Biomarkers in Graft-Versus-Host Disease: from Prediction and Diagnosis to Insights into Complex Graft/Host Interactions

Abstract

Purpose of Review

Acute graft versus host disease (aGVHD) is a frequent cause of treatment-related mortality after allogeneic hematopoietic stem cell transplantation (alloHCT), with few effective treatment options beyond systemic steroids. Discovery of biomarkers for aGVHD may provide insight into the pathophysiology of aGVHD and suggest novel mechanisms for treatment.

Recent Findings

We highlight biomarkers within innate immune activation, T-cell-mediated tissue damage, endothelial damage, dysbiosis, and poor wound healing that can be obtained prior to transplant, in the early transplant period, or at the onset of aGVHD.

Summary

aGVHD biomarkers have predictive and prognostic utility but also suggest novel mechanisms of recipient tissue damage and impaired regenerative capacity. These mechanisms should be further studied and tested in therapeutic clinical trials to improve outcomes post-alloHCT.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rOEOEi

A spherical treadmill system to train head-fixed adult rats

Publication date: 1 March 2018
Source:Journal of Neuroscience Methods, Volume 297
Author(s): Anabel M.M. Miguelez Fernández, Ariel Burman, Alfredo I. Martínez Cáceres, Camilo J. Mininni, B. Silvano Zanutto, Sergio E. Lew
BackgroundWhile spherical treadmills are widely used in mouse models, there are only a few experimental setups suitable for adult rats, and none of them include head-fixation.New methodWe introduce a novel spherical treadmill apparatus for head-fixed rats that allows a wide repertory of natural responses. The rat is secured to a frame and placed on a freely rotating sphere. While being head-fixed, it can walk in any direction and perform different motor tasks.Comparison with existing methodsInstead of being air-lifted, which is acceptable for light animals, the treadmill is sustained by three spherical bearings ensuring a smooth rotation in any direction. Movement detection is accomplished using a video camera that registers a dot pattern plotted on the sphere.ResultsLong Evans rats were trained to perform an auditory discrimination task in a Go/No-Go (walking/not-walking) paradigm. Animals were able to successfully discriminate between a 1 kHz and a 8 kHz auditory stimulus and execute the correct response, reaching the learning criterion (80% of correct responses) in approximately 20 training sessions.ConclusionsOur system broadens the possibilities of head-fixation experiments in adult rats making them compatible with spatial navigation on a spherical treadmill.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rVJ3Ou

Editorial Board

Publication date: 15 January 2018
Source:Journal of Neuroscience Methods, Volume 294





from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GtMP4N

Reconstructing the functional connectivity of multiple spike trains using Hawkes models

Publication date: 1 March 2018
Source:Journal of Neuroscience Methods, Volume 297
Author(s): Régis C. Lambert, Christine Tuleau-Malot, Thomas Bessaih, Vincent Rivoirard, Yann Bouret, Nathalie Leresche, Patricia Reynaud-Bouret
BackgroundStatistical models that predict neuron spike occurrence from the earlier spiking activity of the whole recorded network are promising tools to reconstruct functional connectivity graphs. Some of the previously used methods are in the general statistical framework of the multivariate Hawkes processes. However, they usually require a huge amount of data, some prior knowledge about the recorded network, and/or may produce an increasing number of spikes along time during simulation.New methodHere, we present a method, based on least-square estimators and LASSO penalty criteria, for a particular class of Hawkes processes that can be used for simulation.ResultsTesting our method on small networks modeled with Leaky Integrate and Fire demonstrated that it efficiently detects both excitatory and inhibitory connections. The few errors that occasionally occur with complex networks including common inputs, weak and chained connections, can be discarded based on objective criteria.Comparison with existing methodsWith respect to other existing methods, the present one allows to reconstruct functional connectivity of small networks without prior knowledge of their properties or architecture, using an experimentally realistic amount of data.ConclusionsThe present method is robust, stable, and can be used on a personal computer as a routine procedure to infer connectivity graphs and generate simulation models from simultaneous spike train recordings.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rOB71o

Neutrophilia, gelatinase release and microvascular leakage induced by human mast cell tryptase in a mouse model: Lack of a role of protease activated receptor 2 (PAR2)

Abstract

Background

Tryptase, the most abundant protease of the human mast cell, has been implicated as a key mediator of allergic inflammation that acts through activation of PAR2.

Objectives

To investigate the contribution of PAR2 in the pro-inflammatory actions mediated by tryptase in a mice model.

Methods

We have injected recombinant human βII-tryptase into the peritoneum of PAR2-deficient and wild-type C57BL/6 mice. After 6, 12 and 24 hours mice were euthanized, peritoneal lavage performed and inflammatory changes investigated.

Results

Tryptase stimulated an increase in neutrophil numbers in the peritoneum, but responses did not differ between PAR2-deficient and wild-type mice. Heat-inactivation of tryptase or pre-incubation with a selective tryptase inhibitor reduced neutrophilia, but neutrophil accumulation was not elicited with a peptide agonist of PAR2 (SLIGRL-NH₂). Zymography indicated that tryptase stimulated the release of matrix metalloproteinases (MMP) 2 and 9 in the peritoneum of both mouse strains. Studies involving immunomagnetic isolation of neutrophils suggested that neutrophils represent the major cellular source of tryptase-induced MMP2 and MMP9. At 24 h after tryptase injection there was increased microvascular leakage as indicated by high levels of albumin in peritoneal lavage fluid, and this appeared to be partially abolished by heat-inactivating tryptase or addition of a protease inhibitor. There was no corresponding increase in levels of histamine or total protein. The extent of tryptase-induced microvascular leakage or gelatinase release into the peritoneum did not differ between PAR2-deficient and wild-type mice.

Conclusions

Our findings indicate that tryptase is a potent stimulus for neutrophil accumulation, MMP release and microvascular leakage. Though these actions required an intact catalytic site, the primary mechanism of tryptase in vivo would appear to involve processes independent of PAR2.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ErWjgy

Repeated vaccination with tetanus toxoid of plasma donors with pre-existing specific IgE transiently elevates tetanus-specific IgE but does not induce allergic symptoms

Abstract

IgE responses against allergens have acquired much attention due to their pathogenic nature as mediators of allergic reactions. In contrast, IgE responses against vaccines like Diphtheria-Tetanus-Pertussis (DTP) and the potential persistence of IgE production have received relatively little attention, presumably because of the low prevalence of allergic symptoms. In general, common early sensitivity reactions against vaccines, including tetanus toxoid, consist of mild local reactions and are not contraindicative of future vaccinations (1, 2).

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DQFbQw

Step-down of inhaled corticosteroids in non-eosinophilic asthma: a prospective trial in real life

Abstract

Background

While non-eosinophilic asthmatics are usually considered poorly responsive to inhaled corticosteroids (ICS), studies assessing a step-down of ICS in this specific population are currently lacking.

Objectives

To assess the proportion of non-eosinophilic asthmatics in whom ICS may be withdrawn without any clinical degradation and to determine the predictive markers of a failure to stop treatment with ICS.

Methods

This prospective study was completed by 36 non-eosinophilic asthmatics, defined by sputum eosinophils <3% and blood eosinophils <400/μL. In these patients, whichever the baseline asthma control level, the dose of ICS was gradually reduced every 3 months until they met the failure criteria or successfully discontinued ICS for 6 months. The failure criteria were an ACQ score ≥1.5 with an increase from baseline >0.5 or a number of severe exacerbations during the study which was greater than the number during the year prior to the baseline visit. Receiver-operating characteristic (ROC) curves were constructed to assess predictors of a failure to stop ICS. This study is registered with ClinicalTrials. gov, number NCT02169323.

Results

In 14 patients (39%), ICS were completely withdrawn and in 10 further patients (28%), ICS were stepped-down to a reduced ICS dose without any deterioration of asthma control and exacerbation rate. Baseline predictors of a failure to stop ICS were a greater age (area under ROC curve [ROC AUC] and [95% CI]: 0.77 [0.62-0.93]) and elevated blood eosinophils (ROC AUC [95% CI]: 0.77 [0.61-0.93]). After the first step-down of ICS, the best predictor was an elevated blood eosinophil count (ROC AUC [95% CI]: 0.85 [0.72-0.99]).

Conclusions & Clinical Relevance

Withdrawing or reducing the dose of ICS is feasible in two thirds of non-eosinophilic asthmatics irrespective of baseline asthma control. An elevated blood eosinophil count may predict the failure to stop ICS.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Eoj9p7

Temperature-controlled laminar airflow (TLA) device in the treatment of children with severe atopic eczema: Open-label, proof-of-concept study

Abstract

Background

Children with severe, persistent atopic eczema (AE) have limited treatment options, often requiring systemic immunosuppression.

Objective

To evaluate the effect of the temperature-controlled laminar airflow (TLA) treatment in children/adolescents with severe AE.

Methods

We recruited 15 children aged 2-16 years with longstanding, severe AE and sensitization to ≥1 perennial inhalant allergen. Run-in period of 6-10 weeks (3 visits), was followed by 12-month treatment with overnight TLA (Airsonett^®, Sweden). The primary outcome was eczema severity (SCORAD-Index and Investigator Global Assessment-IGA). Secondary outcomes included child/family dermatology quality of life and family impact questionnaires (CDQLI, FDQLI, DFI), patient oriented eczema measure (POEM), medication requirements, and healthcare contacts. The study is registered as ISRCTN65865773.

Results

There was a significant reduction in AE severity ascertained by SCORAD and IGA during the 12-month intervention period (P<0.001). SCORAD was reduced from a median of 34.9 [interquartile range 28.75-45.15] at baseline to 17.2 [12.95-32.3] at the final visit, and IGA improved significantly from 4 [3-4] to 2 [1-3]. We observed a significant improvement in FDQLI (16.0 [12.25-19.0] to 12 [8-18], P=0.023) and DFI (P=0.011), but not CDQLI or POEM. Compared to 6-month period prior to enrollment, there was a significant reduction at six months after the start of the intervention in potent topical corticosteroids (P=0.033). The exploratory cluster analysis revealed two strongly divergent patterns of response, with 9 patients classified as responders, and 6 as non-responders.

Conclusion and Clinical Relevance

Addition of TLA device to standard pharmacological treatment may be an effective add-on to the management of difficult-to-control AE.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DOR89c

Angiogenesis enhanced by treatment damage to hepatocellular carcinoma through the release of GDF15

Abstract

Transarterial chemoembolization (TACE) is the standard treatment for unresectable hepatocellular carcinoma (HCC). Hypoxia-induced angiogenesis by TACE is linked to treatment failure; however, whether the chemotherapeutic damage of TACE to HCC could increase tumor angiogenesis has not been explored. The molecular effects of chemotherapy-damaged HCC cells on the neo-angiogenesis were investigated in vitro and in vivo. The expression of growth differentiation factor 15 (GDF15) was significantly upregulated in HCC cells exposed to chemotherapeutic agents. GDF15 from chemotherapy-damaged HCC cells promoted the in vitro proliferation, migration, and tube formation of endothelial cells. The pro-angiogenic effect of GDF15 was through the activation of Src and its downstream AKT, MAPK, and NF-κB signaling, which was blocked by thalidomide. The use of thalidomide significantly attenuated the in vivo chemotherapy-damaged HCC cells-promoted angiogenesis in nude mice. In conclusion, the chemotherapeutic damage in TACE to HCC could promote tumor angiogenesis via the increased release of GDF15. Thalidomide could reverse these pro-angiogenic effects.

Chemotherapeutic damage to hepatocellular carcinoma promotes tumor angiogenesis via the increased release of GDF15. Thalidomide could reverse these pro-angiogenic effects.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Gx24Kd

Effectiveness of modified hyper-CVAD chemotherapy regimen in the treatment of adult acute lymphoblastic leukemia: a retrospective experience

Abstract

Several chemotherapy regimens have been developed for the treatment of acute lymphoblastic leukemia (ALL), but relapse still presents the most common obstacles to attaining long-term survival. The hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and prednisolone)/HD MTX and Ara-C (high-dose methotrexate and cytarabine) chemotherapy regimen was first started in the MD Anderson Cancer Center as an intensive regimen for adult patients with ALL. The purpose of this study was to evaluate the effectiveness of a modified hyper-CVAD protocol. We used hyper-CVAD as consolidation/maintenance after remission induction with daunorubicin, vincristine, and prednisolone (and cyclophosphamide for T-cell ALL only) rather than standard hyper-CVAD in order to reduce treatment complications. This study was conducted as a retrospective review of medical records of ALL patients at 501 army hospital, Tehran, Iran, from 2005 to 2015. Three hundred and one patients underwent modified hyper-CVAD chemotherapy regimen. Complete remission and overall survival (OS) rates were measured as primary endpoints. Two hundred and forty-six (81.7%) reached complete remission (CR) during the first 6 months of treatment, and 55 patients (18.3%) did not reach CR. The 5-year OS rate was 51.8% (95% CI (confidence interval): 45.1–57.8%). Modified hyper-CVAD regimen is an efficient intensive chemotherapy regimen for consolidation/maintenance of adults with newly diagnosed ALL and has an acceptable 5-year overall that is comparable to standard hyper-CVAD regimen.

We used a modified hyper-CVAD protocol to reduce treatment-related mortality and simultaneously reach an acceptable overall survival in patients with adult ALL. The results were promising, and it seems that this protocol could be of great benefit for ALL patients.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rTJcSw

Chin Augmentation by Means of Fat Grafting

How does the use of fat grafting compare with other methods for chin augmentation in terms of aesthetic results?
Plastic and Reconstructive Surgery

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DPSeWg

Novel applications for an established antimalarial drug: tumoricidal activity of quinacrine

Future Oncology, Ahead of Print.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DRlAnn

CPX-351: changing the landscape of treatment for patients with secondary acute myeloid leukemia

Future Oncology, Ahead of Print.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nsWSP3

Is there a role of breast pathologist in diagnostic challenges of discordances in ER, PR, and HER2 between primary breast cancer and brain metastasis?

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nsPoLW

Reverse of non-small cell lung cancer drug resistance induced by cancer associated fibroblasts via a paracrine pathway

Abstract

Tumor microenvironment orchestrates the sustained growth, metastasis and recurrence of cancer. As an indispensable component of tumor microenvironment, cancer associated fibroblasts (CAFs) are considered as an essential synthetic machine producing various tumor components, leading to cancer sustained stemness, drug resistance and tumor recurrence. Here, we developed a sustainable primary culture of lung cancer cells fed with lung cancer associated fibroblasts, resulting in enrichment and acquisition of drug resistance in cancer cells. Moreover, IGF2/AKT/Sox2/ABCB1 signaling activation in cancer cells was observed in the presence of cancer associated fibroblasts, which induce P-glycoprotein (P-GP) up-regulated expression and the drug resistance of non-small cell lung cancer cells. Our results demonstrated that cancer associated fibroblast cells constitute a supporting niche for cancer drug resistance acquisition. Thus, traditional chemotherapy combined with IGF2 signaling inhibitor may present an innovative therapeutic strategy for non-small cell lung cancer therapy.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EoJrYg

lncRNA BC005927 upregulates EPHB4 and promotes gastric cancer metastasis under hypoxia

Summary

Hypoxia plays a critical role in the metastasis of gastric cancer (GC), yet the underlying mechanism remains largely unclear. It is also not known if lncRNAs are involved in the contribution of hypoxia to the GC metastasis. In this study, we found that lncRNA BC005927 can be induced by hypoxia in GC cells and mediates hypoxia-induced GC cell metastasis. Furthermore, BC005927 is frequently up-regulated in GC samples and increased BC005927 expression was correlated with a higher tumor-node-metastasis stage. GC patients with higher BC005927 expression had poorer prognoses than those with lower expression. Additional experiments revealed that BC005927 expression is induced by HIF-1a, CHIP assay and luciferase reporter assays confirmed that this lncRNA is a direct transcriptional target of HIF-1a. Next, we found that EPHB4, a metastasis-related gene, is regulated by BC005927 and that the expression of EPHB4 was positively correlated with that of BC005927 in the clinical GC samples assessed. Intriguingly, EPHB4 expression was also increased under hypoxia, and its upregulation by BC005927 resulted in hypoxia-induced GC cell metastasis. These results advance the current understanding of the role of BC005927 in the regulation of hypoxia signaling and offer new avenues for the development of therapeutic interventions against cancer progression.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DJWSAX

Diagnostic patterns and delays in autoimmune blistering diseases of the mouth; a cross-sectional study

Abstract

Objectives

To describe the natural history and factors influencing diagnostic delays among patients with autoimmune blistering diseases of the mouth.

Materials and methods

In this cross-sectional study, 27 newly diagnosed patients were interviewed, and professional and patient delays were calculated. Disease extent and severity scores were determined using Saraswat scoring system.

Results

Twenty-seven patients were interviewed and examined. Patient delay was significantly longer in patients who had desquamative gingivitis as initial presentation, in those who tried to use home remedies and over the counter medications, and in patients with less severe disease. Most patients (n= 21 [77.7%]) made more than one consultation, and the mean time needed to reach a definitive diagnosis (i.e. professional delay) was 83.2 ± 21.4 days (range from 21 to 130 days). Professional delay was significantly correlated with the number of previous consultations (r=0.78), and was significantly longer in patients who had desquamative gingivitis as initial presentation.

Conclusion

Diagnosis of oral blistering diseases is often delayed. Diagnostic delay is more common in patients presenting with desquamative gingivitis and those with less severe disease. Improving patients and health care professionals' awareness about oral blistering diseases might help reduce diagnostic delay.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nr3FcL

Comparing Human and Mouse Salivary Glands: A Practice Guide for Salivary Researchers

Abstract

Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them that must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BF6tas

Exogenous Hydrogen Sulfide Inhibits Oral Mucosal Wound-induced Macrophage Activation via the NF-κB Pathway

Abstract

Objective

This study includes exploring (1) the production of endogenous hydrogen sulfide (H₂S) after mucosal wound generation and (2) the role of compensating the change in H₂S level post mucosal wound generation.

Methods and Materials

A mucosal wound model was established in female C57BL/6J mice. Wound tissues were collected to exam the change in the endogenous H₂S level. To examine the effect of decreased H₂S, GYY4137 was intraperitoneally injected into mice at 50 mg/kg/day before mucosal wounding to compensate for the decreased endogenous H₂S. Finally, we confirmed the role of GYY4137 in inhibiting the M1 phenotype macrophage activation induced by LPS in peritoneal macrophages and RAW264.7.

Results

The production of endogenous H₂S and the expression of cystathionine b-synthase and cystathionine g-lyase in vivo was reduced significantly in early stage after wound. GYY4137 significantly inhibited the activation of the M1 phenotype induced by mucosal wound inflammation in vivo and LPS in vitro. Finally, we confirmed that GYY4137 inhibited iNOS expression via the NF-κB signaling pathway.

Conclusion

The exogenous H₂S donor GYY4137 compensated for the reduced endogenous H₂S post mucosal wound generation and inhibited the induced M1 macrophage activation. Thus, appropriate H₂S supplementation may aid in controlling inflammation associated with mucosal wounds.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2npsNR2

Salivary proteomics in lichen planus: A relationship with pathogenesis?

Abstract

Objectives

Oral lichen planus is a chronic, T-cell-mediated, inflammatory disease that affects the oral cavity. The oral lichen planus pathogenesis is still unclear, however, the main evidence is that the mechanisms of activation of different T lymphocytes pathways induce apoptosis with an increase of Th1 and Th17 subtypes cells, triggered by the release of cytokines; This study analysed saliva proteomics to identify protein markers that might be involved in the pathogenesis and development of the disease.

Material And Methods

Proteins differentially expressed by oral lichen planus and healthy controls were screened using mass spectrometry; the proteins found in oral lichen planus were subjected to bioinformatics analysis, including gene ontology and string networks analysis. The multiplex analysis validation allowed the correlation between the proteins identified and the involved cytokines in Th17 response.

Results

108 proteins were identified in oral lichen planus, of which 17 proteins showed a high interaction between them and indicated an association with the disease. Expression of these proteins was correlated with the triggering of cytokines, more specifically the Th17 cells.

Conclusions

Proteins, such as S100A8, S100A9, Haptoglobin can trigger cytokines and might be associated with a pathological function and antioxidant activities in oral lichen planus.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BF6n2A

Creating diverse synapses from the same molecules

Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51
Author(s): Zoltan Nusser
Research over the past half a century has revealed remarkable diversity among chemical synapses of the CNS. The structural, functional and molecular diversity of synapses was mainly concluded from studying different synapses in distinct brain regions and preparations. It is not surprising that synapses made by molecularly distinct pre-synaptic and post-synaptic cells display different morphological and functional properties with distinct underlying molecular mechanisms. However, synapses made by a single presynaptic cell onto distinct types of postsynaptic cells, or distinct presynaptic inputs onto a single postsynaptic cell, also show remarkable heterogeneity. Here, by reviewing recent experiments, I suggest that robust functional diversity can be achieved by building synapses from the same molecules, but using different numbers, densities and nanoscale arrangements.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Gu09Gq

Towards resolving the presynaptic NMDA receptor debate

Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51
Author(s): Guy Bouvier, Rylan S Larsen, Antonio Rodríguez-Moreno, Ole Paulsen, P Jesper Sjöström
In the classical view, postsynaptic NMDA receptors (NMDARs) trigger Hebbian plasticity via Ca²⁺ influx. However, unconventional presynaptic NMDARs (preNMDARs) which regulate both long-term and short-term plasticity at several synapse types have also been found. A lack of sufficiently specific experimental manipulations and a poor understanding of how preNMDARs signal have contributed to long-standing controversy surrounding these receptors. Although several prior studies linked preNMDARs to neocortical timing-dependent long-term depression (tLTD), a recent study argues that the NMDARs are actually postsynaptic and signal metabotropically, that is, without Ca²⁺. Other recent work indicates that, whereas ionotropic preNMDARs signaling controls evoked release, spontaneous release is regulated by metabotropic NMDAR signaling. We argue that elucidating unconventional NMDAR signaling modes—both presynaptically and metabotropically—is key to resolving the preNMDAR debate.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rVKFrq

Editorial overview: Neurobiology of disease (2018)

Publication date: Available online 30 January 2018
Source:Current Opinion in Neurobiology
Author(s): Claudia Bagni, Anatol C Kreitzer




from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Gx9OMt

REST, a master transcriptional regulator in neurodegenerative disease

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Jee-Yeon Hwang, R Suzanne Zukin
The restrictive element-1 silencing transcription factor)/NRSF (neuron-restrictive silencing factor (NRSF) is a transcriptional repressor which acts via epigenetic remodeling to silence target genes. Emerging evidence indicates that REST is a master transcriptional regulator of neuron-specific genes not only in neurogenesis and neuronal differentiation, but also in differentiated neurons during the critical period in postnatal brain development, where it plays a role in fine-tuning of genes involved in synaptic plasticity, and in normal aging, where it promotes neuroprotection by repressing genes involved in oxidative stress and β-amyloid toxicity. This review focuses on recent findings that dysregulation of REST and REST-dependent epigenetic remodeling provide a central mechanism critical to the progressive neurodegeneration associated with neurologic disorders and diseases including global ischemia, stroke, epilepsy, Alzheimer's and Huntington's disease.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rRZ4VF

Productivity losses due to premature mortality from cancer in Brazil, Russia, India, China, and South Africa (BRICS): A population-based comparison

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Alison Pearce, Linda Sharp, Paul Hanly, Anton Barchuk, Freddie Bray, Marianna de Camargo Cancela, Prakash Gupta, Filip Meheus, You-Lin Qiao, Freddy Sitas, Shao-Ming Wang, Isabelle Soerjomataram
BackgroundOver two-thirds of the world's cancer deaths occur in economically developing countries; however, the societal costs of cancer have rarely been assessed in these settings. Our aim was to estimate the value of productivity lost in 2012 due to cancer-related premature mortality in the major developing economies of Brazil, the Russian Federation, India, China and South Africa (BRICS).MethodsWe applied an incidence-based method using the human capital approach. We used annual adult cancer deaths from GLOBOCAN2012 to estimate the years of productive life lost between cancer death and pensionable age in each country, valued using national and international data for wages, and workforce statistics. Sensitivity analyses examined various methodological assumptions.ResultsThe total cost of lost productivity due to premature cancer mortality in the BRICS countries in 2012 was $46·3 billion, representing 0·33% of their combined gross domestic product. The largest total productivity loss was in China ($28 billion), while South Africa had the highest cost per cancer death ($101,000). Total productivity losses were greatest for lung cancer in Brazil, the Russian Federation and South Africa; liver cancer in China; and lip and oral cavity cancers in India.ConclusionLocally-tailored strategies are required to reduce the economic burden of cancer in developing economies. Focussing on tobacco control, vaccination programs and cancer screening, combined with access to adequate treatment, could yield significant gains for both public health and economic performance of the BRICS countries.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GtYuAG

TGFβ C-509T, TGFβ T869C, XRCC1 Arg194Trp, IKBα C642T, IL4 C-590T Genetic polymorphisms combined with socio-economic, lifestyle, diet factors and gastric cancer risk: A case control study in South Indian population

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Dhayalan Pavithra, Majumdar Gautam, Ranganathan Rama, Rajaraman Swaminathan, Gopisetty Gopal, Ayyalur Seshadri Ramakrishnan, Thangarajan Rajkumar
BackgroundGastric cancer is worldwide the third major cause of cancer related death. Risk factors for gastric cancer includes Helicobacter pylori infection, gastric ulcer, less hygienic condition, use of tobacco, alcohol consumption, use of salted, smoked food, genetic alterations etc. In order to identify the risk factors associated with gastric cancer in South Indian population a case-control study involving 200 proven gastric cancer cases and 400 controls was conducted.MethodsA structured questionnaire was used to interview all the subjects who participated in our study. Genotyping assay was performed using Taqman allelic discrimination assay for 5 Single Nucleotide Polymorphisms (SNPs)-TGFβ C-509T, TGFβ T869C, XRCC1 Arg194Trp, IkBα C642T and IL4C-590T.ResultsOdds Ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Statistical analysis on socio-economic factors, lifestyle factors had showed that subjects from low socio economic status, use of tobacco and consumption of non-vegetarian food had increased risk of developing gastric cancer. Multi-factorial analysis for the SNPs adjusting for the risk factors obtained in this study showed that TGFΒ C-509T TT genotypes had four fold increased risk of gastric cancer (OR = 4.11, CI = 1.02–16.56) and TGFβ T869C CC genotype had a decreased risk of gastric cancer (OR = 0.21, CI = 0.05–0.85).ConclusionEconomic status, tobacco use and food habits play a significant role in gastric cancer development. TT genotype for TGFβ C-509T had an increased risk and CC genotype for TGFβ T869C had a decreased risk of gastric cancer in south Indian population after adjusting for socio-economic factors and lifestyle factors.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rQfk9H

The association between recreational physical activity, sedentary time, and colorectal polyps in a population screened for colorectal cancer

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Darren R. Brenner, Eileen Shaw, Demetra H. Yannitsos, Matthew T. Warkentin, Nigel T. Brockton, S. Elizabeth McGregor, Susanna Town, Robert J. Hilsden
PurposeRegular recreational moderate to vigorous physical activity (rMVPA) has been previously associated with a reduced risk of colorectal cancer (CRC), however, few studies have examined the association of rMVPA with colorectal polyps, the pre-malignant precursor lesions. The objective of this study was to examine the associations between physical activity and sitting time and polyps at the time of screening.MethodsWe conducted a cross-sectional study of 2496 individuals undergoing screening-related colonoscopy in Calgary, Alberta, Canada. Physical activity and sitting time were characterized using hours of rMVPA, meeting physical activity recommendations and hours of sitting time using self-reported data obtained from the International Physical Activity Questionnaire. Logistic regression models were used to estimate the crude and adjusted odds ratios (OR) for presence of polyps associated with rMVPA and sitting time.ResultsMeeting physical activity guidelines of ≥150 min/week was non-significantly associated with a modest decrease in odds of having ≥1 polyp at screening (ORadj = 0.95, 95% CI: 0.80–1.14). In males, threshold effects for sitting time were observed for up to 20 h/week (ORadj per hour sitting = 1.07, 95% CI: 1.01–1.13). In stratified analysis, larger inverse associations were observed between physical activity and the presence of polyps in females, obese individuals, and ever smokers, compared to pooled findings.ConclusionsIn this large CRC screening population, there was a suggestive association between increased rMVPA and reduced prevalence of polyps at screening, particularly among females. Even low amounts of regular sitting time (0–20 h/day) were associated with the presence of polyps, particularly among males. Further research on rMVPA and sitting time is necessary to better inform strategies to reduce the frequency of pre-malignant colorectal lesions.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GykRVG

Promoting Peer Interaction for Preschool Children With Complex Communication Needs and Autism Spectrum Disorder

Purpose

This study investigates the impact of a multicomponent intervention on the social communication and engagement of preschool children with complex communication needs (CCN) and autism spectrum disorder (ASD) and peers without disabilities.

Method

Five dyads of children participated in this research. A multiple probe design across dyads was used to evaluate the effects of intervention on the frequency of communicative turns expressed by children with CCN and ASD in interactions with peers. Frequency of peer turns, percentage of turns taken by peers, and joint engagement were investigated to assess the quality of the interaction. The intervention included (a) provision of a communication app on an Apple iPad Air 2 and (b) dyadic turn-taking training.

Results

Four of the 5 participants with CCN completed training and increased independent communicative turn-taking with peers. The 5th participant showed increased turn-taking during training but little change in independent turn-taking. All peers took more turns in intervention than in baseline, with no negative impact on the turn balance between participants. Average joint engagement increased for all dyads, although session-to-session variability was high.

Conclusion

The results from this study provide support for the use of this intervention to promote peer interaction for children with CCN and ASD.

Supplemental Material

https://doi.org/10.23641/asha.5829678

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FvK6GQ

Concurrent Validity and Reliability for the Communication Complexity Scale

Purpose

The Communication Complexity Scale (CCS; Brady et al., 2012) was created to fill a void in measures of expressive communication skills in individuals who communicate primarily with presymbolic or early symbolic means. CCS scores reflect expressive communication observed during interactive communication contexts.

Method

Two studies were completed to examine the reliability and validity of the revised CCS scores. Participants in both studies had minimal verbal skills (i.e., produced less than 20 functional words). Study 1 examined interobserver agreement, test–retest reliability, and concurrent validity for 239 participants with intellectual disabilities between the ages of 3–66 years, assessed with the protocol developed at the University of Kansas (KU CCS). CCS scores were compared with scores from the Vineland Adaptive Behavior Scales–Second Edition (Sparrow, Cicchetti, & Balla, 2005) and the Communication Matrix (Rowland & Fried-Oken, 2010). Study 2 examined the reliability and concurrent validity for CCS scores derived from 110 children (chronological age = 3–9) with autism from diverse backgrounds. These children were assessed with the Early Social Communication Scale (Mundy et al., 2003). CCS scores were compared with rates of communication derived from the Early Social Communication Scale.

Results

CCS scores were moderately correlated with scores from existing measures of early communication. In addition, CCS scores from different raters were reliable, and test–retest scores were highly similar.

Conclusions

These findings support the validity and reliability of the CCS when used with individuals across a wide range of ages and with various types of disabilities. The CCS can be used in research and clinical practice to describe extant communication levels in individuals with minimal verbal skills.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DYN1dT

Effectiveness of a Method for Teaching Self-Compassion to Communication Sciences and Disorders Graduate Students

Purpose

The purpose of this study is to explore the effects of a daily mindfulness practice and 2 types of journaling on participants' development of self-compassion.

Method

This was a between-groups design. All participants in a graduate counseling course engaged in a short daily mindfulness practice at the beginning of every class. Participants were randomly assigned to a counseling journal or a gratitude journal group. Participants were to write in their journals 2 to 5 times a week for the duration of the class. Participants completed the Self-Compassion Scale (Neff, 2003) and a questionnaire created by the 1st author before any mindfulness sessions were held and again at the completion of the course.

Results

Participants' level of self-compassion increased from pretest to posttest. The self-compassion scores of participants who kept counseling journals increased more than did those of participants who kept gratitude journals. Qualitative data indicated that participants believed that mindfulness was an important quality for clinicians to possess and that they were accepting of the daily mindfulness practice.

Conclusions

Engaging in a 12-min daily mindfulness practice utilizing simple yoga postures, breath work, reflective writing, and journaling done at a separate time appears to be an effective technique for increasing students' levels of self-compassion. Maintaining a counseling journal as opposed to a gratitude journal appears to enhance the effect of the daily mindfulness practice on self-compassion.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FwRj9D

Counseling Issues: Addressing Behavioral and Emotional Considerations in the Treatment of Communication Disorders

Purpose

Counseling is an important fundamental professional activity and an established component of the speech-language pathology/audiology scope of practice as documented by the American Speech-Language-Hearing Association (2004a, 2016a). Appropriate incorporation of counseling into practice can optimize service provision, help address comorbid behavioral and emotional reactions to communication disorders, and enhance prognosis. Practitioner insecurity in incorporating counseling into practice has been documented by Phillips and Mendel (2008), as well as Atkins (2007). This tutorial seeks to present general counseling constructs and treatment applications primarily utilizing a humanistic counseling perspective.

Method

This tutorial incorporated relevant publications from communication disorders and counseling psychology literature databases over a 3-year period. The tutorial evolved through interviews with practicing speech-language pathology practitioners and educators and was undertaken to provide transparency and clarity to support the assertions and recommendations offered.

Results

This tutorial organizes and presents general counseling considerations along with specific suggestions, which can help practitioners who are seeking to expand their understanding, skill, and confidence in incorporating counseling into their practice. The tutorial identifies some of the potential and impactful comorbid emotional and behavioral responses to experiencing a communication disorder and/or to the treatment process for the communication disorder issue(s). Theoretically grounded considerations for mitigating such potentially impactful responses are offered.

Conclusion

Continued and enhanced efforts may be necessary to meet American Speech-Language-Hearing Association's mandate for universal incorporation of empirically supported counseling approaches and in advancing universal speech-language pathology/audiology training in this area. It is hoped that this tutorial serves as an initial guide for addressing this need until universal preparation and practice is achieved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2E34Sk6

A Family-Centered Feeding Intervention to Promote Food Acceptance and Decrease Challenging Behaviors in Children With ASD: Report of Follow-Up Data on a Train-the-Trainer Model Using EAT-UP

Purpose

This research note outlines the usefulness of Easing Anxiety Together with Understanding and Perseverance (EAT-UP), a train-the-trainer, family-centered feeding intervention, for promoting food acceptance of children with autism spectrum disorder (ASD). This report is a follow-up on a pilot study (n = 4) of the EAT-UP intervention previously completed by the same authors.

Method

Participants were 3 families of children with ASD receiving services from an outpatient department of a larger rehabilitation hospital in the northeastern United States. Three professionals working with the families were also recruited and trained by the first author, a speech-language pathologist experienced with the EAT-UP method. Initial assessment was followed by a baseline period for each participant. An individual mealtime plan was drafted for each family. Data on acceptance of less preferred food and the presence of challenging mealtime behaviors were recorded using direct observation and pre-, mid-, and postintervention measures and questionnaires.

Results

All children demonstrated increased food acceptance and dietary diversity and decreased challenging behaviors. Caregivers reported decreases in the frequency of problem behaviors and in the number of problem mealtime behaviors. Measures of procedural fidelity increased from 50% to 100% for registered behavior technicians and parents over the course of the EAT-UP intervention period.

Conclusions

EAT-UP is an effective model for training professionals who work with families of children with ASD and challenging mealtime behavior. Implications for interprofessional practice and research are discussed.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fv9EDR

Spatial heterogeneity and evolutionary dynamics modulate time to recurrence in continuous and adaptive cancer therapies

Treatment of advanced cancers has benefited from new agents that supplement or bypass conventional therapies. However, even effective therapies fail as cancer cells deploy a wide range of resistance strategies. We propose that evolutionary dynamics ultimately determine survival and proliferation of resistant cells. Therefore, evolutionary strategies should be used with conventional therapies to delay or prevent resistance. Using an agent-based framework to model spatial competition among sensitive and resistant populations, we applied anti-proliferative drug treatments to varying ratios of sensitive and resistant cells. We compared a continuous maximum tolerated dose schedule with an adaptive schedule aimed at tumor control via competition between sensitive and resistant cells. Continuous treatment cured mostly sensitive tumors, but with any resistant cells, recurrence was inevitable. We identified two adaptive strategies that control heterogeneous tumors: dose modulation controls most tumors with less drug, while a more vacation-oriented schedule can control more invasive tumors. These findings offer potential modifications to treatment regimens that may improve outcomes and reduce resistance and recurrence.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FuxTCi

Tumorigenic and anti-proliferative properties of the TALE-transcription factors MEIS2D and MEIS2A in neuroblastoma

Neuroblastoma is one of only a few human cancers that can spontaneously regress even after extensive dissemination, a poorly understood phenomenon that occurs in as many as 10% of patients. In this study, we identify the TALE-homeodomain transcription factor MEIS2 as a key contributor to this phenomenon. We identified MEIS2 as a MYCN-independent factor in neuroblastoma and showed that in this setting the alternatively spliced isoforms MEIS2A and MEIS2D exert antagonistic functions. Specifically, expression of MEIS2A was low in aggressive stage 4 neuroblastoma but high in spontaneously regressing stage 4S neuroblastoma. Moderate elevation of MEIS2A expression reduced proliferation of MYCN-amplified human neuroblastoma cells, induced neuronal differentiation and impaired the ability of these cells to form tumors in mice. In contrast, MEIS2A silencing or MEIS2D upregulation enhanced the aggressiveness of the tumor phenotype. Mechanistically, MEIS2A uncoupled a negative feedback loop that restricts accumulation of cellular retinoic acid, an effective agent in neuroblastoma treatment. Overall, our results illuminate the basis for spontaneous regression in neuroblastoma and identify a MEIS2A-specific signaling network as a potential therapeutic target in this common pediatric malignancy.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DZQadp

Modulation of Macropinocytosis-Mediated Internalization Decreases Ocular Toxicity of Antibody-Drug Conjugates

AGS-16C3F is an antibody-drug conjugate (ADC) against ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) containing the mcMMAF linker-payload currently in development for treatment of metastatic renal cell carcinoma. AGS-16C3F and other ADC have been reported to cause ocular toxicity in patients by unknown mechanisms. To investigate this toxicity, we developed an in vitro assay using human corneal epithelial cells (HCEC) and show that HCEC internalized AGS-16C3F and other ADCs by macropinocytosis, causing inhibition of cell proliferation. We observed the same mechanism for target-independent internalization of AGS-16C3F in fibroblasts and human umbilical vein endothelial cells (HUVEC). Macropinocytosis-mediated intake of macromolecules is facilitated by the presence of positive charges or hydrophobic residues on the surface of the macromolecule. Modification of AGS-16C3F, either by attachment of poly-glutamate peptides, mutation of residue K16 to D on AGS-16C3F (AGS-16C3F(K16D)), or decreasing the overall hydrophobicity via attachment of polyethylene glycol moieties, significantly reduced cytotoxicity against HCEC and other primary cells. Rabbits treated with AGS-16C3F showed significant ocular toxicity, whereas those treated with AGS-16C3F(K16D) presented with less severe and delayed toxicities. Both molecules displayed similar anti-tumor activity in a mouse xenograft model. These findings establish a mechanism of action for target-independent toxicities of AGS-16C3F and ADCs in general, and provide methods to ameliorate these toxicities.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Ftkfz6

HER2 overexpression triggers an IL-1{alpha} pro-inflammatory circuit to drive tumorigenesis and promote chemotherapy resistance

Systemic inflammation in breast cancer correlates with poor prognosis but the molecular underpinnings of this connection are not well understood. In this study, we explored the relationship between HER2 overexpression, inflammation and expansion of the mammary stem/progenitor and cancer stem-like cell (CSC) population in breast cancer. HER2-positive epithelial cells initiated and sustained an inflammatory milieu needed to promote tumorigenesis. HER2 induced a feed-forward activation loop of IL-1α and IL-6 that stimulated NF-κB and STAT3 pathways for generation and maintenance of breast CSC. In mice, Il1a genetic deficiency delayed MMTV-Her2-induced tumorigenesis and reduced inflammatory cytokine expression as well as CSC in primary tumors. In clinical specimens of human breast tumor tissues, tissue microarray analysis revealed a strong positive correlation between IL-1α/IL-6 expression and CSC-positive phenotype. Pharmacologic blockade of IL-1α signaling reduced the CSC population and improved chemotherapeutic efficacy. Our findings suggest new therapeutic or prevention strategies for HER2-positive breast cancers.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2E2sGEM

Discovery of potent and selective MRCK inhibitors with therapeutic effect on skin cancer.

The myotonic dystrophy-related Cdc42-binding kinases MRCKα and MRCKβ contribute to the regulation of actin-myosin cytoskeleton organization and dynamics, acting in concert with the Rho-associated coiled-coil kinases ROCK1 and ROCK2. The absence of highly potent and selective MRCK inhibitors has resulted in relatively little knowledge of the potential roles of these kinases in cancer. Here we report the discovery of the azaindole compounds BDP8900 and BDP9066 as potent and selective MRCK inhibitors that reduce substrate phosphorylation, leading to morphological changes in cancer cells along with inhibition of their motility and invasive character. In over 750 human cancer cell lines tested, BDP8900 and BDP9066 displayed consistent anti-proliferative effects with greatest activity in hematological cancer cells. Mass spectrometry identified MRCKα S1003 as an autophosphorylation site, enabling development of a phosphorylation-sensitive antibody tool to report on MRCKα status in tumor specimens. In a two-stage chemical carcinogenesis model of murine squamous cell carcinoma, topical treatments reduced MRCKα S1003 autophosphorylation and skin papilloma outgrowth. In parallel work, we validated a phospho-selective antibody with the capability to monitor drug pharmacodynamics. Taken together, our findings establish an important oncogenic role for MRCK in cancer, and they offer an initial preclinical proof of concept for MRCK inhibition as a valid therapeutic strategy.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FvfWDL

Preserving Salivary Gland Physiology against Genotoxic Damage - The Tousled Way

Abstract

Tousled and its homologs are evolutionarily conserved serine/threonine kinases present in plants and animals. Human Tousled-like kinases, TLK1 and TLK2, are implicated in chromatin assembly during DNA replication, chromosome segregation during mitosis, as well as in DNA damage response and repair. They share a high degree of sequence similarity, but have few non-redundant functions. Our lab has studied TLK1, and found that it increases the resistance of cells to ionizing radiation (IR) damage through expedited double strand break (DSB) repair. DSBs are life-threatening lesions which when repaired restore DNA integrity and promote cell survival. A major focus in our lab is to dissect TLK1′s role in DSB response and repair and study its usefulness in averting salivary gland hypofunction, a condition that invariably afflicts patients undergoing regional radiotherapy. The identification of anti-silencing factor 1 (ASF1), histone H3, and Rad9 as substrates of TLK1 links the protein to chromatin organization and DNA damage response and repair. However, recent findings of new interacting partners that include NEK1 suggest that TLK1 may play a broader role in DSB repair. This review provides a brief overview of the DNA damage response and DSB repair, and it highlights our current understanding of TLK1 in the process.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rQZA69

Reevaluating Order Effects in the Binaural Bithermal Caloric Test

Purpose

The purpose of this study was to determine whether a significant order effect exists in the binaural bithermal caloric test.

Method

Fifteen volunteers (mean age = 24.3 years, range = 18–38 years) with no history of vestibular disorder, hearing loss, concussion, or neurological disease underwent caloric testing on 3 occasions. Irrigations were randomized using 8 possible order combinations. The parameters of interest included unilateral weakness, directional preponderance, total response from the right ear, and total response from the left ear.

Results

Order effects were analyzed using 2 methods. The first analysis was done looking at the 8 possible orders. We also had an a priori established hypothesis that the first irrigation tested would influence the calculation of unilateral weakness more than the other 3 irrigations. To test this hypothesis, the 8 orders were condensed into 4 order conditions based on the first irrigation. The effect of order was determined using analysis of variance tests. Although the first irrigation tended to be the largest, no significant effects were observed.

Conclusions

This experiment demonstrated that while there is great inter-individual and intra-individual variability in caloric test results, the order of irrigations had no significant effect in the test. Future studies may explore the effects of nonphysiological factors on test results.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DMVRbf

Subfascial Primary Breast Augmentation with Fat Grafting: A Review of 156 Cases

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GxIhKE

The Lateral Thigh Perforator Flap for Autologous Breast Reconstruction: A Prospective Analysis of 138 Flaps

Background: The septocutaneous tensor fasciae latae or lateral thigh perforator flap was previously introduced by the authors' group as an alternative flap for autologous breast reconstruction when the abdomen is not suitable as a donor site. The authors analyzed their experience with the lateral thigh perforator flap and present the surgical refinements that were introduced. Methods: A prospective study was conducted of all lateral thigh perforator flap breast reconstructions performed since September of 2012. Patient demographics, operative details, complications, and flap reexplorations were recorded. Preoperative imaging with magnetic resonance angiography was performed in all patients. Surgical refinements introduced during this study included limitation of the flap width and the use of quilting sutures at the donor site. Results: A total of 138 lateral thigh perforator flap breast reconstructions were performed in 86 consecutive patients. Median operative times were 277 minutes (range, 196 to 561 minutes) for unilateral procedures and 451 minutes (range, 335 to 710 minutes) for bilateral. Median flap weight was 348 g (range, 175 to 814 g). Two total flap losses (1.4 percent) were recorded, and 11 flaps (8.0 percent) required reexploration, which resulted in viable flaps. The incidence of donor-site complications was reduced significantly after the surgical refinements were introduced. Wound problems decreased from 40.0 percent to 6.3 percent, seroma decreased from 25.0 percent to 9.5 percent, and infection decreased from 27.5 percent to 9.5 percent. Conclusions: The lateral thigh perforator flap is an excellent option for autologous breast reconstruction, with minimal recipient-site complications. The surgical refinements resulted in a significant reduction of donor-site complications. Therefore, the lateral thigh perforator flap is currently the authors' second choice after the deep inferior epigastric artery perforator flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BEOvF3

Developing, Conducting, and Publishing Appropriate Systematic Review and Meta-Analysis Articles

Summary: The volume of medical literature is growing at a rate that renders decision-making difficult without specialized summary tools. Systematic reviews and meta-analyses are important research instruments used to condense and clarify a broad scope of information into manageable summaries. When used effectively, these reports can pool cumulative data across primary studies, formulate clinical guidelines, and guide future research endeavors. However, errors in study design can result in ineffective or misleading analyses. This article presents the appropriate uses for systematic review and meta-analysis by introducing a framework for creating summary studies, and supplying specific examples of pitfalls in study design and execution.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rRgEJz

Discussion: The Lateral Thigh Perforator Flap for Autologous Breast Reconstruction A Prospective Analysis of 138 Flaps

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BHagnS

Redefining the Rectus Sheath: Implications for Abdominal Wall Repair

Background: The abdominal wall is frequently manipulated in a variety of reconstructive procedures, and its anatomy is well described. The authors' clinical observations, however, contradict the standard depiction of the components of the abdominal wall at various levels—particularly regarding the course of the transversus abdominis muscle. Therefore, the authors sought to characterize the components of the rectus sheath at various surgical landmarks to define anatomic points important to abdominal wall repair. Methods: The authors analyzed the abdominal computed tomographic studies of 100 healthy, young (age, 18 to 35 years; body mass index, 20 to 40 kg/m2) patients with suspected renal calculi. Coordinates of key landmarks were recorded at vertebral levels T12 to L5 using a specially designed computer program that scaled all values and calculated distances between various points. Results: All subjects had significant presence of the transversus abdominis within the rectus sheath (the overlap between the abdominis rectus and transversus abdominis muscles) at the costal margin plane (T12-L1, 4.2 cm). Ninety-nine percent had transversus abdominis presence within the rectus sheath at L1-L2 (3.2 cm), 86 percent at the level of the twelfth rib (L2-L3, 1.4 cm), 36 percent at the umbilicus (L3-L4), and 2 percent slightly above the posterosuperior iliac spine (L5-S1). Conclusions: These findings contradict classic teachings of abdominal wall structure and highlight the need for a cautious revisiting of the various permutations of component separation, particularly posterior component release. Furthermore, these anatomical landmarks may help predict the development or recurrence of ventral hernias, thus guiding patient selection and informing surgical technique.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GxPH0O

Complications and Patient-Reported Outcomes after Abdominally Based Breast Reconstruction: Results of the Mastectomy Reconstruction Outcomes Consortium Study

Background: Abdominal flap reconstruction is the most popular form of autologous breast reconstruction. The current study compared complications and patient-reported outcomes after pedicled transverse rectus abdominis myocutaneous (TRAM), free TRAM, deep inferior epigastric perforator (DIEP), and superficial inferior epigastric artery (SIEA) flaps. Methods: Patients undergoing abdominally based breast reconstruction at 11 centers were prospectively evaluated for abdominal donor-site and breast complications. Patient-reported outcomes were measured by the BREAST-Q and Patient-Reported Outcomes Measurement Information System surveys. Mixed-effects regression models were used to assess the effects of procedure type on outcomes. Results: Seven hundred twenty patients had 1-year follow-up and 587 had 2-year follow-up. Two years after reconstruction, SIEA compared with DIEP flaps were associated with a higher rate of donor-site complications (OR, 2.7; p = 0.001); however, SIEA flaps were associated with higher BREAST-Q abdominal physical well-being scores compared with DIEP flaps at 1 year (mean difference, 4.72, on a scale from 0 to 100; p = 0.053). This difference was not significant at 2 years. Abdominal physical well-being scores at 2 years postoperatively were lower in the pedicled TRAM flap group by 7.2 points (p = 0.006) compared with DIEP flaps and by 7.8 points (p = 0.03) compared with SIEA flaps, and in the free TRAM flap group, scores were lower by 4.9 points (p = 0.04) compared with DIEP flaps. Bilateral reconstruction had significantly lower abdominal physical well-being scores compared with unilateral reconstruction. Conclusions: Although all abdominally based flaps are viable breast reconstruction options, DIEP and SIEA flaps are associated with higher abdominal physical well-being than pedicled and free TRAM flaps. Although SIEA flaps offer the advantage of not violating the fascia, higher rates of donor-site complications may diminish patient satisfaction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nrvfXx

Jack Gunter, M.D: A Man of Passion and a True Friend—with Some of His Own Words

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rQRxGt

Venous Superdrainage in DIEP Flap Breast Reconstruction: The Impact of Superficial Inferior Epigastric Vein Dissection on Abdominal Seroma Formation

Background: Abdominal seroma formation after deep inferior epigastric perforator (DIEP) flap breast reconstruction is a common donor-site complication. Additional dissection of one or both of the superficial inferior epigastric veins (SIEVs) in DIEP flap breast reconstruction allows an additional anastomosis for venous superdrainage if venous congestion occurs. However, generally, SIEV dissection involves greater invasiveness into the inguinal region, which can traumatize lymphatic tissue and lead to lymph accumulation. The aim of this study was to evaluate the impact of SIEV dissection on the incidence of postoperative abdominal seroma. Methods: A series of 100 consecutive cases performed by the Department of Plastic and Reconstructive Surgery at the Medical University of Vienna from 2001 to 2016 was analyzed. Patients were divided into three groups: unilateral, bilateral, and no SIEV dissection. Abdominal seroma rates, length of hospital stay, abdominal drainage duration, and drainage fluid volumes were compared retrospectively. Results: Seromas were observed in 11.5 percent of patients without SIEV dissection, 17.2 percent of patients with unilateral SIEV dissection (p = 0.45 versus no SIEV), and 40 percent of patients with bilateral SIEV dissection (p = 0.02 versus no SIEV). The SIEV was anastomosed to salvage a congested DIEP flap twice. All seromas that developed could be treated with, on average, two fine-needle aspirations without any complications. Conclusions: Bilateral, but not unilateral, SIEV dissection increased abdominal seroma rates significantly. Venous congestion was observed rarely, but when it did occur, it endangered flap viability. Because an additional anastomosis of the SIEV can salvage a flap, unilateral SIEV dissection should be considered when raising a DIEP flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nmBBHy

The Use of Low-Profile Silicone Breast Implants in Male Breast Reconstruction

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Gy0KHa

The Comparison of Strattice and SurgiMend in Acellular Dermal Matrix–Assisted, Implant-Based Immediate Breast Reconstruction

Background: Strattice (porcine derivative) and SurgiMend (bovine derivative) are the two most common acellular dermal matrices used in breast reconstruction in the United Kingdom. This retrospective study compared clinical outcomes in immediate implant-based breast reconstruction patients. Methods: The study, conducted across three hospitals, included all patients who underwent immediate implant-based breast reconstruction using Strattice and SurgiMend. The primary outcome measure was implant loss rate. Secondary outcome measures included acellular dermal matrix loss rate, seroma formation, and minor and major complication rates. Intergroup comparison was performed. Results: Eighty-two patients (Strattice, n = 45; SurgiMend, n = 37) underwent 97 immediate implant-based breast reconstructions (Strattice, n = 54; SurgiMend, n = 43). There were no differences between groups for age, comorbidities, specimen weight, or implant volume. Drains were used in all Strattice and 36 (84 percent) SurgiMend cases. The implant loss rate was higher for Strattice (n = 10, 20 percent) compared with SurgiMend (n = 3, 7 percent) but failed to reach statistical significance (chi-square test, p = 0.077). The acellular dermal matrix loss rate was significantly higher (Fisher's exact test, p = 0.014) in the Strattice group (n = 7, 14 percent), with no acellular dermal matrix loss with SurgiMend. The reoperation rate was also significantly higher (chi-square test, p = 0.002) in the Strattice group (n = 17, 33 percent, versus n = 3, 7 percent). The incidence of red breast was significantly higher (chi-square test, p = 0.022) in the SurgiMend group (n = 9, 21 percent, versus n = 3, 6 percent). Seroma, wound problems, and infection rates were similar. Conclusions: Clinical outcomes, including implant loss, acellular dermal matrix loss, and reoperation rates, are significantly better when using SurgiMend in immediate implant-based breast reconstruction compared with Strattice. An appropriately powered randomized trial is needed to provide further information. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nnxuLd

Evidence-Based Medicine: Abdominoplasty

Learning Objectives: After reading this article, the participant should be able to: 1. Differentiate between techniques for standard abdominoplasty and lipoabdominoplasty. 2. Assess patients for risk associated with abdominoplasty alone and combined with other procedures. 3. Implement newer modalities for abdominoplasty perioperative pain management. 4. Better understand the implications and techniques for rectus diastasis correction by rectus sheath plication. 5. Understand the evidence for eliminating the need for drains in abdominoplasty. Summary: This update to past Maintenance of Certification articles offers new perspectives and builds on past knowledge regarding patient assessment, perioperative management, surgical execution, and complications of abdominoplasty.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rR3lZk

Conceptual Considerations for Payment Bundling in Breast Reconstruction

Summary: Rising health care costs and quality demands have driven both the Centers for Medicare and Medicaid Services and the private sector to seek innovations in health system design by placing institutions at financial risk. Novel care models, such as bundled reimbursement, aim to boost value though quality improvement and cost reduction. The Center for Medicare and Medicaid Innovation is leading the charge in this area with multiple pilots and mandates, including Comprehensive Care for Joint Replacement. Other high-cost and high-volume procedures could be considered for bundling in the future, including breast reconstruction. In this article, conceptual considerations surrounding bundling of breast reconstruction are discussed.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nmXEOc

Secondary Rhinoplasty by the Global Masters

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GxPf2C

Discussion: Conceptual Considerations for Payment Bundling in Breast Reconstruction

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nmWAKl

Reply: Comparison of Outcomes with Tissue Expander, Immediate Implant, and Autologous Breast Reconstruction in Greater Than 1000 Nipple-Sparing Mastectomies

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rWMGE2

Introducing the PRS Video Vignette Masters Series

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BEOd0V

Urinary Excretion of MicroRNA-126 Is a Biomarker for Hemangioma Proliferation

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Gwm0x2

Gluteal Augmentation and Enhancement of the Female Silhouette: Analysis and Technique

Summary: Dr. Constantino Mendieta demonstrates and details his personal technique for gluteal augmentation. The video demonstration is divided into three parts: Part I, Aesthetic Analysis and Preoperative Marking; Part II, Creating the Female Silhouette with Circumferential Lipoplasty; and Part III, Autogenous Gluteal Augmentation. Artistic concepts for gluteal augmentation and contouring the female silhouette and technical considerations for patient safety are emphasized. This Master Series Video article is the first in a planned series of video vignettes.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BEO8KF

Direct-to-Implant Breast Reconstruction in Women Older than 65 Years: A Retrospective Analysis of Complication Rate and Overall Outcomes

Background: Half of all cancers occur in women older than 65 years, yet only 4 to 14 percent of these women undergo reconstruction. Most studies on reconstruction in the elderly have focused on tissue expander/implant or autologous reconstruction. A direct-to-implant approach theoretically reduces the number of operations and postoperative visits, but has yet to be investigated in the elderly. Methods: Institutional review board approval was granted for a retrospective chart review for patients who underwent direct-to-implant reconstruction from 2012 to 2015 with any staff in the authors' department. A control cohort of patients who underwent tissue expander/implant-based reconstruction from the same period was analyzed. Results: Direct-to-implant reconstruction was performed in 24 breasts in 19 patients with at least 30-day follow-up and in 17 breasts in 14 patients with at least 1-year follow-up. A control group analysis of tissue expander/implant patients was performed for 109 breasts in 88 patients. The tissue expander/implant group was significantly younger (p = 0.001), with a lower body mass index (p = 0.004). There was no difference in the rate of seroma, hematoma, infection, necrosis, or failed reconstruction. Direct-to-implant patients had significantly reduced numbers of drain days (p

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BEOykd

Bony/Cartilaginous Mismatch: A Radiologic Investigation into the Cause of Tension Nose Deformity

Background: Tension nose deformity is believed to be caused by an "oversized" septal quadrangular cartilage. Prior studies have shown that quadrangular cartilage size is relatively consistent in populations. The authors hypothesize that the tension nose deformity is actually caused by an external extrusion of a normal sized septal cartilage from an undersized bony septal encasement. Methods: A retrospective case-control study of sagittal computed tomographic scans was conducted, measuring the perimeter and surface area of the quadrangular cartilage and bony septal aperture in tension nose cases and controls. Statistical analysis was performed. Results: Of 23 patients enrolled in the study, 12 patients were sorted into the tension nose group, and 11 patients were considered controls. Both groups had similar perimeter and surface area of their quadrangular cartilage, without statistical difference between the two groups. However, the tension nose group had a statistically significant reduction in bony septal aperture perimeter compared with controls (p

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BEO65v

Past and future

The New Year, or Hogmanay as it is known in these parts, is traditionally a time to reflect and to look forward in expectation of greater things to come. Our specialty has a relatively short history to reflect upon. Fifty years ago a very small number of consultants comprised the British Association of Plastic Surgeons, which published this Journal. Their training, autonomy, junior support, breadth and pattern of work would have been barely recognisable to current NHS consultants. Many of the techniques they employed would have seemed strange to us, inpatient care predominated, and sub-specialisation did not really exist.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rTuCdH

Performance on Auditory and Visual Tasks of Inhibition in English Monolingual and Spanish–English Bilingual Adults: Do Bilinguals Have a Cognitive Advantage?

Purpose

Bilingual individuals have been shown to be more proficient on visual tasks of inhibition compared with their monolingual counterparts. However, the bilingual advantage has not been evidenced in all studies, and very little is known regarding how bilingualism influences inhibitory control in the perception of auditory information. The purpose of the current study was to examine inhibition of irrelevant information using auditory and visual tasks in English monolingual and Spanish–English bilingual adults.

Method

Twenty English monolinguals and 19 early balanced Spanish–English bilinguals participated in this study. All participants were 18–30 years of age, had hearing thresholds < 25 dB HL from 250 to 8000 Hz, bilaterally (American National Standards Institute, 2003), and were right handed. Inhibition was measured using a forced-attention dichotic consonant–vowel listening task and the Simon task, a nonverbal visual test.

Results

Both groups of participants demonstrated a significant right ear advantage on the dichotic listening task; however, no significant differences in performance were evidenced between the monolingual and bilingual groups in any of the dichotic listening conditions. Both groups performed better on the congruent trial than on the incongruent trial of the Simon task and had significantly faster response times on the congruent trial than on the incongruent trial. However, there were no significant differences in performance between the monolingual and bilingual groups on the visual test of inhibition.

Conclusions

No significant differences in performance on auditory and visual tests of inhibition of irrelevant information were evidenced between the monolingual and bilingual participants in this study. These findings suggest that bilinguals may not exhibit an advantage in the inhibition of irrelevant information compared with monolinguals.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EqRoMH

Student competition winners announced at Research Day

At the School of Dentistry's annual Research Day on Tuesday, Kristie Cheng was announced as the winner of the Summer Research Fellowship (SURF) Student Clinician Competition. Cheng, a second-year dental student, presented a study of factors affecting citation rates in oral and maxillofacial surgery.

The post Student competition winners announced at Research Day appeared first on UW School of Dentistry.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2npiMmQ

Resolution of unilateral sensorineural hearing loss in a pediatric patient with a severe phenotype of Muckle-Wells syndrome treated with Anakinra: a case report and review of the literature

Muckle-Wells syndrome (MWS) is a rare auto-inflammatory disease characterized by the presence of recurrent urticaria, deafness and amyloidosis. Progressive sensorineural hearing loss (SNHL) is reported to occu...

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EoqDID

The prevalence of human papillomavirus in pediatric tonsils: a systematic review of the literature

HPV-related head and neck cancer rates have been increasing in recent years, with the tonsils being the most commonly affected site. However, the current rate of HPV infection in the pediatric population remai...

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DO5Flk

International consensus (ICON) on treatment of Ménière's disease

Publication date: Available online 12 January 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): J. Nevoux, M. Barbara, J. Dornhoffer, W. Gibson, T. Kitahara, V. Darrouzet
ObjectiveTo present the international consensus for recommendations for Ménière's disease (MD) treatment.MethodsBased on a literature review and report of 4 experts from 4 continents, the recommendations have been presented during the 21st IFOS congress in Paris, in June 2017 and are presented in this work.ResultsThe recommendation is to change the lifestyle, to use the vestibular rehabilitation in the intercritic period and to propose psychotherapy. As a conservative medical treatment of first line, the authors recommend to use diuretics and Betahistine or local pressure therapy. When medical treatment fails, the recommendation is to use a second line treatment, which consists in the intratympanic injection of steroids. Then as a third line treatment, depending on the hearing function, could be either the endolymphatic sac surgery (when hearing is worth being preserved) or the intratympanic injection of gentamicin (with higher risks of hearing loss). The very last option is the destructive surgical treatment labyrinthectomy, associated or not to cochlear implantation or vestibular nerve section (when hearing is worth being preserved), which is the most frequent option.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GwANrv

Epiglottoplasty technique in endoscopic partial laryngectomy

Publication date: Available online 12 January 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): M. Moulin, C.A. Righini, P.F. Castellanos, I. Atallah
The main advantage of endoscopic laser surgery for laryngeal cancer is to allow tumour resection, while limiting functional sequelae, thereby improving the postoperative course. In this type of surgery, the epiglottis is often partially resected, leaving a raw zone without any reconstruction. The surgical technique described here involves endoscopic reconstruction of the epiglottis after partial resection. The sectioned edge of the epiglottis is sutured to the base of the tongue to create a neoepiglottis and to reconstruct the vallecula, thus resembling preoperative anatomy, allowing improvement of postoperative swallowing.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rNeXMU

Meningeal marginal zone B-cell lymphoma: The meningioma trap

Publication date: Available online 10 January 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): Alexandre Villeneuve, François Rubin, Pierre Bonfils
ObjectiveTo report a case of marginal zone MALT lymphoma of the temporal dura mater, initially mistaken for temporal meningioma.Case reportA 60-year-old immunocompetent woman, followed for more than 10 years for temporal meningioma causing vertigo and mixed hearing loss, presented with cervical lymphadenopathy, revealing marked progression of an intracranial lesion, leading to a diagnosis of marginal zone MALT lymphoma based on histological examination of a cervical lymph node. Treatment with 6 cycles of rituximab and bendamustine allowed complete remission of cervical lymph node and intracranial lesions, confirming the diagnosis of temporal dural mater lymphoma.ConclusionPrimary dural lymphoma must be part of the differential diagnosis of meningioma. Long-term follow-up allows correction of the diagnosis.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GyXSdc

Physiology of the paransal sinus ostia: Endoscopic findings

Publication date: Available online 12 January 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): R. Jankowski, C. Rumeau




from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rRBQyT

Pazopanib maintenance after first-line etoposide and platinum chemotherapy in patients with extensive disease small-cell lung cancer: a multicentre, randomised, placebo-controlled Phase II study (KCSG-LU12-07)

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EqueGl

Treatment with docetaxel in combination with Aneustat leads to potent inhibition of metastasis in a patient-derived xenograft model of advanced prostate cancer

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DMBFGC

WNT5A induces castration-resistant prostate cancer via CCL2 and tumour-infiltrating macrophages

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Eque9j

Reduced mannosidase MAN1A1 expression leads to aberrant N-glycosylation and impaired survival in breast cancer

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DMAIhn

Enrolling children with acute lymphoblastic leukaemia on a clinical trial improves event-free survival: a population-based study

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Eocco4

Indeterminate nodules in osteosarcoma: what’s the follow-up?

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FvzAPI

External validation of risk prediction models for incident colorectal cancer using UK Biobank

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2E1psB6

High burden of subsequent malignant neoplasms and cardiovascular disease in long-term Hodgkin lymphoma survivors

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FvaIYA

A Novel Surgical Approach to Nasolabial Fistula

Abstract

Infection of hair follicle is commonly called 'boil' or furunculosis. This can result in abscess formation leading to accumulation of pus and necrotic tissue. This can be more common in immunocompromised patients such as uncontrolled diabetes mellitus. Commonest organism to cause furunculosis is believed to be Staphylococcus aureus. We present an elderly patient where multiple nasal vestibular furunculosis suppurated resulting in extensive tissue damage and nasolabial fistula. Reconstruction was delayed to accommodate tissue healing from hyperglycemic insult and necrosis. Alar advancement flap was employed to give a suitable 3 layer closure to the fistula.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EnMa4g

TARGET Study Finds Major Differences between Childhood and Adult AML

An NCI-funded study has found significant differences in the genetics of acute myeloid leukemia in younger and older patients. The findings could help guide the development of treatments tailored specifically for childhood AML.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EqGyXc

Serum DNA integrity index as a potential molecular biomarker in endometrial cancer

Circulating cell-free DNA (cfDNA) and its integrity index may represent a rapid and noninvasive "liquid biopsy" biomarker, which gives important complementary information for diagnosis, prognosis, and treatmen...

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DL4wLn

The miR-181 family promotes cell cycle by targeting CTDSPL, a phosphatase-like tumor suppressor in uveal melanoma

MicroRNAs (miRNAs) have been shown to function in many different cellular processes, including proliferation, apoptosis, differentiation and development. miR-181a, -181b, -181c and -181d are miR-181 members of th...

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EnXuNO

Effects of polyphenols on doxorubicin-induced oral keratinocyte cytotoxicity and anticancer potency against oral cancer cells

Abstract

Background

Normal human oral keratinocytes are highly sensitive to anticancer drugs including doxorubicin. Resveratrol, epigallocatechin gallate and tannic acid are polyphenolic compounds were reported to have cardioprotective effect when combined with doxorubicin. However, it is unknown whether these polyphenols could protect normal human oral keratinocytes against doxorubicin-induced cytotoxicity without weakening its cytotoxic potential against oral cancer cells. Here, we examined the effects of the three polyphenolic compounds on doxorubicin-induced cytotoxicity in normal human oral keratinocytes and also investigated their effects on doxorubicin potency in HSC-2 human oral squamous cell carcinoma cells.

Methods

Cell viability was evaluated followed by the analysis of apoptosis and necrosis. The changes in intracellular reactive oxygen species at the early stage after treatment were also examined.

Results

The results revealed that resveratrol in combination with doxorubicin additively augmented doxorubicin cytotoxicity in both types of cells. However, epigallocatechin gallate and tannic acid at a certain concentrations mitigated the doxorubicin-induced keratinocyte toxicity mainly due to reduced doxorubicin-induced necrosis in normal human oral keratinocytes without weaken doxorubicin anticancer efficacy. The exact mechanism is still unknown but intracellular reactive oxygen species might be not the sole factor.

Conclusions

The present study for the first time reported the effects of resveratrol, epigallocatechin gallate and tannic acid on doxorubicin-induced cytotoxicity in normal oral keratinocytes and oral cancer cells. Combined use of epigallocatechin gallate or tannic acid with doxorubicin at a certain concentrations could mitigate doxorubicin-induced keratinocyte cytotoxicity without weakening doxorubicin anticancer efficacy.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FrNwdJ

Investigation of an antitumor drug-delivery system based on anti-HER2 antibody-conjugated BSA nanoparticles

Conjugation of a monoclonal antibody with a nanoparticle often improves its specificity and drug loading in cancer therapy. In this study, we prepared a novel targeting nanodrug-delivery system using 2-methoxy-estradiol (2-ME) based on anti-human epidermal growth factor receptor 2 (HER2) antibody-modified BSA to improve the clinical application and antitumor effect of 2-ME. 2-ME-loaded albumin nanoparticles (2-ME-BSANPs) were prepared using a desolvation method and the anti-HER2 antibodies were conjugated to 2-ME-BSANPs (HER2-2-ME-BSANPs) using the coupling agent, succinimidyl 3-(2-pyridyldithio)propionate. HER2-2-ME-BSANPs were characterized using SDS-polyacrylamide gel electrophoresis, an agglutination test, and an immunofluorescence assay. We found that mouse anti-human anti-HER2 monoclonal antibody was successfully conjugated to the 2-ME-BSANPs. Thereafter, the in-vitro and in-vivo toxicities were evaluated using two cancer cell lines, SK-BR-3 (HER2-overexpressing) and MCF-7 (HER2-underexpressing), using classic pharmacological methods and in-vivo imaging technology. We found that the HER2-2-ME-BSANPs retained the immunospecificity of the anti-HER2 monoclonal antibody, rapidly localized to HER2 receptors, and could be used for targeted cancer therapy. Correspondence to Dr Qingfeng Tian, College of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, China Tel/fax: +86 371 6778 1393; e-mail: 13937156869@126.com Received August 23, 2017 Accepted December 5, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2DNwpqh

Comparison of the effect of the antiandrogen apalutamide (ARN-509) versus bicalutamide on the androgen receptor pathway in prostate cancer cell lines

Apalutamide (ARN-509) is an antiandrogen that binds selectively to androgen receptors (AR) and does not show antagonist-to-agonist switch like bicalutamide. We compared the activity of ARN versus bicalutamide on prostate cancer cell lines. The 22Rv1, PC3, and DU145 cell lines were used to study the effect of ARN and bicalutamide on the expression cytoplasmic/nuclear kinetics of AR, AR-V7 variant, phosphorylated AR, as well as the levels of the AR downstream proteins prostate-specific antigen and TMPRSS2, under exposure to testosterone and/or hypoxia. The effects on autophagic flux (LC3A, p62, TFEB, LAMP2a, cathepsin D) and cell metabolism-related enzymes (hypoxia-inducible factor 1α/2α, BNIP3, carbonic anhydrase 9, LDHA, PDH, PDH-kinase) were also studied. The 22Rv1 cell line responded to testosterone by increasing the nuclear entry of AR, AR-V7, and phosphorylated AR and by increasing the levels of prostate-specific antigen and TMPRSS2. This effect was strongly abrogated by ARN and to a clearly lower extent by bicalutamide at 10 μmol/l, both in normoxia and in hypoxia. ARN had a stronger antiproliferative effect than bicalutamide, which was prominent in the 22Rv1 hormone-responsive cell line, and completely repressed cell proliferation at a concentration of 100 μmol/l. No effect of testosterone or of antiandrogens on autophagy flux, hypoxia-related proteins, or metabolism enzyme levels was noted. The PC3 and DU145 cell lines showed poor expression of the proteins and were not responsive to testosterone. On the basis of in-vitro studies, evidence has been reported that ARN is more potent than bicalutamide in blocking the AR pathway in normoxia and in hypoxia. This reflects a more robust, dose-dependent, repressive effect on cell proliferation. Correspondence to Michael I. Koukourakis, MD, Department of Radiotherapy/Oncology, Democritus University of Thrace, PO Box 12, Alexandroupolis 68100, Greece Tel: +30 255 107 4622; fax: 30 255 103 0349; e-mail: targ@her.forthnet.gr Received September 17, 2017 Accepted December 20, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nqfj6O

Oscillatory activity in the cortico-basal ganglia-thalamic neural circuits in Parkinson's disease

Abstract

Dopamine is an important neurotransmitter that maintains the balance within the basal ganglia between the direct pathway, which promotes movement, and the indirect pathway, which inhibits movement. Degeneration of dopaminergic neurons in the substantia nigra increases the influence of the indirect pathway, resulting in motor dysfunction in Parkinson's disease (PD). The direct and indirect pathways are composed of cortical areas, basal ganglia, and thalamic nuclei, which are interconnected via independent parallel loop circuits and often referred to as cortico-basal ganglia-thalamic (CBT) neural circuits. CBT circuits have been useful in generating hypotheses to describe slowness in PD. Recent work has focused on aberrant neural oscillations within CBT circuits. Although beta (13-30 Hz) oscillations are a common feature of the CBT network, there is growing evidence that abnormally exaggerated beta oscillations, observed after dopamine loss in the CBT circuits, may contribute to motor symptoms of PD. Disruption of abnormal beta oscillations has been associated with the improvement of motor functions during pharmacological treatments, surgical lesions, and electrical stimulation. However, it is not clear how abnormal oscillations originate in the CBT motor network and resonate specifically in the beta band after the loss of dopamine. Most studies have addressed these questions by simultaneous recordings of oscillations in the motor cortex, basal ganglia nuclei, and motor regions of the thalamus in animal models of parkinsonism as well as in PD patients. This review further discusses previous and current studies of the changes in oscillatory activity at the level of CBT neural network in PD.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2rQvpMq

Behavioral Signatures of Backward Planning in Animals

Abstract

Goal-directed planning in behavioral and neural sciences is theorized to involve a prospective mental simulation that, starting from the animal's current state in the environment, expands a decision tree in a forward fashion. Backward planning in the artificial intelligence literature, however, suggests that agents expand a mental tree in a backward fashion starting from a certain goal state they have in mind. Here we show that several behavioral patterns observed in animals and humans, namely outcome-specific Pavlovian-to-instrumental transfer and differential-outcome effect, can be parsimoniously explained by backward planning. Our basic assumption is that the presentation of a cue that has been associated with a certain outcome triggers backward planning from that outcome state. On the basis of evidence pointing to forward and backward planning models, we discuss the possibility of brain using a bidirectional planning mechanism where forward and backward trees are expanded in parallel to achieve higher efficiency.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GtDOZs