Σάββατο, 1 Ιουλίου 2017

Epinephrine use for anaphylaxis: Too seldom, too late

During the past 20 years, food allergy has dramatically increased, with a concomitant increased risk for anaphylaxis.1 Anaphylaxis is “a serious allergic reaction that is rapid in onset and may cause death.”2 Foods are one of the common causes of anaphylaxis3 over medications and insect stings, and food allergy has become a worldwide concern. Anaphylaxis is inadequately treated most of the time4 because of inconsistent signs and symptoms; anaphylaxis can manifest differently in the same person, even when triggered by the same allergen.

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Effects of allergen sensitization on response to therapy in children with eosinophilic esophagitis

In children with eosinophilic esophagitis (EoE) foods are the most common disease triggers, but environmental allergens are also suspected culprits.

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Utility of somatosensory evoked potentials in the assessment of response to IVIG in a long-lasting case of chronic immune sensory polyradiculopathy

Chronic immune sensory polyradiculopathy (CISP) identifies a progressive acquired peripheral dysimmune neuropathy recognized as a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) variant. We de...

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Table of Contents

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Publication date: July–August 2017
Source:American Journal of Otolaryngology, Volume 38, Issue 4





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Guidelines for Contributing Authors

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Publication date: July–August 2017
Source:American Journal of Otolaryngology, Volume 38, Issue 4





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Editorial Board

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Publication date: July–August 2017
Source:American Journal of Otolaryngology, Volume 38, Issue 4





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Evaluation of laser fluorescence in monitoring non-cavitated caries lesion progression on smooth surfaces in vitro

Abstract

The aim of this study was to evaluate the performance of a pen-type laser fluorescence (LF) device (LFpen: DIAGNOdent pen) to detect and monitor the progression of caries-like lesions on smooth surfaces. Fifty-two bovine enamel blocks were submitted to three different demineralisation cycles for caries-like lesion induction using Streptococcus mutans, Lactobacillus casei and Actinomyces naeslundii. At baseline and after each cycle, the enamel blocks were analysed under Knoop surface micro-hardness (SMH) and an LFpen. One enamel block after each cycle was randomly chosen for Raman spectroscopy analysis. Cross-sectional micro-hardness (CSMH) was performed at different depths (20, 40, 60, 80 and 100 μm) in 26 enamel blocks after the second cycle and 26 enamel blocks after the third cycle. Average values of SMH (± standard deviation (SD)) were 319.3 (± 21.5), 80.5 (± 31.9), 39.8 (± 12.7), and 29.77 (± 10.34) at baseline and after the first, second and third cycles, respectively. Statistical significant difference was found among all periods (p < 0.01). The LFpen values were 4.3 (± 1.5), 7.5 (± 9.4), 7.1 (± 7.1) and 5.10 (± 3.58) at baseline and after the first, second, and third cycles, respectively, among all periods (p < 0.05). The CSMH values after the second and third cycles at 20, 40, 60, 80 and 100 μm were 182.8 (± 69.8), 226.1 (± 79.6), 247.20 (± 69.36), 262.35 (± 66.36) and 268.45 (± 65.49), and for the third cycle were 193.7 (± 73.4), 239.5 (± 81.5), 262.64 (± 82.46), 287.10 (± 78.44) and 284.79 (± 72.63) (n = 24 and 23), respectively. No correlation was observed between the LFpen and SMH values (p > 0.05). One sample of each cycle was characterised through Raman spectroscopy analysis. It can be concluded that LF was effective in detecting the first demineralisation on enamel; however, the method did not show any effect in monitoring lesion progression after three cycles of in vitro demineralisation.



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Speech–language pathology in paediatric palliative care: A scoping review of role and practice

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Fluency adaptation in speakers with Parkinson disease: a motor learning perspective

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Radiothérapie stéréotaxique hypofractionnée des métastases surrénaliennes

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Publication date: Available online 30 June 2017
Source:Cancer/Radiothérapie
Author(s): G. Dupic, J. Biau, A. Bellière-Calandry, M. Lapeyre




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Radiothérapie stéréotaxique hypofractionnée des métastases surrénaliennes

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Publication date: Available online 30 June 2017
Source:Cancer/Radiothérapie
Author(s): G. Dupic, J. Biau, A. Bellière-Calandry, M. Lapeyre




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Role of an Autoinducer-2-like Molecule from Veillonella tobetsuensis in Streptococcus gordonii Biofilm Formation

Publication date: Available online 1 July 2017
Source:Journal of Oral Biosciences
Author(s): Izumi Mashima, Futoshi Nakazawa
ObjectivesDental plaque is a multispecies biofilm that causes dental caries and periodontal diseases. In particular, Streptococcus spp. and Veillonella spp. have been identified as early colonizers of oral biofilms. Coaggregation of bacterial species and/or autoinducers using the quorum sensing system has been suggested to plan an important role in biofilm formation. In our previous study, we showed that Veillonella tobetsuensis clearly promoted the development of Streptococcus gordonii biofilms. To clarify the mechanism, coaggregation between S. gordonii and V. tobetsuensis and the effect of an autoinducer-like molecule were investigated in this study.MethodsThe coaggregation assay was performed according to a previously reported method. AI-2-like molecule was detected by a Vibrio harveyi BB170 reporter assay. After partial purification, the effect of the AI-2-like molecule on S. gordonii biofilm formation was examined using the wire method.ResultsNo coaggregation between S. gordonii and V. tobetsuensis was observed. An AI-2-like molecule was detected in large amounts in the culture supernatant of V. tobetsuensis in the mid-exponential growth phase. In addition, the AI-2-like molecule produced by V. tobetsuensis significantly inhibited S. gordonii biofilm formation.ConclusionsThese results suggest that an AI-2-like molecule from V. tobetsuensis is a potential inhibitor of the development of S. gordonii biofilms and could be used for the prevention of early-stage oral biofilm formation. However, the V. tobetsuensis factors that promote the development of S. gordonii biofilms will need to be explored in future studies.



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Circadian Clock and Bone Biology

Publication date: Available online 1 July 2017
Source:Journal of Oral Biosciences
Author(s): Takao Hirai
BackgroundMany metabolic and physiological processes display circadian oscillations that are controlled by the internal circadian clock system. A molecular clock system is generated by the transcriptional-translational feedback loops of clock genes. Circadian oscillators reside in peripheral tissues where they receive timing cues from the central clock in the suprachiasmatic nucleus (SCN). Circadian rhythms have also been identified in bone and cartilage.HighlightRecent findings demonstrated that bone metabolic functions of the major cell types namely osteoblasts, chondrocytes, and osteoclasts, are closely related to an intrinsic biological rhythm, named the circadian clock. Several studies have also shown that clock genes play significant roles in bone formation and resorption. Adrenergic receptor signaling in osteoblasts was previously reported to synchronize clock genes as well as genes that are important for osteoblast function such as Ptgs2 gene encoding prostaglandin G/H synthetase 2, which is a late-limiting enzyme for prostaglandin synthesis. Since the circadian clock regulates key molecules in cellular functions of osteoblasts and osteoclasts, this system may be closely involved in the cellular functions associated with bone remodeling.ConclusionThis review focuses on the latest knowledge on the molecular mechanisms of biological clocks and their roles in bone biology, indicating the potential of this clock system in the treatment of bone disorders.



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Apparent diffusion coefficient as it relates to histopathology findings in post-chemotherapy nephroblastoma: a feasibility study

Abstract

Background

Nephroblastomas represent a group of heterogeneous tumours with variable proportions of distinct histopathological components.

Objective

The purpose of this study was to investigate whether direct comparison of apparent diffusion coefficient (ADC) measurements with post-resection histopathology subtypes is feasible and whether ADC metrics are related to histopathological components.

Materials and methods

Twenty-three children were eligible for inclusion in this retrospective study. All children had MRI including diffusion-weighted imaging (DWI) after preoperative chemotherapy, just before tumour resection. A pathologist and radiologist identified corresponding slices at MRI and postoperative specimens using tumour morphology, the upper/lower calyx and hilar vessels as reference points. An experienced reader performed ADC measurements, excluding non-enhancing areas. A pathologist reviewed the corresponding postoperative slides according to the international standard guidelines. We tested potential associations with the Spearman rank test.

Results

Side-by-side comparison of MRI–DWI with corresponding histopathology slides was feasible in 15 transverse slices in 9 lesions in 8 patients. Most exclusions were related to extensive areas of necrosis/haemorrhage. In one lesion correlation was not possible because of the different orientation of sectioning of the specimen and MRI slices. The 25% ADC showed a strong relationship with percentage of blastema (Spearman rho=−0.71, P=0.003), whereas median ADC was strongly related to the percentage stroma (Spearman rho=0.74, P=0.002) at histopathology.

Conclusion

Side-by-side comparison of MRI–DWI and histopathology is feasible in the majority of patients who do not have massive necrosis and hemorrhage. Blastemal and stromal components have a strong linear relationship with ADC markers.



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The terminal latency of the phrenic nerve correlates with respiratory symptoms in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease that involves limb, axial, bulbar, and respiratory muscles.(Haverkamp et al., 1995) Weakness and fatigue of the respiratory muscles eventually induce respiratory insufficiency, which is the main cause of death in this disease.(Haverkamp et al., 1995) Since respiratory function is an important factor influencing the survival of patients with ALS,(Lechtzin et al., 2001; Lechtzin et al., 2007) its assessment is essential for monitoring disease progression and determining the timing for non-invasive ventilation that is proven to increase the survival and quality of life of patients with ALS.(Bourke et al., 2006; Andersen et al., 2007) Generally, forced vital capacity (FVC) has been suggested to be a prognostic factor for ALS.(Fallat et al., 1979; Czaplinski et al., 2006) In patients with ALS with bulbar symptoms, however, respiratory function tests, such as FVC, are not always reliable in practice; these patients have weak lip seal that impairs the accurate evaluation of their respiratory function.(Pinto et al., 2009) Moreover, assessment of respiratory function depends on cooperation, which is difficult to obtain in patients who are less motivated, depressed, or have behavioral changes as commonly observed in patients with ALS.(Phukan et al., 2007)

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SCOPE-mTL: a non-invasive tool for identifying and lateralizing mesial temporal lobe seizures prior to scalp EEG ictal onset

The first phase in epilepsy presurgical evaluation uses scalp EEG monitoring to record seizures, with the intent of lateralizing and localizing the seizure onset zone. While scalp EEG is non-invasive and cost-effective, several drawbacks frequently hamper interpretation of these recordings. First, scalp EEG recordings are prone to extracerebral artifacts. Myogenic artifacts at the start of a seizure can obscure cerebral activity, making it difficult to lateralize or localize seizure onsets. Second, scalp EEG has poor sensitivity for deep brain structures.

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“Forgotten” Chapters in the History of Transcervical Sterilization: Carl Clauberg and Hans-Joachim Lindemann

Abstract
Transcervical sterilization is a non-surgical method of permanent female sterilization that is widely used and critically discussed. A review of the historiography of the method reveals that instances of its coercive use are not included in the historical account. This study offers a reexamination of the work of Carl Clauberg and Hans-Joachim Lindemann, to more deeply contextualize within the framework of current usage the coercive use of transcervical sterilization during the Third Reich and in postwar Germany. This inquiry is based on postwar criminal trial records on Clauberg, and on archival documents detailing Lindemann’s activities in 1979. A comparative analysis examines arguments by medical historian Karl-Heinz Roth, and identifies shared characteristics and differences between Clauberg and Lindemann, their methods and scientific connections. The results demonstrate that the technique of transcervical sterilization has an abusive potential that may be explained as a function of the person of the physician, of the scientific method itself, and of societal and political influences. The analysis supports the argument that insights from the cases of Clauberg and Lindemann are transferrable geographically and over time, and have the potential to inform current medical practice, such as transcervical sterilization with the Essure device, whose historiographic exploration remains a desideratum.

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“His Native, Hot Country” 1 : Racial Science and Environment in Antebellum American Medical Thought

Abstract
Relying on a close reading of more than 4,000 medicals student theses, this essay explores the evolving medical approaches to race and environment in the early national and antebellum United States and highlights the role that medical school pedagogy played in disseminating and elaborating racial theory. Specifically, it considers the influence of racial science on medical concepts of the relationship of bodies to climates. At their core, monogenesis—belief in a single, unified human race—and polygenesis—the belief that each race was created separately—were theories about the human body’s connections to the natural world. As polygenesis became influential in Atlantic medical thought, physicians saw environmental treatments as a matter of matching bodies to their natural ecology. In the first decades of the nineteenth century, Atlantic physicians understood bodies and places as in constant states of flux. Through proper treatment, people and environments could suffer either degradation or improvement. Practitioners saw African Americans and whites as the same species with their differences being largely superficial and produced by climate. However, by the 1830s and 1840s medical students were learning that each race was inherently different and unalterable by time or temperature. In this paradigm, medical students articulated a vision of racial health rooted in organic relationships between bodies and climates.

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“Enquire into All the Circumstances of the Patient Narrowly”: John Rutherford’s Clinical Lectures in Edinburgh, 1749–53

Abstract
Early eighteenth-century Edinburgh provided a unique learning environment for aspiring practitioners: one in which the unity of medicine and surgery was appreciated and clinical observations and a reasoning practitioner became the well spring of proper patient care. John Rutherford, a surgical apprentice in this environment, student on the wards of London hospitals and under Boerhaave at Leiden, became one of the original medical professors at the University of Edinburgh medical school in 1726. Rutherford taught the popular, theory-based Practice of Medicine for twenty-two years. Then at the end of 1748 he convinced Royal Infirmary of Edinburgh managers to allow him to begin a new lecture series, entitled Clinical Lectures, conducted at the patient's bedside. Pedagogically, the new lecture series integrated medical theory and its application on the ward. Pragmatically, Rutherford used the Clinical Lectures to transition students into practitioners. He oriented the student to the medical profession at large and placed him simultaneously at the patient-disease-physician interface. He taught that systematic patient observation and examination, when combined with experience and reasoning, were essential to accurate diagnoses and proper therapeutic interventions. Importantly too, Rutherford prepared his students for failure through humility, introspection, and the speculative nature of medical practice.

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“One Simply Doesn’t Arbitrate Authorship of Thoughts”: Socialized Medicine, Medical McCarthyism, and the Publishing of Rural Health and Medical Care (1948)

Rural Health and Medical CareFrederick Dodge MottMilton I. Roemersocialized medicine

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Richard H. Nollan. Blood Picture: L. W. Digg’s Sickle Cell Anemia, and the South’s First Blood Bank

NollanRichard H.. Blood Picture: L. W. Digg’s Sickle Cell Anemia, and the South’s First Blood Bank.Knoxville: The University of Tennessee Press, 2016. xii, 187 pp., illus. $45.00 (cloth).

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Catherine L. Thompson. Patient Expectations: How Economics, Religion, and Malpractice Shaped Therapeutics in Early America

ThompsonCatherine L.. Patient Expectations: How Economics, Religion, and Malpractice Shaped Therapeutics in Early America.Amherst and Boston, University of Massachusetts Press, 2015. 188 pp., $26.95 (paper).

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Luis A. Campos. Radium and the Secret of Life

CamposLuis A.. Radium and the Secret of Life.Chicago, University of Chicago Press, 2015. 378 pp., illus.

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Courtney Q. Shah. Sex Ed, Segregated: The Quest for Sexual Knowledge in Progressive-Era America

ShahCourtney Q.. Sex Ed, Segregated: The Quest for Sexual Knowledge in Progressive-Era America.Rochester, University of Rochester, 2015. xvi, 212 pp., $95.00 (cloth).

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Shelley Z. Reuter. Testing Fate: Tay-Sachs Disease and the Right to Be Responsible

ReuterShelley Z.. Testing Fate: Tay-Sachs Disease and the Right to Be Responsible.Minneapolis, University of Minnesota Press, 2016. 280 pp., illus. $27.00.

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Heather H. Vacek. Madness: American Protestant Responses to Mental Illness

VacekHeather H.. Madness: American Protestant Responses to Mental Illness.Waco, Baylor University Press, 2015. xii, 271 pp., $39.95.

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Fenneke Sysling. Racial Science and Human Diversity in Colonial Indonesia

SyslingFenneke. Racial Science and Human Diversity in Colonial Indonesia.Singapore, National University of Singapore Press, 2016. xviii, 305 pp., illus. $SGD42.00.

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Karen Kruse Thomas. Health and Humanity: A History of the Johns Hopkins Bloomberg School of Public Health, 1935-1985

ThomasKaren Kruse. Health and Humanity: A History of the Johns Hopkins Bloomberg School of Public Health, 1935-1985.Baltimore, Johns Hopkins University Press, 2016. xvii, 504 pp., illus. $45.00.

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Helen Zoe Veit. Modern Food, Moral Food: Self Control, Science, and the Rise of Modern American Eating in the Early Twentieth Century

VeitHelen Zoe. Modern Food, Moral Food: Self Control, Science, and the Rise of Modern American Eating in the Early Twentieth Century.Chapel Hill, The University North Carolina Press, 2013. xiii, 300 pp., illus. $27.95 (paper).

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Michael Helquist. Marie Equi: Radical Politics and Outlaw Passions

HelquistMichael. Marie Equi: Radical Politics and Outlaw Passions. Corvallis, Oregon, Oregon State University Press, 2015. 310 pp., illus. $24.95 (paper).

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Anna Katharina Schaffner. Exhaustion: A History

SchaffnerAnna Katharina. Exhaustion: A History. New York, Columbia University Press, 2016. xiii, 291 pp., $30.00 (cloth).

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Raúl Necochea López. A History of Family Planning in Twentieth-Century Peru

LópezRaúl Necochea. A History of Family Planning in Twentieth-Century Peru.Chapel Hill, University of North Carolina Press, 2014. xii, 248 pp., illus. $32. 95 (paper).

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Noise levels and sound pollution associated with various operative procedures and equipments in a pediatric dental environment – A clinical study

Publication date: Available online 1 July 2017
Source:Journal of Oral Biology and Craniofacial Research
Author(s): Mousumi Goswami, Darrel Singh, Binny Vashist, Sugandha Marwaha
AimTo analyse sound levels and sound pollution in a Pediatric Dental Clinic and to analyse whether the levels are significant to the extent of being a health hazard.MethodsNoise levels were measured in a Pediatric dental clinic in an institutional setting with a precision noise level meter ((HTC 1350). Recordings were taken at different times of the day, at the centre, chair-side, reception, play area and four corners of the department keeping the microphone at a distance of 6in. from the operator’s ear. The noise levels of various equipments i.e. suction, micromotor, airotor were measured with the equipments turned on and during cutting operations with the microphone placed at a distance of 6in. from the sound source. The sound levels for the laboratory equipments were taken at a distance of 6in. and 2m.ResultsThe highest mean sound levels were recorded at the reception, play area and chair-side area with least mean sound levels recorded at 9:00am which increased at 11:30am & 2:00pm and reduced again at 3:30pm The maximum sounds were produced by the lathe trimmer, airotor and scaler.ConclusionNoise levels in a pediatric clinic approach the level of risk of hearing loss [85db(A)]. This would have a serious effect on both providers and patients and a concerted effort would be required to control the noise levels and thus avoid the potential health hazards that it poses.



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Expansile radiolucent lesion of the Temporomandibular Joint—A diagnostic enigma

Publication date: Available online 1 July 2017
Source:Journal of Oral Biology and Craniofacial Research
Author(s): Vikas Meshram, Natarajan C., Jayant Landge, Sayali Jadhav




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Scapular tip and latissimus dorsi osteomyogenous free flap for the reconstruction of a maxillectomy defect: A minimally invasive trans-axillary approach

Publication date: Available online 1 July 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Sung Joon Park, Woo-Jin Jeong, Soon-Hyun Ahn
The purpose of this study was to propose a novel, minimally invasive trans-axillary approach for harvesting the scapular tip and latissimus dorsi osteomyogenous free flap for the reconstruction of a maxillectomy defect. A retrospective case series study of 4 patients who underwent reconstruction using a scapular tip compositefree flap via the trans-axillary approach was conducted. The data (age, sex, pathology, previous treatment, and adjuvant treatment) were collected and analysed. Total operation time, number of hospital days, and the cosmetic and functional outcome of reconstruction were analysed. Two male and two female patients were enrolled in this study. The patients’ ages ranged from 52 to 59 years. All the patients had maxillectomy defects, with at least a classification of Okay type II, that were successfully reconstructed using a scapular tip and latissimus dorsifree flap via a minimally invasive trans-axillary approach. The entire operation time for the primary tumour surgery and reconstruction ranged from 6.2 to 12.1 hours (mean, 11.1 hours). The average length of the hospital stay was 13 days (range, 10-16 days). No major donor site morbidity was observed and there was no graft failure which required revision or exploration surgery. The minimally invasive trans-axillary approach for harvesting the scapular tip and latissimus dorsi osteomyogenous free flap for the reconstruction of maxillectomy defect is a promising approach for more favourable functional and aesthetic outcomes when compared to the use of other bone containing free flaps and the classic approach for harvesting scapular tip and latissimus dorsi free flap.



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Down-regulated microRNA-375 expression as a predictive biomarker in non-small cell lung cancer brain metastasis and its prognostic significance

Publication date: Available online 1 July 2017
Source:Pathology - Research and Practice
Author(s): Li-juan Chen, Xing-ya Li, Yan-qiu Zhao, Wen-jing Liu, Hui-juan Wu, Jie Liu, Xiao-qian Mu, Hong-bo Wu
Brain metastases (BM) are common among patients with non-small cell lung cancer (NSCLC) and have been associated with significant morbidity and limited survival. Early and sensitive detection of BM is essential for improving prognosis. Recently,microRNA-375(miR-375) which is specifically expressed in the brain has been found significantly dysregulated in many human cancers. However, there is still no data whether miR-375 is associated with higher risk of BM development in NSCLC. In this study, we detected the miR-375 expression using quantitative real-time PCR (qRT-PCR) and assessed its predictive and prognostic significance. Our result showed that miR-375 expression was significantly down-regulated in NSCLC patients with BM(BM+, N=30) compared with NSCLC without BM(BM-, N=30) (P<0.001). Statistical analysis indicated that low miR-375 expression was linked to advanced disease stage (P<0.001) and brain metastasis (P<0.001) in NSCLC patient. Survival analysis suggested that low-expression group had significantly shorter overall survival than high-expression group in NSCLC patients with BM(log-rank test: P<0.05) as well as the total cases(log-rank test: P<0.01). Multivariate Cox proportional hazards model analysis indicated that low miR-375 expression was independently linked to poor survival of patients with NSCLC (HR=5.48, 95% CI: 1.93-15.56, P=0.001). In addition, we found that VEGF and MMP-9 were over-expressed in down-regulated miR-375 expression cases. Collectively, this study demonstrated that miR-375 may play an important role as a predictive biomarker in brain metastasis and an independent prognostic factor in NSCLC. Over-expression of VEGF and MMP-9 may be the reason for poor prognosis of NSCLC patients with low miR-375 expression.



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Frameshift mutation and loss of expression of PLK2, a serine/threonine kinase-encoding gene, in colorectal cancers

Publication date: Available online 1 July 2017
Source:Pathology - Research and Practice
Author(s): Ju Hwa Lee, Min Sung Kim, Nam Jin Yoo, Sug Hyung Lee




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Morphology based scoring of Chromosomal instability and its correlation with cell viability

Publication date: Available online 1 July 2017
Source:Pathology - Research and Practice
Author(s): Shubhlata Yadav, Alka Bhatia
ObjectiveThe aim of this study was to devise the quantitative scoring system for Chromosomal instability (CIN) based on morphological indicators like MPM, NB, NPB, CS, La and MN in cancer cell line and to correlate it with cell viability and death.MethodsHuman hepatocellular carcinoma (HepG2) cells were treated with drugs like Diethylstilbestrol 0- 100μM, Griseofulvin 0–40μg/ml, Vincristine sulphate 0–25μg/ml, Mitomycin C 0–600ng/ml, Bleomycin 0–10μg/ml, Doxorubicin 0–30μg/ml for 24hours. Following this, the CIN was assessed by counting the morphological indicators like Micronuclei (MN), Nuclear Buds (NB), Nucleoplasmic bridges, Laggards, Multipolar mitosis and chromatin strings/1000 cells in Giemsa stained smears by light microscopy and by determining the percentage of aneuploid cells by flow cytometry. The cell viability was assessed by MTT assay and percentage of apoptotic cells was determined by flow cytometry.ResultsThe MN and NB were most frequently seen indicators and main determinants of morphological CIN. However, the morphological CIN score did not show any correlation with cell viability and apoptosis. Aneuploidy however was found to correlate positively with cell viability and NB score in our study (P-value <0.05).ConclusionsThe study for the 1st time attempted to develop a scoring system for CIN based on morphological parameters. However, a no correlation was observed between the later and cell viability or apoptosis. More robust techniques to quantify CIN may perhaps be more helpful in exploring the true link between CIN and cell viability in future.



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Copyright

Publication date: August 2017
Source:Facial Plastic Surgery Clinics of North America, Volume 25, Issue 3





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Contributors

Publication date: August 2017
Source:Facial Plastic Surgery Clinics of North America, Volume 25, Issue 3





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Contents

Publication date: August 2017
Source:Facial Plastic Surgery Clinics of North America, Volume 25, Issue 3





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Forthcoming Issues

Publication date: August 2017
Source:Facial Plastic Surgery Clinics of North America, Volume 25, Issue 3





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In Pursuit of Perfection: The Art of Facial Restoration

Publication date: August 2017
Source:Facial Plastic Surgery Clinics of North America, Volume 25, Issue 3
Author(s): James B. Lucas




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Facial Reconstruction Post-Mohs Surgery

Publication date: August 2017
Source:Facial Plastic Surgery Clinics of North America, Volume 25, Issue 3
Author(s): James B. Lucas




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Flap Basics II

Publication date: August 2017
Source:Facial Plastic Surgery Clinics of North America, Volume 25, Issue 3
Author(s): Matthew Shew, John David Kriet, Clinton D. Humphrey

Teaser

A mastery of advancement flap design, selection, and execution greatly aids the surgeon in solving reconstructive dilemmas. Advancement flaps involve carefully planned incisions to most efficiently close a primary defect in a linear vector. Advancement flaps are subcategorized as unipedicle, bipedicle, V-to-Y, and Y-to-V flaps, each with their own advantages and disadvantages. When selecting and designing an advancement flap, the surgeon must account for primary and secondary movement to prevent distortion of important facial structural units and boundaries.


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Flap Basics III

Publication date: August 2017
Source:Facial Plastic Surgery Clinics of North America, Volume 25, Issue 3
Author(s): Lauren K. Reckley, Jessica J. Peck, Scottie B. Roofe

Teaser

Paramedian forehead and melolabial flaps are the most common examples of interpolated flaps used by facial plastic surgeons and are excellent options for reconstruction of the midface after Mohs surgery. They provide superior tissue match in terms of thickness, texture, and color, while leaving minimal defects at the tissue donor sites. The main advantage of interpolated flaps is the robust blood supply, which can be either axial of randomly based, and the maintenance of the integrity of facial landmarks. The main disadvantage is the frequent need for a multistage procedure, which eliminates some patients from consideration.


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Skin and Composite Grafting Techniques in Facial Reconstruction for Skin Cancer

Publication date: August 2017
Source:Facial Plastic Surgery Clinics of North America, Volume 25, Issue 3
Author(s): Michael J. Brenner, Jeffrey S. Moyer

Teaser

Skin and composite grafting provide effective resurfacing and reconstruction for cutaneous defects after excision of the malignancy. The goal is to restore a natural appearance and function while preventing distortion of the eyelid, nose, or lips. With careful planning and attention to aesthetic subunits, the surgeon can camouflage incisions and avoid blunting aesthetically sensitive sulci. The surgical plan is also informed by the pathology, as basal or squamous cell carcinomas removed by Mohs micrographic excision have different prognostic and logistical considerations from melanoma. Skin and composite grafting are useful as stand-alone procedures or may complement local flaps and other soft tissue reconstructions.


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Defect of the Eyelids

Publication date: August 2017
Source:Facial Plastic Surgery Clinics of North America, Volume 25, Issue 3
Author(s): Guanning Nina Lu, Ron W. Pelton, Clinton D. Humphrey, John David Kriet

Teaser

Eyelid defects disrupt the complex natural form and function of the eyelids and present a surgical challenge. Detailed knowledge of eyelid anatomy is essential in evaluating a defect and composing a reconstructive plan. Numerous reconstructive techniques have been described, including primary closure, grafting, and a variety of local flaps. This article describes an updated reconstructive ladder for eyelid defects that can be used in various permutations to solve most eyelid defects.


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Repair of Auricular Defects

Publication date: August 2017
Source:Facial Plastic Surgery Clinics of North America, Volume 25, Issue 3
Author(s): Deborah Watson, Avram Hecht

Teaser

Repairing defects of the auricle requires an appreciation of the underlying 3-dimensional framework, the flexible properties of the cartilages, and the healing contractile tendencies of the surrounding soft tissue. In the analysis of auricular defects and planning of their reconstruction, it is helpful to divide the auricle into subunits for which different techniques may offer better functional and aesthetic outcomes. This article reviews many of the reconstructive options for defects of the various auricular subunits.


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Reconstruction of Mohs Defects of the Lips and Chin

Publication date: August 2017
Source:Facial Plastic Surgery Clinics of North America, Volume 25, Issue 3
Author(s): Yuna C. Larrabee, Jeffrey S. Moyer

Teaser

Reconstruction of defects of the lips after Mohs micrographic surgery should encompass functional and aesthetic concerns. The lower lip and chin compose two-thirds of the lower portion of the face. The focus of this article is local tissue transfer for primarily cutaneous defects after Mohs surgery. Various flaps exist for repair. For small defects, elliptical excision with primary closure is a viable option. During reconstruction of the lip, all of the involved layers need to be addressed, including mucosa, muscle, and the vermillion or cutaneous lip. It is especially important to realign the vermillion border precisely for optimal results.


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Reconstruction of Cheek Defects Secondary to Mohs Microsurgery or Wide Local Excision

Publication date: August 2017
Source:Facial Plastic Surgery Clinics of North America, Volume 25, Issue 3
Author(s): John E. Hanks, Jeffrey S. Moyer, Michael J. Brenner

Teaser

Successful reconstruction of the cheek following excision for cutaneous malignancy requires careful consideration of defect location, size, and depth in relation to the anatomic properties of the affected cheek unit. Various reconstructive options are available to the surgeon, ranging from simple excisions to complex cervicofacial advancements to meet the needs for functional and aesthetically pleasing reconstructive outcomes. The surgeon must prevent distortion of mobile structures, such as the eyelid, nose, and lips; respect aesthetic subunits; and avoid blunting natural creases. This discussion covers choice of flap, techniques, and technical considerations for medial/perinasal, perilabial, preauricular, lateral, and zygomatic cheek defects.


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Index

Publication date: August 2017
Source:Facial Plastic Surgery Clinics of North America, Volume 25, Issue 3





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Trichomonas vaginalis infection and risk of prostate cancer: associations by disease aggressiveness and race/ethnicity in the PLCO Trial

Abstract

Purpose

Results from previous sero-epidemiologic studies of Trichomonas vaginalis infection and prostate cancer (PCa) support a positive association between this sexually transmitted infection and aggressive PCa. However, findings from previous studies are not entirely consistent, and only one has investigated the possible relation between T. vaginalis seropositivity and PCa in African-American men who are at highest risk of both infection and PCa. Therefore, we examined this possible relation in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, including separate analyses for aggressive PCa and African-American men.

Methods

We included a sample of participants from a previous nested case–control study of PCa, as well as all additional Caucasian, aggressive, and African-American cases diagnosed since the previous study (total n = 438 Gleason 7 Caucasian cases, 487 more advanced Caucasian cases (≥Gleason 8 or stage III/IV), 201 African-American cases, and 1216 controls). We tested baseline sera for T. vaginalis antibodies.

Results

No associations were observed for risk of Gleason 7 (odds ratio (OR) = 0.87, 95% confidence interval (CI) 0.55–1.37) or more advanced (OR = 0.90, 95% CI 0.58–1.38) PCa in Caucasian men, or for risk of any PCa (OR = 1.06, 95% CI 0.67–1.68) in African-American men.

Conclusions

Our findings do not support an association between T. vaginalis infection and PCa.



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Piezoelectric versus conventional techniques for orthognathic surgery: Systematic review and meta-analysis

Publication date: Available online 1 July 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Luis Eduardo Charles Pagotto, Thiago de Santana Santos, Sara Juliana de Abreu de Vasconcellos, Joanes Silva Santos, Paulo Ricardo Saquete Martins-Filho
PurposeThe purpose of this study was to perform a systematic review and meta-analysis of complications after orthognathic surgery comparing piezosurgery with conventional osteotomy.MethodsWe conducted this study according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a systematic search of PubMed, Scopus, Science Direct, Lilacs, Cochrane Central Register of Controlled Trials, Google Scholar, and OpenThesis to identify randomized and nonrandomized controlled trials (RCTs and nRCTs, respectively) comparing patient outcomes (operative time, intraoperative blood loss, postoperative swelling, pain, neurosensitivity) after orthognathic surgery by piezoelectric or conventional osteotomy. We pooled individual results of continuous and dichotomous outcome data using the mean difference (MD) and risk difference (RD) with the 95% confidence interval, respectively.ResultsThree RCTs and five nRCTs were selected. No difference in operative time was observed between piezosurgery and conventional osteotomies. We found a decrease of intraoperative blood loss with piezosurgery (MD -128 mL; P < 0.001) and a pooled difference in severe blood loss of 35% (P = 0.008) favoring piezosurgery. Based on pooled individual results of studies evaluating neurosensitivity by clinical neurosensory testing, our meta-analysis showed a pooled difference in severe nerve disturbance of 25% (P < 0.0001) favoring piezosurgery. Test for subgroup differences (I2 = 26.6%) indicated that follow-up time may have an effect on neurosensory disturbance. We found differences between piezosurgery and conventional osteotomy at 3 months (RD 28%; P < 0.001) and 6 months (RD 15%; P = 0.001) after surgery. Meta-analyses for pain and swelling were not performed because of a lack of sufficient studies.ConclusionCurrently available evidence suggests that piezosurgery has favorable effects on complications associated with orthognathic surgery, including reductions in intraoperative blood loss and severe nerve disturbance.



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Co-morbidity and polypharmacy in Parkinson’s disease: insights from a large Scottish primary care database

Parkinson’s disease is complicated by comorbidity and polypharmacy, but the extent and patterns of these are unclear. We describe comorbidity and polypharmacy in patients with and without Parkinson’s disease a...

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Piezoelectric versus conventional techniques for orthognathic surgery: Systematic review and meta-analysis

Publication date: Available online 1 July 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Luis Eduardo Charles Pagotto, Thiago de Santana Santos, Sara Juliana de Abreu de Vasconcellos, Joanes Silva Santos, Paulo Ricardo Saquete Martins-Filho
PurposeThe purpose of this study was to perform a systematic review and meta-analysis of complications after orthognathic surgery comparing piezosurgery with conventional osteotomy.MethodsWe conducted this study according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a systematic search of PubMed, Scopus, Science Direct, Lilacs, Cochrane Central Register of Controlled Trials, Google Scholar, and OpenThesis to identify randomized and nonrandomized controlled trials (RCTs and nRCTs, respectively) comparing patient outcomes (operative time, intraoperative blood loss, postoperative swelling, pain, neurosensitivity) after orthognathic surgery by piezoelectric or conventional osteotomy. We pooled individual results of continuous and dichotomous outcome data using the mean difference (MD) and risk difference (RD) with the 95% confidence interval, respectively.ResultsThree RCTs and five nRCTs were selected. No difference in operative time was observed between piezosurgery and conventional osteotomies. We found a decrease of intraoperative blood loss with piezosurgery (MD -128 mL; P < 0.001) and a pooled difference in severe blood loss of 35% (P = 0.008) favoring piezosurgery. Based on pooled individual results of studies evaluating neurosensitivity by clinical neurosensory testing, our meta-analysis showed a pooled difference in severe nerve disturbance of 25% (P < 0.0001) favoring piezosurgery. Test for subgroup differences (I2 = 26.6%) indicated that follow-up time may have an effect on neurosensory disturbance. We found differences between piezosurgery and conventional osteotomy at 3 months (RD 28%; P < 0.001) and 6 months (RD 15%; P = 0.001) after surgery. Meta-analyses for pain and swelling were not performed because of a lack of sufficient studies.ConclusionCurrently available evidence suggests that piezosurgery has favorable effects on complications associated with orthognathic surgery, including reductions in intraoperative blood loss and severe nerve disturbance.



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Improved SNR for combined TMS-fMRI: A support device for commercially available body array coil

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Publication date: Available online 30 June 2017
Source:Journal of Neuroscience Methods
Author(s): Wen-Tung Wang, Benjamin Xu, John A. Butman
BackgroundTranscranial magnetic stimulation (TMS) is a noninvasive brain stimulation tool extensively used in clinical and cognitive neuroscience research. TMS has been applied during functional magnetic resonance imaging (i.e., concurrent/interleaved TMS-fMRI) to understand neural mechanisms underlying cognitive functions. However, no advanced commercial multi-channel whole-brain array MR coils can fit the large TMS coil. We developed a low-cost and easy-to-configure setup that takes advantage of the superior signal-to-noise ratio (SNR) performance of commercially available flexible body array coils that can accommodate the TMS coil.New methodTwo flexible MRI body array coils (i.e., the Combo coil) were fitted on a simple coil support with a TMS-coil holder. Phantom and in vivo images acquired using the Combo coil with and without a TMS coil were compared with those from a product 12-channel (12CH) form-fit head array coil.ResultsRelative to the 12CH head coil, images acquired using the Combo coil were of similar quality, but with increased noise levels, leading to moderately reduced temporal SNR values.Comparison with existing methodA previous study reported that the temporal SNR of a product 12CH head coil was twice that of a transmit/receive volume birdcage coil commonly used in combined TMS-fMRI. Together with the results of the present work, they indicate that the Combo-coil setup improves SNR performance for combined TMS-fMRI acquisition.ConclusionThe inexpensive and easy-to-configure Combo-coil setup offers an effective and likely superior alternative to transmit/receive birdcage coil for combined TMS-fMRI.



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Distribution of Vascular Patterns in Different Subtypes of Renal Cell Carcinoma. A Morphometric Study in Two Distinct Types of Blood Vessels

Abstract

To analyze the presence of mature and immature vessels as a prognostic factor in patients with renal cell carcinoma and propose a classification of renal cancer tumor blood vessels according to morphometric parameters. Tissue samples were obtained from 121 renal cell carcinoma patients who underwent radical nephrectomy. Staining with CD31 and CD34 was used to differentiate between immature (CD31+) and mature (CD34+) blood vessels. We quantified the microvascular density, microvascular area and different morphometric parameters: maximum diameter, minimum diameter, major axis, minor axis, perimeter, radius ratio and roundness. We found that the microvascular density was higher in CD31+ than CD34+ vessels, but CD34+ vessels were larger than CD31+ vessels, as well as being strongly correlated with the ISUP tumor grade. We also identified four vascular patterns: pseudoacinar, fascicular, reticular and diffuse. Pseudoacinar and fascicular patterns were more frequent in clear cell renal cell carcinoma (37.62 and 35.64% respectively), followed by reticular pattern (21.78%), while in chromophobe tumors the reticular pattern predominated (90%). The isolated pattern was present in all papillary tumors (100%). In healthy renal tissue, the pseudoacinar and isolated patterns were differentially found in the renal cortex and medulla respectively. We defined four distinct vascular patterns significantly related with the ISUP tumor grade in renal cell carcinomas. Further studies in larger series are needed in order to validate these results. Analysis of both mature and immature vessels (CD34+ and CD31+) provides additional information when evaluating microvascular density.



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Identification of Potential Gene Network Associated with HCV-Related Hepatocellular Carcinoma Using Microarray Analysis

Abstract

In order to identify potential specific gene networks of Hepatitis C virus (HCV) related hepatocellular carcinoma (HCC), weighted gene co-expression network analysis (WGCNA) was performed, which may provide an insight into the potential mechanism of the HCC development. HCV-related HCC and normal sample data were downloaded from GEO, T test of limma package was used to screen different expression genes (DEGs); KEGG pathway was used to analyze related biochemical pathways, and WGCNA was used to construct clustering trees and screen hub genes in the HCC-specific modules. A total of 1151 DEGs were authenticated between the HCC and normal liver tissue samples, including 433 upregulated and 718 downregulated genes. Among these genes, three specific modules of HCC were constructed, including Tan, Yellow and Cyan, but only Yellow module had a significant enrichment score in substance combination module with three hub genes: SLA2547, EFNA4 and MME. Although Tan and Cyan separately had four and three hub genes, but the bio-functions of them did not have significant enrichment scores (score < 2). SLA2547, EFNA4 and MME may play important roles in the substance combination of HCV-related HCC, so studying the function of this gene network may provide us a deeper understanding of HCV-related HCC.



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Distribution of Vascular Patterns in Different Subtypes of Renal Cell Carcinoma. A Morphometric Study in Two Distinct Types of Blood Vessels

Abstract

To analyze the presence of mature and immature vessels as a prognostic factor in patients with renal cell carcinoma and propose a classification of renal cancer tumor blood vessels according to morphometric parameters. Tissue samples were obtained from 121 renal cell carcinoma patients who underwent radical nephrectomy. Staining with CD31 and CD34 was used to differentiate between immature (CD31+) and mature (CD34+) blood vessels. We quantified the microvascular density, microvascular area and different morphometric parameters: maximum diameter, minimum diameter, major axis, minor axis, perimeter, radius ratio and roundness. We found that the microvascular density was higher in CD31+ than CD34+ vessels, but CD34+ vessels were larger than CD31+ vessels, as well as being strongly correlated with the ISUP tumor grade. We also identified four vascular patterns: pseudoacinar, fascicular, reticular and diffuse. Pseudoacinar and fascicular patterns were more frequent in clear cell renal cell carcinoma (37.62 and 35.64% respectively), followed by reticular pattern (21.78%), while in chromophobe tumors the reticular pattern predominated (90%). The isolated pattern was present in all papillary tumors (100%). In healthy renal tissue, the pseudoacinar and isolated patterns were differentially found in the renal cortex and medulla respectively. We defined four distinct vascular patterns significantly related with the ISUP tumor grade in renal cell carcinomas. Further studies in larger series are needed in order to validate these results. Analysis of both mature and immature vessels (CD34+ and CD31+) provides additional information when evaluating microvascular density.



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Identification of Potential Gene Network Associated with HCV-Related Hepatocellular Carcinoma Using Microarray Analysis

Abstract

In order to identify potential specific gene networks of Hepatitis C virus (HCV) related hepatocellular carcinoma (HCC), weighted gene co-expression network analysis (WGCNA) was performed, which may provide an insight into the potential mechanism of the HCC development. HCV-related HCC and normal sample data were downloaded from GEO, T test of limma package was used to screen different expression genes (DEGs); KEGG pathway was used to analyze related biochemical pathways, and WGCNA was used to construct clustering trees and screen hub genes in the HCC-specific modules. A total of 1151 DEGs were authenticated between the HCC and normal liver tissue samples, including 433 upregulated and 718 downregulated genes. Among these genes, three specific modules of HCC were constructed, including Tan, Yellow and Cyan, but only Yellow module had a significant enrichment score in substance combination module with three hub genes: SLA2547, EFNA4 and MME. Although Tan and Cyan separately had four and three hub genes, but the bio-functions of them did not have significant enrichment scores (score < 2). SLA2547, EFNA4 and MME may play important roles in the substance combination of HCV-related HCC, so studying the function of this gene network may provide us a deeper understanding of HCV-related HCC.



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GNAO1-related movement disorder with life-threatening exacerbations: movement phenomenology and response to DBS

Background

GNAO1 (OMIM 139311) encodes a Gα0CNS protein responsible for regulation of GABA-B and α2-receptors, and neurotransmitter release. Mutations of GNAO1 are reported in patients with epileptic encephalopathy (EE) at times with a movement disorder (MD); some display severe hyperkinetic movements without EE, three underwent Deep Brain Stimulation (DBS) with reduction in exacerbations.1–4 (see online , supporting information (SI)).

Methods

We describe the MD phenomenology and course in three patients identified from neurology services in Brisbane and Glasgow with GNAO1-related MD, highlighting effectiveness of DBS in exacerbations.

Informed consent was obtained. Four MD specialists reviewed videos (baseline, exacerbations, post-DBS) using a Proforma (SI) and reached a consensus on movement phenomenology.

Results

All patients had global delay, central hypotonia and MD noted in early life (see online , patient synopsis, SI). Patient 3 initially showed bradykinesia, rigidity and dystonia; patient 1 resting tremor. All had been diagnosed with dyskinetic Cerebral...



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Towards an early clinical diagnosis of sporadic CJD VV2 (ataxic type)

Introduction

Sporadic Creutzfeldt-Jakob disease (sCJD) includes a broad spectrum of clinical–pathological subtypes, which complicates the clinical differential diagnosis with other rapidly progressive neurological syndromes.

Aim

To provide a better characterisation of clinical features and results of diagnostic investigations, especially at an early disease stage, in patients with sCJDVV2, the second most common sCJD subtype.

Methods

We evaluated neurological symptoms/signs, and results of brain diffusion-weighted resonance imaging (DW-MRI), electroencephalographic recordings (EEG) and cerebrospinal fluid (CSF) biomarker studies in 120 patients with a definite (n=93) or probable (n=27) diagnosis of sCJDVV2.

Results

All patients presented with prominent cerebellar signs, which were often associated with memory loss and/or oculomotor, visual or peripheral/spinal cord signs. In contrast, dementia was invariably a late finding. All CSF samples were positive for the 14-3-3 protein assay and had total-tau protein levels above 1250 pg/mL. Brain DW-MRI showed hyperintensity of basal ganglia, thalamus and cerebral cortex, respectively in 91.5%, 57.4% and 19.1% of cases. EEG revealed periodic sharp-wave complexes in only 17.8% of cases.

Conclusions

sCJDVV2 should be considered in any patient presenting with a rapidly progressive ataxia, especially when associated with oculomotor, visual or peripheral/spinal cord signs, even in the absence of dementia or myoclonus. CSF assays and brain DW-MRI represent sensitive diagnostic tests, even at an early stage. These data strongly suggest that sCJDVV2 can be clinically diagnosed early and accurately based on clinical data, DW-MRI, CSF assays and codon 129 genotyping and provide the basis for improved and subtype-specific diagnostic criteria of sCJD.



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Pooled Analysis of Clinical Outcome of Patients with Chemorefractory Metastatic Colorectal Cancer Treated within Phase I/II Clinical Studies Based on Individual Biomarkers of Susceptibility: A Single-Institution Experience

Abstract

Background

Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according to individual tumor molecular characteristics are expected to provide added value.

Objective

We retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s).

Patients and Methods

From June 2011 to May 2016, 2044 patients with mCRC underwent molecular screening. Eighty patients (3.9%) were enrolled in ad hoc studies; the median age was 60 years (range 36–86) and the median number of previous treatment lines was five (range 2–8). Molecular characteristics exploited within these studies were MGMT promoter hypermethylation (48.7%), HER2 amplification (28.8%), BRAF V600E mutation (20%), and novel gene fusions involving ALK or NTRK (2.5%).

Results

One patient (1%) had RECIST (Response Evaluation Criteria In Solid Tumors) complete response (CR), 13 patients (16.5%) experienced a partial response (PR), and 28 (35%) stable disease (SD). Median progression-free survival (PFS) was 2.8 months (range 2.63–3.83), with 24% of patients displaying PFS >5 months. Median growth modulation index (GMI) was 0.85 (range 0–15.61) and 32.5% of patients had GMI >1.33. KRAS exon 2 mutations were found in 38.5% of patients, and among the 78 patients with known KRAS status, those with wild-type tumors had longer PFS than those with mutated tumors (3.80 [95% CI 2.80–5.03] vs. 2.13 months [95% CI 1.77–2.87], respectively, p = 0.001). Median overall survival (OS) was 7.83 months (range 7.17–9.33) for all patients, and patients with KRAS wild-type tumors had longer OS than those with mutated tumors (7.83 [95% CI 7.33–10.80] vs. 7.18 months [95% CI 5.63–9.33], respectively, p = 0.06).

Conclusions

This single-institution retrospective study indicates that in a heavily pretreated population approximately 4% of mCRC tumors display a potential actionable molecular context suitable for therapeutic intervention. Application of molecular selection is challenging but improves clinical outcome even in later lines of treatment.



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Oral shedding of human herpesviruses in renal transplant recipients

Abstract

Objective

To describe the shedding profile of human herpesviruses in the saliva of renal transplant recipients.

Methods

This is a prospective case-control study of 50 renal transplant recipients and control group of 50 individuals (non-transplanted and immunocompetent). Mouthwash samples were collected via oral rinse and then submitted to screening for the presence of eight types of herpesviruses by using multiplex PCR. Fisher’s exact, chi-square, and Student t tests were used for statistical analysis, and the significance level was set at 5%.

Results

The mean age of the study group was 49.42 ± 12.94 years, 28/50 (56%) were female, and the time elapsed after transplantation was 68.20 ± 67.19 months. Herpes simplex virus 1 (HSV-1) (P = 0.025) and Epstein-Barr virus (EBV) (P = 0.024) were, statistically, more excreted in the saliva of renal transplant recipients compared to control group. Gender (P = 1.00) and age (P = 0.563) did not influence the salivary shedding of herpesviruses in renal transplant recipients. Individuals who excreted varicella-zoster virus in saliva had a shorter mean time of transplantation (22:00 + 2.82 months) (P < 0.001).

Conclusion

Renal transplant recipients excreted herpesviruses more often than controls, especially HSV-1 and EBV, with salivary shedding of herpesviruses being more frequent in patients with recent kidney transplantation.

Clinical relevance

The present findings support other longitudinal studies evaluating the relationship between oral shedding of human herpesviruses and clinical presence of active infection and renal transplant failure.



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Effect of root canal preparation techniques on chlorhexidine substantivity on human dentin: a chemical analysis

Abstract

Objectives

Chlorhexidine binds to dentine to provide sustained action. The aim of the present study was to evaluate and compare the substantivity of chlorhexidine using manual, rotary, and reciprocating systems for root canal preparation.

Methods

Forty-five extracted human single-rooted teeth were used for this study. The samples were divided into three groups (n = 15) according to the instrumentation technique used: manual instrumentation (K-File), rotary instrumentation (ProTaper), and reciprocating instrumentation (Reciproc R25). Chlorhexidine gel (2%) was used as auxiliary chemical substance during root canal preparation. Longitudinal grooves were carved on the free surfaces of the roots, providing two halves of each root and resulting in 30 samples per group. Each group was randomly divided into three subgroups (n = 10), and substantivity was evaluated after 48 h, 7 days, and 30 days of incubation. The amount of CHX (in mg/mL) was measured through reverse-phase high-performance liquid chromatography. Statistical analysis was performed by analysis of variance and the Tukey test for post hoc comparisons (α = 0.05).

Results

The manual did not show a statistical significant difference with rotary instrumentation (P > 0.05), but higher CHX substantivity was recorded in all periods of observation when compared to reciprocating instrumentation (P < 0.05).

Conclusions

The CHX substantivity on human dentine is lowest when using reciprocating compared to manual and rotary instrumentation.

Clinical significance

Using chemical analysis, this study showed that a manual and rotary multi-instrument system results in greater chlorhexidine substantivity on human dentin than a reciprocating single-instrument system.



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Validation of ApneaLink™ Plus for the diagnosis of sleep apnea

Abstract

Purpose

The aim of this study is to evaluate the validation of ApneaLink™ Plus (ALP) based on a large number of subjects in a prospective design.

Method

We recommended enrolling of 200 consecutive patients who had been referred because of habitual snoring or witnessed apnea during sleep. If consent was obtained, patients underwent standard polysomnography (PSG) and ALP evaluation simultaneously at the hospital (ALPlab), and repeated ALP at home (ALPhome) within 1 month. The parameters of ALP were scored based on three different systems, Manual, Auto AASM, and Auto scoring systems.

Result

Among the 200 patients who were recommended for enrollment, 149 completed the study. Sensitivity was good for all three scoring systems, while specificity was poor for the Auto scoring system. The area under curve was highest for the manual scoring system and lowest for the auto scoring system, and increased as the apnea-hypopnea index (AHI) cutoff value increased from 5 to 30. Regarding agreement with PSG, the manual scoring system was most superior, followed by the Auto AASM, and Auto scoring systems. The degree of agreement between PSG and ALP was affected by sleep efficiency and the arousal index. Moderate agreement between PSG and ALP based on central apnea index was observed.

Conclusion

ALP is an accurate and reliable device for the diagnosis of OSA. Manual scoring is recommended; however, Auto AASM is also acceptable. ALP detects central sleep apnea to a certain degree. Both sleep efficiency and the arousal index affect the results of ALP.



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Validation of ApneaLink™ Plus for the diagnosis of sleep apnea

Abstract

Purpose

The aim of this study is to evaluate the validation of ApneaLink™ Plus (ALP) based on a large number of subjects in a prospective design.

Method

We recommended enrolling of 200 consecutive patients who had been referred because of habitual snoring or witnessed apnea during sleep. If consent was obtained, patients underwent standard polysomnography (PSG) and ALP evaluation simultaneously at the hospital (ALPlab), and repeated ALP at home (ALPhome) within 1 month. The parameters of ALP were scored based on three different systems, Manual, Auto AASM, and Auto scoring systems.

Result

Among the 200 patients who were recommended for enrollment, 149 completed the study. Sensitivity was good for all three scoring systems, while specificity was poor for the Auto scoring system. The area under curve was highest for the manual scoring system and lowest for the auto scoring system, and increased as the apnea-hypopnea index (AHI) cutoff value increased from 5 to 30. Regarding agreement with PSG, the manual scoring system was most superior, followed by the Auto AASM, and Auto scoring systems. The degree of agreement between PSG and ALP was affected by sleep efficiency and the arousal index. Moderate agreement between PSG and ALP based on central apnea index was observed.

Conclusion

ALP is an accurate and reliable device for the diagnosis of OSA. Manual scoring is recommended; however, Auto AASM is also acceptable. ALP detects central sleep apnea to a certain degree. Both sleep efficiency and the arousal index affect the results of ALP.



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Magnesium-Zinc-Calcium-Vitamin D Co-supplementation Improves Hormonal Profiles, Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Data on the effects of magnesium-zinc-calcium-vitamin D co-supplementation on hormonal profiles, biomarkers of inflammation, and oxidative stress among women with polycystic ovary syndrome (PCOS) are scarce. The objective of this study was to assess the effects of magnesium-zinc-calcium-vitamin D co-supplementation on hormonal profiles, biomarkers of inflammation, and oxidative stress in women with PCOS. Sixty PCOS women were randomized into two groups and treated with 100 mg magnesium, 4 mg zinc, 400 mg calcium plus 200 IU vitamin D supplements (n = 30), or placebo (n = 30) twice a day for 12 weeks. Hormonal profiles, biomarkers of inflammation, and oxidative stress were assessed at baseline and at end-of-treatment. After the 12-week intervention, compared with the placebo, magnesium-zinc-calcium-vitamin D co-supplementation resulted in significant reductions in hirsutism (−2.4 ± 1.2 vs. −0.1 ± 0.4, P < 0.001), serum high sensitivity C-reactive protein (−0.7 ± 0.8 vs. +0.2 ± 1.8 mg/L, P < 0.001), and plasma malondialdehyde (−0.4 ± 0.3 vs. +0.2 ± 1.0 μmol/L, P = 0.01), and a significant increase in plasma total antioxidant capacity concentrations (+46.6 ± 66.5 vs. −7.7 ± 130.1 mmol/L, P = 0.04). We failed to find any significant effect of magnesium-zinc-calcium-vitamin D co-supplementation on free androgen index, and other biomarkers of inflammation and oxidative stress. Overall, magnesium-zinc-calcium-vitamin D co-supplementation for 12 weeks among PCOS women had beneficial effects on hormonal profiles, biomarkers of inflammation, and oxidative stress.



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Diffusion-weighted MRI in image-guided adaptive brachytherapy: Tumor delineation feasibility study and comparison with GEC-ESTRO guidelines

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Publication date: Available online 30 June 2017
Source:Brachytherapy
Author(s): Antoine Schernberg, Corinne Balleyguier, Isabelle Dumas, Sébastien Gouy, Alexandre Escande, Enrica Bentivegna, Philippe Morice, Eric Deutsch, Christine Haie-Meder, Cyrus Chargari
PurposeTo examine the feasibility of using diffusion-weighted images (DWIs) coregistered with T2-weighted (T2w) sequence in treatment planning system to improve target delineation for image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer patients.Methods and MaterialsWe retrospectively examined the records of consecutive patients who were referred to our institution for pulse-dose-rate IGABT between May and December 2015 after concurrent chemoradiation. An MRI with T2w and DWI sequences with a maximum diffusion factor of 1000 s/mm2 on a 1.5 or 3.0-T MR scanner was performed after placement of the vaginal mold applicator. T2w defined gross tumor volume (GTVT2) and diffusion volume on DWI sequences (CTVDWI) were retrospectively delineated, if achievable, by radiologist and radiation oncologist. Concordances between CTVDWI and GTVT2, high-risk and intermediate-risk clinical target volumes (CTVHR and CTVIR) were evaluated.ResultsForty-four patients were identified: 23 patients (52%) had a GTVT2 delineated, CTVDWI was delineated in 42 patients (95%). Intraobserver and interobserver conformity indexes were <0.75 in 11 patients (26%) and 23 patients (54%), respectively. There was a positive correlation between GTVT2 and CTVDWI volumes (p = 0.038, r = 0.58). Median CTVHR and CTVDWID90 were 37.3 Gy (17.1–48.9 Gy) and 33 Gy (22–97 Gy), respectively (p = 0.659). CTVDWI could have pointed CTVHR delineation modifications in a total of 32 of 44 (73%) patients with CTVDWI/CTVHR conformity < 1. CTVDWI volume was totally encompassed by CTVIR in all patients.ConclusionsThese results suggest that DWI images as anatomical sequence without apparent diffusion coefficient mapping might have led to CTVHR modifications. Still, interobserver and intraobserver variations in delineation are substantial, and artifacts make it difficult to implement.



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American Brachytherapy Society consensus report for accelerated partial breast irradiation using interstitial multicatheter brachytherapy

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Publication date: Available online 1 July 2017
Source:Brachytherapy
Author(s): Jaroslaw T. Hepel, Douglas Arthur, Simona Shaitelman, Csaba Polgár, Dorin Todor, Imran Zoberi, Mitchell Kamrava, Tibor Major, Catheryn Yashar, David E. Wazer
PurposeTo develop a consensus report for the quality practice of accelerated partial breast irradiation (APBI) using interstitial multicatheter brachytherapy (IMB).Methods and MaterialsThe American Brachytherapy Society Board appointed an expert panel with clinical and research experience with breast brachytherapy to provide guidance for the current practice of IMB. This report is based on a comprehensive literature review with emphasis on randomized data and expertise of the panel.ResultsRandomized trials have demonstrated equivalent efficacy of APBI using IMB compared with whole breast irradiation for select patients with early-stage breast cancer. Several techniques for placement of interstitial catheters are described, and importance of three-dimensional planning with appropriate optimization is reviewed. Optimal target definition is outlined. Commonly used dosing schemas include 50 Gy delivered in pulses of 0.6–0.8 Gy/h using pulsed-dose-rate technique and 34 Gy in 10 fractions, 32 Gy in eight fractions, or 30 Gy in seven fractions using high-dose-rate technique. Potential toxicities and strategies for toxicity avoidance are described in detail. Dosimetric constraints include limiting whole breast volume that receives ≥50% of prescription dose to <60%, skin dose to ≤100% of prescription dose (≤60–70% preferred), chest wall dose to ≤125% of prescription dose, Dose Homogeneity Index to >0.75 (>0.85 preferred), V150 < 45 cc, and V200 < 14 cc. Using an optimal implant technique coupled with optimal planning and appropriate dose constraints, a low rate of toxicity and a good-to-excellent cosmetic outcome of ≥90% is expected.ConclusionsIMB is an effective technique to deliver APBI for appropriately selected women with early-stage breast cancer. This consensus report has been created to assist clinicians in the appropriate practice of APBI using IMB.



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Patient preferences for the attributes of a non-invasive treatment for superficial Basal cell carcinoma: a discrete choice experiment

Abstract

To examine which attributes of a non-invasive treatment for superficial BCC (sBCC) are valued by patients, a discrete choice experiment (DCE) was performed alongside a clinical trial in which methylaminolevulinate photodynamic therapy (MAL-PDT), 5-fluorouracil and imiquimod were compared.1

Treatment options were described by the following attributes: effectiveness, cosmetic result, treatment process and side-effects. Effectiveness was defined as the probability that complete tumour clearance is achieved 12 months after treatment with levels of 75%,80%,85% and 90%.2-4

This article is protected by copyright. All rights reserved.



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Functional melanoma-risk variant IRF4 rs12203592 associated with Breslow thickness: a pooled international study of primary melanomas

Abstract

Breslow thickness is considered to be the most important prognostic tumor feature in melanoma patients and is associated with age, sex, and phenotypic risk factors for melanoma such as number of nevi. However, its association with inherited genetic variants in recently identified melanoma risk loci is largely unknown.

In a Western Australian Melanoma Health Study (WAMHS) study, published in the British Journal of Dermatology, IRF4 rs12203592, OCA2 rs1800401 and TP53 rs1042522 were significantly associated (P < 0.05) with Breslow thickness; however, these associations did not pass false discovery.

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Lack of Response to Intravenous Sodium Thiosulfate in Three Cases of Extensive Connective Tissue Disease-Associated Calcinosis Cutis

Abstract

Dystrophic calcinosis cutis is a debilitating condition of calcium salt deposition in the skin often occurring in association with connective tissue disease (CTD). Available treatments for calcinosis cutis are unsatisfactory, but given the recent use of topical and intralesional sodium thiosulfate (STS) to treat calcifying disorders, we sought to describe the use of intravenous (IV) STS for CTD-associated dystrophic calcinosis cutis. We report three patients with longstanding and extensive CTD-associated calcinosis cutis treated with IV STS after having failed multiple prior therapies. All three patients experienced fatigue and nausea with STS infusions, and none of the patients had notable clinical or symptomatic improvement of calcinosis. It remains to be seen whether the administration of IV STS earlier in the onset of calcinosis might be of benefit given that these patients all had longstanding and refractory CTD-associated calcinosis. Given the small number of patients in this series, further investigation into the use of IV STS in calcinosis cutis is warranted.

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Invasive dermatophyte infection with trichophyton interdigitale is associated with prurigo induced pseudoperforation and a STAT3 mutation

Abstract

Invasive dermatophyte infection, with extention beyond the dermis, in immunocompetent hosts is exceptionally rare. Dermatophytes are keratinophilic and are usually confined to the stratum corneum, hair and nails. Susceptibility to dermatophyte infections is incompletely understood but inherited mutations in key signaling pathways of the innate immune system have been identified.1 We report the first case of an invasive dermatophyte infection associated with abrupt onset of a prurigo induced pseudoperforation and a loss of function mutation in Signal transducer and activator of transcription 3 (STAT 3).

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Experiences of rosacea and its treatment: An interpretative phenomenological analysis

Abstract

Background

Whilst rosacea is a chronic skin condition, the condition can often have a large psychosocial impact on the individual. There is therefore a need to understand the experience of living with rosacea from the patient perspective.

Objectives

To examine the experience of living with rosacea and the experience of seeking and receiving treatment.

Methods

Nine participants took part in semi-structured interviews, which were analysed using interpretative phenomenological analysis.

Results

Three superordinate themes were identified within the data; self-consciousness, which focused on the fear of others’ assigning blame to participants for having caused symptoms; avoidance, concealment, and hiding emotions, referring to the coping strategies participants employed in response to rosacea; and inconsistencies in GP treatment and guidance, which focused on the need for medical professionals to assess the psychosocial well-being of patients with rosacea.

Conclusions

Rosacea can have a negative impact on the daily life of people with the condition, contributing to lowered self-esteem, embarrassment, and feelings of shame. Engaging in emotion-focused and behavioural/avoidant-focused coping strategies increased participant's confidence and reduced their avoidance of social situations. However, such strategies might still serve to maintain underlying unhelpful cognitive processes. Consequently, it is important for medical professionals to assess for the presence of cognitive factors that might contribute to maintaining distress in patients with rosacea, and where unhelpful thoughts or beliefs are reported, patients may need to be referred for psychological support.

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Hidradenitis Suppurativa and electrocardiographic changes – a cross-sectional population study

Abstract

Background

Hidradenitis Suppurativa (HS) is a chronic, inflammatory skin disease, recently associated with metabolic syndrome, subclinical atherosclerosis and increased risk of cardiovascular disease.

Objectives

The aim of the study was to investigate the hitherto unknown electrocardiographic changes associated with HS, which recently have been associated with significant cardiovascular burden.

Methods

Data were derived from the cross-sectional population study, The Danish General Population Study (GESUS). HS diagnosis was based on a validated self-reported questionnaire and 404 individuals met the HS diagnosis criteria and 19,001 controls without HS were identified in the population. Severity of HS was staged according to a modified Hurley score. The electrocardiographic parameters, Heart Rate (HR), PR-interval, QRS-duration, JTc-interval and QTc-interval, were obtained from 12-lead resting electrocardiograms. We investigated the difference in means by unpaired t-test or the analysis of variance (ANOVA) test.

Results

Heart rate was significantly higher (mean difference: 2.3 bpm [1.2:3.4] p<0.01) when adjusting for age and gender but when multivariate adjusting, there was no significant difference (0.3 bpm [-0.7:1.4] p=0.52). Severe HS was significantly associated with increased heart rate across all models (2.9 bpm [0.7:5.1] p=0.01). Mean QRS-duration was significantly shorter in the mild HS group, but not in the moderate- and severe HS groups

Conclusion

Mean resting heart rate in severe HS was significantly higher compared to controls. Given that resting heart rate is associated with increased risk of all-cause and cardiovascular mortality, and that HS patients have increased risk of cardiovascular events, this finding is potentially important, easily testable and intervenable.

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A hyaluronic acid-based microneedle patch to treat psoriatic plaques: A pilot open trial

Abstract

Psoriasis, a common, chronic, relapsing, inflammatory skin disease characterised by multiple erythematous papules and plaques with silvery scales, affects 0.5–3% of the world's population. Recently, great advances have been made in the treatment of psoriasis, including the introduction of targeted biological agents.1 However, topical treatment remains important; most patients have mild disease affecting less than 2% of the body surface area.2

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AGREE II assessments of recent acne treatment guidelines: how well do they reveal trustworthiness as defined by the Institute of Medicine (IOM) criteria?

Abstract

Background

Up-to-date, trustworthy guidelines are a widely relied-upon means of promoting excellent patient care.

Objectives

To determine the quality of recently published acne treatment guidelines by utilizing the Appraisal of Guidelines for Research and Evaluation (AGREE) II Reporting Checklist, the US Institute of Medicine's (IOM) criteria of trustworthiness, Lenzer et al’s red flags and CheckUp.

Methods

Systematic searches were conducted in bibliographic databases, guideline depositories and using Google to identify acne treatment guidelines published since 2013. Six assessors independently scored each guideline using the AGREE II Reporting Checklist. Guidelines were concomitantly assessed for trustworthiness using the IOM criteria and for Lenzer et al's red flags indicative of potential bias. Updates were screened using CheckUp.

Results

Eight guidelines were identified, two of which were updates. Lowest scoring AGREE II domains across all guidelines were rigour (6/8 poor, one fair, one average) and applicability (4/8 poor, one fair, three average). Two out of the three highest scoring guidelines were developed using AGREE II. No guideline fully met each IOM criterion and all raised at least one red flag indicative of potential bias. One updated guideline did not address seven of 16 items on CheckUp and the other did not address four. Patient involvement in guideline development was minimal.

Conclusions

Use of the AGREE II Instrument during guideline development did not have as great an effect on guideline quality as might be expected. There is considerable room for improvement in acne treatment guidelines in order to satisfy the IOM trustworthiness criteria and avoid bias.

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European Heart SCORE may underestimates cardiovascular risk after assessing cardiovascular disease with carotid ultrasound in Hidradenitis Suppurativa

Abstract

Hidradenitis suppurativa (HS) is chronic recurrent inflammatory disease affecting intertriginous areas, especially the axilla and the groin1. It is characterized by painful, deep-seated, inflamed lesions, including nodules, abscesses, and sinus tracts2. A recent meta-analysis found an association between HS and traditional cardiovascular (CV) risk factors and metabolic syndrome3.

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Peak inspiratory flow as predictor for tracheotomy

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Publication date: Available online 30 June 2017
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): M. Lesnik, J. J. Sanchez-Guerrero, O. De Crouy Chanel, C. Hervé, J. Guerlain, S. Périé
ObjectivesQuantitative evaluation of upper airway obstruction cannot be commonly performed under acute dyspnea, especially in head and neck cancer (HNC); the decision whether or not to perform airway control surgery may be difficult to reach. Peak inspiratory flow (PIF) has been previously demonstrated to be a useful tool to decide on decannulation after HNC surgery. The aim of the present study was to assess the role of PIF as a standardized non-invasive tool in quantifying severe inspiratory dyspnea requiring emergency tracheostomy.Materials and methodsA single-center prospective observational pilot study analyzed PIF measurements in 22 patients exhibiting acute dyspnea due to upper airway obstruction.Main outcome measuresThe decision whether or not to perform tracheotomy was taken prior to PIF measurement. PIF was measured with a hand-held PIF meter (In-Check method), and laryngeal fiberoscopy was then performed. Obstruction severity was defined by PIF values.ResultsPIF could be measured prior to tracheotomy (imminent in 21 cases, postponed in 1) in all cases. PIF values below 53.1 L/min (i.e., 18.3% of theoretic value) correlated with necessity for emergency tracheotomy. This threshold is concordant with that previously found for the feasibility of decannulation (60L/min).ConclusionsPIF is a non-invasive quantitative parameter assessing severity of upper airway obstruction, that may be helpful in decision-making for tracheostomy. Testing is simple, quick and reproducible.



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A pigmented lesion of the nasopharynx

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Publication date: Available online 30 June 2017
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): J.-W. Kim, S.-D. Kim, K.-S. Cho




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Oral shedding of human herpesviruses in renal transplant recipients

Abstract

Objective

To describe the shedding profile of human herpesviruses in the saliva of renal transplant recipients.

Methods

This is a prospective case-control study of 50 renal transplant recipients and control group of 50 individuals (non-transplanted and immunocompetent). Mouthwash samples were collected via oral rinse and then submitted to screening for the presence of eight types of herpesviruses by using multiplex PCR. Fisher’s exact, chi-square, and Student t tests were used for statistical analysis, and the significance level was set at 5%.

Results

The mean age of the study group was 49.42 ± 12.94 years, 28/50 (56%) were female, and the time elapsed after transplantation was 68.20 ± 67.19 months. Herpes simplex virus 1 (HSV-1) (P = 0.025) and Epstein-Barr virus (EBV) (P = 0.024) were, statistically, more excreted in the saliva of renal transplant recipients compared to control group. Gender (P = 1.00) and age (P = 0.563) did not influence the salivary shedding of herpesviruses in renal transplant recipients. Individuals who excreted varicella-zoster virus in saliva had a shorter mean time of transplantation (22:00 + 2.82 months) (P < 0.001).

Conclusion

Renal transplant recipients excreted herpesviruses more often than controls, especially HSV-1 and EBV, with salivary shedding of herpesviruses being more frequent in patients with recent kidney transplantation.

Clinical relevance

The present findings support other longitudinal studies evaluating the relationship between oral shedding of human herpesviruses and clinical presence of active infection and renal transplant failure.



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Effect of root canal preparation techniques on chlorhexidine substantivity on human dentin: a chemical analysis

Abstract

Objectives

Chlorhexidine binds to dentine to provide sustained action. The aim of the present study was to evaluate and compare the substantivity of chlorhexidine using manual, rotary, and reciprocating systems for root canal preparation.

Methods

Forty-five extracted human single-rooted teeth were used for this study. The samples were divided into three groups (n = 15) according to the instrumentation technique used: manual instrumentation (K-File), rotary instrumentation (ProTaper), and reciprocating instrumentation (Reciproc R25). Chlorhexidine gel (2%) was used as auxiliary chemical substance during root canal preparation. Longitudinal grooves were carved on the free surfaces of the roots, providing two halves of each root and resulting in 30 samples per group. Each group was randomly divided into three subgroups (n = 10), and substantivity was evaluated after 48 h, 7 days, and 30 days of incubation. The amount of CHX (in mg/mL) was measured through reverse-phase high-performance liquid chromatography. Statistical analysis was performed by analysis of variance and the Tukey test for post hoc comparisons (α = 0.05).

Results

The manual did not show a statistical significant difference with rotary instrumentation (P > 0.05), but higher CHX substantivity was recorded in all periods of observation when compared to reciprocating instrumentation (P < 0.05).

Conclusions

The CHX substantivity on human dentine is lowest when using reciprocating compared to manual and rotary instrumentation.

Clinical significance

Using chemical analysis, this study showed that a manual and rotary multi-instrument system results in greater chlorhexidine substantivity on human dentin than a reciprocating single-instrument system.



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Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08)

Abstract

Background

Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013–08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy.

Methods

The BOOG 2013–08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1–2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up.

Discussion

If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival.

Trial registration

The BOOG 2013–08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. http://ift.tt/2ssLB6G



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Inhibition of HDAC6 activity through interaction with RanBPM and its associated CTLH complex

Abstract

Background

Histone deacetylase 6 (HDAC6) is a microtubule-associated deacetylase that promotes many cellular processes that lead to cell transformation and tumour development. We previously documented an interaction between Ran-Binding Protein M (RanBPM) and HDAC6 and found that RanBPM expression inhibits HDAC6 activity. RanBPM is part of a putative E3 ubiquitin ligase complex, termed the C-terminal to LisH (CTLH) complex. Here, we investigated the involvement of the CTLH complex on HDAC6 inhibition and assessed the outcome of this regulation on the cellular motility induced by HDAC6.

Methods

Cell lines (Hela, HEK293 and immortalized mouse embryonic fibroblasts) stably or transiently downregulated for several components of the CTLH complex were employed for the assays used in this study. Interactions of HDAC6, RanBPM and muskelin were assessed by co-immunoprecipitations. Quantifications of western blot analyses were employed to evaluate acetylated α-tubulin levels. Confocal microscopy analyses were used to determine microtubule association of HDAC6 and CTLH complex members. Cell migration was evaluated using wound healing assays.

Results

We demonstrate that RanBPM-mediated inhibition of HDAC6 is dependent on its association with HDAC6. We show that, while HDAC6 does not require RanBPM to associate with microtubules, RanBPM association with microtubules requires HDAC6. Additionally, we show that Twa1 (Two-hybrid-associated protein 1 with RanBPM) and MAEA (Macrophage Erythroblast Attacher), two CTLH complex members, also associate with α-tubulin and that muskelin, another component of the CTLH complex, is able to associate with HDAC6. Downregulation of CTLH complex members muskelin and Rmnd5A (Required for meiotic nuclear division homolog A) resulted in decreased acetylation of HDAC6 substrate α-tubulin. Finally, we demonstrate that the increased cell migration resulting from downregulation of RanBPM is due to the relief in inhibition of HDAC6 α-tubulin deacetylase activity.

Conclusions

Our work shows that RanBPM, together with the CTLH complex, associates with HDAC6 and restricts cell migration through inhibition of HDAC6 activity. This study uncovers a novel function for the CTLH complex and suggests that it could have a tumour suppressive role in restricting HDAC6 oncogenic properties.



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