULTS: Eighty-seven subjects were recruited in this study. Fifty-four infants with egg allergy had previous mild allergic reactions after exposure to eggs or egg-related products. They were associated with a family history of egg hypersensitivity, personal history of acute gastroenteritis and upper respiratory tract infections. Two of them developed cutaneous rashes post vaccination during observation, but none developed anaphylactic or anaphylactoid reactions. Two infants among those without egg allergy had post vaccination fever. There was no association between egg allergy and hypersensitivity reactions to MMR vaccine (p=0.632).
CONCLUSIONS: MMR vaccine can be safely administered to children with mild egg allergy, hence admission for vaccination in the hospital is not warranted. Risk stratification is required to ensure only infants with severe reactions will be admitted for vaccination.

PMID: 27770112 [PubMed - in process]



http://ift.tt/2dzQe2o

Global initiative for meticillin-resistant Staphylococcus aureus pneumonia (GLIMP): an international, observational cohort study.

http:--linkinghub.elsevier.com-ihub-imag Related Articles

Global initiative for meticillin-resistant Staphylococcus aureus pneumonia (GLIMP): an international, observational cohort study.

Lancet Infect Dis. 2016 Sep 1;:

Authors: Aliberti S, Reyes LF, Faverio P, Sotgiu G, Dore S, Rodriguez AH, Soni NJ, Restrepo MI, GLIMP investigators

Abstract
BACKGROUND: Antibiotic resistance is a major global health problem and pathogens such as meticillin-resistant Staphylococcus aureus (MRSA) have become of particular concern in the management of lower respiratory tract infections. However, few data are available on the worldwide prevalence and risk factors for MRSA pneumonia. We aimed to determine the point prevalence of MRSA pneumonia and identify specific MRSA risk factors in community-dwelling patients hospitalised with pneumonia.
METHODS: We did an international, multicentre study of community-dwelling, adult patients admitted to hospital with pneumonia who had microbiological tests taken within 24 h of presentation. We recruited investigators from 222 hospitals in 54 countries to gather point-prevalence data for all patients admitted with these characteristics during 4 days randomly selected during the months of March, April, May, and June in 2015. We assessed prevalence of MRSA pneumonia and associated risk factors through logistic regression analysis.
FINDINGS: 3702 patients hospitalised with pneumonia were enrolled, with 3193 patients receiving microbiological tests within 24 h of admission, forming the patient population. 1173 (37%) had at least one pathogen isolated (culture-positive population). The overall prevalence of confirmed MRSA pneumonia was 3·0% (n=95), with differing prevalence between continents and countries. Three risk factors were independently associated with MRSA pneumonia: previous MRSA infection or colonisation (odds ratio 6·21, 95% CI 3·25-11·85), recurrent skin infections (2·87, 1·10-7·45), and severe pneumonia disease (2·39, 1·55-3·68).
INTERPRETATION: This multicountry study shows low prevalence of MRSA pneumonia and specific MRSA risk factors among community-dwelling patients hospitalised with pneumonia.
FUNDING: None.

PMID: 27593581 [PubMed - as supplied by publisher]



http://ift.tt/2euCo7u

Schistosomal appendicitis in Kuwait A5-year study.

Schistosomal appendicitis in Kuwait A5-year study.

Int J Surg Case Rep. 2016 Oct 17;28:303-309

Authors: Abo-Alhassan F, Faras F, Malek YM, Joneja M, Dhar PM

Abstract
BACKGROUND: Appendicular schistosomiasis is an unusual etiology of acute appendicitis, which has been reported in countries endemic in schistosomiasis, such as sub-saharan Africa and South America. Nowadays, due to globalization, this disease has been diagnosed in non-endemic countries. Kuwait is a country possessing a larger percentage of foreigners than national citizens. Therefore, several cases of schistosomal appendicitis were found.
METHOD: The clinicopathological records of all patients that underwent appendectomy during January 2007 and December 2011 were recorded from the archives of Al-Adan Hospital in Kuwait. All cases of schistosomal appendicitis were retrieved and the histopathologic slides reconfirmed by the histopathologist.
RESULTS: During the 5-year study period, 3012 appendectomies were performed and 8 schistosomal appendicitis were found. They were all Egyptian males that were admitted for a clinical suspicion of acute appendicitis. The age ranged between 24 and 42 years, with a mean age of 32.75 years. All cases showed histological features of acute or acute suppurative inflammation, with ova seen in the vasculature of all layers of appendicular wall.
CONCLUSION: Although schistosomiasis is a rare causative agent of acute appendicitis, this however can't be confirmed until histological evaluation. Therefore, adequate follow up postoperatively is necessary to insure eradication of the disease and to prevent further serious consequences.

PMID: 27770739 [PubMed - as supplied by publisher]



http://ift.tt/2ejyIDG

Scrotal dartos-fascio-myo-cutaneous flaps for penis elongation after catastrophic iatrogenic skin shaft sub-amputation: A case of recovery using an extremely adaptable flap.

Scrotal dartos-fascio-myo-cutaneous flaps for penis elongation after catastrophic iatrogenic skin shaft sub-amputation: A case of recovery using an extremely adaptable flap.

Int J Surg Case Rep. 2016 Oct 15;28:300-302

Authors: Innocenti A, Tanini S, Mori F, Melita D, Innocenti M

Abstract
INTRODUCTION: Genitalia are linked to self-esteem and male sexual identity, especially among young men, who sometimes require a surgical procedure to acquire more confidence. Among the surgical procedures requested for aesthetical purposes, circumcision is one of the most popular. Although it can be considered to be a simple surgical practice, it may cause severe complications such as penile skin necrosis.
PRESENTATION OF CASE: We report a case of a catastrophic situation after a circumcision performed on a 27-year-old HIV positive man resulted in a drastic reduction in the length of the penile shaft due to extensive skin loss; this was subsequently restored using dartos-fascio-myo-cutaneous flaps. Primary healing occurred in 10days. No infection, dehiscence or flap ischemia were reported. Donor site morbidity was minimal. An adequate aesthetical appearance and satisfactory functional results were obtained.
DISCUSSION AND CONCLUSION: Various techniques are available for penile skin covering, such as skin grafts or cutaneous flaps. The skin of the scrotum seems to be the most suitable tissue to be used to reconstruct the skin covering of the shaft as it is the most similar. Dartos-fascio-myo-cutaneous flap is a single stage procedure that is easy and safe to perform. It can provide satisfactory cosmetic and functional results, offering a large amount of tissue, with minimal donor site morbidity.

PMID: 27770738 [PubMed - as supplied by publisher]



http://ift.tt/2eGTNpC

Surgical sponge forgotten for nine years in the abdomen: A case report.

Surgical sponge forgotten for nine years in the abdomen: A case report.

Int J Surg Case Rep. 2016 Oct 14;28:296-299

Authors: Susmallian S, Raskin B, Barnea R

Abstract
INTRODUCTION: Retained surgical sponge or other items in patients' bodies happens more frequently than is reported. Healthcare personnel can forget to remove textile material or instruments during complicated, extended, or emergency surgery. In addition, changes in the operating team can influence the occurrence of such errors.
PRESENTATION OF CASE: We present a case with a symptomatic gossypiboma nine years after a previous cesarean section. A 34-year-old woman was admitted to the emergency room having experienced abdominal pain and fever for the previous month. An abdominal computed tomography revealed an abscess in the lower abdomen. A laparotomy was performed, and a resection and block were carried out. A surgical sponge was extracted from an omental abscess.
DISCUSSION: Surgical sponges are the most common foreign materials retained (70%) in the abdominal cavity because of their frequent usage and small size. Moreover, a blood-soaked sponge in a hemorrhagic abdomen can be difficult to distinguish from blood.
CONCLUSION: Whenever the accounting for material depends on humans, mistakes will continue to be committed. A falsely correct sponge count was reported in 71.42% of cases [14]; therefore, a new count system must be developed for post-surgical situations.

PMID: 27770737 [PubMed - as supplied by publisher]



http://ift.tt/2ejxW9t

Efficacy of Water Resistance Therapy in Subjects Diagnosed With Behavioral Dysphonia: A Randomized Controlled Trial.

Efficacy of Water Resistance Therapy in Subjects Diagnosed With Behavioral Dysphonia: A Randomized Controlled Trial.

J Voice. 2016 Oct 18;:

Authors: Guzman M, Jara R, Olavarria C, Caceres P, Escuti G, Medina F, Medina L, Madrid S, Muñoz D, Laukkanen AM

Abstract
PURPOSE: The purpose of the present study was to determine the efficacy of water resistance therapy (WRT) in a long-term period of voice treatment in subjects diagnosed with voice disorders.
METHODS: Twenty participants, with behavioral dysphonia, were randomly assigned to one of two treatment groups: (1) voice treatment with WRT, and (2) voice treatment with tube phonation with the distal end in air (TPA). Before and after voice therapy, participants underwent aerodynamic, electroglottographic, acoustic, and auditory-perceptual assessments. The Voice Handicap Index and self-assessment of resonant voice quality were also performed. The treatment included eight voice therapy sessions. For the WRT group, the exercises consisted of a sequence of five phonatory tasks performed with a drinking straw submerged 5 cm into water. For the TPA, the exercises consisted of the same phonatory tasks, and all of them were performed into the same straw but the distal end was in air.
RESULTS: Wilcoxon test showed significant improvements for both groups for Voice Handicap Index (decrease), subglottic pressure (decrease), phonation threshold pressure (decrease), and self-perception of resonant voice quality (increase). Improvement in auditory-perceptual assessment was found only for the TPA group. No significant differences were found for any acoustic or electroglottographic variables. No significant differences were found between WRT and TPA groups for any variable.
CONCLUSIONS: WRT and TPA may improve voice function and self-perceived voice quality in individuals with behavioral dysphonia. No differences between these therapy protocols should be expected.

PMID: 27769697 [PubMed - as supplied by publisher]



http://ift.tt/2eGRNO3

Preferred reporting of case series in surgery; the PROCESS guidelines.

Preferred reporting of case series in surgery; the PROCESS guidelines.

Int J Surg. 2016 Oct 19;:

Authors: Agha RA, Fowler AJ, Rajmohan S, Barai I, Orgill DP, PROCESS Group

Abstract
INTRODUCTION: Case series have been a long held tradition within the surgical literature and are still frequently published. Reporting guidelines can improve transparency and reporting quality. No guideline exists for reporting case series and our recent systematic review highlights key data being missed from such reports. Our objective was to develop reporting guidelines for surgical case series.
METHODS: A Delphi consensus exercise was conducted to determine items to include in the reporting guideline. Items included those identified from a previous systematic review on case series and those included in the SCARE Guidelines for case reports. The Delphi questionnaire was administered via Google Forms and conducted using standard Delphi Methodology. A multidisciplinary group of surgeons and others with expertise in the reporting of case series were invited to participate. In round one, participants voted to define case series and also what elements should be included in them. In round two, participants voted on what items to include in the PROCESS guideline using a nine-point Likert scale to assess agreement as proposed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) working group.
RESULTS: In round one, there was a 49% (29/59) response rate. Following adjustment of the guideline with the incorporation of recommended changes, round two commenced and there was an 81% (48/59) response rate. All but one of the items were approved by the participants with Likert scores 7-9 awarded by >70% of respondents. The final guideline consists of an eight item checklist.
CONCLUSION: We present the PROCESS Guideline, consisting of an eight item checklist that will improve the reporting quality of surgical case series. We encourage authors, reviewers, editors, journals, publishers and the wider surgical and scholarly community to adopt these.

PMID: 27770639 [PubMed - as supplied by publisher]



http://ift.tt/2ecz5yD

Evaluation of the surgical outcome and complications of total laparoscopic hysterectomy in patients with enlarged uteruses.

Evaluation of the surgical outcome and complications of total laparoscopic hysterectomy in patients with enlarged uteruses.

Int J Surg. 2016 Oct 19;:

Authors: Terzi H, Hasdemir PS, Biler A, Kale A, Sendag F

Abstract
OBJECTIVE: The aim of this study was to investigate whether uterine weight has a deleterious effect on the operation time, complication rates, length of hospital stay and incidence of intraoperative haemorrhage during total laparoscopic hysterectomy operation.
METHODS: A total of 282 patients who underwent total laparoscopic hysterectomy for benign gynaecologic indications were retrospectively analyzed. The median operation time of 70 min was accepted as an index number, and a cut-off point of ≥300 g was calculated for uterine weight by using reciever operator characteristics (ROC) curve analysis.
RESULTS: There was no statistically significant relationship between the uterine weight and haemoglobin drop rate (1.27 ± 0.89 vs 1.21 ± 0.88, p = 0.905), complication rate (10.83% vs 9.26%, p = 0.062) and length of hospital stay (3.27 ± 1.23 vs 3.37 ± 1.35 days, p = 0.505) based on this cut. Lee-Huang point was preferred for abdominal entry in cases with uteruses reached the level of umbilicus -2 cm in physical examination.
CONCLUSIONS: Uterine weight was not effected the complication rate, estimated blood loss and length of hospital stay in total laparoscopic hysterectomy operation. A cut-off value of 300 g could be used for an increased operation time.

PMID: 27770638 [PubMed - as supplied by publisher]



http://ift.tt/2dyvjla

The efficacy of intraoperative autologous platelet gel in total knee arthroplasty: A meta-analysis.

The efficacy of intraoperative autologous platelet gel in total knee arthroplasty: A meta-analysis.

Int J Surg. 2016 Oct 19;:

Authors: Kuang MJ, Han C, Ma JX, Li F, Zhao J, Fu L, Ma XL

Abstract
PURPOSE: Autologous platelet gel, developed from fresh autologous blood, is a breakthrough in the promotion and acceleration of soft tissue and bone repair. The application of autologous platelet gel has been reported to improve haemostasis and promote function recovery. We screened the randomized controlled trials and controlled clinical trials of high quality to investigate whether autologous platelet gel makes a better performance for postoperative bleeding and functional recovery in patients after total knee arthroplasty.
METHOD: The Web of Science, the Cochrane Library, EMBASE, and PubMed databases were comprehensively searched. A total of 1234 patients with 1333 knees were included in the twelve studies. The PRISMA guidelines and Cochrane Handbook were applied to appraise the results published in all included studies. Review Manager 5.3 for Windows was used to analyse the extracted data.
RESULTS: Compared with the placebo group, the autologous platelet gel group showed a significant decrease in visual analogue scale. No significant differences were found in the drop of haemoglobin, knee society score, Western ontario mcmaster osteoarthritis index, length of hospital stay, postoperative narcotics, and range of motion during post-operative follow-up.
CONCLUSIONS: Compared with placebo, APG offers superior pain control after total knee arthroplasties. However, APG has no advantage in blood loss, functional recovery, postoperative narcotics and length of stay. The use of autologous platelet gel is not worthy of being recommended as a bioactive autologous material to improve the clinical outcomes in total knee arthroplasty patients.

PMID: 27770637 [PubMed - as supplied by publisher]



http://ift.tt/2etJTu0

Lugol's iodine in Graves' disease - Revisited.

Lugol's iodine in Graves' disease - Revisited.

Int J Surg. 2016 Oct 18;:

Authors: Reddy AC, Sabaretnam M

PMID: 27769925 [PubMed - as supplied by publisher]



http://ift.tt/2ecBXeN

Cryptococcosis mimicking lung carcinoma with brain metastases in an immunocompetent patient.

Cryptococcosis mimicking lung carcinoma with brain metastases in an immunocompetent patient.

J Clin Neurosci. 2016 Oct 18;:

Authors: Ang SY, Ng VW, Kumar SD, Low SY

Abstract
Cryptococcosis is a fungal infection caused by Cryptococcus spp. that enters the body via inhalation. This ubiquitous yeast has gained notoriety as an opportunistic pathogen in the immunosuppressed population. The authors report a case of a previously-well adult male presented with left-sided weakness. Imaging demonstrated a pulmonary mass and 2 contrast-enhancing intracranial lesions-all features suggestive of a primary lung carcinoma with brain metastases. However, further investigations confirmed disseminated cryptococcosis, without evidence of malignancy. The patient was successfully treated with a course of antifungals. To the authors' knowledge, this is the first reported case of dissemintated cryptococcosis in an immunocompetent adult male, simulating as primary lung carcinoma with brain metastases.

PMID: 27769644 [PubMed - as supplied by publisher]



http://ift.tt/2euEUuo

Gamma knife radiosurgery for residual or recurrent intracranial hemangiopericytomas.

Gamma knife radiosurgery for residual or recurrent intracranial hemangiopericytomas.

J Clin Neurosci. 2016 Oct 18;:

Authors: Kim BS, Kong DS, Seol HJ, Nam DH, Lee JI

Abstract
Residual or recurrent hemangiopericytoma (HPC) has been treated with radiosurgery; however, its long-term outcome is not well known. This study is to investigate the long-term outcome of gamma knife radiosurgery (GKS) for residual or recurrent HPCs. We conducted a retrospective analysis of 18 patients who underwent gamma knife radiosurgery for residual or recurrent HPCs. Of the 18 patients, 10 patients had high-grade HPCs (27 tumors) and 8 had low-grade HPCs (13 tumors). Median overall survival (OS) after the first GKS was 134.7months and actuarial survival rate at 1, 5, and 10years was 85.6%, 85.6%, and 37.4%, respectively. At the last follow-up, local tumor control was achieved in 32 (80.0%) of the 40 GKS-treated tumors. New lesions developed out of initial GKS target in 8 patients (44.4%). They were also treated with additional GKS. The actuarial local control rate of 40 tumors at 1-, 3-, and 5-years was 89.3%, 60.9%, and 37.5%, respectively. The median local recurrence-free interval of 40 tumors after initial GKS for each lesion was 86.1months for low-grade and 40.5months for high-grade tumors (p=0.010). Extracranial metastases developed in 7 (38.9%) patients with high-grade pathology and became a cause of death in 3 patients. Intracranial tumor control can be achieved over the long term, though additional GKS is frequently necessary. Extracranial metastasis is common in HPC of high-grade pathology. Close surveillance and aggressive treatment is recommended not only for intracranial tumor but also for possible extracranial metastases.

PMID: 27769643 [PubMed - as supplied by publisher]



http://ift.tt/2dzRdj9

COMT Val(158)Met polymorphism is associated with post-traumatic stress disorder and functional outcome following mild traumatic brain injury.

COMT Val(158)Met polymorphism is associated with post-traumatic stress disorder and functional outcome following mild traumatic brain injury.

J Clin Neurosci. 2016 Oct 18;:

Authors: Winkler EA, Yue JK, Ferguson AR, Temkin NR, Stein MB, Barber J, Yuh EL, Sharma S, Satris GG, McAllister TW, Rosand J, Sorani MD, Lingsma HF, Tarapore PE, Burchard EG, Hu D, Eng C, Wang KK, Mukherjee P, Okonkwo DO, Diaz-Arrastia R, Manley GT, TRACK-TBI Investigators

Abstract
Mild traumatic brain injury (mTBI) results in variable clinical trajectories and outcomes. The source of variability remains unclear, but may involve genetic variations, such as single nucleotide polymorphisms (SNPs). A SNP in catechol-o-methyltransferase (COMT) is suggested to influence development of post-traumatic stress disorder (PTSD), but its role in TBI remains unclear. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val(158)Met polymorphism is associated with PTSD and global functional outcome as measured by the PTSD Checklist - Civilian Version and Glasgow Outcome Scale Extended (GOSE), respectively. Results in 93 predominately Caucasian subjects with mTBI show that the COMT Met(158) allele is associated with lower incidence of PTSD (univariate odds ratio (OR) of 0.25, 95% CI [0.09-0.69]) and higher GOSE scores (univariate OR 2.87, 95% CI [1.20-6.86]) 6-months following injury. The COMT Val(158)Met genotype and PTSD association persists after controlling for race (multivariable OR of 0.29, 95% CI [0.10-0.83]) and pre-existing psychiatric disorders/substance abuse (multivariable OR of 0.32, 95% CI [0.11-0.97]). PTSD emerged as a strong predictor of poorer outcome on GOSE (multivariable OR 0.09, 95% CI [0.03-0.26]), which persists after controlling for age, GCS, and race. When accounting for PTSD in multivariable analysis, the association of COMT genotype and GOSE did not remain significant (multivariable OR 1.73, 95% CI [0.69-4.35]). Whether COMT genotype indirectly influences global functional outcome through PTSD remains to be determined and larger studies in more diverse populations are needed to confirm these findings.

PMID: 27769642 [PubMed - as supplied by publisher]



http://ift.tt/2euC7BH

3D printed complex tissue construct using stem cell-laden decellularized extracellular matrix bioinks for cardiac repair.

3D printed complex tissue construct using stem cell-laden decellularized extracellular matrix bioinks for cardiac repair.

Biomaterials. 2016 Oct 14;112:264-274

Authors: Jang J, Park HJ, Kim SW, Kim H, Park JY, Na SJ, Kim HJ, Park MN, Choi SH, Park SH, Kim SW, Kwon SM, Kim PJ, Cho DW

Abstract
Stem cell therapy is a promising therapeutic method for the treatment of ischemic heart diseases; however, some challenges prohibit the efficacy after cell delivery due to hostile microenvironment of the injured myocardium. 3D printed pre-vascularized stem cell patch can enhance the therapeutic efficacy for cardiac repair through promotion of rapid vascularization after patch transplantation. In this study, stem cell-laden decellularized extracellular matrix bioinks are used in 3D printing of pre-vascularized and functional multi-material structures. The printed structure composed of spatial patterning of dual stem cells improves cell-to-cell interactions and differentiation capability and promotes functionality for tissue regeneration. The developed stem cell patch promoted strong vascularization and tissue matrix formation in vivo. The patterned patch exhibited enhanced cardiac functions, reduced cardiac hypertrophy and fibrosis, increased migration from patch to the infarct area, neo-muscle and capillary formation along with improvements in cardiac functions. Therefore, pre-vascularized stem cell patch provides cardiac niche-like microenvironment, resulting in beneficial effects on cardiac repair.

PMID: 27770630 [PubMed - as supplied by publisher]



http://ift.tt/2dLJYIb

The potential role of amlodipine on experimentally induced bacterial rhinosinusitis.

The potential role of amlodipine on experimentally induced bacterial rhinosinusitis.

Braz J Otorhinolaryngol. 2016 Sep 28;:

Authors: Tatar A, Korkmaz M, Yayla M, Polat E, Uslu H, Halici Z, Parlak SN

Abstract
INTRODUCTION: For the treatment of rhinosinusitis antibiotics are used frequently. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of discovery of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity.
OBJECTIVE: In this study we aimed to investigate the potential role of amlodipine in treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation.
METHODS: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte (PMNL) infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione) and an oxidative product (malondialdehyde) were determined.
RESULTS: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline) and although not superior to cefazolin, amlodipine decreased PMNL infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups.
CONCLUSION: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.

PMID: 27769794 [PubMed - as supplied by publisher]



http://ift.tt/2ekjnVF

Shape of Thyroid Cartilage Influences Outcome of Montgomery Medialization Thyroplasty: A Gender Issue.

Shape of Thyroid Cartilage Influences Outcome of Montgomery Medialization Thyroplasty: A Gender Issue.

J Voice. 2016 Oct 18;:

Authors: Desuter G, Henrard S, Van Lith-Bijl JT, Amory A, Duprez T, van Benthem PP, Sjögren E

Abstract
OBJECTIVE: This study aimed to determine whether the shape of the thyroid cartilage and gender influence voice outcomes after a Montgomery thyroplasty implant system (MTIS).
METHODS: A retrospective cohort study was performed on 20 consecutive patients who underwent MTIS. Voice outcome variables were the relative decrease in Voice Handicap Index (%) and the absolute increase in maximum phonation time (MPT) (in seconds). Material variables were the angle between the thyroid cartilage laminae (α-angle), the size of the prosthesis, and a combination of both (the α-ratio). Continuous variables were analyzed using medians and were compared between groups using the Mann-Whitney U test. Factors associated with the outcome variables were assessed by multivariable linear regression. A Pearson coefficient was calculated between material variables.
RESULTS: The absolute increase in MPT between the pre- and postoperative period was significantly different between men and women, with a median absolute increase of 11.0 seconds for men and of 1.3 seconds for women (P < 0.001). A strong inverse correlation between the α-ratio and the absolute increase in MPT is observed in all patients, with a Pearson correlation coefficient R = -0.769 (P < 0.001). No factors were significantly associated with the relative Voice Handicap Index decrease in univariable or multivariable analyses. A better Pearson coefficient between the α-angle and the prosthesis size was found for females (0.8 vs 0.71).
CONCLUSION: The MTIS is a good thyroplasty modality for male patients, but inadequate design of MTIS female implants leads to poor MPT outcomes. This represents a gender issue that needs to be further studied and eventually tackled.

PMID: 27769698 [PubMed - as supplied by publisher]



http://ift.tt/2dywNfd

Empowering patients for radiation therapy safety: Results of the EMPATHY study.

Empowering patients for radiation therapy safety: Results of the EMPATHY study.

Cancer Radiother. 2016 Oct 18;:

Authors: Bibault JE, Pernet A, Mollo V, Gourdon L, Martin O, Giraud P

Abstract
PURPOSE: With the increase of treatment complexity, enhancing safety is a key concern in radiation oncology. Beyond the involvement of the healthcare professional, patient involvement and empowerment could play a major role in that setting. We explored how patients perceived and fulfilled that role during their radiation treatment.
MATERIALS AND METHODS: A voluntary and anonymous questionnaire was administered to all patients treated in our department between November 2013 and May 2014. The following data were collected: sociodemographic profile; information received and initiatives to search for additional information; behavior when an unusual treatment event was perceived; active involvement in the safety of the treatment; nature and perception of their own involvement. A statistical analysis was performed to assess behavioral predictors.
RESULTS: A total of 155 patients answered the survey. Most of them were treated for prostate (n=58, 37.4%), lung (n=27, 17.4%), head and neck (n=26, 16.8%) and breast (n=25, 16.1%). Only eight patients (5%) had previously received radiation therapy. Ninety-five percent of the patients estimated they had received enough information about their treatment, but 48% would have wanted more. When patients noticed an unusual event during their treatment session, most of them (61%) reported it to the radiation therapist.
CONCLUSION: Patient participation to radiation therapy safety should be encouraged to ensure a cooperative risk management. Healthcare professionals need to inform the patients on the basic technical processes involved in their treatment. Patient empowerment should be added to the verifications made by the radiation therapists and physicians but should not replace them.

PMID: 27769636 [PubMed - as supplied by publisher]



http://ift.tt/2eGp1vJ

Chondrosarcoma of the hyoid bone - Report of a case and a literature review of the suitable treatment strategy.

Chondrosarcoma of the hyoid bone - Report of a case and a literature review of the suitable treatment strategy.

Auris Nasus Larynx. 2016 Oct 18;:

Authors: Maki D, Mori T, Teshima M, Kobayashi K, Matsumoto F, Sakai A, Okami K, Yoshimoto S

Abstract
Chondrosarcoma is a rare malignant tumor occurring in the trunk and long bones. We present an extremely rare case of chondrosarcoma of the hyoid bone with clinical and pathological correlation and a literature review. We searched all cases of the hyoid chondrosarcoma in PubMed (MEDLINE) between 1990 and 2015. Eighteen cases were analyzed, including the present case. Most of them were low grade type. In 12 cases where intraoperative findings were recorded, no adhesion to the surrounding tissue was observed. Chondrosarcoma of the hyoid bone is usually low grade type, and there may be no invasion to the adjacent structures even if invasion is suspected by imaging findings. In order to preserve swallowing and laryngeal function, total hyoidectomy without laryngectomy should be indicated according to the intraoperative findings. Needle biopsy is an effective diagnostic technique, but open biopsy should be avoided to prevent the dissemination. To the best of our knowledge, this is the first presentation of hyoid bone chondrosarcoma with the investigation of intraoperative findings and pre-operative diagnostic modality.

PMID: 27769535 [PubMed - as supplied by publisher]



http://ift.tt/2eGpM8h

Elevated methylation of CMTM3 promoter in the male laryngeal squamous cell carcinoma patients.

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Elevated methylation of CMTM3 promoter in the male laryngeal squamous cell carcinoma patients.

Clin Biochem. 2016 Nov;49(16-17):1278-1282

Authors: Shen Z, Chen X, Li Q, Zhou C, Xu Y, Yu R, Ye H, Li J, Duan S

Abstract
OBJECTIVE: CKLF-like MARVEL transmembrane domain containing 3 (CMTM3), as a tumor suppressor gene, plays an important role in the suppression of cell growth and apoptosis. The goal of our study is to investigate the association between CMTM3 promoter methylation and laryngeal squamous cell carcinoma (LSCC).
DESIGN AND METHODS: Using the bisulfite pyrosequencing technology, DNA methylation levels of seven CpG sites in CMTM3 promoter are measured in tumor tissues and their adjacent tissues of 76 male LSCC patients.
RESULTS: Our results reveal a significantly elevated promoter methylation of CMTM3 in tumor tissues compared with their adjacent tissues (P<0.001). A breakdown analysis by age shows that significant association of CMTM3 promoter methylation with cancer risk is specific to the LSCC patients older than 55years (P<0.001) but not in the younger patients (P=0.305). Moreover, the association is only observed in the LSCC patients with smoking behavior (P=0.001). Breakdown analysis also shows that CMTM3 promoter methylation is associated with cancer risk among patients with stage I LSCC (P<0.001).
CONCLUSION: In conclusion, our study indicates that elevated CMTM3 methylation is a risk factor in male LSCC patients, especially in the patients with age over 55years and with smoking behavior.

PMID: 27521994 [PubMed - in process]



http://ift.tt/2dLHLMY

Nuclear p16INK4a expression predicts enhanced radiation response in head and neck cancers.

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Nuclear p16INK4a expression predicts enhanced radiation response in head and neck cancers.

Oncotarget. 2016 Jun 21;7(25):38785-38795

Authors: Dok R, Abbasi Asbagh L, Van Limbergen EJ, Sablina A, Nuyts S

Abstract
Immunohistochemistry analysis of p16INK4a in head and neck squamous cell carcinomas (HNSCC) tumor samples revealed that 28% of tumors showed nuclear/cytoplasmic p16INK4a localization, while 37% of tumors had cytoplasmic p16INK4a. Our previous study showed that p16INK4a inhibits the DNA repair response independently of its function in the cell cycle, suggesting that p16INK4a subcellular localization should be considered during stratification of HNSCC patients.Using p16INK4a mutants with different localization signals, we found that expression of nuclear p16INK4a, but not cytoplasmic p16INK4a impaired RAD51 foci formation, indicating that nuclear localization of p16INK4a is crucial for its function in DNA repair. We next investigated the role of p16INK4a subcellular localization in radiation response in a retrospective cohort of 261 HNSCC patients treated with chemoradiation. We found that only HNSCC patients expressing nuclear p16INK4a expression showed better outcome, locoregional control and disease free survival, after chemoradiation. In concordance with the patient data, only expression of nuclear p16INK4a increased radiosensitivity of HNSCC cells. These results implicate nuclear p16INK4a expression as a potent marker to predict radiation response of HNSCC patients and should be taken into account in intensification or de-escalation studies.

PMID: 27246975 [PubMed - in process]



http://ift.tt/2eGr1V2

Selective antitumor activity of roscovitine in head and neck cancer.

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Selective antitumor activity of roscovitine in head and neck cancer.

Oncotarget. 2016 Jun 21;7(25):38598-38611

Authors: Gary C, Hajek M, Biktasova A, Bellinger G, Yarbrough WG, Issaeva N

Abstract
Radiation and chemotherapy that are commonly used to treat human cancers damage cellular DNA. DNA damage appears to be more toxic to cancer cells than normal cells, most likely due to deregulated checkpoint activation and/or deficiency in DNA repair pathways that are characteristics of many tumors. However, unwanted side effects arise as a result of DNA damage to normal cells during the treatment.Here, we show that roscovitine, a cyclin-dependent kinase (CDK) inhibitor that inhibits CDK-1, CDK-2, CDK-5, CDK-7, and CDK-9 due to competitive binding to the ATP site on the kinases, causes significant DNA damage followed by p53-dependent cell death in human papilloma virus (HPV)-positive, but not in HPV-negative, head and neck cancer cells. Since HPV positivity was a molecular marker for increased sensitivity of cells to roscovitine, we reasoned that systemic roscovitine administration would not be toxic to healthy HPV-negative tissue. Indeed, low roscovitine doses significantly inhibited the growth of HPV-associated xenografted tumors in mice without causing any detectable side effects.Given that inhibition of CDKs has been shown to inhibit replication of several viruses, we suggest that roscovitine treatment may represent a selective and safe targeted therapeutic option against HPV-positive head and neck cancer.

PMID: 27233076 [PubMed - in process]



http://ift.tt/2dLHKbS

Blockade of MCP-1/CCR4 signaling-induced recruitment of activated regulatory cells evokes an antitumor immune response in head and neck squamous cell carcinoma.

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Blockade of MCP-1/CCR4 signaling-induced recruitment of activated regulatory cells evokes an antitumor immune response in head and neck squamous cell carcinoma.

Oncotarget. 2016 Jun 21;7(25):37714-37727

Authors: Sun W, Li WJ, Wei FQ, Wong TS, Lei WB, Zhu XL, Li J, Wen WP

Abstract
FoxP3+ regulatory T (Treg) cells have diverse functions in the suppression of antitumor immunity. We show that FoxP3hiCD45RA-CD4+ Treg cells [activated Treg (aTreg) cells] are the predominant cell population among tumor-infiltrating FoxP3+ T cells, and that high aTreg cell-infiltrating content is associated with reduced survival in patients with head and neck squamous cell carcinoma (HNSCC). In vitro studies have demonstrated that aTreg cells can suppress tumor-associated antigen (TAA) effector T cell immune responses in HNSCC. Moreover, C-C chemokine receptor 4 (CCR4) was specifically expressed by aTreg cells in the peripheral blood of HNSCC patients. Using a RayBiotech human chemokine antibody array, we showed that monocyte chemoattractant protein-1 (MCP-1), an endogenous CCR4-binding ligand, was specifically upregulated in the HNSCC microenvironment compared to the other four CCR4-binding ligands. Blocking MCP-1/CCR4 signaling-induced aTreg cell recruitment using a CCR4 antagonist evoked antitumor immunity in mice, and lead to inhibition of tumor growth and prolonged survival. Therefore, blocking aTreg cell trafficking in tumors using CCR4-binding agents may be an effective immunotherapy for HNSCC.

PMID: 27177223 [PubMed - in process]



http://ift.tt/2eGu3bA

"Oncotarget"[jour]; +121 new citations

121 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Oncotarget"[jour]

These pubmed results were generated on 2016/10/23

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.



http://ift.tt/2ekk01L

Leptin promotes epithelial-mesenchymal transition of breast cancer via the upregulation of pyruvate kinase M2.

Leptin promotes epithelial-mesenchymal transition of breast cancer via the upregulation of pyruvate kinase M2.

J Exp Clin Cancer Res. 2016 Oct 21;35(1):166

Authors: Wei L, Li K, Pang X, Guo B, Su M, Huang Y, Wang N, Ji F, Zhong C, Yang J, Zhang Z, Jiang Y, Liu Y, Chen T

Abstract
BACKGROUND: Accumulating researches have shown that epithelial-mesenchymal transition (EMT) contributes to tumor metastasis. Leptin, a key adipokine secreted from adipocytes, shapes the tumor microenvironment, potentiates the migration of breast cancer cells and angiogenesis, and is also involved in EMT. However, the potential mechanism remains unknown. This study aims to explore the effect of leptin on EMT in breast cancer cells and the underlying mechanism.
METHODS: With the assessment of EMT-associated marker expression in MCF-7, SK-BR-3, and MDA-MB-468 cells, the effect of leptin on breast cancer cells was analyzed. Besides, an array of pathway inhibitors as well as RNA interference targeting pyruvate kinase M2 (PKM2) were used to clarify the underlying mechanism of leptin-mediated EMT in vitro and in vivo.
RESULTS: The results demonstrated that leptin promoted breast cancer cells EMT, visibly activated the PI3K/AKT signaling pathway, and upregulated PKM2 expression. An antibody against the leptin receptor (anti-ObR) and the PI3K/AKT signaling pathway inhibitor LY294002 significantly abolished leptin-induced PKM2 expression and EMT-associated marker expression. SiRNA targeting PKM2 partially abolished leptin-induced migration, invasion, and EMT-associated marker expression. In vivo xenograft experiments indicated that RNA interference against PKM2 suppressed breast cancer growth and metastasis.
CONCLUSIONS: Our data suggest that leptin promotes EMT in breast cancer cells via the upregulation of PKM2 expression as well as activation of PI3K/AKT signaling pathway, and PKM2 might be one of the key points and potential targets for breast cancer therapy.

PMID: 27769315 [PubMed - in process]



http://ift.tt/2dyuj0l

Incorporation of Antiangiogenic Therapy Into the Non-Small-Cell Lung Cancer Paradigm.

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Incorporation of Antiangiogenic Therapy Into the Non-Small-Cell Lung Cancer Paradigm.

Clin Lung Cancer. 2016 Nov;17(6):493-506

Authors: Chu BF, Otterson GA

Abstract
Although molecular targeted agents have improved the treatment of lung cancer, their use has largely been restricted to limited subsets of the overall population that carry specific mutations. Angiogenesis, the formation of new blood vessels from existing networks, is an attractive, more general process for the development of targeted anticancer therapies, because it is critical for the growth of solid tumors, including non-small-cell lung cancer. Growing tissues require a vascular supply within a few millimeters. Therefore, solid tumors create a proangiogenic microenvironment to facilitate the development of new tumor-associated blood vessels, thus providing an adequate vascular supply for continued tumor growth. Antiangiogenic agents can specifically target the vascular endothelial growth factor (VEGF) signaling pathways, broadly inhibit multiple tyrosine kinases, or interfere with other angiogenic processes, such as disruption of existing tumor vasculature. The present report provides an overview of antiangiogenic therapy for non-small-cell lung cancer, including both currently approved antiangiogenic therapies (bevacizumab [anti-VEGF] and ramucirumab [anti-VEGF receptor 2] monoclonal antibodies), and a variety of promising novel agents in development. Although recent data have demonstrated promising efficacy for some novel agents, the overall development of antiangiogenic therapy has been hampered by redundancy in signaling pathways and the highly heterogeneous nature of tumors. An improved understanding of the molecular basis of angiogenesis will guide the development of new antiangiogenic therapies and the identification of biomarkers to predict which patients with lung cancer are most likely to benefit from antiangiogenic therapy.

PMID: 27381269 [PubMed - in process]



http://ift.tt/2ecxI32

Stochasticity in the Genotype-Phenotype Map: Implications for the Robustness and Persistence of Bet-Hedging.

Stochasticity in the Genotype-Phenotype Map: Implications for the Robustness and Persistence of Bet-Hedging.

Genetics. 2016 Oct 21;:

Authors: Nichol D, Robertson-Tessi M, Jeavons P, Anderson AR

Abstract
Non-genetic variation in phenotypes, or bet-hedging, has been observed as a driver of drug resistance in both bacterial infections and cancers. Here, we study how bet-hedging emerges in the genotype-phenotype mapping through a simple interaction model: a molecular switch. We use simple Chemical Reaction Networks to implement stochastic switches that map gene products to phenotypes and investigate the impact of structurally distinct mappings on the evolution of phenotypic heterogeneity. Bet-hedging naturally emerges within this model and is robust to evolutionary loss through mutations to both the expression of individual genes and to the network itself. This robustness explains an apparent paradox of bet-hedging - why does it persist in environments where natural selection necessarily acts to remove it? The structure of the underlying molecular mechanism, itself subject to selection, can slow the evolutionary loss of bet-hedging to ensure a survival mechanism against environmental catastrophes even when they are rare. Critically, these properties taken together have profound implications for the use of treatment-holidays to combat bet-hedging-driven resistant disease, as the efficacy of breaks from treatment will ultimately be determined by the structure of the genotype-phenotype mapping.

PMID: 27770034 [PubMed - as supplied by publisher]



http://ift.tt/2dyuid2

BRAF Exon 15 Mutations in Pediatric Renal Stromal Tumors: Prevalence in Metanephric Stromal Tumors.

BRAF Exon 15 Mutations in Pediatric Renal Stromal Tumors: Prevalence in Metanephric Stromal Tumors.

Hum Pathol. 2016 Oct 18;:

Authors: Marsden L, Jennings LJ, Gadd S, Yu M, Perlman EJ, Cajaiba MM

Abstract
Metanephric stromal tumors are rare renal stromal tumors that predominantly affect children. They belong to the metanephric family of tumors along with metanephric adenofibroma and metanephric adenoma. The previous documentation of BRAF exon 15 mutations in 88% of metanephric adenomas and in isolated cases of metanephric adenofibroma prompted us to investigate the prevalence of these mutations in metanephric stromal tumors and in other pediatric renal stromal tumors. In this study, 17 metanephric stromal tumors, 22 congenital mesoblastic nephromas and 6 ossifying renal tumors of infancy were selected for BRAF exon 15 testing. Tumor genomic DNA was extracted from formalin-fixed paraffin-embedded tissue, followed by PCR amplification and Sanger dideoxy sequencing with primers flanking the BRAF exon 15 gene. BRAF exon 15 mutations were found in 11/17 cases (65%) of metanephric stromal tumors, all corresponding to a thymidine to adenine substitution at codon 600 (BRAF V600E). All other renal stromal tumors tested were negative for BRAF exon 15 mutations. In conclusion, BRAF V600E mutations are encountered in the majority of metanephric stromal tumors, supporting a link with other metanephric tumors and suggesting a clonal event possibly affecting primordial renal cells. In addition, BRAF V600E mutations have been associated with oncogene-induced senescence in other benign tumors, providing clues to the pathogenesis of these neoplasms in keeping with their overall benign behavior. Our results also suggest a potential diagnostic use for BRAF exon 15 mutations in differentiating metanephric stromal tumors from other pediatric renal stromal tumors, particularly in limited samples.

PMID: 27769870 [PubMed - as supplied by publisher]



http://ift.tt/2ecxsRm

Shape of Thyroid Cartilage Influences Outcome of Montgomery Medialization Thyroplasty: A Gender Issue.

Shape of Thyroid Cartilage Influences Outcome of Montgomery Medialization Thyroplasty: A Gender Issue.

J Voice. 2016 Oct 18;:

Authors: Desuter G, Henrard S, Van Lith-Bijl JT, Amory A, Duprez T, van Benthem PP, Sjögren E

Abstract
OBJECTIVE: This study aimed to determine whether the shape of the thyroid cartilage and gender influence voice outcomes after a Montgomery thyroplasty implant system (MTIS).
METHODS: A retrospective cohort study was performed on 20 consecutive patients who underwent MTIS. Voice outcome variables were the relative decrease in Voice Handicap Index (%) and the absolute increase in maximum phonation time (MPT) (in seconds). Material variables were the angle between the thyroid cartilage laminae (α-angle), the size of the prosthesis, and a combination of both (the α-ratio). Continuous variables were analyzed using medians and were compared between groups using the Mann-Whitney U test. Factors associated with the outcome variables were assessed by multivariable linear regression. A Pearson coefficient was calculated between material variables.
RESULTS: The absolute increase in MPT between the pre- and postoperative period was significantly different between men and women, with a median absolute increase of 11.0 seconds for men and of 1.3 seconds for women (P < 0.001). A strong inverse correlation between the α-ratio and the absolute increase in MPT is observed in all patients, with a Pearson correlation coefficient R = -0.769 (P < 0.001). No factors were significantly associated with the relative Voice Handicap Index decrease in univariable or multivariable analyses. A better Pearson coefficient between the α-angle and the prosthesis size was found for females (0.8 vs 0.71).
CONCLUSION: The MTIS is a good thyroplasty modality for male patients, but inadequate design of MTIS female implants leads to poor MPT outcomes. This represents a gender issue that needs to be further studied and eventually tackled.

PMID: 27769698 [PubMed - as supplied by publisher]



http://ift.tt/2dywNfd

Chondrosarcoma of the hyoid bone - Report of a case and a literature review of the suitable treatment strategy.

Chondrosarcoma of the hyoid bone - Report of a case and a literature review of the suitable treatment strategy.

Auris Nasus Larynx. 2016 Oct 18;:

Authors: Maki D, Mori T, Teshima M, Kobayashi K, Matsumoto F, Sakai A, Okami K, Yoshimoto S

Abstract
Chondrosarcoma is a rare malignant tumor occurring in the trunk and long bones. We present an extremely rare case of chondrosarcoma of the hyoid bone with clinical and pathological correlation and a literature review. We searched all cases of the hyoid chondrosarcoma in PubMed (MEDLINE) between 1990 and 2015. Eighteen cases were analyzed, including the present case. Most of them were low grade type. In 12 cases where intraoperative findings were recorded, no adhesion to the surrounding tissue was observed. Chondrosarcoma of the hyoid bone is usually low grade type, and there may be no invasion to the adjacent structures even if invasion is suspected by imaging findings. In order to preserve swallowing and laryngeal function, total hyoidectomy without laryngectomy should be indicated according to the intraoperative findings. Needle biopsy is an effective diagnostic technique, but open biopsy should be avoided to prevent the dissemination. To the best of our knowledge, this is the first presentation of hyoid bone chondrosarcoma with the investigation of intraoperative findings and pre-operative diagnostic modality.

PMID: 27769535 [PubMed - as supplied by publisher]



http://ift.tt/2eGpM8h

Comparison of nerve combing and percutaneous radiofrequency thermocoagulation in the treatment for idiopathic trigeminal neuralgia.

Comparison of nerve combing and percutaneous radiofrequency thermocoagulation in the treatment for idiopathic trigeminal neuralgia.

Braz J Otorhinolaryngol. 2016 Sep 27;:

Authors: Du Y, Yu W

PMID: 27769795 [PubMed - as supplied by publisher]



http://ift.tt/2euzT5e

The potential role of amlodipine on experimentally induced bacterial rhinosinusitis.

The potential role of amlodipine on experimentally induced bacterial rhinosinusitis.

Braz J Otorhinolaryngol. 2016 Sep 28;:

Authors: Tatar A, Korkmaz M, Yayla M, Polat E, Uslu H, Halici Z, Parlak SN

Abstract
INTRODUCTION: For the treatment of rhinosinusitis antibiotics are used frequently. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of discovery of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity.
OBJECTIVE: In this study we aimed to investigate the potential role of amlodipine in treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation.
METHODS: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte (PMNL) infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione) and an oxidative product (malondialdehyde) were determined.
RESULTS: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline) and although not superior to cefazolin, amlodipine decreased PMNL infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups.
CONCLUSION: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.

PMID: 27769794 [PubMed - as supplied by publisher]



http://ift.tt/2ekjnVF

[Cerebral infarction after pituitary apoplexy: Description of a case and review of the literature].

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[Cerebral infarction after pituitary apoplexy: Description of a case and review of the literature].

Neurocirugia (Astur). 2016 Nov - Dec;27(6):310-314

Authors: Serramito García R, Santín Amo JM, Román Pena P, Pita Buezas L, González Gómez L, García Allut A

Abstract
Pituitary apoplexy is usually the result of hemorrhagic infarction in a pituitary adenoma. The clinical presentation varies widely and includes asymptomatic cases, classical pituitary apoplexy and even sudden death. Cerebral ischemia due to pituitary apoplexy is very rare. It may be caused by vasospasm or direct compression of cerebral vessels by the tumor. We report a case of pituitary apoplexy associated with cerebral infarction and discuss the relationship between the two events.

PMID: 27265252 [PubMed - in process]



http://ift.tt/2e0bq2z

[Cerebral infarction after pituitary apoplexy: Description of a case and review of the literature].

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[Cerebral infarction after pituitary apoplexy: Description of a case and review of the literature].

Neurocirugia (Astur). 2016 Nov - Dec;27(6):310-314

Authors: Serramito García R, Santín Amo JM, Román Pena P, Pita Buezas L, González Gómez L, García Allut A

Abstract
Pituitary apoplexy is usually the result of hemorrhagic infarction in a pituitary adenoma. The clinical presentation varies widely and includes asymptomatic cases, classical pituitary apoplexy and even sudden death. Cerebral ischemia due to pituitary apoplexy is very rare. It may be caused by vasospasm or direct compression of cerebral vessels by the tumor. We report a case of pituitary apoplexy associated with cerebral infarction and discuss the relationship between the two events.

PMID: 27265252 [PubMed - in process]



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Genetic landscape of T- and NK-cell post-transplant lymphoproliferative disorders.

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Genetic landscape of T- and NK-cell post-transplant lymphoproliferative disorders.

Oncotarget. 2016 Jun 21;7(25):37636-37648

Authors: Margolskee E, Jobanputra V, Jain P, Chen J, Ganapathi K, Nahum O, Levy B, Morscio J, Murty V, Tousseyn T, Alobeid B, Mansukhani M, Bhagat G

Abstract
Post-transplant lymphoproliferative disorders of T- or NK-cell origin (T/NK-PTLD) are rare entities and their genetic basis is unclear. We performed targeted sequencing of 465 cancer-related genes and high-resolution copy number analysis in 17 T-PTLD and 2 NK-PTLD cases. Overall, 377 variants were detected, with an average of 20 variants per case. Mutations of epigenetic modifier genes (TET2, KMT2C, KMT2D, DNMT3A, ARID1B, ARID2, KDM6B, n=11). and inactivation of TP53 by mutation and/or deletion(n=6) were the most frequent alterations, seen across disease subtypes, followed by mutations of JAK/STAT pathway genes (n=5). Novel variants, including mutations in TBX3 (n=3), MED12 (n=3) and MTOR (n=1), were observed as well. High-level microsatellite instability was seen in 1 of 14 (7%) cases, which had a heterozygous PMS2 mutation. Complex copy number changes were detected in 8 of 16 (50%) cases and disease subtype-specific aberrations were also identified. In contrast to B-cell PTLDs, the molecular and genomic alterations observed in T/NK-PTLD appear similar to those reported for peripheral T-cell lymphomas occurring in immunocompetent hosts, which may suggest common genetic mechanisms of lymphoma development.

PMID: 27203213 [PubMed - in process]



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Frequent overexpression of PDK1 in primary nasopharyngeal carcinoma is associated with poor prognosis

Publication date: Available online 20 October 2016
Source:Pathology - Research and Practice
Author(s): Guangzao Xiang, Xianhui Li, Longhe Cao, Chuansai Zhu, Zhijian Dai, Shenhua Pan, Sen Lin
ObjectivePyruvate dehydrogenase kinase 1 (PDK1) is reported to be up-regulated and play multiple functions in several cancers. Herein, we investigated its roles in primary nasopharyngeal carcinoma.MethodsExpression of PDK1 protein was examined by immunohistochemical staining in 102 samples of primary nasopharyngeal carcinoma (pNPC) and 31 samples of chronic nasopharyngitis. The relationships of PDK1 expression levels with clinical features and prognosis in NPC patients were analyzed.ResultsPDK1 protein expression was significantly greater in pNPC tissues than in the chronic nasopharyngitis tissues (P<0.01). In addition, overexpression of PDK1 was associated with advanced clinical stage (P<0.01), advanced N classification (P=0.024), and distant metastasis (P=0.048). Kaplan–Meier survival analysis demonstrated that patients with higher PDK1 expression had significantly shorter overall survival (P=0.006), disease-free survival (P=0.015), loco-regional relapse-free survival (P=0.008), and distant metastasis-free survival (P=0.017). Furthermore, multi-variate analysis showed that PDK1 expression was an independent prognostic factor in pNPC patients.ConclusionPDK1 is frequently upregulated in pNPC and may serve as a prognostic marker.



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EPSTEIN BARR VIRUS HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS RELATED TO RITUXIMAB USE AND IMMUNOPATHOGENETIC INSIGHTS

Publication date: Available online 17 October 2016
Source:Pathology - Research and Practice
Author(s): Sotirios G. Papageorgiou, Sotirios Tsiodras, Georgios Siakallis, Efthimia Bazani, Aris Spathis, Garyfalia Poulakou, Penelope Korkolopoulou, Ioannis Panayiotides, Vasiliki Pappa
Anti-CD20-based chemo-immunotherapeutic regimens have been suggested to assist in the management of Epstein-Barr virus (EBV)-induced hemophagocytic lymphohistiocytosis (HLH) and EBV-associated post-transplant lymphoproliferative disorders (EBV-PTLD), by reducing EBV viral load and EBV-induced inflammation.Herein we report a fatal EBV-related HLH in the context of Hodgkin lymphoma (HL)-like Richter's transformation of B chronic lymphocytic leukemia (B-CLL), two months after rituximab treatment. The complex balance between EBV driven T-cell stimulation and immunosuppressive therapy in the context of multiple immune deficits is discussed.



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Primary cardiac B cell lymphoma: Manifestation of Felty’s syndrome or TNFα antagonist

Publication date: Available online 17 October 2016
Source:Pathology - Research and Practice
Author(s): Nazim Benzerdjeb, Fatima Ameur, Jean-Fortune Ikoli, Henri Sevestre
Primary cardiac B cell lymphoma is rare. To date, fewer than 90 cases have been described in the literature. We report a 67-year-old woman with a 30-year history of rheumatoid arthritis, who had received treatment with leflunomide for 10 years and infliximab for 2 years. Secondary Felty's syndrome appeared. She was admitted to the hospital for abdominal pain. Investigations disclosed a 5cm cardiac mass in the right atrium. Histopathologic examination of tissue specimens obtained at surgical myocardial biopsy demonstrated primary cardiac B cell lymphoma. The other iatrogenic lymphoproliferative disorders are reviewed. This lesion might be a manifestation of long term TNFα antagonists treatment.



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Solid-Pseudopapillary Neoplasm of the Pancreas: a Clinicopathological Review of 20 Cases Including Rare Examples

Publication date: Available online 21 October 2016
Source:Pathology - Research and Practice
Author(s): Ayca Ersen, Anil Aysal Agalar, Erdener Ozer, Cihan Agalar, Tarkan Unek, Tufan Egeli, Mucahit Ozbilgin, Ibrahim Astarcioglu, Mustafa Olguner, Funda Obuz, Ozgul Sagol
AimsSolid-pseudopapillary neoplasm (SPN) is an uncommon malignant tumor of the pancreas with a favorable prognosis unlike other pancreatic neoplasms. We investigated the clinicopathological features of 20 patients with SPN in details.MethodsThe patients diagnosed as SPN in Dokuz Eylul University Hospital between January 2005 and March 2016 were reviewed in terms of clinical and histopathological data.ResultsMean age of the patients was 33. Three of our cases were male and 4 were children. Some patients had synchronuous malignancies. Nine patients were diagnosed by fine needle aspiration cytology (FNAC). One of our tumors had 2×1mm of pancreas endocrine neoplasm in addition to SPN. One case had foci of atypical and multinucleated giant cells. All cases were positive for vimentin and CD10 antibodies and most were positive for PR and β-catenin. The mean follow-up duration was 40 mo (range 2-110 mo). Only one case showed liver metastasis.ConclusionHerein we present a series of 20 patients with 3 male and 4 pediatric cases, almost half of which were diagnosed with FNAC findings, and most of which are clinically being followed with one patient showing progression. Our series includes rare examples like collision tumor of SPN and pancreas endocrine neoplasm, SPN with multinucleated giant cells. Also cases with no surgical treatment and no progression, as well as cases with synchronous malignancies are presented. We believe that FNAC findings of any pancreatic mass should be investigated in detail for the designation of a therapy plan especially for the patients with high operation risks. The findings in our series also show that extensive necrosis, angioinvasion, perineurial invasion and larger tumor size might be predictive for worse prognosis and these patients should be more closely followed up.



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Impact of pharmacists as immunizers on vaccination rates: A systematic review and meta-analysis

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Publication date: 11 November 2016
Source:Vaccine, Volume 34, Issue 47
Author(s): J.E. Isenor, N.T. Edwards, T.A. Alia, K.L. Slayter, D.M. MacDougall, S.A. McNeil, S.K. Bowles
BackgroundUnderutilization of vaccination programs remains a significant public health concern. Pharmacists serve as educators, facilitators, and in some jurisdictions, as administrators of vaccines. Though pharmacists have been involved with immunizations in various ways for many years, there has yet to be a systematic review assessing the impact of pharmacists as immunizers in these three roles.ObjectiveTo complete a systematic review of the literature on the impact of pharmacists as educators, facilitators, and administrators of vaccines on immunization rates.MethodsWe identified 2825 articles searching the following databases from inception until October 2015: PubMed, EMBASE, Cochrane Libraries, Cumulative Index to Nursing and Allied Health Literature, International Pharmaceutical Abstracts, Google Scholar. Grey literature was identified through use of the Canadian Agency for Drugs and Technology in Health "Grey Matters" search tool. Content from relevant journals and references of included studies were also searched. Inclusion criteria were clinical or epidemiologic studies in which pharmacists were involved in the immunization process. Studies were excluded if no comparator was reported. Two reviewers independently completed data extraction and bias assessments using standardized forms.ResultsThirty-six studies were included in the review, 22 assessed the role of pharmacists as educators and/or facilitators and 14 assessed their role as administrators of vaccines. All studies reviewed found an increase in vaccine coverage when pharmacists were involved in the immunization process, regardless of role (educator, facilitator, administrator) or vaccine administered (e.g., influenza, pneumococcal), when compared to vaccine provision by traditional providers without pharmacist involvement. Limitations of the results include the large number of non-randomized trials and the heterogeneity between study designs.ConclusionsPharmacist involvement in immunization, whether as educators, facilitators, or administrators of vaccines, resulted in increased uptake of immunizations.PROSPERO Registration: CRD42013005067.



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Editorial Board/Aims and Scope

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Publication date: 11 November 2016
Source:Vaccine, Volume 34, Issue 47





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A comparison of language use in pro- and anti-vaccination comments in response to a high profile Facebook post,

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Publication date: 11 November 2016
Source:Vaccine, Volume 34, Issue 47
Author(s): Kate Faasse, Casey J. Chatman, Leslie R. Martin
BackgroundVaccinations are important for controlling the spread of disease, yet an increasing number of people are distrustful of vaccines, and choose not to (fully) vaccinate themselves and their children. One proposed contributor to this distrust is anti-vaccination misinformation available on the internet, where people search for and discuss health information. The language people use in these discussions can provide insights into views about vaccination.MethodsFollowing a prominent Facebook post about childhood vaccination, language used by participants in a comment thread was analysed using LIWC (Linguistic Inquiry and Word Count). Percentage of words used across a number of categories was compared between pro-vaccination, anti-vaccination, and unrelated (control) comments.ResultsBoth pro- and anti-vaccination comments used more risk-related and causation words, as well as fewer positive emotion words compared to control comments. Anti-vaccine comments were typified by greater analytical thinking, lower authenticity, more body and health references, and a higher percentage of work-related word use in comparison to pro-vaccine comments, plus more money references than control comments. In contrast, pro-vaccination comments were more authentic, somewhat more tentative, and evidenced higher anxiety words, as well as more references to family and social processes when compared to anti-vaccination comments.ConclusionAlthough the anti-vaccination stance is not scientifically-based, comments showed evidence of greater analytical thinking, and more references to health and the body. In contrast, pro-vaccination comments demonstrated greater comparative anxiety, with a particular focus on family and social processes. These results may be indicative of the relative salience of these issues and emotions in differing understandings of the benefits and risks of vaccination. Text-based analysis is a potentially useful and ecologically valid tool for assessing perceptions of health issues, and may provide unique information about particular concerns or arguments expressed on social media that could inform future interventions.



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