Publication date: Available online 18 February 2016
Source:Annales de Dermatologie et de Vénéréologie
Author(s): J.-L. Schmutz
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Cervical treatment of oral maxillary squamous cell carcinoma (SCC) remains controversial. We determined the metastases incidence and evaluated its predictive factors. Systematic review and meta-analysis was conducted of 23 Chinese and English-language articles retrieved from PubMed, Ovid, Embase, Cochrane Library, China National Knowledge Infrastructure, and Chinese Scientific and Technological Journal databases. Total cervical metastases and occult metastases rate was 32% and 21%, respectively. Positive lymph node detection was likeliest from levels I to III. The maxillary gingival metastases rate was higher than that of the hard palate. Advanced-stage tumors had higher metastatic risk than early-stage tumors. Well-differentiated tumors had a significantly higher metastases rate than medium and poor-differentiation tumors. N0 cases had survival benefit compared with N+ cases. Metastases rate of oral maxillary SCC correlates significantly with T classification and pathological stage. T and N classifications impact outcome significantly. Therefore, levels I to III selective neck dissection is recommended for patients with T3/4 cN0 disease. © 2016 Wiley Periodicals, Inc. Head Neck, 2016
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Risk after breast-conserving operation is lower with 'high-volume' surgeons, researchers say
Source: HealthDay
Related MedlinePlus Pages: Mastectomy, Women's Health
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But supplements don't offer the same protection, researchers say
Source: HealthDay
Related MedlinePlus Pages: Allergy, Pregnancy and Nutrition, Vitamin D
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The purpose of this study was to investigate whether multidisciplinary team care (MDTC) is associated with outcomes in oral cavity squamous cell carcinoma (SCC).
We retrospectively examined 1616 patients with oral cavity SCC who underwent radical surgery between 1996 and 2011. The study participants were classified into 2 subgroups according to the use of MDTC.
Five-year outcomes were significantly better in the MDTC group than in the no-MDTC group (neck control, 88% vs 84%, p = .0397; disease-specific survival [DSS], 83% vs 78%, p = .0114; and overall survival [OS], 70% vs 64%, p = .0002, respectively). Among patients who were scheduled to undergo adjuvant therapy, the number who completed their adjuvant treatment was significantly higher in the MDTC group than in the no-MDTC group (90% vs 60% to 70%, p < .001).
The association of MDTC with improved outcomes may be potentially explained by a better therapeutic alliance between the patient and the tumor board, and/or a greater thoroughness in clinical management. © 2016 Wiley Periodicals, Inc. Head Neck, 2016
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The purpose of this study was to assess the efficacy and safety of induction chemotherapy with docetaxel-S-1, and radiotherapy (RT) with concurrent daily cisplatin in locally advanced head and neck carcinoma.
Fifty patients received 2 cycles of induction chemotherapy with induction chemotherapy with docetaxel and S-1, followed by 7 cycles of RT with concurrent daily cisplatin.
The most frequent grade 3 to 4 hematologic toxicity was neutropenia (14%). Forty of 50 patients who completed induction chemotherapy with docetaxel and S-1 subsequently started RT with concurrent daily cisplatin, all within 3 to 4 weeks after the start of the second cycle of induction chemotherapy with docetaxel and S-1. The best response to induction chemotherapy with docetaxel and S-1 and after completion of RT with concurrent daily cisplatin was partial response (PR) in 52.5% and complete response in 47.5%, respectively. With a median follow-up of 61 months, 5-year progression-free survival (PFS) and overall survival (OS) were 63.3% and 65.7%, respectively.
Administration of induction chemotherapy with docetaxel and S-1 before RT with concurrent daily cisplatin chemoradiotherapy (CRT) resulted in a high response rate with good tolerability, and did not compromise subsequent CRT. © 2016 Wiley Periodicals, Inc. Head Neck, 2016
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Publication date: 1 April 2016
Source:NeuroImage, Volume 129
Author(s): P.D. Watson, E.J. Paul, G.E. Cooke, N. Ward, J.M. Monti, K.M. Horecka, C.M. Allen, C.H. Hillman, N.J. Cohen, A.F. Kramer, A.K. Barbey
Healthy adults have robust individual differences in neuroanatomy and cognitive ability not captured by demographics or gross morphology (Luders, Narr, Thompson, & Toga, 2009). We used a hierarchical independent component analysis (hICA) to create novel characterizations of individual differences in our participants (N=190). These components fused data across multiple cognitive tests and neuroanatomical variables. The first level contained four independent, underlying sources of phenotypic variance that predominately modeled broad relationships within types of data (e.g., "white matter," or "subcortical gray matter"), but were not reflective of traditional individual difference measures such as sex, age, or intracranial volume. After accounting for the novel individual difference measures, a second level analysis identified two underlying sources of phenotypic variation. One of these made strong, joint contributions to both the anatomical structures associated with the core fronto-parietal "rich club" network (van den Heuvel & Sporns, 2011), and to cognitive factors. These findings suggest that a hierarchical, data-driven approach is able to identify underlying sources of individual difference that contribute to cognitive-anatomical variation in healthy young adults.
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Health care staff gives much needed break, allows caregivers to connect with each other
Source: HealthDay
Related MedlinePlus Pages: Caregivers, Stroke
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Researchers at the University of Cincinnati (UC) have discovered that a human cancer-causing gene, called DEK, can be detected in the plasma of head and neck cancer patients.
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Long-term Canadian study followed participants until age 36
Source: HealthDay
Related MedlinePlus Pages: Bullying, Mental Health, Premature Babies
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Publication date: March 2016
Source:NeuroImage, Volume 128
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Publication date: 15 April 2016
Source:NeuroImage, Volume 130
Author(s): Niklas Kasenburg, Matthew Liptrot, Nina Linde Reislev, Silas N. Ørting, Mads Nielsen, Ellen Garde, Aasa Feragen
Tractography is the standard tool for automatic delineation of white matter tracts from diffusion weighted images. However, the output of tractography often requires post-processing to remove false positives and ensure a robust delineation of the studied tract, and this demands expert prior knowledge. Here we demonstrate how such prior knowledge, or indeed any prior spatial information, can be automatically incorporated into a shortest-path tractography approach to produce more robust results. We describe how such a prior can be automatically generated (learned) from a population, and we demonstrate that our framework also retains support for conventional interactive constraints such as waypoint regions. We apply our approach to the open access, high quality Human Connectome Project data, as well as a dataset acquired on a typical clinical scanner. Our results show that the use of a learned prior substantially increases the overlap of tractography output with a reference atlas on both populations, and this is confirmed by visual inspection. Furthermore, we demonstrate how a prior learned on the high quality dataset significantly increases the overlap with the reference for the more typical yet lower quality data acquired on a clinical scanner. We hope that such automatic incorporation of prior knowledge and the obviation of expert interactive tract delineation on every subject, will improve the feasibility of large clinical tractography studies.
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Publication date: 1 April 2016
Source:NeuroImage, Volume 129
Author(s): Aline W. de Borst, Giancarlo Valente, Iiro P. Jääskeläinen, Pia Tikka
In the perceptual domain, it has been shown that the human brain is strongly shaped through experience, leading to expertise in highly-skilled professionals. What has remained unclear is whether specialization also shapes brain networks underlying mental imagery. In our fMRI study, we aimed to uncover modality-specific mental imagery specialization of film experts. Using multi-voxel pattern analysis we decoded from brain activity of professional cinematographers and sound designers whether they were imagining sounds or images of particular film clips. In each expert group distinct multi-voxel patterns, specific for the modality of their expertise, were found during classification of imagery modality. These patterns were mainly localized in the occipito-temporal and parietal cortex for cinematographers and in the auditory cortex for sound designers. We also found generalized patterns across perception and imagery that were distinct for the two expert groups: they involved frontal cortex for the cinematographers and temporal cortex for the sound designers. Notably, the mental representations of film clips and sounds of cinematographers contained information that went beyond modality-specificity. We were able to successfully decode the implicit presence of film genre from brain activity during mental imagery in cinematographers. The results extend existing neuroimaging literature on expertise into the domain of mental imagery and show that experience in visual versus auditory imagery can alter the representation of information in modality-specific association cortices.
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A supportive confidant improves odds of sustained well-being
Source: HealthDay
Related MedlinePlus Pages: Mental Health, Suicide
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Adjuvante Therapie
Alt, gebrechlich und befallene Lymphknoten – Patienten mit solchen Merkmalen sterben besonders früh nach einer Kolonkarzinom-Therapie. Wie gut die Prognose ist, lässt sich jetzt relativ gut berechnen.
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Justicidin A is a structurally defined arylnaphthalide lignan, which has been shown anti-cancer activity; however, the neuroprotective effect of justicidin A is still untested. In this study, we investigated the action of justicidin A on amyloid beta (Aβ)25–35-induced neuronal cell death via inhibition of the hyperphosphorylation of tau and induction of autophagy in SH-SY5Y cells. Pretreatment with justicidin A significantly elevated cell viability in cells treated with Aβ25–35. Western blot data demonstrated that justicidin A inhibited the Aβ25–35-induced up-regulation the levels of hyperphosphorylation of tau in SH-SY5Y cells. In addition, treatment with justicidin A significantly induced autophagy as measured by the increasing LC3 II/I ratio, an important autophagy marker. These studies showed that justicidin A inhibited activity of glycogen synthase kinase-3beta (GSK-3β), which is an important kinase in up-stream signaling pathways; inhibited hyperphosphorylation of tau in AD; and enhanced activity of AMP-activated protein kinase (AMPK), which is the key molecule for both hyperphosphorylation of tau and induction of autophagy. These data provide the first evidence that justicidin A protects SH-SY5Y cells from Aβ25–35-induced neuronal cell death through inhibition of hyperphosphorylation of tau and induction of autophagy via regulation the activity of GSK-3β and AMPK, and they also provide some insights into the relationship between tau protein hyperphosphorylation and autophagy. Thus, we conclude that justicidin A may have a potential role for neuroprotection and, therefore, may be used as a therapeutic agent for AD.
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Publication date: Available online 18 February 2016
Source:Hearing Research
Author(s): Rebecca Lim, Alan M. Brichta
We describe the development of the human inner ear with the invagination of the otic vesicle at 4 weeks gestation (WG), the growth of the semicircular canals from 5 WG, and the elongation and coiling of the cochlea at 10 WG. As the membranous labyrinth takes shape, there is a concomitant development of the sensory neuroepithelia and their associated structures within. This review details the growth and differentiation of the vestibular and auditory neuroepithelia, including synaptogenesis, the expression of stereocilia and kinocilia, and innervation of hair cells by afferent and efferent nerve fibres. Along with development of essential sensory structures we outline the formation of crucial accessory structures of the vestibular system – the cupula and otolithic membrane and otoconia as well as the three cochlea compartments and the tectorial membrane. Recent molecular studies have elaborated on classical anatomical studies to characterize the development of prosensory and sensory regions of the fetal human cochlea using the transcription factors, PAX2, MAF-B, SOX2, and SOX9. Further advances are being made with recent physiological studies that are beginning to describe when hair cells are becoming functionally active during human gestation.
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Publication date: Available online 18 February 2016
Source:Hearing Research
Author(s): Gavin M. Bidelman, Caitlin Nelms, Shaum P. Bhagat
The mammalian cochlea functions as a filter bank that performs a spectral, Fourier-like decomposition on the acoustic signal. While tuning can be compromised (e.g., broadened with hearing impairment), whether or not human cochlear frequency resolution can be sharpened through experiential factors (e.g., training or learning) has not yet been established. Previous studies have demonstrated sharper psychophysical tuning curves in trained musicians compared to nonmusicians, implying superior peripheral tuning. However, these findings are based on perceptual masking paradigms, and reflect engagement of the entire auditory system rather than cochlear tuning, per se. Here, by directly mapping physiological tuning curves from stimulus frequency otoacoustic emissions (SFOAEs)—cochlear emitted sounds—we show that estimates of human cochlear tuning in a high-frequency cochlear region (4 kHz) is further sharpened (by a factor of 1.5x) in musicians and improves with the number of years of their auditory training. These findings were corroborated by measurements of psychophysical tuning curves (PTCs) derived via simultaneous masking, which similarly showed sharper tuning in musicians. Comparisons between SFOAE and PTCs revealed closer correspondence between physiological and behavioral curves in musicians, indicating that tuning is also more consistent between different levels of auditory processing in trained ears. Our findings demonstrate an experience-dependent enhancement in the resolving power of the cochlear sensory epithelium and the spectral resolution of human hearing and provide a peripheral account for the auditory perceptual benefits observed in musicians. Both local and feedback (e.g., medial olivocochlear efferent) mechanisms are discussed as potential mechanisms for experience-dependent tuning.
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A co-authored collaboration between a theatre practitioner and a clinical psychiatrist, this paper will examine Rough for Theatre II (RFTII) and Beckett's demonstration of the way records are used to understand the human subject. Using Beckett's play to explore interdisciplinary issues of embodiment and diagnosis, the authors will present a dialogue that makes use of the 'best sources' in precisely the same manner as the play's protagonists. One of those sources will be Beckett himself, as Heron will locate the play in its theatrical context through reflections upon his own practice (with Fail Better Productions, UK) as well as recent studies such as Beckett, Technology and the Body (Maude 2009) and Performing Embodiment in Samuel Beckett's Drama (McMullan 2010); another source will be the philosopher Wilhelm Windleband, whose 1901 History of Philosophy was read and noted upon by Beckett in the 1930s, as Broome will introduce a philosophical and psychiatric context to the exchange. Windelband is now a neglected figure in philosophy; but as one of the key figures of Neo-Kantianism in the late 19th century, his work was an important impetus to that of Rickert, Weber and Heidegger. Specifically, Windelband gives us the distinction between idiographic and nomothetic understanding of individuals, an approach that is of relevance to the psychiatric encounter. This academic dialogue will consider tensions between subjectivity and objectivity in clinical and performance practice, while examining Beckett's analysis of the use of case notes and relating them back to Windelband's ideas on the understanding of others. The dialogue took place in 2011 at the University of Warwick, and has since been edited by the authors.
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Primal Pictures resources are the world's most medically accurate and detailed 3D graphic rendering of human anatomy. With benchmark anatomy, physiology and clinical content, Primal Pictures is widely accepted as the best in class and used by thousands of health science educators, students and practitioners worldwide to teach, learn and practice.
More specifically, the Primal Pictures 3D Human Anatomy Package with the added bonus of the 3D Human Anatomy & Physiology title will provide your institution with a greater insight with content equivalent to the major anatomy and physiology textbooks and adheres to Human Anatomy and Physiology Society guidelines.
Primal's 3D Human Anatomy and Physiology also gives Faculty access to additional content via a dedicated Faculty area. They can access a library of images, animations, slides for creating lectures and a bank of quiz questions that are compatible with many Learning Management Systems.
Created to help your students learn, recall and apply their knowledge interactively:
Please click here or call 800-901-5494 if you would like to schedule a webinar to review custom options specifically suited for your institution, and a STAT!Ref representative will be in touch with you shortly.
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An Unusual Cause of a Solitary Lung Cavity.
Conn Med. 2016 Jan;80(1):25-8
Authors: Yap V, Salerno E, Datta D
Abstract
Sarcoidosis is a systemic granulomatous disease of unknown etiology. Pulmonary involvement is common, but lung nodules in sarcoidosis are uncommon, and solitary nodules that cavitate are extremely rare. Nodular sarcoidosis is usually found in young, healthy, predominantly female individuals. These lesions need to be differentiated from multiple other conditions, including neoplasms and granulomatous infections. A thorough workup for other etiologies of cavitary lung lesions is required for diagnosis. Despite an ominous presentation, nodular cavitary sarcoidosis portends a favorable outcome. We report a patient who presented with a solitary cavitary nodular lung lesion that was diagnosed as sarcoidosis after extensive workup.
PMID: 26882788 [PubMed - in process]
Infectious salmon anaemia virus (ISAV) is an orthomyxovirus infecting salmonid fish. The virus is adapted to low temperature and has a replication optimum between 10–15 °C. In this study the subcellular localization and protein interactions for the protein encoded by the largest open reading frame of gene segment 8 (s8ORF2) were investigated. In ISAV infected cells the s8ORF2 protein was found mainly in the cytosol but a minor fraction of cells expressed the protein in the nucleus as well. Green fluorescent protein-tagged s8ORF2 did not leak out of the cell when the plasma membrane was permeabilized, suggesting interactions with intracellular structural components. The s8ORF2 protein exists both as monomer and homodimer, and co-immunoprecipitation experiments strongly suggests it binds to the ISAV fusion-, nucleo- and matrix proteins. Two versions of s8ORF2 were detected with apparent molecular weights of 24–26 and 35 kDa in lysates of infected cells. The 35 kDa type is an early viral protein while the smaller version appears during the later phases of infection. The 24–26 kDa type was also the predominant form in viral particles. The s8ORF2 protein has previously been shown to bind RNA and interfere with interferon induction and signaling. Here we found that a fraction of the s8ORF2 protein pool in infected cells is likely to be conjugated to the interferon stimulated gene 15 (ISG15) and ubiquitin. Furthermore, several endogenous proteins pulled down by the s8ORF2 protein were identified by liquid chromatography mass spectrometry (LC-MS).
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This book is the 2nd edition of soft tissue tumours from the illustrious Biopsy Interpretation series. As I am not acquainted with the first edition, this review will be based entirely on this iteration of the book.
I would like to start by saying that this book truly emerges like a 'good deed in a bad world'. This skilfully crafted and aesthetically pleasing book is written in a clear, succinct and unambiguous manner and covers a prodigious range of soft tissue tumours.
The book opens with an instructive chapter on handling, reporting and grading soft tissue tumours. The remaining 22 chapters broadly group entities based on tumour lineage and morphology, including the morphological appearance of lesional cells and growth pattern of tumours. This is a prudent and practical method to present these chapters, as often, particularly in limited samples, soft tissue tumours present themselves as one of a number…
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The paper Nikesitch, N. & Ling, S. C. 2015. Molecular mechanisms in multiple myeloma drug resistance. J Clin Pathol. Published in November 2015 has been updated to reflect the change in name of Western Sydney University.
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There is limited published data on the mode of relapse presentation in acute myeloid leukaemia (AML) and the efficacy of routine outpatient monitoring in detecting relapse. In diffuse large B cell lymphoma, studies looking at postremission surveillance imaging found that the majority of relapses were detected at patient self-presentation;1 however, there is no similar data available for AML. Such information would be of relevance to all patients in occupations requiring medical checks for public safety reasons, such as pilots and public transport drivers, where the risk of acute incapacitation must be assessed prior to employment health clearance.
A retrospective analysis was conducted of 101 cases meeting criteria for relapsed AML that were treated in our centre from September 2007 to February 2014, focusing on the mode of presentation and the severity of symptoms at the time of relapse. Patient characteristics are shown in table 1….
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It is well recognised that genomic, proteomic and biomarker studies require properly annotated and well-characterised biospecimens. Consequently, this necessitates biobanks to collect, store and distribute biospecimens under stringent quality control and assurance measures. However, despite this realisation, there remains a lack of standardisation in quality management among biobanks and consensus as to which quality indicators provide the optimal molecular diagnostic performance tools and information for biospecimens. In an attempt to identify key factors that predict tissue specimen integrity and quality, this systematic review investigated the measures reported in the literature, which characterised the collection, processing and storage of high-quality tissue specimens. Our findings demonstrated RNA integrity, alone, may not be an effective measure of tissue quality. Furthermore, the frequently reported parameters related to biospecimen integrity, such as storage time, temperature, time to cryopreservation and tissue morphology were also not effective indicators of quality control and assurance. These findings suggest that it is unlikely that a single marker will provide the optimal diagnostic and performance information for biospecimens, but rather, a panel of markers assessing the molecular integrity of the lifespan of the biospecimen is required. Further work is needed to identify which factors predict specimen integrity and quality in biobanked tissue specimens.
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Aims
MYC rearrangements with or without BCL2 rearrangements have been shown to be associated with poor prognosis and inferior survival in diffuse large B-cell lymphomas (DLBCL). Most of these cases are still diagnosed by fluorescent in situ hybridisation (FISH) testing, which is expensive, requires expertise and is not routinely available in all laboratories. Immunohistochemistry (IHC) is widely available and has the potential to be used as a screening test to identify cases with increased protein expression and select cases that require confirmatory testing. We correlated the expression of MYC and BCL2 by IHC with FISH studies in an attempt to define a cut-off value, which can be used by laboratories to select cases requiring confirmatory FISH testing. The prevalence of MYC-positive DLBCL and double-hit lymphoma (DHL) has also been studied.
Methods
209 cases comprising of 15 cases of Burkitt lymphoma (BL), 13 cases of intermediate BL/DLBCL and 181 cases of DLBCL were included. IHC and FISH for MYC and BCL2 were performed and the results were correlated.
Results
The prevalence of MYC-positive DLBCL and MYC/BCL2DHL was 13.4% and 7.4%, respectively, in our study. Germinal-centre subtype was more common in MYC-positive DLBCL and DHL. MYC-positive DLBCL also showed higher median Ki-67 (>90%) and CD10 positivity as compared with MYC-negative cases.
Conclusions
IHC can be used for screening cases, which require further confirmatory FISH testing. We recommend a cut-off value of ≥30% for MYC by IHC; however, international standardisation of these values is necessary to provide uniformity among laboratories.
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Aim
This survey investigated the variation in the use of the breast core biopsy categories B1 normal and B2 benign.
Method
A survey with case scenarios was circulated to 701 breast pathologists in the UK.
Results
The response rate was 40%. If there was concordance between the radiological and histological findings, then there was a clear consensus on the appropriate B category. However, if there was discordance between the radiological and histological findings, then frequently there was poor agreement on the appropriate category. Analysis of these cases and supplementary questions on the criteria used to make a pathological categorisation showed that some pathologists are influenced by the radiological features or by the multidisciplinary discussion, rather than just using the histological features.
Conclusions
This survey shows that pathologists frequently do not follow the National Health Service breast screening guideline that B categories should be based solely on the histological changes.
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Aims
B3 lesions of the breast represent a difficult management dilemma. The umbrella term 'B3' incorporates lesions with little associated malignancy risk as well as lesions with significant risk of concurrent neoplasia. Diagnosis of B3 lesions in screening populations is largely made on needle core biopsy, which provides little tissue to adequately diagnose pathologically diverse lesions. The advent of vacuum-assisted biopsy (VAB) provides the multidisciplinary team with a more representative pathology sample to direct management.
Methods
In this unit, in 2009, a pathway to guide management of B3 lesions detected on needle core biopsy in screening patients was implemented to assess whether VAB was a safe and viable alternative to surgery in selected cases.
Here we present the 5-year follow-up results of this pathway.
Results
398 patients with B3 lesions were suitable for this pathway, of which 321 went on to have second-line VAB. 24% of these patients subsequently required surgery for malignancy or ongoing concerns, and thus 245 avoided surgery being subsequently referred for 5-year mammographic surveillance or back to screening. Median follow-up was 3 years (IQR 2), and no cancers were detected at the original B3 site during follow-up.
Conclusions
We have demonstrated here that with large volume tissue sampling for indeterminate lesions of the breast surgery can be safely avoided in selected B3 lesions with and without atypia.
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Aims
Several lines of evidence point to hypercoagulability as an important factor for heart failure (HF) pathogenesis.
Methods
We hypothesised that endothelial tissue factor (TF) expression reflects altered tissue haemostasis which is related to the severity of HF. Accordingly, we investigated TF expression in the biopsies of 60 patients with HF and 22 without HF. In addition, we assessed the relationship between endothelial TF expression and clinical markers of HF severity.
Results
The control subjects without HF presented absent or weak TF expression in few microvessels, while the endomyocardial biopsies of patients with HF, capillary vessels presented both weak and severe staining patterns by immunohistochemistry usually with regional distribution. This was collaborated by the immune electron microscopic study. The severe microvessel TF antigen expression was found in 11 (18.3%) patients with HF. The endothelial TF expression was inversely associated with left ventricular ejection fraction (r=–0.42, p=0.001) and positively with N-terminal brain natriuretic peptide (r=0.36, p<0.023), markers of HF severity.
Conclusions
Regional upregulation of the TF in the capillary endothelial cells suggests local myocardial thrombogenicity. Furthermore, the relationship between endothelial TF and HF severity would be keeping in line with the hypothesis that an altered tissue haemostasis is most profoundly expressed in patients with severe HF. Weak TF expression found in several microvessels of the biopsy specimens patients without HF pathology might be potentially related to a low basal level of activation of the clotting system in normal individuals.
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Aim
Insufficient attention for the Ki-67 immunohistochemistry has been given to the importance of tissue handling for surgical breast cancer specimens. We sought to investigate the effect of fixation status on the Ki-67.
Methods
We examined the effect of fixative, time to and duration of fixation using surgical specimens, and finally, compared the paired Ki-67 index in the tumour between core needle and surgical specimen.
Results
The Ki-67 was significantly higher when 10% neutral buffered formalin was used (p=0.0276). Insufficient fixation caused a drastic reduction in the Ki-67 index (p=0.0177), but not significant in oestrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Sixteen hours delayed time to fixation also caused a reduction of the Ki-67 (p=0.0284), but not significant in ER. Prolonged fixation significantly led to a gradual reduction in the Ki-67 in a time-dependent manner, but not in both ER and HER2. Finally, cutting the tumour before fixation improved fixation status and consequently caused an increased level of the Ki-67 index (p=0.0181), which resulted in a strong correlation of the Ki-67 between core needle and surgical specimen (r=0.8595).
Conclusions
Tissue handling of surgical specimen is critical for assessing the Ki-67 compared with ER and HER2. We should pay more attention to tissue fixation status for the standard assessment of the Ki-67 index.
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Background
Oxidative stress may play pathogenic roles in the mechanisms underlying chronic hepatitis C (CHC). The impact of excessive oxidative stress and iron dysregulation on the development of hepatocellular carcinoma (HCC) after interferon therapy has not been established.
Methods
We investigated the impact of oxidative stress and iron deposition on HCC development after therapy with pegylated interferon (PegIFN)+ribavirin in CHC patients. Systemic and intracellular iron homeostasis was evaluated in liver tissues, peripheral blood mononuclear cells and sera.
Results
Of 203 patients enrolled, 13 developed HCC during the 5.6-year follow-up. High hepatic 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were significantly associated with HCC development in multivariate analysis (p=0.0012) which was also significantly correlated with severity of hepatic iron deposition before therapy (p<0.0001). Systemic and intracellular iron regulators of hepcidin and F-box and leucine-rich repeat protein 5 (FBXL5) expression levels were significantly suppressed in CHC patients (p=0.0032 and p=0.016, respectively) despite their significantly higher levels of serum iron and ferritin compared with controls. However, intracellular iron regulators of FBXL5 and iron regulatory proteins were regulated in balance with hepatic iron deposition. Significant correlations were observed among IL-6, bone morphogenetic protein 6, hepcidin and ferroportin, as regards systemic iron regulation.
Conclusions
Measurement of hepatic oxidative stress before antiviral therapy is useful for the prediction of HCC development after interferon therapy. Low baseline levels of the intracellular iron regulators of FBXL5 in addition to a suppressed hepcidin level might be associated with severe hepatic iron deposition in CHC patients.
Trial registration number
UMIN 000001031.
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UK cancer cases soar by 12% since mid-90s to 352,000 each year https://t.co/r6QQ8OwLQb
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Cardiovascular diseases and, among them, channelopathies and cardiomyopathies are a major cause of death worldwide. The molecular and genetic defects underlying these cardiac disorders are complex, leading to a large range of structural and functional heart phenotypes. Identification of molecular and functional mechanisms disrupted by mutations causing channelopathies and cardiomyopathies is essential to understanding the link between an altered gene and clinical phenotype. The development of animal models has been proven to be efficient for functional studies in channelopathies and cardiomyopathies. In particular, the Drosophila model has been largely applied for deciphering the molecular and cellular pathways affected in these inherited cardiac disorders and for identifying their genetic modifiers. Here we review the utility and the main contributions of the fruitfly models for the better understanding of channelopathies and cardiomyopathies. We also discuss the investigated pathological mechanisms and the discoveries of evolutionarily conserved pathways which reinforce the value of Drosophila in modeling human cardiac diseases.
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Various stem cells gradually turned to be critical players in tissue engineering and regenerative medicine therapies. Current evidence has demonstrated that in addition to growth factors and the extracellular matrix, multiple metabolic pathways definitively provide important signals for stem cell self-renewal and differentiation. In this review, we mainly focus on a detailed overview of stem cell metabolism in vitro. In stem cell metabolic biology, the dynamic balance of each type of stem cell can vary according to the properties of each cell type, and they share some common points. Clearly defining the metabolic flux alterations in stem cells may help to shed light on stemness features and differentiation pathways that control the fate of stem cells.
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Breast cancers which are particularly complex and diverse, as judged by a test used in ecology to analyse species of animals and plants, are particularly likely to progress and lead to death, a new study shows. The test could be used in the clinic to…
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We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo), a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L) for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARγ-coactivator 1 α, as well as the inhibition of α-amylase and α-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus.
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Purpose of review: This article reviews the current literature and summarizes the latest developments in screening and early detection of oral cancers and looks at the future possibilities. Recent findings: Oral cancer is the best model for screening and prevention. The screening for oral cancer can be population based, opportunistic, or targeted. A long-term 15-year follow-up data of a randomized controlled study from a developing country setting indicated a sustained reduction in oral cancer mortality in high-risk individuals. Visual oral examination remains the mainstay in the screening. Several adjunctive techniques have been described to aid in the clinical examination of these lesions. A Cochrane review revealed that there is no evidence to recommend these adjuncts in clinically visible lesions. Salivary biomarkers seem to be promising as a tool for screening in the future. A Targeted Evidence Update for the US Preventive Services Task Force found no evidence on screening either in the general or selected high-risk population for oral cancer in the United States or on benefit of any adjunctive device affecting the performance of the screening examination. Summary: Current evidence shows that community based screening has a value in reducing the oral cancer mortality in high-risk group of population. But this evidence may not be universally applicable. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
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