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Find video protocols related to scientific articles indexed in Pubmed.
Dying neurons in thalamus of asphyxiated term newborns and rats are autophagic.
Ann. Neurol.
PUBLISHED: 09-16-2014
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Neonatal hypoxic-ischemic encephalopathy (HIE) still carries a high burden by its mortality and long-term neurological morbidity in survivors. Apart from hypothermia, there is no acknowledged therapy for HIE, reflecting the lack of mechanistic understanding of its pathophysiology. (Macro)autophagy, a physiological intracellular process of lysosomal degradation, has been proposed to be excessively activated in excitotoxic conditions such as HIE. The present study examines whether neuronal autophagy in the thalamus of asphyxiated human newborns or P7 rats is enhanced and related to neuronal death processes.
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Using a rainforest-flame forest mosaic to test the hypothesis that leaf and litter fuel flammability is under natural selection.
Oecologia
PUBLISHED: 08-14-2014
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We used a mosaic of infrequently burnt temperate rainforest and adjacent, frequently burnt eucalypt forests in temperate eastern Australia to test whether: (1) there were differences in flammability of fresh and dried foliage amongst congeners from contrasting habitats, (2) habitat flammability was related to regeneration strategy, (3) litter fuels were more flammable in frequently burnt forests, (4) the severity of a recent fire influenced the flammability of litter (as this would suggest fire feedbacks), and (5) microclimate contributed to differences in fire hazard amongst habitats. Leaf-level comparisons were made among 11 congeneric pairs from rainforest and eucalypt forests. Leaf-level ignitability, combustibility and sustainability were not consistently higher for taxa from frequently burnt eucalypt forests, nor were they higher for species with fire-driven recruitment. The bulk density of litter-bed fuels strongly influenced flammability, but eucalypt forest litter was not less dense than rainforest litter. Ignitability, combustibility and flame sustainability of community surface fuels (litter) were compared using fuel arrays with standardized fuel mass and moisture content. Forests previously burned at high fire severity did not have consistently higher litter flammability than those burned at lower severity or long unburned. Thus, contrary to the Mutch hypothesis, there was no evidence of higher flammability of litter fuels or leaves from frequently burnt eucalypt forests compared with infrequently burnt rainforests. We suggest the manifest pyrogenicity of eucalypt forests is not due to natural selection for more flammable foliage, but better explained by differences in crown openness and associated microclimatic differences.
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Involvement of autophagy in hypoxic-excitotoxic neuronal death.
Autophagy
PUBLISHED: 03-11-2014
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Neuronal autophagy is increased in numerous excitotoxic conditions including neonatal cerebral hypoxia-ischemia (HI). However, the role of this HI-induced autophagy remains unclear. To clarify this role we established an in vitro model of excitotoxicity combining kainate treatment (Ka, 30 µM) with hypoxia (Hx, 6% oxygen) in primary neuron cultures. KaHx rapidly induced excitotoxic death that was completely prevented by MK801 or EGTA. KaHx also stimulated neuronal autophagic flux as shown by a rise in autophagosome number (increased levels of LC3-II and punctate LC3 labeling) accompanied by increases in lysosomal abundance and activity (increased SQSTM1/p62 degradation, and increased LC3-II levels in the presence of lysosomal inhibitors) and fusion (shown using an RFP-GFP-LC3 reporter). To determine the role of the enhanced autophagy we applied either pharmacological autophagy inhibitors (3-methyladenine or pepstatinA/E64) or lentiviral vectors delivering shRNAs targeting Becn1 or Atg7. Both strategies reduced KaHx-induced neuronal death. A prodeath role of autophagy was also confirmed by the enhanced toxicity of KaHx in cultures overexpressing BECN1 or ATG7. Finally, in vivo inhibition of autophagy by intrastriatal injection of a lentiviral vector expressing a Becn1-targeting shRNA increased the volume of intact striatum in a rat model of severe neonatal cerebral HI. These results clearly show a death-mediating role of autophagy in hypoxic-excitotoxic conditions and suggest that inhibition of autophagy should be considered as a neuroprotective strategy in HI brain injuries.
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Role of activin-A and myostatin and their signaling pathway in human myometrial and leiomyoma cell function.
J. Clin. Endocrinol. Metab.
PUBLISHED: 02-25-2014
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Uterine leiomyomas are highly prevalent benign tumors of premenopausal women and the most common indication for hysterectomy. However, the exact etiology of this tumor is not fully understood.
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Can contrast-enhanced ultrasound distinguish malignant from reactive lymph nodes in patients with head and neck cancers?
Ultrasound Med Biol
PUBLISHED: 01-22-2014
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The purpose of this study was to investigate the utility of contrast-enhanced ultrasound in differentiating benign from malignant cervical lymph nodes in patients with squamous cell carcinoma of the head and neck. A consecutive series of 17 patients with known head and neck malignancy scheduled for neck surgery and lymph node clearance were recruited for contrast-enhanced ultrasound evaluation. Sonographic signal intensity as a function of time, comparing features of time to peak, time to arrival and time to wash-out, was quantified. The selected node was removed surgically and submitted for histology. Contrast-enhanced ultrasound examination had 100% sensitivity and 85.7% specificity for lymph node involvement. Functional analysis revealed contrast peaks significantly earlier in the malignant nodes (mean ± standard deviation) of 24.14 ± 2.7 s compared with 29.33 ± 3.4 s (p = 0.0128). Contrast-enhanced ultrasound holds promise in the detection and characterization of metastatic nodes that would not be diagnosed as abnormal on the basis of conventional ultrasound criteria.
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Seasonality and facilitation drive tree establishment in a semi-arid floodplain savanna.
Oecologia
PUBLISHED: 01-10-2014
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A popular hypothesis for tree and grass coexistence in savannas is that tree seedlings are limited by competition from grasses. However, competition may be important in favourable climatic conditions when abiotic stress is low, whereas facilitation may be more important under stressful conditions. Seasonal and inter-annual fluctuations in abiotic conditions may alter the outcome of tree-grass interactions in savanna systems and contribute to coexistence. We investigated interactions between coolibah (Eucalyptus coolabah) tree seedlings and perennial C4 grasses in semi-arid savannas in eastern Australia in contrasting seasonal conditions. In glasshouse and field experiments, we measured survival and growth of tree seedlings with different densities of C4 grasses across seasons. In warm glasshouse conditions, where water was not limiting, competition from grasses reduced tree seedling growth but did not affect tree survival. In the field, all tree seedlings died in hot dry summer conditions irrespective of grass or shade cover, whereas in winter, facilitation from grasses significantly increased tree seedling survival by ameliorating heat stress and protecting seedlings from herbivory. We demonstrated that interactions between tree seedlings and perennial grasses vary seasonally, and timing of tree germination may determine the importance of facilitation or competition in structuring savanna vegetation because of fluctuations in abiotic stress. Our finding that trees can grow and survive in a dense C4 grass sward contrasts with the common perception that grass competition limits woody plant recruitment in savannas.
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The illusion of caries from anatomical variance: a case report.
Prim Dent J
PUBLISHED: 12-18-2013
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This paper presents two examples of unusual radiolucencies caused by grossly distorted anatomy. In the circumstances these could easily have been misdiagnosed as caries. Some of the more common artefacts presenting as caries are discussed. This article highlights the importance of combining radiographical and clinical findings to produce an accurate diagnosis.
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Autosis is a Na+,K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-25-2013
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A long-standing controversy is whether autophagy is a bona fide cause of mammalian cell death. We used a cell-penetrating autophagy-inducing peptide, Tat-Beclin 1, derived from the autophagy protein Beclin 1, to investigate whether high levels of autophagy result in cell death by autophagy. Here we show that Tat-Beclin 1 induces dose-dependent death that is blocked by pharmacological or genetic inhibition of autophagy, but not of apoptosis or necroptosis. This death, termed "autosis," has unique morphological features, including increased autophagosomes/autolysosomes and nuclear convolution at early stages, and focal swelling of the perinuclear space at late stages. We also observed autotic death in cells during stress conditions, including in a subpopulation of nutrient-starved cells in vitro and in hippocampal neurons of neonatal rats subjected to cerebral hypoxia-ischemia in vivo. A chemical screen of ?5,000 known bioactive compounds revealed that cardiac glycosides, antagonists of Na(+),K(+)-ATPase, inhibit autotic cell death in vitro and in vivo. Furthermore, genetic knockdown of the Na(+),K(+)-ATPase ?1 subunit blocks peptide and starvation-induced autosis in vitro. Thus, we have identified a unique form of autophagy-dependent cell death, a Food and Drug Administration-approved class of compounds that inhibit such death, and a crucial role for Na(+),K(+)-ATPase in its regulation. These findings have implications for understanding how cells die during certain stress conditions and how such cell death might be prevented.
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Neuroscience, quantum indeterminism and the Cartesian soul.
Brain Cogn
PUBLISHED: 07-22-2013
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Quantum indeterminism is frequently invoked as a solution to the problem of how a disembodied soul might interact with the brain (as Descartes proposed), and is sometimes invoked in theories of libertarian free will even when they do not involve dualistic assumptions. Taking as example the Eccles-Beck model of interaction between self (or soul) and brain at the level of synaptic exocytosis, I here evaluate the plausibility of these approaches. I conclude that Heisenbergian uncertainty is too small to affect synaptic function, and that amplification by chaos or by other means does not provide a solution to this problem. Furthermore, even if Heisenbergian effects did modify brain functioning, the changes would be swamped by those due to thermal noise. Cells and neural circuits have powerful noise-resistance mechanisms, that are adequate protection against thermal noise and must therefore be more than sufficient to buffer against Heisenbergian effects. Other forms of quantum indeterminism must be considered, because these can be much greater than Heisenbergian uncertainty, but these have not so far been shown to play a role in the brain.
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Redesign and Implementation of the Radiology Clerkship: From Traditional to Longitudinal and Integrative.
J Am Coll Radiol
PUBLISHED: 03-15-2013
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The authors discuss the evolution and application of 3 radiology teaching methods-a fundamentals-of-imaging course, a combined clinical-radiology case conference, and a radiology objective structured clinical examination-to medical education at the Brigham and Womens Hospital site of Harvard Medical School.
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Multiple interacting cell death mechanisms in the mediation of excitotoxicity and ischemic brain damage: a challenge for neuroprotection.
Prog. Neurobiol.
PUBLISHED: 03-05-2013
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There is currently no approved neuroprotective pharmacotherapy for acute conditions such as stroke and cerebral asphyxia. One of the reasons for this may be the multiplicity of cell death mechanisms, because inhibition of a particular mechanism leaves the brain vulnerable to alternative ones. It is therefore essential to understand the different cell death mechanisms and their interactions. We here review the multiple signaling pathways underlying each of the three main morphological types of cell death--apoptosis, autophagic cell death and necrosis--emphasizing their importance in the neuronal death that occurs during cerebral ischemia and hypoxia-ischemia, and we analyze the interactions between the different mechanisms. Finally, we discuss the implications of the multiplicity of cell death mechanisms for the design of neuroprotective strategies.
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Excitotoxicity-induced endocytosis mediates neuroprotection by TAT-peptide-linked JNK inhibitor.
J. Neurochem.
PUBLISHED: 11-09-2011
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Excitotoxicity and cerebral ischemia induce strong endocytosis in neurons, and we here investigate its functional role in neuroprotection by a functional transactivator of transcription (TAT)-peptide, the c-Jun N-terminal kinase (JNK) inhibitor D-JNKI1, against NMDA-excitotoxicity in vitro and neonatal ischemic stroke in P12 Sprague-Dawley rats. In both situations, the neuroprotective efficacy of D-JNKI1 was confirmed, but excessively high doses were counterproductive. Importantly, the induced endocytosis was necessary for neuroprotection, which required that the TAT-peptide be administered at a time when induced endocytosis was occurring. Uptake by other routes failed to protect, and even promoted cell death at high doses. Blocking the induced endocytosis of D-JNKI1 with heparin or with an excess of D-TAT-peptide eliminated the neuroprotection. We conclude that excitotoxicity-induced endocytosis is a basic property of stressed neurons that can target neuroprotective TAT-peptides into the neurons that need protection. Furthermore, it is the main mediator of neuroprotection by D-JNKI1. This may explain promising reports of strong neuroprotection by TAT-peptides without apparent side effects, and warns that the timing of peptide administration is crucial.
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Beclin 1-independent autophagy contributes to apoptosis in cortical neurons.
Autophagy
PUBLISHED: 10-01-2011
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Neuronal autophagy is enhanced in many neurological conditions, such as cerebral ischemia and traumatic brain injury, but its role in associated neuronal death is controversial, especially under conditions of apoptosis. We therefore investigated the role of autophagy in the apoptosis of primary cortical neurons treated with the widely used and potent pro-apoptotic agent, staurosporine (STS). Even before apoptosis, STS enhanced autophagic flux, as shown by increases in autophagosomal (LC3-II level, LC3 punctate labeling) and lysosomal (cathepsin D, LAMP1, acid phosphatase, ?-hexasominidase) markers. Inhibition of autophagy by 3-methyladenine, or by lentivirally-delivered shRNAs against Atg5 and Atg7, strongly reduced the STS-induced activation of caspase-3 and nuclear translocation of AIF, and gave partial protection against neuronal death. Pan-caspase inhibition with Q-VD-OPH likewise protected partially against neuronal death, but failed to affect autophagy. Combined inhibition of both autophagy and caspases gave strong synergistic neuroprotection. The autophagy contributing to apoptosis was Beclin 1-independent, as shown by the fact that Beclin 1 knockdown failed to reduce it but efficiently reduced rapamycin-induced autophagy. Moreover the Beclin 1 knockdown sensitized neurons to STS-induced apoptosis, indicating a cytoprotective role of Beclin 1 in cortical neurons. Caspase-3 activation and pyknosis induced by two other pro-apoptotic stimuli, MK801 and etoposide, were likewise found to be associated with Beclin 1-independent autophagy and reduced by the knockdown of Atg7 but not Beclin 1. In conclusion, Beclin 1-independent autophagy is an important contributor to both the caspase-dependent and -independent components of neuronal apoptosis and may be considered as an important therapeutic target in neural conditions involving apoptosis.
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Indigenous message tailoring increases consumption of fresh vegetables by clients of community pantries.
Health Commun
PUBLISHED: 06-24-2011
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This study tested whether message tailoring of recipes and food-use tips for low-income households is superior to providing a generic version of the material. The field experiment was conducted in the busy conditions found at community food pantries, and included 10 food distributions at each of six sites. We analyzed the consumption of fresh vegetables 6 days following distributions, and retention of print materials 6 weeks later. Self-determination and reactance theories guided the development of tailoring in an indigenous fashion, allowing each pantry client to choose recipes and food tips thought personally useful. This contrasted against paternalistic tailoring, common in health communication, where a motivational theory is used to regulate the health messages given to recipients. Results demonstrated benefits of tailoring over both generic and control conditions and uncovered the degree of tailoring that produced the largest effects. As suggested by construal level theory, the intervention addressed recipients immediate and concrete decisions about healthy eating, instead of distant or abstract goals like prevention of illnesses. We documented per-client costs of tailored information. Results also suggested that benefits from social capital at sites offering a health outreach may exceed the impact of message tailoring on outcomes of interest.
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VATS thymectomy for nonthymomatous myasthenia gravis: standardized outcome assessment using the myasthenia gravis foundation of America clinical classification.
Innovations (Phila)
PUBLISHED: 06-20-2011
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: Video-assisted thoracoscopic (VATS) thymectomy has been practiced in Australia for nearly two decades. Our aim was to assess the complete stable remission and asymptomatic disease rates after VATS thymectomy in nonthymomatous myasthenia gravis. There remains doubt that minimally invasive techniques achieve equal remission rates to open maximal operations. Therefore, we report our outcomes using the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification and Kaplan-Meier analysis and compare the results to the literature.
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Neuronal autophagy as a mediator of life and death: contrasting roles in chronic neurodegenerative and acute neural disorders.
Neuroscientist
PUBLISHED: 04-27-2011
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Autophagy is a cellular mechanism for degrading proteins and organelles. It was first described as a physiological process essential for cellular health and survival, and this is its role in most cells. However, it can also be a mediator of cell death, either by the triggering of apoptosis or by an independent "autophagic" cell death mechanism. This duality is important in the central nervous system, where the activation of autophagy has recently been shown to be protective in certain chronic neurodegenerative diseases but deleterious in acute neural disorders such as stroke and hypoxic/ischemic injury. The authors here discuss these distinct roles of autophagy in the nervous system with a focus on the role of autophagy in mediating neuronal death. The development of new therapeutic strategies based on the manipulation of autophagy will need to take into account these opposing roles of autophagy.
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Evaluation of factors affecting post-treatment quality of life in oral and oropharyngeal cancer patients primarily treated with curative surgery: an exploratory study.
Eur Arch Otorhinolaryngol
PUBLISHED: 04-19-2011
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The aim was to explore the impact of important clinico-demographic factors on the post-treatment quality of life (QOL) in surgically treated oral and oropharyngeal cancer patients. 63 consecutive follow-up oral and oropharyngeal cancer patients treated primarily with surgery were recruited. 55 patients sent the completed questionnaires and finally included in this study. QOL and important sub-domains of the QOL were assessed. Mean QOL scores (SD) were computed, level of significance was set at P < 0.05. The mean composite QOL score and standard deviation (SD) for oral and oropharyngeal cancer patients were 76.6 (15.2) and 73.4 (13.9), respectively. Patients with higher T-stage (T3 and T4) and higher overall-stage (III and IV) had lower mean QOL scores as against early T (T1 and T2) and overall early-stage (I and II); mean scores (SD) 64.3 (13.6) and 72.3 (13.8), and 76.6 (13.6) and 81.7 (14.1), respectively. Younger patients had lower mean scores (SD) than older patients; mean QOL scores (SD) 69.7 (14.0) and 79.6 (SD), respectively. Patients with reconstruction had lower mean QOL scores as compared to those without reconstruction; mean scores (SD) 67.6 (16.0) and 77.4 (12.5), respectively. In conclusion, tumor-stage, overall-stage, age of patients, and reconstruction had a significant direct effect on the post-treatment QOL of oral and oropharyngeal cancer patients.
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An exploratory study of the influence of clinico-demographic variables on swallowing and swallowing-related quality of life in a cohort of oral and oropharyngeal cancer patients treated with primary surgery.
Eur Arch Otorhinolaryngol
PUBLISHED: 04-16-2011
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There are insufficient data on swallowing and the consequences of its dysfunction in patients with cancers of the oral cavity (OC) and oropharynx (OP) that are treated with primary surgery. The study attempts to explore the effect of important clinico-demographic variables on post-treatment swallowing and related quality of life (QOL) in post-surgical OC and OP cancer patients. Sixty-two consecutive OC and OP cancer patients completed the MD Anderson Dysphagia Inventory (MDADI) questionnaire. Mean scores were computed. Comparison of scores based on mean ranks were performed using Mann-Whitney U test or Kruskal-Wallis test. Level of significance was set at P ? 0.02. Adjustments were made for multiple comparisons. Significantly worse mean (SD) QOL scores were observed in late T-stage (T3/T4) versus early T-stage (T1/T2) patients for global domain, physical domain, functional domain and emotional domains [44.4 (21.9) vs. 78.7 (22.7) (P < 0.001); 50.0 (9.4) vs. 75.9 (16.3), (P < 0.0001); 57.8 (20.6) vs. 84.1 (16.7), (P < 0.001) and 55.2 (18.0) vs. 78.5 (16.3), (P < 0.001)], respectively. Patients undergoing reconstruction versus without reconstruction had worse QOL scores; 58.8 (26.9) versus 79.5 (22.8), (P < 0.01); 61.2 (15.1) versus 76.4 (17.5), (P = 0.002); 65.4 (20.5) versus 86.3 (15.9), (P < 0.0001) and 63.3 (18.8) versus 79.8 (16.3), (P < 0.01), respectively, for global, physical, functional and emotional domains. Advanced T-stage, reconstruction, younger age and base of tongue tumours have a negative impact on post-treatment swallow function and related QOL in these patients.
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Development and validation of first-ever speech-specific perceptual speech evaluation tool for patients with head and neck cancer: the London speech evaluation (LSE) scale.
Head Neck
PUBLISHED: 04-05-2011
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The aim of this study was to develop and validate the first ever speech-specific perceptual speech-evaluation tool for patients with head and neck cancer.
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Survey of the use of tests for human papilloma virus and epidermal growth factor receptor for squamous cell carcinoma of the head and neck in UK head and neck multidisciplinary teams.
Br J Oral Maxillofac Surg
PUBLISHED: 02-07-2011
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Human papilloma virus (HPV), usually type 16, has emerged as an aetiological and prognostic marker of oropharyngeal carcinomas, and epidermal growth factor receptor (EGFR) has been associated with poor prognosis in patients with carcinoma of the head and neck. This makes the identification of cancers associated with these biomarkers important in the management of patients. We surveyed UK head and neck multidisciplinary teams by email using an online form to assess the use of biomarker testing. Overall 33 cancer networks were contacted and 28 (85%) responded. HPV tests were used in departments by 22 (79%) of our respondents, while only 3 (11%) used EGFR tests. The commonest reasons for not using them were lack of availability and lack of clinical indication.
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Reconstruction of pharyngolaryngectomy defects using the jejunal free flap: a 10-year experience from a single reconstructive center.
Plast. Reconstr. Surg.
PUBLISHED: 12-03-2010
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Reconstruction following pharyngolaryngectomy presents a complex reconstructive challenge, and a single-stage, reliable reconstruction allowing prompt discharge from the hospital and return of swallowing and speech function is required. The authors present their 10-year experience of 43 jejunal free flaps for pharyngolaryngectomy reconstruction by a single team and outline their operative algorithm to minimize postoperative morbidity.
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Phase I/II study of oncolytic HSV GM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck.
Clin. Cancer Res.
PUBLISHED: 07-31-2010
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This study sought to define the recommended dose of JS1/34.5-/47-/GM-CSF, an oncolytic herpes simplex type-1 virus (HSV-1) encoding human granulocyte-macrophage colony-stimulating factor (GM-CSF), for future studies in combination with chemoradiotherapy in patients with squamous cell cancer of the head and neck (SCCHN).
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Role of the c-Jun N-terminal kinase pathway in retinal excitotoxicity, and neuroprotection by its inhibition.
J. Neurochem.
PUBLISHED: 03-25-2010
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Retinal excitotoxicity is associated with retinal ischemia, and with glaucomatous and traumatic optic neuropathy. The present study investigates the role of c-Jun N-terminal kinase (JNK) activation in NMDA-mediated retinal excitotoxicity and determines whether neuroprotection can be obtained with the JNK pathway inhibitor, D-form of JNK-inhibitor 1 (D-JNKI-1). Young adult rats received intravitreal injections of 20 nmol NMDA, which caused extensive neuronal death in the inner nuclear and ganglion cell layers. This excitotoxicity was associated with strong activation of calpain, as revealed by fodrin cleavage, and of JNK. The cell-permeable peptide D-JNKI-1 was used to inhibit JNK. Within 40 min of its intravitreal injection, FITC-labeled D-JNKI-1 spread through the retinal ganglion cell layer into the inner nuclear layer and interfered with the NMDA-induced phosphorylation of JNK. Injections of unlabeled D-JNKI-1 gave unprecedentedly strong neuroprotection against cell death in both layers, lasting for at least 10 days. The NMDA-induced calpain-specific fodrin cleavage was likewise strongly inhibited by D-JNKI-1. Moreover the electroretinogram was partially preserved by D-JNKI-1. Thus, the JNK pathway is involved in NMDA-mediated retinal excitotoxicity and JNK inhibition by D-JNKI-1 provides strong neuroprotection as shown morphologically, biochemically and physiologically.
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Validation of the Sydney Swallow Questionnaire (SSQ) in a cohort of head and neck cancer patients.
Oral Oncol.
PUBLISHED: 02-04-2010
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Impairment of swallowing function is a common multidimensional symptom complex seen in 50-75% of head and neck cancer (HNC) survivors. Although there are a number of validated swallowing-specific questionnaires, much of their focus is on the evaluation of swallowing-related quality of life (QOL) rather than swallowing as a specific function. The aim of this study was to validate the Sydney Swallow Questionnaire (SSQ) as a swallowing-specific instrument in HNC patients. Fifty-four consecutive patients in follow-up for oral and oropharyngeal cancer completed the SSQ and MD Anderson Dysphagia Inventory (MDADI). Thirty-one patients completed both questionnaires again four weeks later to address test-retest reliability. Internal consistency and test-retest reliability was assessed using Cronbachs alpha and Spearmans correlation coefficient, respectively. Construct validity (including group validity) and criterion validity were determined using Spearmans correlation coefficient and Mann-Whitney U-test. Internal consistency, test-retest reliability, construct validity, group validity and criterion validity of the SSQ was found to be significant (P<0.01). We were able to demonstrate the reliability and validity of the SSQ in HNC patients. The SSQ is a precise, reliable and valid tool for assessing swallow in this patient group.
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Comprehensive review of small bowel metastasis from head and neck squamous cell carcinoma.
Oral Oncol.
PUBLISHED: 01-18-2010
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Secondary tumours of small intestine account for 10% of all small bowel cancers. The most common sites of primary tumour metastasizing to small bowel are uterus, cervix, colon, lung, breast and melanoma. The majority of these metastatic tumours come from adenocarcinoma primaries; squamous cell carcinoma constitutes a very small proportion of all metastatic small intestinal lesions. Metastasis to small bowel by head and neck squamous cell carcinoma is extremely rare and carries an unfavourable prognosis. Owing to the limited number of published studies, its characteristic features, clinical presentation and outcomes are poorly described. This work aims at specifying these characteristics by reviewing, compiling, analysing and reporting all published cases in the published literature on small bowel metastasis secondary to head and neck squamous cell carcinoma. To the best of our knowledge, this is the first comprehensive review article on the small intestinal metastasis from head and neck squamous cell carcinoma.
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Enhancement of autophagic flux after neonatal cerebral hypoxia-ischemia and its region-specific relationship to apoptotic mechanisms.
Am. J. Pathol.
PUBLISHED: 10-08-2009
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The multiplicity of cell death mechanisms induced by neonatal hypoxia-ischemia makes neuroprotective treatment against neonatal asphyxia more difficult to achieve. Whereas the roles of apoptosis and necrosis in such conditions have been studied intensively, the implication of autophagic cell death has only recently been considered. Here, we used the most clinically relevant rodent model of perinatal asphyxia to investigate the involvement of autophagy in hypoxic-ischemic brain injury. Seven-day-old rats underwent permanent ligation of the right common carotid artery, followed by 2 hours of hypoxia. This condition not only increased autophagosomal abundance (increase in microtubule-associated protein 1 light chain 3-11 level and punctuate labeling) but also lysosomal activities (cathepsin D, acid phosphatase, and beta-N-acetylhexosaminidase) in cortical and hippocampal CA3-damaged neurons at 6 and 24 hours, demonstrating an increase in the autophagic flux. In the cortex, this enhanced autophagy may be related to apoptosis since some neurons presenting a high level of autophagy also expressed apoptotic features, including cleaved caspase-3. On the other hand, enhanced autophagy in CA3 was associated with a more purely autophagic cell death phenotype. In striking contrast to CA3 neurons, those in CA1 presented only a minimal increase in autophagy but strong apoptotic characteristics. These results suggest a role of enhanced autophagy in delayed neuronal death after severe hypoxia-ischemia that is differentially linked to apoptosis according to the cerebral region.
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Targeting autophagy to prevent neonatal stroke damage.
Autophagy
PUBLISHED: 10-05-2009
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Cell death due to cerebral ischemia has been attributed to necrosis and apoptosis, but autophagic mechanisms have recently been implicated as well. Using rats exposed to neonatal focal cerebral ischemia, we have shown that lysosomal and autophagic activities are increased in ischemic neurons, and have obtained strong neuroprotection by post-ischemic inhibition of autophagy.
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Woody-grass ratios in a grassy arid system are limited by multi-causal interactions of abiotic constraint, competition and fire.
Oecologia
PUBLISHED: 09-28-2009
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Predicting changes in vegetation structure in fire-prone arid/semi-arid systems is fraught with uncertainty because the limiting factors to coexistence between grasses and woody plants are unknown. We investigated abiotic and biotic factors influencing boundaries and habitat membership in grassland (Triodia or spinifex grassland)-shrubland (Acacia aneura or mulga shrubland) mosaics in semi-arid central Australia. We used a field experiment to test for the effects of: (1) topographic relief (dune/swale habitat), (2) adult neighbour removal, and (3) soil type (sand/clay) on seedling survival in three shrub and two grass species in reciprocal field plantings. Our results showed that invasion of the shrubland (swale) by neighbouring grassland species is negated by abiotic limitations but competition limits shrubland invasion of the grassland (dune). All species from both habitats had significantly reduced survival in the grassland (dune) in the presence of the dominant grass (Triodia) regardless of soil type or shade. Further, the removal of the dominant grass allowed the shrubland dominant (A. aneura) to establish outside its usual range. Seedling growth and sexual maturation of the shrubland dominant (A. aneura) was slow, implying that repeated fire creates an immaturity risk for this non-sprouter in flammable grassland. By contrast, rapid growth and seed set in the grassland shrubs (facultative sprouters) provides a solution to fire exposure prior to reproductive onset. In terms of landscape dynamics, we argue that grass competition and fire effects are important constraints on shrubland patch expansion, but that their relative importance will vary spatially throughout the landscape because of spatial and temporal rainfall variability.
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Information design to promote better nutrition among pantry clients: four methods of formative evaluation.
Public Health Nutr
PUBLISHED: 08-26-2009
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To demonstrate the use of four different qualitative methods in creating content, including text and graphic design for print interventions to support better nutrition in low-income households that rely on charitable pantries.
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Electroglottographic and perceptual evaluation of tracheoesophageal speech.
J Voice
PUBLISHED: 07-17-2009
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To optimize tracheoesophageal (TO) speech after total laryngectomy, it is vital to have a robust tool of assessment to help investigate deficiencies, document changes, and facilitate therapy. We sought to evaluate and validate electroglottography (EGG) as an important tool in the multidimensional assessment of TO speech. This study is a cross-sectional study of the largest cohort of TO speakers treated by a single surgeon. A second group of normal laryngeal speakers served as a control group. EGG analysis of both groups using connected speech and sustained vowels was performed. Two trained expert raters undertook perceptual evaluation using two accepted scales. EGG measures were then analyzed for correlation with treatment variables. A separate correlation analysis was performed to identify EGG measures that may be associated with perceptual dimensions. Our data from EGG analysis are similar to data obtained from conventional acoustic signal analysis of TO speakers. Sustained vowel and connected speech parameters were poorer in TO speakers than in normal laryngeal speakers. In perceptual evaluation, only grade (G) of the GRBAS scale and Overall Voice Quality appeared reproducible and reliable. T stage, pharyngeal reconstruction and method of closure, cricopharyngeal myotomy, and postoperative complications appear to be correlated with the EGG measures. Five voice measures-jitter, shimmer, average frequency, normalized noise energy, and irregularity-correlated well with the key dimensions of perceptual assessment. EGG is an important assessment tool of TO speech, and can now be reliably used in a clinical setting.
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Postischemic treatment of neonatal cerebral ischemia should target autophagy.
Ann. Neurol.
PUBLISHED: 06-25-2009
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To evaluate the contributions of autophagic, necrotic, and apoptotic cell death mechanisms after neonatal cerebral ischemia and hence define the most appropriate neuroprotective approach for postischemic therapy.
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Forging links between nutrition and healthcare using community-based partnerships.
Fam Community Health
PUBLISHED: 06-16-2009
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This pilot project tested the feasibility of a community-based partnership between community clinics and food pantries as an approach to combat diet-related illnesses and engage low-income individuals in healthcare. Many communities possess both kinds of agencies, which serve similar clienteles and are geographically near each other, but these types of agencies rarely have partnered. The "LINKS" program built partnerships between clinics and food pantries at 2 sites. For more than 6 months, the clinics conducted health screenings and provided referrals during scheduled pantry food distributions. Results indicate that clinics can effectively partner with food pantries, an overlooked resource for health promotion.
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Aggressive fibromatosis of the oropharynx: a multidisciplinary approach to a benign disease.
Ear Nose Throat J
PUBLISHED: 05-16-2009
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We present the case of a 23-year-old woman with aggressive fibromatosis of the oropharynx that was initially treated elsewhere as a peritonsillar abscess. We discuss the characteristics of this rare tumor and review the literature, stressing the importance of postoperative follow-up for peritonsillar abscesses to avoid missing other important diagnoses, such as the one described here.
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[The two faces of autophagy in the nervous system].
Med Sci (Paris)
PUBLISHED: 05-05-2009
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Autophagy is a cellular mechanism for degrading proteins and organelles. It was first described as a physiological process essential for maintaining homeostasis and cell survival, but understanding its role in conditions of stress has been complicated by the recognition of a new type of cell death ("type 2") characterized by deleterious autophagic activity. This paradox is important in the central nervous system where the activation of autophagy seems to be protective in certain neurodegenerative diseases but deleterious in cerebral ischemia. The development of new therapeutic strategies based on the manipulation of autophagy will need to take into account these opposing roles of autophagy.
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An exploratory study into the role of dynamic contrast-enhanced magnetic resonance imaging or perfusion computed tomography for detection of intratumoral hypoxia in head-and-neck cancer.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 04-22-2009
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Hypoxia in patients with head-and-neck cancer (HNC) is well established and known to cause radiation resistance and treatment failure in the management of HNC. This study examines the role of parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perfusion computed tomography (CT) as surrogate markers of intratumoral hypoxia, defined by using the exogenous marker of hypoxia pimonidazole and the endogenous marker carbonic anhydrase 9 (CA9).
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Excitotoxicity-induced endocytosis confers drug targeting in cerebral ischemia.
Ann. Neurol.
PUBLISHED: 04-01-2009
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Targeting neuroprotectants specifically to the cells that need them is a major goal in biomedical research. Many peptidic protectants contain an active sequence linked to a carrier such as the transactivator of transcription (TAT) transduction sequence, and here we test the hypothesis that TAT-linked peptides are selectively endocytosed into neurons stressed by excitotoxicity and focal cerebral ischemia.
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Evaluation of speech outcomes following treatment of oral and oropharyngeal cancers.
Cancer Treat. Rev.
PUBLISHED: 03-10-2009
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Oral and oropharyngeal cancers are amongst the commonest cancers worldwide and present a major health problem. Owing to their critical anatomical location and complex physiologic functions, the treatment of oral and oropharyngeal cancers often affects important functions, including speech. The importance of speech in a patients life can not be overemphasized, as its loss is often associated with severe functional and psychosocial problems and a poor quality of life. A thorough understanding of the speech problems that are faced by these patients and their timely management is the key to providing a better functional quality of life, which must be one of the major goals of modern oncologic practice. This review summarises key methods of evaluation and outcome of speech functions in the literature on oral and oropharyngeal cancer published between January 2000 and December 2008. Speech has been generally overlooked and poorly investigated in this group of patients. This review is an attempt to fill this gap by conducting the first speech-specific review for oral and oropharyngeal cancer patients. We have proposed guidelines for better understanding and management of speech problems faced by these patients in their day-to-day life.
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Limited role of the c-Jun N-terminal kinase pathway in a neonatal rat model of cerebral hypoxia-ischemia.
J. Neurochem.
PUBLISHED: 02-25-2009
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D-JNKI1, a cell-permeable peptide inhibitor of the c-Jun N-terminal kinase (JNK) pathway, has been shown to be a powerful neuroprotective agent after focal cerebral ischemia in adult mice and young rats. We have investigated the potential neuroprotective effect of D-JNKI1 and the involvement of the JNK pathway in a neonatal rat model of cerebral hypoxia-ischemia (HI). Seven-day-old rats underwent a permanent ligation of the right common carotid artery followed by 2 h of hypoxia (8% oxygen). Treatment with D-JNKI1 (0.3 mg/kg intraperitoneally) significantly reduced early calpain activation, late caspase 3 activation and, in the thalamus, autophagosome formation, indicating an involvement of JNK in different types of cell death: necrotic, apoptotic, and autophagic. However, the size of the lesion was unchanged. Further analysis showed that neonatal HI induced an immediate decrease in JNK phosphorylation (reflecting mainly JNK1 phosphorylation) followed by a slow progressive increase (including JNK3 phosphorylation 54 kDa), whereas c-jun and c-fos expression were both strongly activated immediately after HI. In conclusion, unlike in adult ischemic models, JNK is only moderately activated after severe cerebral HI in neonatal rats and the observed positive effects of D-JNKI1 are insufficient to give neuroprotection. Thus, for perinatal asphyxia, D-JNKI1 can only be considered in association with other therapies.
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Calpain hydrolysis of alpha- and beta2-adaptins decreases clathrin-dependent endocytosis and may promote neurodegeneration.
J. Biol. Chem.
PUBLISHED: 02-24-2009
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Clathrin-dependent endocytosis is mediated by a tightly regulated network of molecular interactions that provides essential protein-protein and protein-lipid binding activities. Here we report the hydrolysis of the alpha- and beta2-subunits of the tetrameric adaptor protein complex 2 by calpain. Calcium-dependent alpha- and beta2-adaptin hydrolysis was observed in several rat tissues, including brain and primary neuronal cultures. Neuronal alpha- and beta2-adaptin cleavage was inducible by glutamate stimulation and was accompanied by the decreased endocytosis of transferrin. Heterologous expression of truncated forms of the beta2-adaptin subunit significantly decreased the membrane recruitment of clathrin and inhibited clathrin-mediated receptor endocytosis. Moreover, the presence of truncated beta2-adaptin sensitized neurons to glutamate receptor-mediated excitotoxicity. Proteolysis of alpha- and beta2-adaptins, as well as the accessory clathrin adaptors epsin 1, adaptor protein 180, and the clathrin assembly lymphoid myeloid leukemia protein, was detected in brain tissues after experimentally induced ischemia and in cases of human Alzheimer disease. The present study further clarifies the central role of calpain in regulating clathrin-dependent endocytosis and provides evidence for a novel mechanism through which calpain activation may promote neurodegeneration: the sensitization of cells to glutamate-mediated excitotoxicity via the decreased internalization of surface receptors.
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Induction of a chemoattractant transcriptional response by a Campylobacter jejuni boiled cell extract in colonocytes.
BMC Microbiol.
PUBLISHED: 02-04-2009
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Campylobacter jejuni, the commonest cause of bacterial diarrhoea worldwide, can also induce colonic inflammation. To understand how a previously identified heat stable component contributes to pro-inflammatory responses we used microarray and real-time quantitative PCR to investigate the transcriptional response to a boiled cell extract of Campylobacter jejuni NCTC 11168.
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Unconjugated TAT carrier peptide protects against excitotoxicity.
Neurotox Res
PUBLISHED: 01-30-2009
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We report in this article for the first time the neuroprotective effects of unconjugated TAT carrier peptide against a mild excitotoxic stimulus both in vitro and in vivo. In view of the widespread use of TAT peptides to deliver neuroprotectants into cells, it is important to know the effects of the carrier itself. Unconjugated TAT carrier protects dissociated cortical neurons against NMDA but not against kainate, suggesting that TAT peptides may interfere with NMDA signaling. Furthermore, a retro-inverso form of the carrier peptide caused a reduction in lesion volume (by about 50%) in a rat neonatal cerebral ischemia model. Thus, even though TAT is designed merely as a carrier, its own pharmacological activity will need to be considered in the analysis of TAT-linked neuroprotectant peptides.
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Craniofacial resection and its role in the management of sinonasal malignancies.
Expert Rev Anticancer Ther
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Sinonasal malignancy is rare, and its presentation is commonly late. There is a wide variety of pathologies with varying natural histories and survival rates. Anatomy of the skull base is extremely complex and tumors are closely related to orbits, frontal lobes and cavernous sinus. Anatomical detail and the late presentation render surgical management a challenging task. A thorough understanding of anatomy and pathology combined with modern neuroimaging and reliable reconstruction within a multidisciplinary team is imperative to carry out skull base surgery effectively. While endoscopic approaches are gaining credibility, clearly, it will be some time before meaningful comparisons with craniofacial resection can be made. Until then, craniofacial resection will remain the gold standard for managing the sinonasal malignancies of the anterior skull base, as it has proved to be safe and effective.
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Guidelines for the use and interpretation of assays for monitoring autophagy.
Daniel J Klionsky, Fábio C Abdalla, Hagai Abeliovich, Robert T Abraham, Abraham Acevedo-Arozena, Khosrow Adeli, Lotta Agholme, Maria Agnello, Patrizia Agostinis, Julio A Aguirre-Ghiso, Hyung Jun Ahn, Ouardia Ait-Mohamed, Slimane Ait-Si-Ali, Takahiko Akematsu, Shizuo Akira, Hesham M Al-Younes, Munir A Al-Zeer, Matthew L Albert, Roger L Albin, Javier Alegre-Abarrategui, Maria Francesca Aleo, Mehrdad Alirezaei, Alexandru Almasan, Maylin Almonte-Becerril, Atsuo Amano, Ravi Amaravadi, Shoba Amarnath, Amal O Amer, Nathalie Andrieu-Abadie, Vellareddy Anantharam, David K Ann, Shailendra Anoopkumar-Dukie, Hiroshi Aoki, Nadezda Apostolova, Giuseppe Arancia, John P Aris, Katsuhiko Asanuma, Nana Y O Asare, Hisashi Ashida, Valerie Askanas, David S Askew, Patrick Auberger, Misuzu Baba, Steven K Backues, Eric H Baehrecke, Ben A Bahr, Xue-Yuan Bai, Yannick Bailly, Robert Baiocchi, Giulia Baldini, Walter Balduini, Andrea Ballabio, Bruce A Bamber, Edward T W Bampton, Gábor Bánhegyi, Clinton R Bartholomew, Diane C Bassham, Robert C Bast, Henri Batoko, Boon-Huat Bay, Isabelle Beau, Daniel M Béchet, Thomas J Begley, Christian Behl, Christian Behrends, Soumeya Bekri, Bryan Bellaire, Linda J Bendall, Luca Benetti, Laura Berliocchi, Henri Bernardi, Francesca Bernassola, Sébastien Besteiro, Ingrid Bhatia-Kiššová, Xiaoning Bi, Martine Biard-Piechaczyk, Janice S Blum, Lawrence H Boise, Paolo Bonaldo, David L Boone, Beat C Bornhauser, Karina R Bortoluci, Ioannis Bossis, Fréderic Bost, Jean-Pierre Bourquin, Patricia Boya, Michaël Boyer-Guittaut, Peter V Bozhkov, Nathan R Brady, Claudio Brancolini, Andreas Brech, Jay E Brenman, Ana Brennand, Emery H Bresnick, Patrick Brest, Dave Bridges, Molly L Bristol, Paul S Brookes, Eric J Brown, John H Brumell, Nicola Brunetti-Pierri, Ulf T Brunk, Dennis E Bulman, Scott J Bultman, Geert Bultynck, Lena F Burbulla, Wilfried Bursch, Jonathan P Butchar, Wanda Buzgariu, Sérgio P Bydlowski, Ken Cadwell, Monika Cahova, Dongsheng Cai, Jiyang Cai, Qian Cai, Bruno Calabretta, Javier Calvo-Garrido, Nadine Camougrand, Michelangelo Campanella, Jenny Campos-Salinas, Eleonora Candi, Lizhi Cao, Allan B Caplan, Simon R Carding, Sandra M Cardoso, Jennifer S Carew, Cathleen R Carlin, Virginie Carmignac, Leticia A M Carneiro, Serena Carra, Rosario A Caruso, Giorgio Casari, Caty Casas, Roberta Castino, Eduardo Cebollero, Francesco Cecconi, Jean Celli, Hassan Chaachouay, Han-Jung Chae, Chee-Yin Chai, David C Chan, Edmond Y Chan, Raymond Chuen-Chung Chang, Chi-Ming Che, Ching-Chow Chen, Guang-Chao Chen, Guo-Qiang Chen, Min Chen, Quan Chen, Steve S-L Chen, WenLi Chen, Xi Chen, Xiangmei Chen, Xiequn Chen, Ye-Guang Chen, Yingyu Chen, Yongqiang Chen, Yu-Jen Chen, Zhixiang Chen, Alan Cheng, Christopher H K Cheng, Yan Cheng, Heesun Cheong, Jae-Ho Cheong, Sara Cherry, Russ Chess-Williams, Zelda H Cheung, Eric Chevet, Hui-Ling Chiang, Roberto Chiarelli, Tomoki Chiba, Lih-Shen Chin, Shih-Hwa Chiou, Francis V Chisari, Chi Hin Cho, Dong-Hyung Cho, Augustine M K Choi, DooSeok Choi, Kyeong Sook Choi, Mary E Choi, Salem Chouaib, Divaker Choubey, Vinay Choubey, Charleen T Chu, Tsung-Hsien Chuang, Sheau-Huei Chueh, Taehoon Chun, Yong-Joon Chwae, Mee-Len Chye, Roberto Ciarcia, Maria R Ciriolo, Michael J Clague, Robert S B Clark, Peter G H Clarke, Robert Clarke, Patrice Codogno, Hilary A Coller, María I Colombo, Sergio Comincini, Maria Condello, Fabrizio Condorelli, Mark R Cookson, Graham H Coombs, Isabelle Coppens, Ramón Corbalán, Pascale Cossart, Paola Costelli, Safia Costes, Ana Coto-Montes, Eduardo Couve, Fraser P Coxon, James M Cregg, José L Crespo, Marianne J Cronjé, Ana Maria Cuervo, Joseph J Cullen, Mark J Czaja, Marcello D'Amelio, Arlette Darfeuille-Michaud, Lester M Davids, Faith E Davies, Massimo De Felici, John F de Groot, Cornelis A M de Haan, Luisa De Martino, Angelo De Milito, Vincenzo De Tata, Jayanta Debnath, Alexei Degterev, Benjamin Dehay, Lea M D Delbridge, Francesca Demarchi, Yi Zhen Deng, Jörn Dengjel, Paul Dent, Donna Denton, Vojo Deretic, Shyamal D Desai, Rodney J Devenish, Mario Di Gioacchino, Gilbert Di Paolo, Chiara Di Pietro, Guillermo Díaz-Araya, Inés Díaz-Laviada, Maria T Diaz-Meco, Javier Diaz-Nido, Ivan Dikic, Savithramma P Dinesh-Kumar, Wen-Xing Ding, Clark W Distelhorst, Abhinav Diwan, Mojgan Djavaheri-Mergny, Svetlana Dokudovskaya, Zheng Dong, Frank C Dorsey, Victor Dosenko, James J Dowling, Stephen Doxsey, Marlène Dreux, Mark E Drew, Qiuhong Duan, Michel A Duchosal, Karen Duff, Isabelle Dugail, Madeleine Durbeej, Michael Duszenko, Charles L Edelstein, Aimee L Edinger, Gustavo Egea, Ludwig Eichinger, N Tony Eissa, Suhendan Ekmekcioglu, Wafik S El-Deiry, Zvulun Elazar, Mohamed Elgendy, Lisa M Ellerby, Kai Er Eng, Anna-Mart Engelbrecht, Simone Engelender, Jekaterina Erenpreisa, Ricardo Escalante, Audrey Esclatine, Eeva-Liisa Eskelinen, Lucile Espert, Virginia Espina, Huizhou Fan, Jia Fan, Qi-Wen Fan, Zhen Fan, Shengyun Fang, Yongqi Fang, Manolis Fanto, Alessandro Fanzani, Thomas Farkas, Jean-Claude Farré, Mathias Faure, Marcus Fechheimer, Carl G Feng, Jian Feng, Qili Feng, Youji Feng, László Fésüs, Ralph Feuer, Maria E Figueiredo-Pereira, Gian Maria Fimia, Diane C Fingar, Steven Finkbeiner, Toren Finkel, Kim D Finley, Filomena Fiorito, Edward A Fisher, Paul B Fisher, Marc Flajolet, Maria L Florez-McClure, Salvatore Florio, Edward A Fon, Francesco Fornai, Franco Fortunato, Rati Fotedar, Daniel H Fowler, Howard S Fox, Rodrigo Franco, Lisa B Frankel, Marc Fransen, José M Fuentes, Juan Fueyo, Jun Fujii, Kozo Fujisaki, Eriko Fujita, Mitsunori Fukuda, Ruth H Furukawa, Matthias Gaestel, Philippe Gailly, Malgorzata Gajewska, Brigitte Galliot, Vincent Galy, Subramaniam Ganesh, Barry Ganetzky, Ian G Ganley, Fen-Biao Gao, George F Gao, Jinming Gao, Lorena Garcia, Guillermo Garcia-Manero, Mikel Garcia-Marcos, Marjan Garmyn, Andrei L Gartel, Evelina Gatti, Mathias Gautel, Thomas R Gawriluk, Matthew E Gegg, Jiefei Geng, Marc Germain, Jason E Gestwicki, David A Gewirtz, Saeid Ghavami, Pradipta Ghosh, Anna M Giammarioli, Alexandra N Giatromanolaki, Spencer B Gibson, Robert W Gilkerson, Michael L Ginger, Henry N Ginsberg, Jakub Golab, Michael S Goligorsky, Pierre Golstein, Candelaria Gomez-Manzano, Ebru Goncu, Céline Gongora, Claudio D Gonzalez, Ramon Gonzalez, Cristina González-Estévez, Rosa Ana González-Polo, Elena Gonzalez-Rey, Nikolai V Gorbunov, Sharon Gorski, Sandro Goruppi, Roberta A Gottlieb, Devrim Gozuacik, Giovanna Elvira Granato, Gary D Grant, Kim N Green, Aleš Gregorc, Frédéric Gros, Charles Grose, Thomas W Grunt, Philippe Gual, Jun-Lin Guan, Kun-Liang Guan, Sylvie M Guichard, Anna S Gukovskaya, Ilya Gukovsky, Jan Gunst, Asa B Gustafsson, Andrew J Halayko, Amber N Hale, Sandra K Halonen, Maho Hamasaki, Feng Han, Ting Han, Michael K Hancock, Malene Hansen, Hisashi Harada, Masaru Harada, Stefan E Hardt, J Wade Harper, Adrian L Harris, James Harris, Steven D Harris, Makoto Hashimoto, Jeffrey A Haspel, Shin-Ichiro Hayashi, Lori A Hazelhurst, Congcong He, You-Wen He, Marie-Josee Hebert, Kim A Heidenreich, Miep H Helfrich, Gudmundur V Helgason, Elizabeth P Henske, Brian Herman, Paul K Herman, Claudio Hetz, Sabine Hilfiker, Joseph A Hill, Lynne J Hocking, Paul Hofman, Thomas G Hofmann, Jörg Höhfeld, Tessa L Holyoake, Ming-Huang Hong, David A Hood, Gökhan S Hotamisligil, Ewout J Houwerzijl, Maria Høyer-Hansen, Bingren Hu, Chien-An A Hu, Hong-Ming Hu, Ya Hua, Canhua Huang, Ju Huang, Shengbing Huang, Wei-Pang Huang, Tobias B Huber, Won-Ki Huh, Tai-Ho Hung, Ted R Hupp, Gang Min Hur, James B Hurley, Sabah N A Hussain, Patrick J Hussey, Jung Jin Hwang, Seungmin Hwang, Atsuhiro Ichihara, Shirin Ilkhanizadeh, Ken Inoki, Takeshi Into, Valentina Iovane, Juan L Iovanna, Nancy Y Ip, Yoshitaka Isaka, Hiroyuki Ishida, Ciro Isidoro, Ken-Ichi Isobe, Akiko Iwasaki, Marta Izquierdo, Yotaro Izumi, Panu M Jaakkola, Marja Jäättelä, George R Jackson, William T Jackson, Bassam Janji, Marina Jendrach, Ju-Hong Jeon, Eui-Bae Jeung, Hong Jiang, Hongchi Jiang, Jean X Jiang, Ming Jiang, Qing Jiang, Xuejun Jiang, Alberto Jiménez, Meiyan Jin, Shengkan Jin, Cheol O Joe, Terje Johansen, Daniel E Johnson, Gail V W Johnson, Nicola L Jones, Bertrand Joseph, Suresh K Joseph, Annie M Joubert, Gábor Juhász, Lucienne Juillerat-Jeanneret, Chang Hwa Jung, Yong-Keun Jung, Kai Kaarniranta, Allen Kaasik, Tomohiro Kabuta, Motoni Kadowaki, Katarina Kågedal, Yoshiaki Kamada, Vitaliy O Kaminskyy, Harm H Kampinga, Hiromitsu Kanamori, Chanhee Kang, Khong Bee Kang, Kwang Il Kang, Rui Kang, Yoon-A Kang, Tomotake Kanki, Thirumala-Devi Kanneganti, Haruo Kanno, Anumantha G Kanthasamy, Arthi Kanthasamy, Vassiliki Karantza, Gur P Kaushal, Susmita Kaushik, Yoshinori Kawazoe, Po-Yuan Ke, John H Kehrl, Ameeta Kelekar, Claus Kerkhoff, David H Kessel, Hany Khalil, Jan A K W Kiel, Amy A Kiger, Akio Kihara, Deok Ryong Kim, Do-Hyung Kim, Dong-Hou Kim, Eun-Kyoung Kim, Hyung-Ryong Kim, Jae-Sung Kim, Jeong Hun Kim, Jin Cheon Kim, John K Kim, Peter K Kim, Seong Who Kim, Yong-Sun Kim, Yonghyun Kim, Adi Kimchi, Alec C Kimmelman, Jason S King, Timothy J Kinsella, Vladimir Kirkin, Lorrie A Kirshenbaum, Katsuhiko Kitamoto, Kaio Kitazato, Ludger Klein, Walter T Klimecki, Jochen Klucken, Erwin Knecht, Ben C B Ko, Jan C Koch, Hiroshi Koga, Jae-Young Koh, Young Ho Koh, Masato Koike, Masaaki Komatsu, Eiki Kominami, Hee Jeong Kong, Wei-jia Kong, Viktor I Korolchuk, Yaichiro Kotake, Michael I Koukourakis, Juan B Kouri Flores, Attila L Kovács, Claudine Kraft, Dimitri Krainc, Helmut Krämer, Carole Kretz-Remy, Anna M Krichevsky, Guido Kroemer, Rejko Krüger, Oleg Krut, Nicholas T Ktistakis, Chia-Yi Kuan, Róza Kucharczyk, Ashok Kumar, Raj Kumar, Sharad Kumar, Mondira Kundu, Hsing-Jien Kung, Tino Kurz, Ho Jeong Kwon, Albert R La Spada, Frank Lafont, Trond Lamark, Jacques Landry, Jon D Lane, Pierre Lapaquette, Jocelyn F Laporte, Lajos László, Sergio Lavandero, Josée N Lavoie, Robert Layfield, Pedro A Lazo, Weidong Le, Laurent Le Cam, Daniel J Ledbetter, Alvin J X Lee, Byung-Wan Lee, Gyun Min Lee, Jongdae Lee, Ju-Hyun Lee, Michael Lee, Myung-Shik Lee, Sug Hyung Lee, Christiaan Leeuwenburgh, Patrick Legembre, Renaud Legouis, Michael Lehmann, Huan-Yao Lei, Qun-Ying Lei, David A Leib, José Leiro, John J Lemasters, Antoinette Lemoine, Maciej S Lesniak, Dina Lev, Victor V Levenson, Beth Levine, Efrat Levy, Faqiang Li, Jun-lin Li, Lian Li, Sheng Li, Weijie Li, Xue-Jun Li, Yan-Bo Li, Yi-Ping Li, Chengyu Liang, Qiangrong Liang, Yung-Feng Liao, Pawel P Liberski, Andrew Lieberman, Hyunjung J Lim, Kah-Leong Lim, Kyu Lim, Chiou-Feng Lin, Fu-Cheng Lin, Jian Lin, Jiandie D Lin, Kui Lin, Wan-Wan Lin, Weei-Chin Lin, Yi-Ling Lin, Rafael Linden, Paul Lingor, Jennifer Lippincott-Schwartz, Michael P Lisanti, Paloma B Liton, Bo Liu, Chun-Feng Liu, Kaiyu Liu, Leyuan Liu, Qiong A Liu, Wei Liu, Young-Chau Liu, Yule Liu, Richard A Lockshin, Chun-Nam Lok, Sagar Lonial, Benjamin Loos, Gabriel Lopez-Berestein, Carlos Lopez-Otin, Laura Lossi, Michael T Lotze, Péter Low, Binfeng Lu, Bingwei Lu, Bo Lu, Zhen Lu, Fredéric Luciano, Nicholas W Lukacs, Anders H Lund, Melinda A Lynch-Day, Yong Ma, Fernando Macian, Jeff P MacKeigan, Kay F Macleod, Frank Madeo, Luigi Maiuri, Maria Chiara Maiuri, Davide Malagoli, May Christine V Malicdan, Walter Malorni, Na Man, Eva-Maria Mandelkow, Stéphen Manon, Irena Manov, Kai Mao, Xiang Mao, Zixu Mao, Philippe Marambaud, Daniela Marazziti, Yves L Marcel, Katie Marchbank, Piero Marchetti, Stefan J Marciniak, Mateus Marcondes, Mohsen Mardi, Gabriella Marfè, Guillermo Mariño, Maria Markaki, Mark R Marten, Seamus J Martin, Camille Martinand-Mari, Wim Martinet, Marta Martinez-Vicente, Matilde Masini, Paola Matarrese, Saburo Matsuo, Raffaele Matteoni, Andreas Mayer, Nathalie M Mazure, David J McConkey, Melanie J McConnell, Catherine McDermott, Christine McDonald, Gerald M McInerney, Sharon L McKenna, BethAnn McLaughlin, Pamela J McLean, Christopher R McMaster, G Angus McQuibban, Alfred J Meijer, Miriam H Meisler, Alicia Meléndez, Thomas J Melia, Gerry Melino, Maria A Mena, Javier A Menendez, Rubem F S Menna-Barreto, Manoj B Menon, Fiona M Menzies, Carol A Mercer, Adalberto Merighi, Diane E Merry, Stefania Meschini, Christian G Meyer, Thomas F Meyer, Chao-Yu Miao, Jun-Ying Miao, Paul A M Michels, Carine Michiels, Dalibor Mijaljica, Ana Milojkovic, Saverio Minucci, Clelia Miracco, Cindy K Miranti, Ioannis Mitroulis, Keisuke Miyazawa, Noboru Mizushima, Baharia Mograbi, Simin Mohseni, Xavier Molero, Bertrand Mollereau, Faustino Mollinedo, Takashi Momoi, Iryna Monastyrska, Martha M Monick, Mervyn J Monteiro, Michael N Moore, Rodrigo Mora, Kevin Moreau, Paula I Moreira, Yuji Moriyasu, Jorge Moscat, Serge Mostowy, Jeremy C Mottram, Tomasz Motyl, Charbel E-H Moussa, Sylke Müller, Sylviane Muller, Karl Münger, Christian Münz, Leon O Murphy, Maureen E Murphy, Antonio Musarò, Indira Mysorekar, Eiichiro Nagata, Kazuhiro Nagata, Aimable Nahimana, Usha Nair, Toshiyuki Nakagawa, Kiichi Nakahira, Hiroyasu Nakano, Hitoshi Nakatogawa, Meera Nanjundan, Naweed I Naqvi, Derek P Narendra, Masashi Narita, Miguel Navarro, Steffan T Nawrocki, Taras Y Nazarko, Andriy Nemchenko, Mihai G Netea, Thomas P Neufeld, Paul A Ney, Ioannis P Nezis, Huu Phuc Nguyen, Daotai Nie, Ichizo Nishino, Corey Nislow, Ralph A Nixon, Takeshi Noda, Angelika A Noegel, Anna Nogalska, Satoru Noguchi, Lucia Notterpek, Ivana Novak, Tomoyoshi Nozaki, Nobuyuki Nukina, Thorsten Nürnberger, Beat Nyfeler, Keisuke Obara, Terry D Oberley, Salvatore Oddo, Michinaga Ogawa, Toya Ohashi, Koji Okamoto, Nancy L Oleinick, F Javier Oliver, Laura J Olsen, Stefan Olsson, Onya Opota, Timothy F Osborne, Gary K Ostrander, Kinya Otsu, Jing-hsiung James Ou, Mireille Ouimet, Michael Overholtzer, Bulent Ozpolat, Paolo Paganetti, Ugo Pagnini, Nicolas Pallet, Glen E Palmer, Camilla Palumbo, Tianhong Pan, Theocharis Panaretakis, Udai Bhan Pandey, Zuzana Papackova, Issidora Papassideri, Irmgard Paris, Junsoo Park, Ohkmae K Park, Jan B Parys, Katherine R Parzych, Susann Patschan, Cam Patterson, Sophie Pattingre, John M Pawelek, Jianxin Peng, David H Perlmutter, Ida Perrotta, George Perry, Shazib Pervaiz, Matthias Peter, Godefridus J Peters, Morten Petersen, Goran Petrovski, James M Phang, Mauro Piacentini, Philippe Pierre, Valérie Pierrefite-Carle, Gérard Pierron, Ronit Pinkas-Kramarski, Antonio Piras, Natik Piri, Leonidas C Platanias, Stefanie Pöggeler, Marc Poirot, Angelo Poletti, Christian Poüs, Mercedes Pozuelo-Rubio, Mette Prætorius-Ibba, Anil Prasad, Mark Prescott, Muriel Priault, Nathalie Produit-Zengaffinen, Ann Progulske-Fox, Tassula Proikas-Cezanne, Serge Przedborski, Karin Przyklenk, Rosa Puertollano, Julien Puyal, Shu-Bing Qian, Liang Qin, Zheng-Hong Qin, Susan E Quaggin, Nina Raben, Hannah Rabinowich, Simon W Rabkin, Irfan Rahman, Abdelhaq Rami, Georg Ramm, Glenn Randall, Felix Randow, V Ashutosh Rao, Jeffrey C Rathmell, Brinda Ravikumar, Swapan K Ray, Bruce H Reed, John C Reed, Fulvio Reggiori, Anne Regnier-Vigouroux, Andreas S Reichert, John J Reiners, Russel J Reiter, Jun Ren, Jose L Revuelta, Christopher J Rhodes, Konstantinos Ritis, Elizete Rizzo, Jeffrey Robbins, Michel Roberge, Hernan Roca, Maria C Roccheri, Stéphane Rocchi, H Peter Rodemann, Santiago Rodríguez de Córdoba, Bärbel Rohrer, Igor B Roninson, Kirill Rosen, Magdalena M Rost-Roszkowska, Mustapha Rouis, Kasper M A Rouschop, Francesca Rovetta, Brian P Rubin, David C Rubinsztein, Klaus Ruckdeschel, Edmund B Rucker, Assaf Rudich, Emil Rudolf, Nelson Ruiz-Opazo, Rossella Russo, Tor Erik Rusten, Kevin M Ryan, Stefan W Ryter, David M Sabatini, Junichi Sadoshima, Tapas Saha, Tatsuya Saitoh, Hiroshi Sakagami, Yasuyoshi Sakai, Ghasem Hoseini Salekdeh, Paolo Salomoni, Paul M Salvaterra, Guy Salvesen, Rosa Salvioli, Anthony M J Sanchez, José A Sánchez-Alcázar, Ricardo Sánchez-Prieto, Marco Sandri, Uma Sankar, Poonam Sansanwal, Laura Santambrogio, Shweta Saran, Sovan Sarkar, Minnie Sarwal, Chihiro Sasakawa, Ausra Sasnauskiene, Miklós Sass, Ken Sato, Miyuki Sato, Anthony H V Schapira, Michael Scharl, Hermann M Schätzl, Wiep Scheper, Stefano Schiaffino, Claudio Schneider, Marion E Schneider, Regine Schneider-Stock, Patricia V Schoenlein, Daniel F Schorderet, Christoph Schüller, Gary K Schwartz, Luca Scorrano, Linda Sealy, Per O Seglen, Juan Segura-Aguilar, Iban Seiliez, Oleksandr Seleverstov, Christian Sell, Jong Bok Seo, Duska Separovic, Vijayasaradhi Setaluri, Takao Setoguchi, Carmine Settembre, John J Shacka, Mala Shanmugam, Irving M Shapiro, Eitan Shaulian, Reuben J Shaw, James H Shelhamer, Han-Ming Shen, Wei-Chiang Shen, Zu-Hang Sheng, Yang Shi, Kenichi Shibuya, Yoshihiro Shidoji, Jeng-Jer Shieh, Chwen-Ming Shih, Yohta Shimada, Shigeomi Shimizu, Takahiro Shintani, Orian S Shirihai, Gordon C Shore, Andriy A Sibirny, Stan B Sidhu, Beata Sikorska, Elaine C M Silva-Zacarin, Alison Simmons, Anna Katharina Simon, Hans-Uwe Simon, Cristiano Simone, Anne Simonsen, David A Sinclair, Rajat Singh, Debasish Sinha, Frank A Sinicrope, Agnieszka Sirko, Parco M Siu, Efthimios Sivridis, Vojtech Skop, Vladimir P Skulachev, Ruth S Slack, Soraya S Smaili, Duncan R Smith, María S Soengas, Thierry Soldati, Xueqin Song, Anil K Sood, Tuck Wah Soong, Federica Sotgia, Stephen A Spector, Claudia D Spies, Wolfdieter Springer, Srinivasa M Srinivasula, Leonidas Stefanis, Joan S Steffan, Ruediger Stendel, Harald Stenmark, Anastasis Stephanou, Stephan T Stern, Cinthya Sternberg, Björn Stork, Peter Stralfors, Carlos S Subauste, Xinbing Sui, David Sulzer, Jiaren Sun, Shi-Yong Sun, Zhi-Jun Sun, Joseph J Y Sung, Kuninori Suzuki, Toshihiko Suzuki, Michele S Swanson, Charles Swanton, Sean T Sweeney, Lai-King Sy, Gyorgy Szabadkai, Ira Tabas, Heinrich Taegtmeyer, Marco Tafani, Krisztina Takács-Vellai, Yoshitaka Takano, Kaoru Takegawa, Genzou Takemura, Fumihiko Takeshita, Nicholas J Talbot, Kevin S W Tan, Keiji Tanaka, Kozo Tanaka, Daolin Tang, Dingzhong Tang, Isei Tanida, Bakhos A Tannous, Nektarios Tavernarakis, Graham S Taylor, Gregory A Taylor, J Paul Taylor, Lance S Terada, Alexei Terman, Gianluca Tettamanti, Karin Thevissen, Craig B Thompson, Andrew Thorburn, Michael Thumm, Fengfeng Tian, Yuan Tian, Glauco Tocchini-Valentini, Aviva M Tolkovsky, Yasuhiko Tomino, Lars Tönges, Sharon A Tooze, Cathy Tournier, John Tower, Roberto Towns, Vladimir Trajkovic, Leonardo H Travassos, Ting-Fen Tsai, Mario P Tschan, Takeshi Tsubata, Allan Tsung, Boris Turk, Lorianne S Turner, Suresh C Tyagi, Yasuo Uchiyama, Takashi Ueno, Midori Umekawa, Rika Umemiya-Shirafuji, Vivek K Unni, Maria I Vaccaro, Enza Maria Valente, Greet Van den Berghe, Ida J van der Klei, Wouter van Doorn, Linda F van Dyk, Marjolein van Egmond, Leo A van Grunsven, Peter Vandenabeele, Wim P Vandenberghe, Ilse Vanhorebeek, Eva C Vaquero, Guillermo Velasco, Tibor Vellai, Jose Miguel Vicencio, Richard D Vierstra, Miquel Vila, Cécile Vindis, Giampietro Viola, Maria Teresa Viscomi, Olga V Voitsekhovskaja, Clarissa von Haefen, Marcela Votruba, Keiji Wada, Richard Wade-Martins, Cheryl L Walker, Craig M Walsh, Jochen Walter, Xiang-Bo Wan, Aimin Wang, Chenguang Wang, Dawei Wang, Fan Wang, Fen Wang, Guanghui Wang, Haichao Wang, Hong-Gang Wang, Horng-Dar Wang, Jin Wang, Ke Wang, Mei Wang, Richard C Wang, Xinglong Wang, Xuejun Wang, Ying-Jan Wang, Yipeng Wang, Zhen Wang, Zhigang Charles Wang, Zhinong Wang, Derick G Wansink, Diane M Ward, Hirotaka Watada, Sarah L Waters, Paul Webster, Lixin Wei, Conrad C Weihl, William A Weiss, Scott M Welford, Long-Ping Wen, Caroline A Whitehouse, J Lindsay Whitton, Alexander J Whitworth, Tom Wileman, John W Wiley, Simon Wilkinson, Dieter Willbold, Roger L Williams, Peter R Williamson, Bradly G Wouters, Chenghan Wu, Dao-Cheng Wu, William K K Wu, Andreas Wyttenbach, Ramnik J Xavier, Zhijun Xi, Pu Xia, Gengfu Xiao, Zhiping Xie, Zhonglin Xie, Da-zhi Xu, Jianzhen Xu, Liang Xu, Xiaolei Xu, Ai Yamamoto, Akitsugu Yamamoto, Shunhei Yamashina, Michiaki Yamashita, Xianghua Yan, Mitsuhiro Yanagida, Dun-Sheng Yang, Elizabeth Yang, Jin-Ming Yang, Shi Yu Yang, Wannian Yang, Wei Yuan Yang, Zhifen Yang, Meng-Chao Yao, Tso-Pang Yao, Behzad Yeganeh, Wei-Lien Yen, Jia-Jing Yin, Xiao-Ming Yin, Ook-Joon Yoo, Gyesoon Yoon, Seung-Yong Yoon, Tomohiro Yorimitsu, Yuko Yoshikawa, Tamotsu Yoshimori, Kohki Yoshimoto, Ho Jin You, Richard J Youle, Anas Younes, Li Yu, Long Yu, Seong-Woon Yu, Wai Haung Yu, Zhi-Min Yuan, Zhenyu Yue, Cheol-Heui Yun, Michisuke Yuzaki, Olga Zabirnyk, Elaine Silva-Zacarin, David Zacks, Eldad Zacksenhaus, Nadia Zaffaroni, Zahra Zakeri, Herbert J Zeh, Scott O Zeitlin, Hong Zhang, Hui-Ling Zhang, Jianhua Zhang, Jing-Pu Zhang, Lin Zhang, Long Zhang, Ming-Yong Zhang, Xu Dong Zhang, Mantong Zhao, Yi-Fang Zhao, Ying Zhao, Zhizhuang J Zhao, Xiaoxiang Zheng, Boris Zhivotovsky, Qing Zhong, Cong-Zhao Zhou, Changlian Zhu, Wei-Guo Zhu, Xiao-feng Zhu, Xiongwei Zhu, Yuangang Zhu, Teresa Zoladek, Wei-Xing Zong, Antonio Zorzano, Jürgen Zschocke, Brian Zuckerbraun.
Autophagy
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In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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Autophagic cell death exists.
Autophagy
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The term autophagic cell death (ACD) initially referred to cell death with greatly enhanced autophagy, but is increasingly used to imply a death-mediating role of autophagy, as shown by a protective effect of autophagy inhibition. In addition, many authors require that autophagic cell death must not involve apoptosis or necrosis. Adopting these new and restrictive criteria, and emphasizing their own failure to protect human osteosarcoma cells by autophagy inhibition, the authors of a recent Editors Corner article in this journal argued for the extreme rarity or nonexistence of autophagic cell death. We here maintain that, even with the more stringent recent criteria, autophagic cell death exists in several situations, some of which were ignored by the Editors Corner authors. We reject their additional criterion that the autophagy in ACD must be the agent of ultimate cell dismantlement. And we argue that rapidly dividing mammalian cells such as cancer cells are not the most likely situation for finding pure ACD.
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Evaluation of swallowing by Sydney Swallow Questionnaire (SSQ) in oral and oropharyngeal cancer patients treated with primary surgery.
Dysphagia
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This work aimed at evaluating patients swallowing functions by a newly validated swallow-specific questionnaire, the Sydney Swallow Questionnaire (SSQ), in a cohort of oral and oropharyngeal cancer patients. Mean/median SSQ scores were calculated and compared with study variables using the Mann-Whitney U test and Kruskal-Wallis test. The mean composite SSQ scores (SD) for the base of tongue, oral tongue, and tonsillar cancer patients were 663.8 (382.8), 456.2 (407.6), and 283.0 (243.1), respectively (p = 0.005); for advanced vs. early T stage disease they were 918.1 (319.5) vs. 344.8 (292.1) (p ? 0.001); for patients <60 years vs. ?60 years they were 549.3 (415.1) vs. 314.0 (247.3) (p = 0.02); and for patients with reconstruction vs. without reconstruction they were 676.5 (410.5) vs. 331.9 (286.5) (p = 0.002). SSQ is a useful tool for evaluation of swallowing in head and neck cancer patients. Site of cancer, T stage, patients age, and reconstruction directly affect post-treatment swallow outcome.
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The limits of brain determinacy.
Proc. Biol. Sci.
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The genes do not control everything that happens in a cell or an organism, because thermally induced molecular movements and conformation changes are beyond genetic control. The importance of uncontrolled events has been argued from the differences between isogenic organisms reared in virtually identical environments, but these might alternatively be attributed to subtle, undetected differences in the environment. The present review focuses on the uncontrolled events themselves in the context of the developing brain. These are considered at cellular and circuit levels because even if cellular physiology was perfectly controlled by the genes (which it is not), the interactions between different cells might still be uncoordinated. A further complication is that the brain contains mechanisms that buffer noise and others that amplify it. The final resultant of the battle between these contrary mechanisms is that developmental stochasticity is sufficiently low to make neurobehavioural defects uncommon, but a chance component of neural development remains. Thus, our brains and behaviour are not entirely determined by a combination of genes-plus-environment.
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Evaluation of speech outcomes using English version of the Speech Handicap Index in a cohort of head and neck cancer patients.
Oral Oncol.
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The aim of this study was to explore post-treatment speech impairments using English version of Speech Handicap Index (SHI) (first speech-specific questionnaire) in a cohort of oral cavity (OC) and oropharyngeal (OP) cancer patients. Sixty-three consecutive OC and OP cancer patients in follow-up participated in this study. Descriptive analyses have been presented as percentages, while Mann-Whitney U-test and Kruskall-Wallis test have been used for the quantitative variables. Statistical Package for Social Science-15 statistical software (SPSS Inc., Chicago, IL) was used for the statistical analyses. Over a third (36.1%) of patients reported their speech as either average or bad. Speech intelligibility and articulation were the main speech concerns for 58.8% and 52.9% OC and 31.6% and 34.2% OP cancer patients, respectively. While feeling of incompetent and being less outgoing were the speech-related psychosocial concerns for 64.7% and 23.5% OC and 15.8% and 18.4% OP cancer patients, respectively. Worse speech outcomes were noted for oral tongue and base of tongue cancers vs. tonsillar cancers, mean (SD) values were 56.7 (31.3) and 52.0 (38.4) vs. 10.9 (14.8) (P<0.001) and late vs. early T stage cancers 65.0 (29.9) vs. 29.3 (32.7) (P<0.005). The English version of the SHI is a reliable, valid and useful tool for the evaluation of speech in HNC patients. Over one-third of OC and OP cancer patients reported speech problems in their day-do-day life. Advanced T-stage tumors affecting the oral tongue or base of tongue are particularly associated with poor speech outcomes.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.