Head and Neck Diseases by Alexandros G.Sfakianakis: 10/19/16

Non-melanoma skin cancers are among the most commonly diagnosed skin cancers in the world. Ultraviolet radiation is a primary carcinogen resulting in UV induced mutations, loss of activity in tumour suppressor genes and the over expression of oncogenes in keratinocytes resulting in the development of skin malignancies. With the continued rising rate of non-melanoma skin cancer, topical therapies have become an established treatment method for effective lesion clearance. Current topical therapies include 5-fluorouracil, imiquimod, diclofenac, ingenol mebutate and photodynamic therapy. With high lesion recurrence rates still presenting as an issue following topical treatment, lack of drug selectivity for cancer cells, severe side effects from topical agent use and patient non-compliance due to prolonged treatment periods, new novel topical therapies need to be explored and developed. New therapies must target and clear both subclinical and clinically presenting skin cancers by interrupting the molecular mechanisms that induce and sustain the proliferation of neoplastic cells. Piperlongumine and EBC-46 are two naturally occurring small molecules which have demonstrated effective induction of cancer cell death. Piperlongumine, an amide isolated from the pepper, Piper longum, has demonstrated cancer cell death selectivity yet has no impact on healthy rapidly dividing primary cells. EBC-46 is a diterpene ester isolated from the seed of the fruit, Fontainea picrosperma. EBC-46 induces rapid inflammation and necrosis resulting in tumour ablation following intra-lesional injection. The development of Piperlongumine and EBC-46, as new topical agents offers a unique opportunity to further explore and exploit these selective properties for a more efficient and targeted approach to topical non -melanoma skin cancer treatment.

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Meta-analysis Reveals No Association of DNMT3B -149 C>T Gene Polymorphism With Overall Cancer Risk

Background: DNA methyltransferase-3B (DNMT3B) plays a key role in establishment and maintenance of genomic methylation patterns. Polymorphism in promoter region -149 C>T (C46359T) of DNMT3B gene may alter DNMT3B activity which leads to increased susceptibility to cancer. Inconsistent results regarding this have been reported in a number of studies. Objective: To carry out a meta-analysis of the studies reported to assess the precise relationship between the DNMT3B -149 C>T polymorphism and the overall cancer risk. Method: PubMed (MEDLINE) web database was searched for the studies concerning DNMT3B -149 C>T polymorphism and its association with cancer risk. The pooled odds ratios (ORs) along with 95% confidence intervals (95% CIs) were calculated for all the genetic models, from the selected case-control studies, by meta-analysis. Results: Overall eighteen studies containing 5583 cancer cases and 7618 controls were analyzed. No significant risk was observed overall for T allele carrier (T vs. C: p=0.303; OR=1.032, 95% CI=0.972- 1.097), homozygous (TT vs. CC: p=0.336; OR=1.063, 95% CI=0.939–1.204), heterozygous (CT vs. CC: p=0.802; OR=1.022, 95% CI=0.860-1.216), dominant (TT vs. CC+CT: p=0.298; OR=1.101, 95% CI=0.919-1.319) and recessive (TT+CT vs. CC: p=0.656; OR=1.021, 95% CI=0.931-1.121) genetic models. Subgroup analysis of Asian and Caucasian populations also did not demonstrate any cancer risk in all the genetic models studied. Conclusion: Our meta-analysis proposes that the DNMT3B -149 C>T polymorphism may not be an independent predisposing factor for the risk of cancer. However, larger sample size and expression studies are required to confirm the observation. 

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Targeting autophagy sensitizes BRAF-mutant thyroid cancer to vemurafenib

The Journal of Clinical Endocrinology &Metabolism, Early Release.

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Effects of Testosterone Supplementation for 3-Years on Muscle Performance and Physical Function in Older Men

The Journal of Clinical Endocrinology &Metabolism, Early Release.

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Thyroid autoimmunity impairs the thyroidal response to hCG: two population-based prospective cohort studies

The Journal of Clinical Endocrinology &Metabolism, Early Release.

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Body composition changes after very low-calorie-ketogenic diet in obesity evaluated by three standardized methods

The Journal of Clinical Endocrinology &Metabolism, Early Release.

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Low-dose aspirin and sporadic anovulation in the EAGeR randomized trial

The Journal of Clinical Endocrinology &Metabolism, Early Release.

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The effect of TSH-suppression on vertebral trabecular bone scores in patients with differentiated thyroid carcinoma

The Journal of Clinical Endocrinology &Metabolism, Early Release.

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Familial Multiplicity of Estrogen Insensitivity Associated with a Loss-of-Function ESR1 Mutation

The Journal of Clinical Endocrinology &Metabolism, Early Release.

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Diagnosis of ABCC8 congenital hyperinsulinism of infancy in a 20 year-old man evaluated for factitious hypoglycemia.

The Journal of Clinical Endocrinology &Metabolism, Early Release.

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Oral nitrite circumvents antiseptic mouthwash-induced disruption of enterosalivary circuit of nitrate and promotes nitrosation and blood pressure lowering effect

Publication date: Available online 18 October 2016
Source:Free Radical Biology and Medicine
Author(s): Lucas C. Pinheiro, Graziele C. Ferreira, Jefferson H. Amaral, Rafael L. Portella, Sandra de O.C. Tella, Madla A. Passos, Jose E. Tanus-Santos
The nitric oxide (NO^•) metabolites nitrite and nitrate exert antihypertensive effects by mechanisms that involve gastric formation of S-nitrosothiols. However, while the use of antiseptic mouthwash (AM) is known to attenuate the responses to nitrate by disrupting its enterosalivary cycle, there is little information about whether AM attenuates the effects of orally administered nitrite. We hypothesized that the antihypertensive effects of orally administered nitrite would not be prevented by AM because, in contrast to oral nitrate, oral nitrite could promote S-nitrosothiols formation in the stomach without intereference by AM. Chronic effects of oral nitrite or nitrate were studied in two-kidney, one-clip (2K1C) hypertensive rats (and normotensive controls) treated with AM (or vehicle) once/day. We found that orally administered nitrite exerts antihypertensive effects that were not affected by AM. This finding contrasts with lack of antihypertensive responses to oral nitrate in 2K1C hypertensive rats treated with AM. Nitrite and nitrate treatments increased plasma nitrites, nitrates, and S-nitrosothiols concentrations. However, while treatment with AM attenuated the increases in plasma nitrite concentrations after both nitrite and nitrate treatments, AM attenuated the increases in S-nitrosothiols in nitrate-treated rats, but not in nitrite-treated rats. Moreover, AM attenuated vascular S-nitrosylation (detected by the SNO-RAC method) after nitrate, but not after nitrite treatment. Significant correlations were found between the hypotensive responses and S-nitrosothiols, and vascular S-nitrosylation levels. These results show for the first time that oral nitrite exerts antihypertensive effects notwithstanding the fact that antiseptic mouthwash disrupts the enterosalivary circulation of nitrate. Our results support a major role for S-nitrosothiols formation resulting in vascular S-nitrosylation as a key mechanism for the antihypertensive effects of both oral nitrite and nitrate.

Graphical abstract

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Degradation of the cytostatic 5-Fluorouracil in water by Fenton and photo-assisted oxidation processes

Abstract

Cytostatics are part of the forefront research topics due to their high prescription, high toxicity, and the lack of effective solutions to stop their entrance and spread in the environment. Among them, 5-Fluorouracil (5-Fu) has received particular attention because is one of the most prescribed active substances in chemotherapy worldwide. The degradation of 5-Fu by advanced oxidation processes (AOPs) is a poorly addressed topic, and this work brings valuable inputs concerning this matter. Herein, the efficacy of Fenton's process in the degradation of 5-Fu is explored for the first time; the study of the main variables and its successful application to the treatment of real wastewaters is demonstrated. Moreover, hydrogen peroxide-based and photo-assisted techniques (direct photolysis, photodegradation with H₂O₂ and photo-Fenton) are also investigated for purposes of comparison. Under the best operation conditions obtained (T = 30 °C, [Fe²⁺]₀ = 0.5 mM; [H₂O₂]₀ = 240 mM and pH = 3 for [5-Fu]₀ = 0.38 mM), 5-Fu was completely eliminated after 2 h of Fenton's reaction and about 50 % of mineralization was reached after 8 h. The best performance was obtained by the photo-Fenton process, with 5-Fu mineralization level as high as 67 %, using an iron dose within the legal limits required for direct water discharge. Toxicity (towards Vibrio fischeri) of the effluents that resulted from the application of the above-mentioned AOPs was also evaluated; it was found that the degradation products generated from the photo-assisted processes are less toxic than the parent compound, putting into evidence the relevance of such technologies for degradation of cytostatics like 5-Fu.

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Calcium polysulphide, its applications and emerging risk of environmental pollution—a review article

Abstract

Easy availability, preparation technique, and economic value make calcium polysulphide (CaS_x ) a very useful inorganic chemical for various field and industrial applications. In this article, disparate applications of CaS_x solution have been reviewed to suggest potential and future consolidation. This article also encompasses the physiochemical properties and production of CaS_x solution, with critical appraisal on research focusing on CaS_x application in agriculture industries and removal of potentially toxic elements (PTEs) from the environment. The kinetics of CaS_x , technical issues associated with optimization of its dosage and environmental fate is also discussed in detail. This study covers almost all of the peer-reviewed research that has been performed since 1914. Some of the critiques in this article include the lack of integration between the exposure effect and the efficiency of treatment method, effects of oxidizing environments on the long-term performance of CaS_x solution, and kinetics of CaS_x solution with the PTEs. The working model of CaS_x with PTEs is still system dependent, and therefore cannot be used with other applications. The kinetics of CaS_x is described in detail with various phase stoichiometric reactions. Environmental fate is discussed based on applications, government reports, peer-reviewed articles and kinetics of CaS_x , which provides a clear picture of emerging contaminants in the environment in relation to the insect resistance and ecotoxicology. Real time, lab based research articles are needed to identify toxicity limits of CaS_x in environment in order to describe its effective permissible limit in environmental system. This review article provides a risk assessment of environmental pollution by CaS_x based on its physicochemical characteristic, stoichiometry, kinetics, field, and industrial applications.

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A modeling approach to direct interspecies electron transfer process in anaerobic transformation of ethanol to methane

Abstract

Recent studies have shown that direct interspecies electron transfer (DIET) plays an important part in contributing to methane production from anaerobic digestion. However, so far anaerobic digestion models that have been proposed only consider two pathways for methane production, namely, acetoclastic methanogenesis and hydrogenotrophic methanogenesis, via indirect interspecies hydrogen transfer, which lacks an effective way for incorporating DIET into this paradigm. In this work, a new mathematical model is specifically developed to describe DIET process in anaerobic digestion through introducing extracellular electron transfer as a new pathway for methane production, taking anaerobic transformation of ethanol to methane as an example. The developed model was able to successfully predict experimental data on methane dynamics under different experimental conditions, supporting the validity of the developed model. Modeling predictions clearly demonstrated that DIET plays an important role in contributing to overall methane production (up to 33 %) and conductive material (i.e., carbon cloth) addition would significantly promote DIET through increasing ethanol conversion rate and methane production rate. The model developed in this work will potentially enhance our current understanding on syntrophic metabolism via DIET.

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Technoeconomic perspectives on sustainable CO 2 capture and utilization

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Humor Appreciation Involves Parametric and Synchronized Activity in the Medial Prefrontal Cortex and Hippocampus

Humor perception is a ubiquitous phenomenon in human societies. In theories of humor perception, three factors, non-seriousness, social context, and incongruity, have been implicated in humor. In another theory, however, elaboration and reinterpretation of contexts are considered to play a role in eliciting humor. Although the neural correlates of humor appreciation have been investigated using neuroimaging methods, only a few studies have conducted such experiments under natural conditions. In the present study, two functional magnetic resonance imaging experiments, using a comedy movie as a stimulus, were conducted to investigate the neural correlates of humor under natural conditions. The subjects' brain activity was measured while watching and enjoying a movie. In experiment 1, a parametric analysis showed that the medial prefrontal cortex (MPFC) and hippocampus/amygdala had a positive relationship with the subjective rating of funniness. In experiment 2, intersubject correlation was analyzed to investigate synchronized activity across all participants. Signal synchronization that paralleled increased funniness ratings was observed in the MPFC and hippocampus. Thus, it appears that both parametric and synchronized activity in the MPFC and hippocampus are important during humor appreciation. The present study has revealed the brain regions that are predominantly involved in humor sensation under natural condition.

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An Accurate Method of Designing and Performing Individual-Specific Genioglossus Advancement

There is too much individual patient variation in mandibular anatomy for any single described genioglossus advancement technique to be used consistently. Virtual surgical planning allows surgeons to design genioglossus osteotomy that captures the structures of interest. Intraoperative osteotomy and positioning guides mitigate known risks of the procedure while maximizing the reproducibility and efficacy of the procedure. In this report, we demonstrate the protocol step by step as it had been used on 10 patients, and we highlight 3 clinical scenarios that exemplify its utility.

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MACF1 Controls Migration and Positioning of Cortical GABAergic Interneurons in Mice

GABAergic interneurons develop in the ganglionic eminence in the ventral telencephalon and tangentially migrate into the cortical plate during development. However, key molecules controlling interneuron migration remain poorly identified. Here, we show that microtubule-actin cross-linking factor 1 (MACF1) regulates GABAergic interneuron migration and positioning in the developing mouse brain. To investigate the role of MACF1 in developing interneurons, we conditionally deleted the MACF1 gene in mouse interneuron progenitors and their progeny using Dlx5/6-Cre-IRES-EGFP and Nkx2.1-Cre drivers. We found that MACF1 deletion results in a marked reduction and defective positioning of interneurons in the mouse cerebral cortex and hippocampus, suggesting abnormal interneuron migration. Indeed, the speed and mode of interneuron migration were abnormal in the MACF1-mutant brain, compared with controls. Additionally, MACF1-deleted interneurons showed a significant reduction in the length of their leading processes and dendrites in the mouse brain. Finally, loss of MACF1 decreased microtubule stability in cortical interneurons. Our findings suggest that MACF1 plays a critical role in cortical interneuron migration and positioning in the developing mouse brain.

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Human-derived extracellular matrix from Wharton’s jelly: an untapped substrate to build up a standardized and homogeneous coating for vascular engineering

Publication date: Available online 18 October 2016
Source:Acta Biomaterialia
Author(s): Pan Dan, Émilie Velot, Grégory Francius, Patrick Menu, Véronique Decot
One of the outstanding goals in tissue engineering is to develop a natural coating surface which is easy to manipulate, effective for cell adhesion and fully biocompatible. The ideal surface would be derived from human tissue, perfectly controllable, and pathogen-free, thereby satisfying all of the standards of the health authorities. This paper reports an innovative approach to coating surfaces using a natural extracellular matrix (ECM) extracted from the Wharton's jelly (WJ) of the umbilical cord (referred to as WJ-ECM). We have shown by atomic force microscopy (AFM), that the deposition of WJ-ECM on surfaces is homogenous with a controllable thickness, and that this easily-prepared coating is appropriate for both the adhesion and proliferation of human mesenchymal stem cells and mature endothelial cells. Furthermore, under physiological shear stress conditions, a larger number of cells remained adhered to WJ-ECM than to a conventional coating such as collagen − a result supported by the higher expression of both integrins α2 and β1 in cells cultured on WJ-ECM. Our data clearly show that Wharton's jelly is a highly promising coating for the design of human biocompatible surfaces in tissue engineering as well as in regenerative medicine.Statement of SignificanceDiscovery and design of biomaterial surface are a hot spot in the tissue engineering field. Natural matrix is preferred to mimic native cell microenvironment but its use is limited due to poor resource availability. Moreover, current studies often use single or several components of natural polymers, which is not the case in human body. This paper reports a natural extracellular matrix with full components derived from healthy human tissue: Wharton's jelly of umbilical cord. Reconstituting this matrix as a culture surface, our easily-prepared coating provides superior biocompatibility for stem and mature cells. Furthermore, we observed improved cell performance on this coating under both static and dynamic condition. This novel human derived ECM would be a promising choice for regenerative medicine.

Graphical abstract

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Mucoadhesive chitosan hydrogels as rectal drug delivery vessels to treat ulcerative colitis

Publication date: Available online 18 October 2016
Source:Acta Biomaterialia
Author(s): Jinke Xu, Mifong Tam, Sepideh Samadei, Sophie Lerouge, Jake Barralet, Mary M. Stevenson, Marta Cerruti
Mucoadhesive drug delivery systems stick to mucosal tissues and prolong the local retention time of drugs. Since the colon is covered by a mucosal layer, mucoadhesive rectal formulations may improve treatment of such diseases as hypertension or colon cancer. Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic inflammation of the colonic mucosa. It is commonly treated with sulfasalazine (SSZ), which is metabolized by the intestinal flora into the therapeutic 5-aminosalicylic acid (5-ASA) and a toxic by-product sulfapyridine (SP). SSZ can be administered orally or rectally. The latter route avoids unintended absorption of the drug or its degradation products in the upper gastrointestinal tract, but often fails due to limited retention time. Here, we propose a mucoadhesive hydrogel to improve the efficacy of rectal SSZ administration. The gel is made of catechol modified-chitosan (Cat-CS) crosslinked by genipin. After loading the gel with SSZ, we evaluated its efficacy in a mouse model of UC. Compared to oral SSZ treatment, rectal SSZ/Cat-CS delivery was more therapeutic, showed equivalent histological scores, and induced a lower plasma concentration of the potentially toxic SP by-product. These results show SSZ/Cat-CS rectal hydrogels are more effective and safer formulations for UC treatment than oral SSZ.

Graphical abstract

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Functional improvement of hemostatic dressing by addition of recombinant batroxobin

Publication date: Available online 18 October 2016
Source:Acta Biomaterialia
Author(s): Gyeung Mi Seon, Mi Hee Lee, Byeong-Ju Kwon, Min Sung Kim, Min-Ah Koo, Dohyun Kim, Young Seomun, Jong-Tak Kim, Jong-Chul Park
Although a number of natural materials have been used as hemostatic agents, many substances do not act quickly enough. Here, we created a novel dressings using collagen and chitosan with recombinant batroxobin (r-Bat) to promote faster and more effective hemostasis. We hypothesized that r-Bat would promote synergetic blood coagulation because it contains a blood coagulation active site different than those of collagen and chitosan. Our results suggest that each substances can maintain hemostatic properties while in the mixed dressings and that our novel hemostatic dressings promotes potent control of bleeding, as demonstrated by a whole blood assay and rat hemorrhage model. In a rat femoral artery model, the scaffold with a high r-Bat concentration more rapidly controlled excessive bleeding. This novel dressings has enormous possible for rapidly controlling bleeding and it improves upon the effect of collagen and chitosan used alone. Our novel r-Bat dressings is a possible candidate for improving preoperative care and displays promising properties as an absorbable agent in hemostasis.Statement of significanceDespite the excellent hemostatic properties of collagen and chitosan pads, they reported to brittle behavior and lack sufficient hemostatic effect within relevant time. Therefore, we created a novel pad using collagen and chitosan with recombinant batroxobin (r-Bat). r-Bat acts as a thrombin-like enzyme in the coagulation cascade. Specifically, r-Bat, in contrast to thrombin, only splits fibrinopeptide A off and does not influence other hemostatic factors or cells, which makes it clinically useful as a stable hemostatic agent. Also the materials in the pad have synergetic effect because they have different hemostatic mechanisms in the coagulation cascade. This report propose the novel hemostatic pad isreasonable that a great potential for excessive bleeding injury and improve effects of natural substance hemostatic pad.

Graphical abstract

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Carbon nanotube-composite hydrogels promote intercalated disc assembly in engineered cardiac tissues through β1-integrin mediated FAK and RhoA pathway

Publication date: Available online 18 October 2016
Source:Acta Biomaterialia
Author(s): Hongyu Sun, Jiajia Tang, Yongchao Mou, Jing Zhou, Linlin Qu, Kayla Duval, Zhu Huang, Ning Lin, Ruiwu Dai, Chengxiao Liang, Zi Chen, Lijun Tang, Fuzhou Tian
Carbon nanotube (CNT)-based hydrogels have been shown to support cardiomyocyte growth and function. However, their role in cellular integrity among cardiomyocytes has not been studied in detail and the mechanisms underlying this process remain unclear. Here, single walled CNTs incorporated into gelatin with methacrylate anhydride (CNT/GelMA) hydrogels were utilized to construct cardiac tissues, which enhanced cardiomyocyte adhesion and maturation. Furthermore, through the use of immunohistochemical staining, transmission electron microscopy and intracellular calcium transient measurement, the incorporation of CNTs into the scaffolds was observed to markedly enhance the assembly and formation in the cardiac constructs. Importantly, we further explored the underlying mechanism behind these effects through the use of immunohistochemical staining and western blotting. The β1-integrin-mediated FAK and RhoA signaling pathways were found to be responsible for CNT-induced upregulation of electrical and mechanical junction proteins respectively. Together, our study provides new insights into the facilitative effects of CNTs on ID formation, which has important significance for improving the quality of engineered cardiac tissue and applying them to cardiac regenerative therapies.Statement of SignificanceCurrently, the bottleneck to engineering cardiac tissues (ECTs) for cardiac regeneration is the lack of efficient cellular integrity among adjacent cells, especially the insufficient remodeling of intercalated discs (IDs) in ECTs. Recently, carbon nanotube (CNT) hydrogels provide an advantageous supporting microenvironment and therefore benefit greatly the functional performance of ECTs. Although their beneficial effect in modulating ECT performance is evident, the influence of CNTs on structural integrity of ECTs has not been studied in detail, and the mechanisms underlying the process remain to be determined. Here, we utilized carbon nanotube incorporated into gelatin with methacrylate anhydride (CNT/GelMA) hydrogels to construct cardiac tissues, determined the influence of CNTs on intercalated discs (IDs) assembly and formation and explored the underlying mechanisms.

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Enzyme-mediated stiffening hydrogels for probing activation of pancreatic stellate cells

Publication date: Available online 18 October 2016
Source:Acta Biomaterialia
Author(s): Hung-Yi Liu, Tanja Greene, Tsai-Yu Lin, Camron S. Dawes, Murray Korc, Chien-Chi Lin
The complex network of biochemical and biophysical cues in the pancreatic desmoplasia not only presents challenges to the fundamental understanding of tumor progression, but also hinders the development of therapeutic strategies against pancreatic cancer. Residing in the desmoplasia, pancreatic stellate cells (PSCs) are the major stromal cells affecting the growth and metastasis of pancreatic cancer cells by means of paracrine effects and extracellular matrix protein deposition. PSCs remain in a quiescent/dormant state until they are 'activated' by various environmental cues. While the mechanisms of PSC activation are increasingly being described in literature, the influence of matrix stiffness on PSC activation is largely unexplored. To test the hypothesis that matrix stiffness affects myofibroblastic activation of PSCs, we have prepared cell-laden hydrogels capable of being dynamically stiffened through an enzymatic reaction. The stiffening of the microenvironment was created by using a peptide linker with additional tyrosine residues, which were susceptible to tyrosinase-mediated crosslinking. Tyrosinase catalyzes the oxidation of tyrosine into dihydroxyphenylalanine (DOPA), DOPA quinone, and finally into DOPA dimer. The formation of DOPA dimer led to additional crosslinks and thus stiffening the cell-laden hydrogel. In addition to systematically studying the various parameters relevant to the enzymatic reaction and hydrogel stiffening, we also designed experiments to probe the influence of dynamic matrix stiffening on cell fate. Protease-sensitive peptides were used to crosslink hydrogels, whereas integrin-binding ligands (e.g., RGD motif) were immobilized in the network to afford cell-matrix interaction. PSC-laden hydrogels were placed in media containing tyrosinase for 6 hours to achieve in situ gel stiffening. We found that PSCs encapsulated and cultured in a stiffened matrix expressed higher levels of αSMA and hypoxia-inducible factor 1α (HIF-1α), suggestive of a myofibroblastic phenotype. This hydrogel platform offers a facile means of in situ stiffening of cell-laden matrices and should be valuable for probing cell fate process dictated by dynamic matrix stiffness.Statement of SignificanceHydrogels with spatial-temporal controls over crosslinking kinetics (i.e., dynamic hydrogel) are increasingly being developed for studying mechanobiology in 3D. The general principle of designing dynamic hydrogel is to perform cell encapsulation within a hydrogel network that allows for postgelation modification in gel crosslinking density. The enzyme-mediated in situ gel stiffening is innovative because of the specificity and efficiency of enzymatic reaction. Although tyrosinase has been used for hydrogel crosslinking and in situ cell encapsulation, to the best of our knowledge tyrosinase-mediated DOPA formation has not been explored for in situ stiffening of cell-laden hydrogels. Furthermore, the current work provides a gradual matrix stiffening strategy that may more closely mimic the process of tumor development.

Graphical abstract

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Polymeric nanoparticles enable reversing macrophage in tumor microenvironment for immunotherapy

Publication date: January 2017
Source:Biomaterials, Volume 112
Author(s): Yi Wang, Yao-Xin Lin, Sheng-Lin Qiao, Hong-Wei An, Yang Ma, Zeng-Ying Qiao, R.P.Yeshan J. Rajapaksha, Hao Wang
Immunotherapy has shown a promising effect for a variety of cancers. However, the immune treatment efficiency of solid tumor is limited due to barely infiltration of immune cells in solid tumor. Researchers realized conversion of tumor supportive macrophages to tumor against ones was an effective method to induce the functional reverse of macrophage and contributed to the subsequent antitumor response. The current challenge in the field is that while making use of cytokines usually coupled with poor-distribution and systemic side effects. As a solution to this issue, we designed and synthesized microenvironment-responsive nanoparticles (P) with IL-12 payload (IL-12⊂P1), the IL-12⊂P1 which could adopt by systemic administration and release IL-12 in the tumor microenvironment, the local-responsive property of IL-12⊂P1 re-educate tumor-associated macrophages (TAMs) subsequently. Particularly, it illustrated great therapeutic effects which derived from functional conversion of macrophages. Our strategy was to design a microenvironment-responsive material for local macrophage reverse modification which could overcome the physiological barrier of solid tumor. The shifting of macrophages by IL-12⊂P1 realized immunomodulation in microenvironment for cancer therapy with negligible cytotoxicity. We expected that regulating the function of TAMs by pH-responsive nanomaterials would be a promising therapeutic approach for cancer immunotherapy.

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Synergistic thermoradiotherapy based on PEGylated Cu3BiS3 ternary semiconductor nanorods with strong absorption in the second near-infrared window

Publication date: January 2017
Source:Biomaterials, Volume 112
Author(s): Ang Li, Xiang Li, Xujiang Yu, Wei Li, Ruyi Zhao, Xiao An, Daxiang Cui, Xiaoyuan Chen, Wanwan Li
In this work, we report a successful synthesis of copper bismuth sulfide nanorods (NRs) with broad and strong photoabsorption ranging from ultraviolet (UV) to near-infrared (NIR) wavelengths, which can be used as a 1064 nm-laser-driven photothermal agent with the photothermal conversion efficiency of 40.7%, noticeably higher than most of the reported PTT agents working in NIR-II window. The as-prepared PEGylated Cu3BiS3 NRs were used as photoacoustic imaging (PAI) and CT imaging agents due to their strong NIR absorption and large X-ray attenuation coefficient of bismuth. We are the first to demonstrate that a small quantity of PEGylated Cu3BiS3 NRs in tumors can concentrate radiation energy and trigger mild PTT under NIR-II irradiation and thus, these particles could be used as a novel, synergistic thermoradiotheraputic agent that enhances the efficacy of radiotherapy.

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Micellar nanocomplexes for biomagnetic delivery of intracellular proteins to dictate axon formation during neuronal development

Publication date: January 2017
Source:Biomaterials, Volume 112
Author(s): Giulia Suarato, Seong-Il Lee, Weiyi Li, Sneha Rao, Tanvir Khan, Yizhi Meng, Maya Shelly
During mammalian embryonic development, neurons polarize to create distinct cellular compartments of axon and dendrite that inherently differ in form and function, providing the foundation for directional signaling in the nervous system. Polarization results from spatio-temporal segregation of specific proteins' activities to discrete regions of the neuron to dictate axonal vs. dendritic fate. We aim to manipulate axon formation by directed subcellular localization of crucial intracellular protein function. Here we report critical steps toward the development of a nanotechnology for localized subcellular introduction and retention of an intracellular kinase, LKB1, crucial regulator of axon formation. This nanotechnology will spatially manipulate LKB1-linked biomagnetic nanocomplexes (LKB1-NCs) in developing rodent neurons in culture and in vivo. We created a supramolecular assembly for LKB1 rapid neuronal uptake and prolonged cytoplasmic stability. LKB1-NCs retained kinase activity and phosphorylated downstream targets. NCs were successfully delivered to cultured embryonic hippocampal neurons, and were stable in the cytoplasm for 2 days, sufficient time for axon formation. Importantly, LKB1-NCs promoted axon formation in these neurons, representing unique proof of concept for the sufficiency of intracellular protein function in dictating a central developmental event. Lastly, we established NC delivery into cortical progenitors in live rat embryonic brain in utero. Our nanotechnology provides a viable platform for spatial manipulation of intracellular protein-activity, to dictate central events during neuronal development.

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Hearing Aid Batteries: The Past, Present, and Future

Modern digital hearing aids offer a huge variety of form factors, features, and wireless connectivity options that allow for individual hearing solutions. However, the price of functions like situation-based real-time processing, binaural algorithms, or streaming is an increased demand on battery performance. So far, the topic of efficient powering has received only scant attention, but this may change soon due to the many good reasons for using rechargeable batteries.

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Monitoring Progression of 12 Cases of Non-Operated Middle Ear Cholesteatoma With Non-Echoplanar Diffusion Weighted Magnetic Resonance Imaging: Our Experience.

Aim: The aim of this study is to gain insight into the disease progression and behavior of primary cholesteatoma in a cohort of patients who did not have surgery using non-echoplanar diffusion-weighted magnetic resonance imaging (DW MRI) serial monitoring. Methods: Retrospective longitudinal observational study of 12 cases of middle ear cleft cholesteatoma diagnosed between 2009 and 2014 where surgery was not performed for various reasons. All cases were monitored radiologically with non-echoplanar half-Fourier acquisition single-shot turbo spin-echo diffusion weighted imaging annually for a median period of 23 months (between 11 and 45 mo) to evaluate for changes in disease volume and direction of growth. Results: Of the 12 cases, there was one outlier where the cholesteatoma growth was disproportionately high compared with the rest of the cases outside the standard deviation range. A third of the cases had radiological evidence of cholesteatoma growth. The mean growth was about 11.9% of the initial disease volume per year. Seven out of the 12 cases had radiological evidence of cholesteatoma regression in terms of size, with three cases having negative follow-up DW-MRI scans as early as 17 months. The mean regression rate was much higher than the mean growth rate at 54.3% of the initial disease volume per year. The direction of greatest growth is craniocaudally. Conclusion: Within the limits of our longitudinal study, we have shown that by monitoring with non-echoplanar diffusion weighted imaging, cholesteatoma can progress or regress when left untreated by surgery. The greatest progression was recorded in the craniocaudal direction. Copyright (C) 2016 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Evaluation of Rigid Cochlear Models for Measuring Cochlear Implant Electrode Position.

Objective: To investigate the accuracy of rigid cochlear models in measuring intra-cochlear positions of cochlear implant (CI) electrodes. Patients: Ninety three adults who had undergone CI and pre- and postoperative computed tomographic (CT) imaging. Main Outcome Measures: Seven rigid models of cochlear anatomy were constructed using micro-CTs of cochlear specimens. Using each of the seven models, the position of each electrode in each of the 98 ears in our dataset was measured as its depth along the length of the cochlea, its distance to the basilar membrane, and its distance to the modiolus. Cochlear duct length was also measured using each model. Results: Standard deviation (SD) across rigid cochlear models in measures of electrode depth, distance to basilar membrane, distance to modiolus, and length of the cochlear duct at two turns were 0.68, 0.11, 0.15, and 1.54 mm. Comparing the estimated position of the electrodes with respect to the basilar membrane, i.e., deciding whether an electrode was located within the scala tympani (ST) or the scala vestibuli (SV), there was not a unanimous agreement between the models for 19% of all the electrodes. With respect to the modiolus, each electrode was classified into one of the three groups depending on its modiolar distance: close, medium, and far. Rigid models did not unanimously agree on modiolar distance for approximately 50% of the electrodes tested. Conclusions: Inter-model variance of rigid cochlear models exists, demonstrating that measurements made using rigid cochlear models are limited in terms of accuracy because of non-rigid inter-subject variations in cochlear anatomy. Copyright (C) 2016 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Bilateral Facial Paralysis as Presenting Symptoms in Acute Lymphoblastic Leukemia.

No abstract available

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An Unusual Case of Lymphoepithelioma-Like Carcinoma of the External Auditory Canal.

No abstract available

http://ift.tt/2ek9iEi

Diagnostic Criteria for Detection of Vestibular Schwannomas in the VA Population.

Objective: To investigate the prevalence of vestibular schwannoma (VS) and asymmetric sensorineural hearing loss in the Veterans Administration hospital population and analyze a more efficient method of diagnosing VS in a population with significant noise exposure. Study Design: Retrospective review of South Central (VISN 16) Veterans Administration hospitals. Methods: Record query for ICD-9 codes for asymmetric sensorineural hearing loss or VS between 1999 and 2012. Patient demographics, signs and symptoms at presentation, audiogram and imaging data, and management data were collected and analyzed. Audiograms from tumor patients were compared with controls matched for age, sex, combat experience, and medical comorbidity (2:1 control to case ratio). Results: The prevalence of VS was 1 per 1,145 patients in this population, with average age at diagnosis of 62. Patients with VS presented more commonly with unilateral tinnitus, rollover, and absent acoustic reflexes when compared with matched controls, but positive predictive value was low. Published criteria for defining hearing asymmetry showed variable sensitivity (51-89%) and low specificity (0-42%) for the detection of VS in this population. Criteria meeting the definitions of significant asymmetry with specificity for VS of 80% or greater were as follows: >15 dB threshold difference at 3 kHz and unilateral tinnitus, >=45 dB threshold difference at 3 kHz regardless of tinnitus, or when the word recognition score difference was >=80%. With serial audiograms 2.5 years apart or greater, a >=10 dB threshold increase at any frequency between 0.5 and 4 kHz had a 100% sensitivity for tumor and a >=10 dB increase at 3 kHz had a specificity of 84%. The majority of patients were observed, whereas only 30% had surgery. Patients who were observed were older than those treated with surgery or radiation (p

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Posterior Fossa Spontaneous Cerebrospinal Fluid Leaks.

Objective: Describe the diagnosis and management of spontaneous lateral skull base cerebrospinal fluid (CSF) leaks that originate from the posterior fossa. Study Design: Retrospective case review. Setting: Tertiary university hospital. Patients: Adult patients from 2005 to 2015 who underwent surgical repair of a spontaneous lateral skull base CSF leak with intraoperative confirmation of a posterior fossa leak source. Intervention: Surgical repair. Main Outcome Measures: CSF leak resolution. Results: Five patients had CSF leaks from the posterior fossa. The mean age at presentation was 54 years old (range, 19-79), the mean body mass index (BMI) was 32.6 (standard deviation [SD], 8.4), and the mean follow-up length was 34.6 months (SD, 19.4). Presentations did not differ from CSF leaks through middle fossa defects, including three patients with a history of meningitis and all patients with clear otorrhea following tympanostomy tube placement. All patients had resolution of the leak after surgical repair, but two patients required revision surgery for persistent leaks and one patient had a postoperative infection. Surgical approaches included one middle fossa, two transmastoid, one combined middle fossa/transmastoid, and one transcanal. Radiographic studies suggested a posterior fossa source in all cases but findings were often subtle. Conclusion: Posterior fossa CSF leaks represent a rare subset of spontaneous lateral skull base leaks. Diligent radiographic review and intraoperative assessment of the posterior fossa plate are crucial. The size and location of the defect dictates the optimal surgical approach. Surgeons should consider a posterior fossa source in failed repairs or when the initial surgery did not fully evaluate the posterior fossa plate. Copyright (C) 2016 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Cochlear Implantation in the Elderly: Does Age Matter?.

Objective: To compare the outcome of hearing rehabilitation in younger versus older adult cochlear implant recipients. Analysis of surgical and postoperative complications, as well as the number of auditory therapy sessions in the two age groups. Study Design: Individual retrospective cohort study. Methods: A cohort of 145 postlingually deafened adults was evaluated in this study. The patients were divided into two age groups based on the age at implantation: Group I, 18 to 69 years; and Group II, 70 and older. Postoperative hearing performance was measured based on the German Freiburg monosyllabic word test (FM) and the Oldenburg sentence test (OLSA). Results: Postoperative hearing evaluation results in both groups plateaued and remained constant after 12 months of implantation. The results remained constant at the 2 and 3-year time intervals. There was a significant difference in complications arising after cochlear implantation. Group II showed more cases of vertigo and dysgeusia. The number of auditory therapy sessions in both groups was similar. Conclusion: Cochlear implantation in the elderly is highly effective; the postoperative hearing performance is at the same level as younger adult recipients. Complex hearing tasks, such as hearing in background noise, requires an equally long time for comprehension. The recovery period of vestibular dysfunction after surgery may be longer in the elderly. Auditory therapy rehabilitation is not more time consuming in the elderly compared with the younger counterparts. Copyright (C) 2016 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Τετάρτη 19 Οκτωβρίου 2016

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Αρχειοθήκη ιστολογίου