Fetal malformation in maternal toxoplasma and rubella co-infection in Cameroon: a case report

There has been a recent increase in the number of newborns with brain malformations due to congenital infections, but the impact of these diseases remains largely under ascertained in middle-income and low-inc...

http://ift.tt/2gSEDky

Possible failure of novel direct-acting oral anticoagulants in management of pulmonary embolism: a case report

The relative effectiveness of vitamin K antagonists compared with novel oral anticoagulants in treating pulmonary embolism remains unclear. Recent trials comparing the efficacy of vitamin K antagonists with fa...

http://ift.tt/2fXi6Pk

Osteoid osteoma of the acetabulum successfully treated with computed tomography-guided resection and ablation using a standard electrosurgical generator: a case report

Osteoid osteoma accounts for approximately 10% of all benign bone tumors. The most common sites of osteoid osteoma are the subcortical shaft and metaphyses of long bones, but any other skeletal bone site can b...

http://ift.tt/2fTsFb1

Exendin-4 protects HUVECs from tunicamycin-induced apoptosis via inhibiting the IRE1a/JNK/caspase-3 pathway

Abstract

Purpose

The abnormal increase of apoptosis of endothelial cells induced by endoplasmic reticulum stress is a significant factor for vascular disease, especially for atherosclerosis. Protecting endothelial cells from endoplasmic reticulum stress is a crucial strategies to combate these diseases. The goal of this study was to explore the effect of Exendin-4, a glucagon-like peptide-1 receptor agonist, on tunicamycin-induced apoptosis in human umbilical vein endothelial cells.

Methods

All studies were performed in primary human umbilical vein endothelial cells treated with tunicamycin with or without Exendin-4 pretreatment. Markers of cell viability and apoptosis were assessed in all cells, as well as the protein expression levels of IRE1α (inositol requiring enzyme-1а), p-IRE1α, JNK (c-Jun N-terminal kinase), p-JNK, and caspase-3.

Results

Following tunicamycin administration, human umbilical vein endothelial cells viability was gradually reduced in a dose-dependent manner, and fluorescence microscopy confirmed that tunicamycin was inducing human umbilical vein endothelial cells apoptosis. This apoptotic effect was attenuated by Exendin-4 pretreatment. Similarly, the ratio of p-IRE1α/IRE1α, p-JNK/JNK and active caspase-3/procaspase-3 were increased by tunicamycin (10 μg/ml); an effect that was counteracted by Exendin-4. The effect of exendin-4 was similar to that of the anti-endoplasmic reticulum stress agent, tauroursodeoxycholic acid (TUDCA).

Conclusions

This study demonstrates that Exendin-4 can protect human umbilical vein endothelial cells from tunicamycin-induced apoptosis. Furthermore, our data suggests that the mechanism for this effect is mediated by inhibiting the IRE1α/JNK/caspase-3 pathway.

http://ift.tt/2g5fu58

Sinonasal adamantinoma-like Ewing sarcoma: a case report.

Publication date: Available online 2 December 2016
Source:Pathology - Research and Practice
Author(s): Borislav A. Alexiev, Yanki Tumer, Justin A. Bishop
We describe the case of a sinonasal adamantinoma-like Ewing sarcoma in a 41-year-old male. Histologically, the tumor exhibited distinctive areas of nested growth pattern with prominent stromal fibrosis and metaplastic bone formation. The tumor cells were small and uniform with minimal amount of pale eosinophilic to clear cytoplasm and round or oval nuclei with finely dispersed chromatin and small nucleoli. Approximately 20% of the tumor parenchyma comprised of small clusters of basaloid cells within an osteofibrous background resembling adamantinoma. The tumor showed strong expression of keratins, p63, CD99 and Fli-1, and EWSR1 rearrangement. The diagnosis of sinonasal Ewing family tumors is particularly problematic owing to the large number of potential mimics. For any poorly differentiated or undifferentiated head and neck tumor, cellular monotony and CD99 immunoreactivity should prompt consideration for molecular studies that include analysis of both EWSR1 and FLI1, even in the presence of strong cytokeratin expression or focal keratinization.



http://ift.tt/2glCwlP

UNUSUAL ASYMPTOMATIC PRESENTATION OF BLADDER CANCER METASTATIC TO THE PENIS

Publication date: Available online 2 December 2016
Source:Pathology - Research and Practice
Author(s): Francesca Giunchi, Francesco Vasuri, Vagnoni Valerio, Ilaria Montagnani, Federico Nelli, Michelangelo Fiorentino, Maria Rosaria Raspollini
Penile metastasis is an extremely rare event and mainly originate from primary pelvic tumor sites such us urinary bladder, gastro-intestinal tract and prostate and more rarely from respiratory system, bone tumors and melanoma. Here we describe the unusual presentation of two bladder urothelial cancer metastatic to the penis with no relevant clinical symptoms. Namely, a 69 years-old man with a warthy lesions of the foreskin and the glans misunderstood for a condylomata that at histological and immunohistochemical analysis showed a bladder urothelial carcinoma; and a 71 years-old man with reddish skin lesion of the glans, a previous history of bladder and urethral carcinoma and histological pagetoid spread of urothelial cancer to the glans.Recurrent bladder urothelial carcinoma is usually a visceral disease that rarely presents as a superficial asymptomatic skin lesion. The two reported cases were asymptomatic superficial penis metastases with a relatively slow growth and a fairy good prognosis after conservative surgical approach. Accurate clinical examination of the penis is mandatory for males with history of bladder cancer.



http://ift.tt/2gzA8uL

Methods of Soil Resampling to Monitor Changes in the Chemical Concentrations of Forest Soils.

Methods of Soil Resampling to Monitor Changes in the Chemical Concentrations of Forest Soils.

J Vis Exp. 2016 Nov 25;(117):

Authors: Lawrence GB, Fernandez IJ, Hazlett PW, Bailey SW, Ross DS, Villars TR, Quintana A, Ouimet R, McHale MR, Johnson CE, Briggs RD, Colter RA, Siemion J, Bartlett OL, Vargas O, Antidormi MR, Koppers MM

Abstract
Recent soils research has shown that important chemical soil characteristics can change in less than a decade, often the result of broad environmental changes. Repeated sampling to monitor these changes in forest soils is a relatively new practice that is not well documented in the literature and has only recently been broadly embraced by the scientific community. The objective of this protocol is therefore to synthesize the latest information on methods of soil resampling in a format that can be used to design and implement a soil monitoring program. Successful monitoring of forest soils requires that a study unit be defined within an area of forested land that can be characterized with replicate sampling locations. A resampling interval of 5 years is recommended, but if monitoring is done to evaluate a specific environmental driver, the rate of change expected in that driver should be taken into consideration. Here, we show that the sampling of the profile can be done by horizon where boundaries can be clearly identified and horizons are sufficiently thick to remove soil without contamination from horizons above or below. Otherwise, sampling can be done by depth interval. Archiving of sample for future reanalysis is a key step in avoiding analytical bias and providing the opportunity for additional analyses as new questions arise.

PMID: 27911419 [PubMed - in process]

http://ift.tt/2gzCY38

Synthesis and Characterization of Fe-doped Aluminosilicate Nanotubes with Enhanced Electron Conductive Properties.

Synthesis and Characterization of Fe-doped Aluminosilicate Nanotubes with Enhanced Electron Conductive Properties.

J Vis Exp. 2016 Nov 15;(117):

Authors: Shafia E, Esposito S, Bahadori E, Armandi M, Manzoli M, Bonelli B

Abstract
The goal of the protocol is to synthesize Fe-doped aluminosilicate nanotubes of the imogolite type with the formula (OH)3Al2-xFexO3SiOH. Doping with Fe aims at lowering the band gap of imogolite, an insulator with the chemical formula (OH)3Al2O3SiOH, and at modifying its adsorption properties towards azo-dyes, an important class of organic pollutants of both wastewater and groundwater. Fe-doped nanotubes are obtained in two ways: by direct synthesis, where FeCl3 is added to an aqueous mixture of the Si and Al precursors, and by post-synthesis loading, where preformed nanotubes are put in contact with a FeCl3•6H2O aqueous solution. In both synthesis methods, isomorphic substitution of Al(3+) by Fe(3+) occurs, preserving the nanotube structure. Isomorphic substitution is indeed limited to a mass fraction of ~1.0% Fe, since at a higher Fe content (i.e., a mass fraction of 1.4% Fe), Fe2O3 clusters form, especially when the loading procedure is adopted. The physicochemical properties of the materials are studied by means of X-ray powder diffraction (XRD), N2 sorption isotherms at -196 °C, high resolution transmission electron microscopy (HRTEM), diffuse reflectance (DR) UV-Vis spectroscopy, and ζ-potential measurements. The most relevant result is the possibility to replace Al(3+) ions (located on the outer surface of the nanotubes) by post-synthesis loading on preformed imogolite without perturbing the delicate hydrolysis equilibria occurring during nanotube formation. During the loading procedure, an anionic exchange occurs, where Al(3+) ions on the outer surface of the nanotubes are replaced by Fe(3+) ions. In Fe-doped aluminosilicate nanotubes, isomorphic substitution of Al(3+) by Fe(3+) is found to affect the band gap of doped imogolite. Nonetheless, Fe(3+) sites on the outer surface of nanotubes are able to coordinate organic moieties, like the azo-dye Acid Orange 7, through a ligand-displacement mechanism occurring in an aqueous solution.

PMID: 27911418 [PubMed - in process]

http://ift.tt/2glD9vG

Plasma-assisted Molecular Beam Epitaxy of N-polar InAlN-barrier High-electron-mobility Transistors.

Plasma-assisted Molecular Beam Epitaxy of N-polar InAlN-barrier High-electron-mobility Transistors.

J Vis Exp. 2016 Nov 24;(117):

Authors: Hardy MT, Storm DF, Katzer DS, Downey BP, Nepal N, Meyer DJ

Abstract
Plasma-assisted molecular beam epitaxy is well suited for the epitaxial growth of III-nitride thin films and heterostructures with smooth, abrupt interfaces required for high-quality high-electron-mobility transistors (HEMTs). A procedure is presented for the growth of N-polar InAlN HEMTs, including wafer preparation and growth of buffer layers, the InAlN barrier layer, AlN and GaN interlayers and the GaN channel. Critical issues at each step of the process are identified, such as avoiding Ga accumulation in the GaN buffer, the role of temperature on InAlN compositional homogeneity, and the use of Ga flux during the AlN interlayer and the interrupt prior to GaN channel growth. Compositionally homogeneous N-polar InAlN thin films are demonstrated with surface root-mean-squared roughness as low as 0.19 nm and InAlN-based HEMT structures are reported having mobility as high as 1,750 cm(2)/V∙sec for devices with a sheet charge density of 1.7 x 10(13) cm(-2).

PMID: 27911417 [PubMed - in process]

http://ift.tt/2gzCNot

The Indirect Neuron-astrocyte Coculture Assay: An In Vitro Set-up for the Detailed Investigation of Neuron-glia Interactions.

The Indirect Neuron-astrocyte Coculture Assay: An In Vitro Set-up for the Detailed Investigation of Neuron-glia Interactions.

J Vis Exp. 2016 Nov 14;(117):

Authors: Gottschling C, Dzyubenko E, Geissler M, Faissner A

Abstract
Proper neuronal development and function is the prerequisite of the developing and the adult brain. However, the mechanisms underlying the highly controlled formation and maintenance of complex neuronal networks are not completely understood thus far. The open questions concerning neurons in health and disease are diverse and reaching from understanding the basic development to investigating human related pathologies, e.g., Alzheimer's disease and Schizophrenia. The most detailed analysis of neurons can be performed in vitro. However, neurons are demanding cells and need the additional support of astrocytes for their long-term survival. This cellular heterogeneity is in conflict with the aim to dissect the analysis of neurons and astrocytes. We present here a cell-culture assay that allows for the long-term cocultivation of pure primary neurons and astrocytes, which share the same chemically defined medium, while being physically separated. In this setup, the cultures survive for up to four weeks and the assay is suitable for a diversity of investigations concerning neuron-glia interaction.

PMID: 27911416 [PubMed - in process]

http://ift.tt/2glFlna

Extraction of Plant-based Capsules for Microencapsulation Applications.

Extraction of Plant-based Capsules for Microencapsulation Applications.

J Vis Exp. 2016 Nov 09;(117):

Authors: Potroz MG, Mundargi RC, Park JH, Tan EL, Cho NJ

Abstract
Microcapsules derived from plant-based spores or pollen provide a robust platform for a diverse range of microencapsulation applications. Sporopollenin exine capsules (SECs) are obtained when spores or pollen are processed so as to remove the internal sporoplasmic contents. The resulting hollow microcapsules exhibit a high degree of micromeritic uniformity and retain intricate microstructural features related to the particular plant species. Herein, we demonstrate a streamlined process for the production of SECs from Lycopodium clavatum spores and for the loading of hydrophilic compounds into these SECs. The current SEC isolation procedure has been recently optimized to significantly reduce the processing requirements which are conventionally used in SEC isolation, and to ensure the production of intact microcapsules. Natural L. clavatum spores are defatted with acetone, treated with phosphoric acid, and extensively washed to remove sporoplasmic contents. After acetone defatting, a single processing step using 85% phosphoric acid has been shown to remove all sporoplasmic contents. By limiting the acid processing time to 30 hr, it is possible to isolate clean SECs and avoid SEC fracturing, which has been shown to occur with prolonged processing time. Extensive washing with water, dilute acids, dilute bases, and solvents ensures that all sporoplasmic material and chemical residues are adequately removed. The vacuum loading technique is utilized to load a model protein (Bovine Serum Albumin) as a representative hydrophilic compound. Vacuum loading provides a simple technique to load various compounds without the need for harsh solvents or undesirable chemicals which are often required in other microencapsulation protocols. Based on these isolation and loading protocols, SECs provide a promising material for use in a diverse range of microencapsulation applications, such as, therapeutics, foods, cosmetics, and personal care products.

PMID: 27911415 [PubMed - in process]

http://ift.tt/2gzJqac

Isolation and Culture of Primary Endothelial Cells from Canine Arteries and Veins.

Isolation and Culture of Primary Endothelial Cells from Canine Arteries and Veins.

J Vis Exp. 2016 Nov 18;(117):

Authors: Oosterhoff LA, Kruitwagen HS, Spee B, van Steenbeek FG

Abstract
Cardiovascular disease is studied in both human and veterinary medicine. Endothelial cells have been used extensively as an in vitro model to study vasculogenesis, (tumor) angiogenesis, and atherosclerosis. The current standard for in vitro research on human endothelial cells (ECs) is the use of Human Umbilical Vein Endothelial Cells (HUVECs) and Human Umbilical Artery Endothelial Cells (HUAECs). For canine endothelial research, only one cell line (CnAOEC) is available, which is derived from canine aortic endothelium. Although currently not completely understood, there is a difference between ECs originating from either arteries or veins. For a more direct approach to in vitro functionality studies on ECs, we describe a new method for isolating Canine Primary Endothelial Cells (CaPECs) from a variety of vessels. This technique reduces the chance of contamination with fast-growing cells such as fibroblasts and smooth muscle cells, a problem that is common in standard isolation methods such as flushing the vessel with enzymatic solutions or mincing the vessel prior to digestion of the tissue containing all cells. The technique we describe was optimized for the canine model, but can easily be utilized in other species such as human.

PMID: 27911414 [PubMed - in process]

http://ift.tt/2glssJP

Fabricating a UV-Vis and Raman Spectroscopy Immunoassay Platform.

Fabricating a UV-Vis and Raman Spectroscopy Immunoassay Platform.

J Vis Exp. 2016 Nov 10;(117):

Authors: Hanson C, Israelsen ND, Sieverts M, Vargis E

Abstract
Immunoassays are used to detect proteins based on the presence of associated antibodies. Because of their extensive use in research and clinical settings, a large infrastructure of immunoassay instruments and materials can be found. For example, 96- and 384-well polystyrene plates are available commercially and have a standard design to accommodate ultraviolet-visible (UV-Vis) spectroscopy machines from various manufacturers. In addition, a wide variety of immunoglobulins, detection tags, and blocking agents for customized immunoassay designs such as enzyme-linked immunosorbent assays (ELISA) are available. Despite the existing infrastructure, standard ELISA kits do not meet all research needs, requiring individualized immunoassay development, which can be expensive and time-consuming. For example, ELISA kits have low multiplexing (detection of more than one analyte at a time) capabilities as they usually depend on fluorescence or colorimetric methods for detection. Colorimetric and fluorescent-based analyses have limited multiplexing capabilities due to broad spectral peaks. In contrast, Raman spectroscopy-based methods have a much greater capability for multiplexing due to narrow emission peaks. Another advantage of Raman spectroscopy is that Raman reporters experience significantly less photobleaching than fluorescent tags(1). Despite the advantages that Raman reporters have over fluorescent and colorimetric tags, protocols to fabricate Raman-based immunoassays are limited. The purpose of this paper is to provide a protocol to prepare functionalized probes to use in conjunction with polystyrene plates for direct detection of analytes by UV-Vis analysis and Raman spectroscopy. This protocol will allow researchers to take a do-it-yourself approach for future multi-analyte detection while capitalizing on pre-established infrastructure.

PMID: 27911413 [PubMed - in process]

http://ift.tt/2gzBLbK

Reproducible Arterial Denudation Injury by Infrarenal Abdominal Aortic Clamping in a Murine Model.

Reproducible Arterial Denudation Injury by Infrarenal Abdominal Aortic Clamping in a Murine Model.

J Vis Exp. 2016 Nov 24;(117):

Authors: Shirali AS, McDonald AI, Mack JJ, Iruela-Arispe ML

Abstract
Percutaneous vascular interventions uniformly result in arterial denudation injuries that subsequently lead to thrombosis and restenosis. These complications can be attributed to impairments in re-endothelialization within the wound margins. Yet, the cellular and molecular mechanisms of re-endothelialization remain to be defined. While several animal models to study re-endothelialization after arterial denudation are available, few are performed in the mouse because of surgical limitations. This undermines the opportunity to exploit transgenic mouse lines and investigate the contribution of specific genes to the process of re-endothelialization. Here, we present a step-by-step protocol for creating a highly reproducible murine model of arterial denudation injury in the infrarenal abdominal aorta using external vascular clamping. Immunocytochemical staining of injured aortas for fibrinogen and β-catenin demonstrate the exposure of a pro-thrombotic surface and the border of intact endothelium, respectively. The method presented here has the advantages of speed, excellent overall survival rate, and relative technical ease, creating a uniquely practical tool for imposing arterial denudation injury in transgenic mouse models. Using this method, investigators may elucidate the mechanisms of re-endothelialization under normal or pathological conditions.

PMID: 27911412 [PubMed - in process]

http://ift.tt/2glAnGU

Preparation and In Vivo Use of an Activity-based Probe for N-acylethanolamine Acid Amidase.

Preparation and In Vivo Use of an Activity-based Probe for N-acylethanolamine Acid Amidase.

J Vis Exp. 2016 Nov 23;(117):

Authors: Romeo E, Pontis S, Ponzano S, Bonezzi F, Migliore M, Di Martino S, Summa M, Piomelli D

Abstract
Activity-based protein profiling (ABPP) is a method for the identification of an enzyme of interest in a complex proteome through the use of a chemical probe that targets the enzyme's active sites. A reporter tag introduced into the probe allows for the detection of the labeled enzyme by in-gel fluorescence scanning, protein blot, fluorescence microscopy, or liquid chromatography-mass spectrometry. Here, we describe the preparation and use of the compound ARN14686, a click chemistry activity-based probe (CC-ABP) that selectively recognizes the enzyme N-acylethanolamine acid amidase (NAAA). NAAA is a cysteine hydrolase that promotes inflammation by deactivating endogenous peroxisome proliferator-activated receptor (PPAR)-alpha agonists such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). NAAA is synthesized as an inactive full-length proenzyme, which is activated by autoproteolysis in the acidic pH of the lysosome. Localization studies have shown that NAAA is predominantly expressed in macrophages and other monocyte-derived cells, as well as in B-lymphocytes. We provide examples of how ARN14686 can be used to detect and quantify active NAAA ex vivo in rodent tissues by protein blot and fluorescence microscopy.

PMID: 27911411 [PubMed - in process]

http://ift.tt/2gzEBxN

Experimental Infection with Listeria monocytogenes as a Model for Studying Host Interferon-γ Responses.

Experimental Infection with Listeria monocytogenes as a Model for Studying Host Interferon-γ Responses.

J Vis Exp. 2016 Nov 16;(117):

Authors: Ahn JJ, Selvanantham T, Zhang MA, Mallevaey T, Dunn SE

Abstract
L. monocytogenes is a gram-positive bacterium that is a cause of food borne disease in humans. Experimental infection of mice with this pathogen has been highly informative on the role of innate and adaptive immune cells and specific cytokines in host immunity against intracellular pathogens. Production of IFN-γ by innate cells during sublethal infection with L. monocytogenes is important for activating macrophages and early control of the pathogen(1-3). In addition, IFN-γ production by adaptive memory lymphocytes is important for priming the activation of innate cells upon reinfection(4). The L. monocytogenes infection model thus serves as a great tool for investigating whether new therapies that are designed to increase IFN-γ production have an impact on IFN-γ responses in vivo and have productive biological effects such as increasing bacterial clearance or improving mouse survival from infection. Described here is a basic protocol for how to conduct intraperitoneal infections of C57BL/6J mice with the EGD strain of L. monocytogenes and to measure IFN-γ production by NK cells, NKT cells, and adaptive lymphocytes by flow cytometry. In addition, procedures are described to: (1) grow and prepare the bacteria for inoculation, (2) measure bacterial load in the spleen and liver, and (3) measure animal survival to endpoints. Representative data are also provided to illustrate how this infection model can be used to test the effect of specific agents on IFN-γ responses to L. monocytogenes and survival of mice from this infection.

PMID: 27911410 [PubMed - in process]

http://ift.tt/2glzFJQ

Measuring Progressive Neurological Disability in a Mouse Model of Multiple Sclerosis.

Measuring Progressive Neurological Disability in a Mouse Model of Multiple Sclerosis.

J Vis Exp. 2016 Nov 14;(117):

Authors: Gilli F, Royce DB, Pachner AR

Abstract
After intracerebral infection with the Theiler's Murine Encephalomyelitis Virus (TMEV), susceptible SJL mice develop a chronic-progressive demyelinating disease, with clinical features similar to the progressive forms of multiple sclerosis (MS). The mice show progressive disability with loss of motor and sensory functions, which can be assessed with multiple apparatuses and protocols. Among them, the Rotarod performance test is a very common behavioral test, its advantage being that it provides objective measurements, but it is often used assuming that it is straightforward and simple. In contrast to visual scoring systems used in some models of MS, which are highly subjective, the Rotarod test generates an objective, measurable, continuous variable (i.e., length of time), allowing almost perfect inter-rater concordances. However, inter-laboratory reliability is only achieved if the various testing parameters are replicated. In this manuscript, recommendations of specific testing parameters, such as size, speed, and acceleration of the rod; amount of training given to the animals; and data processing, are presented for the Rotarod test.

PMID: 27911409 [PubMed - in process]

http://ift.tt/2gzuYim

Defining Substrate Specificities for Lipase and Phospholipase Candidates.

Defining Substrate Specificities for Lipase and Phospholipase Candidates.

J Vis Exp. 2016 Nov 23;(117):

Authors: Sahonero-Canavesi DX, Zavaleta-Pastor M, Martínez-Aguilar L, López-Lara IM, Geiger O

Abstract
Microorganisms produce a wide spectrum of (phospho)lipases that are secreted in order to make external substrates available for the organism. Alternatively, other (phospho)lipases may be physically associated with the producing organism causing a turnover of intrinsic lipids and frequently giving rise to a remodeling of the cellular membranes. Although potential (phospho)lipases can be predicted with a number of algorithms when the gene/protein sequence is available, experimental proof of the enzyme activities, substrate specificities, and potential physiological functions has frequently not been obtained. This manuscript describes the optimization of assay conditions for prospective (phospho)lipases with unknown substrate specificities and how to employ these optimized conditions in the search for the natural substrate of a respective (phospho)lipase. Using artificial chromogenic substrates, such as p-nitrophenyl derivatives, may help to detect a minor enzymatic activity for a predicted (phospho)lipase under standard conditions. Having encountered such a minor enzymatic activity, the distinct parameters of an enzyme assay can be varied in order to obtain a more efficient hydrolysis of the artificial substrate. After having determined the conditions under which an enzyme works well, a variety of potential natural substrates should be assayed for their degradation, a process that can be followed employing distinct chromatographic methods. The definition of substrate specificities for new enzymes, often provides hypotheses for a potential physiological role of these enzymes, which then can be tested experimentally. Following these guidelines, we were able to identify a phospholipase C (SMc00171) that degrades phosphatidylcholine to phosphocholine and diacylglycerol, in a crucial step for the remodeling of membranes in the bacterium Sinorhizobium meliloti upon phosphorus-limiting conditions of growth. For two predicted patatin-like phospholipases (SMc00930 and SMc01003) of the same organism, we could redefine their substrate specificities and clarify that SMc01003 is a diacylglycerol lipase.

PMID: 27911408 [PubMed - in process]

http://ift.tt/2gluSIf

Preparation of CD4+ T Cells for Analysis of GD3 and GD2 Ganglioside Membrane Expression by Microscopy.

Preparation of CD4+ T Cells for Analysis of GD3 and GD2 Ganglioside Membrane Expression by Microscopy.

J Vis Exp. 2016 Nov 08;(117):

Authors: Villanueva-Cabello TM, Martinez-Duncker I

Abstract
The methods described herein for activation of naïve CD4(+) T cells in suspension and their adherence in coverslips for confocal microscopy analysis allow the spatial localization and visualization of gangliosides involved in CD4(+) T cell activation, that complement expression profiling experiments such as flow cytometry, western blotting or real-time PCR. The quantification of ganglioside expression through flow cytometry and their cellular localization through microscopy can be obtained by the use of anti-ganglioside antibodies with high affinity and specificity. Nonetheless, an adequate handling of cells in suspension involves the treatment of culture plates to promote the necessary adherence required for fluorescence or confocal microscopy acquisition. In this work, we describe a protocol for determining GD3 and GD2 ganglioside expression and colocalization with the TCR during naïve CD4(+) T cell activation. Also, real-time PCR experiments using <40,000 cells are described for the determination of the GD3 and GM2/GD2 synthase genes, demonstrating that gene analysis experiments can be performed with a low number of cells and without the need of additional low input RNA kits.

PMID: 27911407 [PubMed - in process]

http://ift.tt/2gzGMkD

Ultrasound-guided Botulinum Toxin-A Injections: A Method of Treating Sialorrhea.

Ultrasound-guided Botulinum Toxin-A Injections: A Method of Treating Sialorrhea.

J Vis Exp. 2016 Nov 09;(117):

Authors: Barbero P, Busso M, Artusi CA, De Mercanti S, Tinivella M, Veltri A, Durelli L, Clerico M

Abstract
Neurological diseases can be complicated by sialorrhea, an excessive flow of saliva. Patients suffering from moderate to severe sialorrhea have an impaired quality of life, often worsened by correlated complications such as aspiration pneumonia, oral infections, dental caries, and maceration of the skin. Diverse therapeutic approaches have been proposed for the treatment of sialorrhea, including surgery and the use of anticholinergic agents, with limited results and the possible occurrence of serious adverse events. Recently, botulinum toxin (BoNT) injection within the major salivary glands has been proposed in patients refractory to anticholinergic therapy, with the aim of inhibiting local acetylcholine release and gland activity. In order to obtain a better outcome in terms of reduction of saliva production, efficacy, duration, and avoidance of major adverse events, we developed an ultrasound-guided BoNT-type A injection technique accurately described in the text. Here we present a method of treating sialorrhea with bilateral parotid and submandibular gland BoNT-type A injections under ultrasound guidance. Four quadrants of the parotid gland and two quadrants of the submandibular gland are visualized and injected using two accesses and one access, respectively. The ultrasound-guided procedure provides a simple, non-invasive, real-time visualization of the muscular and glandular tissues and their surrounding structures, optimizing treatment efficacy and safety.

PMID: 27911406 [PubMed - in process]

http://ift.tt/2glwSjR

Automated Robotic Dispensing Technique for Surface Guidance and Bioprinting of Cells.

Automated Robotic Dispensing Technique for Surface Guidance and Bioprinting of Cells.

J Vis Exp. 2016 Nov 18;(117):

Authors: Bhuthalingam R, Lim PQ, Irvine SA, Venkatraman SS

Abstract
This manuscript describes the introduction of cell guidance features followed by the direct delivery of cells to these features in a hydrogel bioink using an automated robotic dispensing system. The particular bioink was selected as it allows cells to sediment towards and sense the features. The dispensing system bioprints viable cells in hydrogel bioinks using a backpressure assisted print head. However, by replacing the print head with a sharpened stylus or scalpel, the dispensing system can also be employed to create topographical cues through surface etching. The stylus movement can be programmed in steps of 10 µm in the X, Y and Z directions. The patterned grooves were able to orientate mesenchymal stem cells, influencing them to adopt an elongated morphology in alignment with the grooves' direction. The patterning could be designed using plotting software in straight lines, concentric circles, and sinusoidal waves. In a subsequent procedure, fibroblasts and mesenchymal stem cells were suspended in a 2% gelatin bioink, for bioprinting in a backpressure driven extrusion printhead. The cell bearing bioink was then printed using the same programmed coordinates used for the etching. The bioprinted cells were able to sense and react to the etched features as demonstrated by their elongated orientation along the direction of the etched grooves.

PMID: 27911405 [PubMed - in process]

http://ift.tt/2gzHO0e

Using Capillary Electrophoresis to Quantify Organic Acids from Plant Tissue: A Test Case Examining Coffea arabica Seeds.

Using Capillary Electrophoresis to Quantify Organic Acids from Plant Tissue: A Test Case Examining Coffea arabica Seeds.

J Vis Exp. 2016 Nov 12;(117):

Authors: Vaughan MJ, Chanon A, Blakeslee JJ

Abstract
Carboxylic acids are organic acids containing one or more terminal carboxyl (COOH) functional groups. Short chain carboxylic acids (SCCAs; carboxylic acids containing three to six carbons), such as malate and citrate, are critical to the proper functioning of many biological systems, where they function in cellular respiration and can serve as indicators of cell health. In foods, organic acid content can have significant impact on taste, with increased SCCA levels resulting in a sour or "acid" taste. Because of this, methods for the rapid analysis of organic acid levels are of particular interest to the food and beverage industries. Unfortunately, however, most methods used for SCCA quantification are dependent on time-consuming protocols requiring the derivatization of samples with hazardous reagents, followed by costly chromatographic and/or mass spectrometric analyses. This method details an alternate method for the detection and quantification of organic acids from plant material and food samples using free zonal capillary electrophoresis (CZE), sometimes simply referred to as capillary electrophoresis (CE). CZE provides a cost-effective method for measuring SCCAs with a low limit of detection (0.005 mg/ml). This article details the extraction and quantification of SCCAs from plant samples. While the method provided focuses on measurement of SCCAs from coffee beans, the method provided can be applied to multiple plant-based food materials.

PMID: 27911404 [PubMed - in process]

http://ift.tt/2glCryt

Preparation and Reactivity of a Triphosphenium Bromide Salt: A Convenient and Stable Source of Phosphorus(I).

Preparation and Reactivity of a Triphosphenium Bromide Salt: A Convenient and Stable Source of Phosphorus(I).

J Vis Exp. 2016 Nov 22;(117):

Authors: Kosnik SC, Binder JF, Nascimento MC, Macdonald CL

Abstract
We present herein the optimized synthesis of a triphosphenium bromide salt. Apart from being a versatile metathesis reagent, this unusually stable low-valent-phosphorus-containing compound acts as a useful P(+) transfer agent. Unlike traditional methods employed to access low-coordinate phosphorus species which usually require pyrophoric phosphorus-containing precursors (white phosphorus, Tris(trimethylsilyl)phosphine, etc.), or harsh reducing agents (alkali metals, potassium graphite, etc.), the current approach does not involve pyrophoric or explosive reagents and can be done on large scales (>20 g) in excellent yields by undergraduates with basic air-free synthetic training. The bromide counter ion is readily exchanged with other anions such as tetraphenyl borate (described herein) using typical salt metathesis reagents to obtain materials with desired properties and reactivities. The versatility of this P(+) transfer approach is exemplified by the reactions of these triphosphenium precursors with an N-heterocyclic carbene and an anionic bisphosphine, each of which readily displace the neutral bisphosphine to give an NHC-stabilized phosphorus(I) cation and a phosphorus(I) containing zwitterion, respectively.

PMID: 27911403 [PubMed - in process]

http://ift.tt/2gzJpDa

Utilizing the Ethylene-releasing Compound, 2-Chloroethylphosphonic Acid, as a Tool to Study Ethylene Response in Bacteria.

Utilizing the Ethylene-releasing Compound, 2-Chloroethylphosphonic Acid, as a Tool to Study Ethylene Response in Bacteria.

J Vis Exp. 2016 Nov 10;(117):

Authors: Augimeri RV, Varley AJ, Strap JL

Abstract
Ethylene (C2H4) is a gaseous phytohormone that is involved in numerous aspects of plant development, playing a dominant role in senescence and fruit ripening. Exogenous ethylene applied during early plant development triggers the triple response phenotype; a shorter and thicker hypocotyl with an exaggerated apical hook. Despite the intimate relationship between plants and bacteria, the effect of exogenous ethylene on bacteria has been greatly overlooked. This is partly due to the difficulty of controlling gaseous ethylene within the laboratory without specialized equipment. 2-Chloroethylphosphonic acid (CEPA) is a compound that decomposes into ethylene, chlorine, and phosphate in a 1:1:1:1 molar ratio when dissolved in an aqueous medium of pH 3.5 or greater. Here we describe the use of CEPA to produce in situ ethylene for the investigation of ethylene response in bacteria using the fruit-associated, cellulose-producing bacterium Komagataeibacter xylinus as a model organism. The protocols described herein include both the verification of ethylene production from CEPA via the Arabidopsis thaliana triple response assay and the effects of exogenous ethylene on K. xylinus cellulose production, pellicle properties and colonial morphology. These protocols can be adapted to examine the effect of ethylene on other microbes using appropriate growth media and phenotype analyses. The use of CEPA provides researchers with a simple and efficient alternative to pure ethylene gas for the routine determination of bacterial ethylene response.

PMID: 27911402 [PubMed - in process]

http://ift.tt/2glD7E4

An Optimized Protocol to Analyze Glycolysis and Mitochondrial Respiration in Lymphocytes.

An Optimized Protocol to Analyze Glycolysis and Mitochondrial Respiration in Lymphocytes.

J Vis Exp. 2016 Nov 21;(117):

Authors: Traba J, Miozzo P, Akkaya B, Pierce SK, Akkaya M

Abstract
Lymphocytes respond to a variety of stimuli by activating intracellular signaling pathways, which in turn leads to rapid cellular proliferation, migration and differentiation, and cytokine production. All of these events are tightly linked to the energy status of the cell, and therefore studying the energy-producing pathways may give clues about the overall functionality of these cells. The extracellular flux analyzer is a commonly used device for evaluating the performance of glycolysis and mitochondrial respiration in many cell types. This system has been used to study immune cells in a few published reports, yet a comprehensive protocol optimized particularly for lymphocytes is lacking. Lymphocytes are fragile cells that survive poorly in ex vivo conditions. Oftentimes lymphocyte subsets are rare, and working with low cell numbers is inevitable. Thus, an experimental strategy that addresses these difficulties is required. Here, we provide a protocol that allows for rapid isolation of viable lymphocytes from lymphoid tissues, and for the analysis of their metabolic states in the extracellular flux analyzer. Furthermore, we provide results of experiments in which the metabolic activities of several lymphocyte subtypes at different cell densities were compared. These observations suggest that our protocol can be used to achieve consistent, well-standardized results even at low cell concentrations, and thus it may have broad applications in future studies focusing on the characterization of metabolic events in immune cells.

PMID: 27911401 [PubMed - in process]

http://ift.tt/2gztVio

Visualizing Stromule Frequency with Fluorescence Microscopy.

Visualizing Stromule Frequency with Fluorescence Microscopy.

J Vis Exp. 2016 Nov 23;(117):

Authors: Brunkard JO, Runkel AM, Zambryski P

Abstract
Stromules, or "stroma-filled tubules", are narrow, tubular extensions from the surface of the chloroplast that are universally observed in plant cells but whose functions remain mysterious. Alongside growing attention on the role of chloroplasts in coordinating plant responses to stress, interest in stromules and their relationship to chloroplast signaling dynamics has increased in recent years, aided by advances in fluorescence microscopy and protein fluorophores that allow for rapid, accurate visualization of stromule dynamics. Here, we provide detailed protocols to assay stromule frequency in the epidermal chloroplasts of Nicotiana benthamiana, an excellent model system for investigating chloroplast stromule biology. We also provide methods for visualizing chloroplast stromules in vitro by extracting chloroplasts from leaves. Finally, we outline sampling strategies and statistical approaches to analyze differences in stromule frequencies in response to stimuli, such as environmental stress, chemical treatments, or gene silencing. Researchers can use these protocols as a starting point to develop new methods for innovative experiments to explore how and why chloroplasts make stromules.

PMID: 27911400 [PubMed - in process]

http://ift.tt/2glAn9S

Real time measurement of transient event emissions of air toxics by tomographic remote sensing in tandem with mobile monitoring

Publication date: February 2017
Source:Atmospheric Environment, Volume 150
Author(s): Eduardo P. Olaguer, Jochen Stutz, Matthew H. Erickson, Stephen C. Hurlock, Ross Cheung, Catalina Tsai, Santo F. Colosimo, James Festa, Asanga Wijesinghe, Bradley S. Neish
During the Benzene and other Toxics Exposure (BEE-TEX) study, a remote sensing network based on long path Differential Optical Absorption Spectroscopy (DOAS) was set up in the Manchester neighborhood beside the Ship Channel of Houston, Texas in order to perform Computer Aided Tomography (CAT) scans of hazardous air pollutants. On 18–19 February 2015, the CAT scan network detected large nocturnal plumes of toluene and xylenes most likely associated with railcar loading and unloading operations at Ship Channel petrochemical facilities. The presence of such plumes during railcar operations was confirmed by a mobile laboratory equipped with a Proton Transfer Reaction—Mass Spectrometer (PTR-MS), which measured transient peaks of toluene and C2-benzenes of 50 ppb and 57 ppb respectively around 4 a.m. LST on 19 February 2015. Plume reconstruction and source attribution were performed using the 4D variational data assimilation technique and a 3D micro-scale forward and adjoint air quality model based on both tomographic and PTR-MS data. Inverse model estimates of fugitive emissions associated with railcar transfer emissions ranged from 2.0 to 8.2 kg/hr for toluene and from 2.2 to 3.5 kg/hr for xylenes in the early morning of 19 February 2015.



http://ift.tt/2gMKNA9

Spatially resolved intake fraction estimates for primary and secondary particulate matter in the United States

Publication date: February 2017
Source:Atmospheric Environment, Volume 150
Author(s): Carmen Lamancusa, Fatema Parvez, Kristina Wagstrom
This study uses intake fraction, the fraction of emissions that are inhaled from a given source, to quantify how emissions from different regions proportionally contribute to human exposure to both primary and secondary particulate matter species. The intake fraction for secondary species is defined using the common atomic constituents between precursor species and products, allowing estimates to include both primary and secondary species. The Particulate Matter Source Apportionment Technology (PSAT) in the Comprehensive Air Quality Model with Extensions (CAMx) regional air quality model is used to calculate the intake fraction for twenty-five source regions throughout the contiguous United States over four seasons. The calculations use spatially explicit emissions and population density to more accurately capture the variation in intake fraction between regions. The spatially explicit emissions allow for the calculation of spatial trends and variations within the intake fraction. More specifically it allows for the calculation of the amount of intake that occurs within a given distance of the emissions source or source region. Based on the results sulfate inhalation occurs over larger distances than other particulate matter species. For most regions, a substantial fraction (>75%) of the inhalation occurs within 50 km for all seasons, demonstrating that efforts to reduce emissions will have the largest health impact on the local community. Furthermore the distance over which 75% of the inhalation occurs increases by 20% for all species during the winter and a larger percentage of pollutants emitted during the winter are inhaled relative to pollutants emitted during other seasons. This demonstrates that emission reductions during the winter will have a greater impact on health than reductions during other seasons.

Graphical abstract

http://ift.tt/2gMOLsj

Mortality and air pollution in Beijing: The long-term relationship

Publication date: February 2017
Source:Atmospheric Environment, Volume 150
Author(s): Guiqian Tang, Pusheng Zhao, Yinghong Wang, Wenkang Gao, Mengtian Cheng, Jinyuan Xin, Xin Li, Yuesi Wang
Since the 1980s, air pollution has become a major problem in northern China. Exposure to the extremely high concentrations of aerosols and trace gases might lead to important human health outcomes, including respiratory, cardiovascular and cerebrovascular diseases and malignant tumours. In this study, we collected data on mortality, visibility and the concentrations of certain air pollutants in Beijing from 1949 to 2011. Our goal was to investigate the mortality trends of different types of diseases and the relationship between mortality and air pollution. Based on the chemical compositions in particles and satellite formaldehyde, we found that mortality due to circulatory diseases was correlated with sulphate, nitrate and formaldehyde, whereas respiratory diseases were correlated with calcium, sulphate and nitrate, and malignant tumours was correlated with ammonium, nitrate and formaldehyde with an 11-year lag. The different responses to different air pollutants for different diseases are primarily a result of energy usage.

Graphical abstract

http://ift.tt/2gMON3q

Development, Fabrication and Evaluation of a Novel Biomimetic Human Breast Tissue Derived Breast Implant Surface

Publication date: Available online 2 December 2016
Source:Acta Biomaterialia
Author(s): S. Barr, E.W. Hill, A. Bayat
Breast implant use has tripled in the last decade with over 320,000 breast implant based reconstructions and augmentations performed in the US per annum. Unfortunately a considerable number of women will experience capsular contracture, the irrepressible and disfiguring, tightening and hardening of the fibrous capsule that envelops the implant. Functionalising implant surfaces with biocompatible tissue-specific textures may improve in-vivo performance. A novel biomimetic breast implant is presented here with anti-inflammatory in-vitro abilities.Topographical assessment of native breast tissue facilitated the development of a statistical model of adipose tissue. 3D grayscale photolithography and ion etching were combined to successfully replicate a surface modelled upon the statistics of breast tissue.Pro-inflammatory genes ILβ1, TNFα, and IL6 were downregulated (p<0.001) and anti-inflammatory gene IL-10 were upregulated on the novel surface. Pro-inflammatory cytokines Gro-Alpha, TNFα and neutrophil chemoattractant IL8 were produced in lower quantities and anti-inflammatory IL-10 in higher quantities in culture with the novel surface (p<0.01). Immunocytochemistry and SEM demonstrated favourable fibroblast and macrophage responses to these novel surfaces.This study describes the first biomimetic breast tissue derived breast implant surface. Our findings attest to its potential translational ability to reduce the inflammatory phase of the implant driven foreign body reaction.Statement of significanceBreast implants are still manufactured using outdated techniques and have changed little since their inception in the 1960's. Breast implants can cause a medical condition, capsular contracture which often results in disfigurement, pain, implant removal and further surgery. This condition is due to the body's reaction to these breast implants. This article describes the successful manufacture and testing of a novel breast implant surface inspired by the native shapes present in breast tissue. Results show that this novel implant surface is capable of reducing the negative reaction of human cells to these surfaces to help reduce capsular contracture. This work represents the first steps in producing a more successful breast implant.

Graphical abstract

http://ift.tt/2gZ1ZS2

Clinicopathological features and clinical outcomes associated with TP53 and BRAF(N)(on-)(V)(600) mutations in cutaneous melanoma patients.

Clinicopathological features and clinical outcomes associated with TP53 and BRAF(N)(on-)(V)(600) mutations in cutaneous melanoma patients.

Cancer. 2016 Dec 02;:

Authors: Kim DW, Haydu LE, Joon AY, Bassett RL, Siroy AE, Tetzlaff MT, Routbort MJ, Amaria RN, Wargo JA, McQuade JL, Kemnade J, Hwu P, Woodman SE, Roszik J, Kim KB, Gershenwald JE, Lazar AJ, Davies MA

Abstract
BACKGROUND: BRAF(V600) , NRAS, TP53, and BRAF(Non-V600) are among the most common mutations detected in non-acral cutaneous melanoma patients. Although several studies have identified clinical and pathological features associated with BRAF(V600) and NRAS mutations, limited data are available regarding the correlates and significance of TP53 and BRAF(Non-V600) mutations.
METHODS: This study analyzed the patient demographics, primary tumor features, and clinical outcomes of a large cohort of non-acral cutaneous melanoma patients who had undergone clinically indicated molecular testing (n = 926).
RESULTS: The prevalence of BRAF(V600) , NRAS, TP53, and BRAF(Non-V600) mutations was 43%, 21%, 19%, and 7%, respectively. The presence of a TP53 mutation was associated with older age (P = .019), a head and neck primary tumor site (P = .0001), and longer overall survival (OS) from the diagnosis of stage IV disease in univariate (P = .039) and multivariate analyses (P = .015). BRAF(Non-V600) mutations were associated with older age (P = .005) but not with primary tumor features or OS from stage IV. Neither TP53 nor BRAF(Non-V600) mutations correlated significantly with OS with frontline ipilimumab treatment, and the TP53 status was not significantly associated with outcomes with frontline BRAF inhibitor therapy. Eleven patients with BRAF(Non-V600) mutations were treated with a BRAF inhibitor. Three patients were not evaluable for a response because of treatment cessation for toxicities; the remaining patients had disease progression as the best response to therapy.
CONCLUSIONS: These results add to the understanding of the clinical features associated with TP53 and BRAF(Non-V600) mutations in advanced cutaneous melanoma patients, and they support the rationale for evaluating the prognostic significance of TP53 in other cohorts of melanoma patients. Cancer 2016. © 2016 American Cancer Society.

PMID: 27911979 [PubMed - as supplied by publisher]

http://ift.tt/2glx8z3

Back to the Past for the Future of Medicine: Special Series on Bedside Medicine.

Back to the Past for the Future of Medicine: Special Series on Bedside Medicine.

South Med J. 2016 Dec;109(12):735

Authors: Holt GR

PMID: 27911961 [PubMed - in process]

http://ift.tt/2gzxvt8

Microvascular decompression of the cochleovestibular nerve for treatment of tinnitus and vertigo: a systematic review and meta-analysis of individual patient data.

Microvascular decompression of the cochleovestibular nerve for treatment of tinnitus and vertigo: a systematic review and meta-analysis of individual patient data.

J Neurosurg. 2016 Dec 02;:1-14

Authors: van den Berge MJ, van Dijk JM, Posthumus IA, Smidt N, van Dijk P, Free RH

Abstract
OBJECTIVE Microvascular decompression (MVD) is regarded as a valid treatment modality in neurovascular conflicts (NVCs) causing, for example, trigeminal neuralgia and hemifacial spasms. An NVC of the cochleovestibular nerve might cause tinnitus and/or vertigo; however, general acceptance of MVD for this indication is lacking. The aim of this study was to investigate the effectiveness, safety, and prognostic factors for success of MVD of the cochleovestibular nerve. METHODS A systematic review and meta-analysis of individual patient data (IPD) were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Individual Patient Data (PRISMA-IPD) guidelines. By a comprehensive search (conducted in January 2016) in MEDLINE, EMBASE, and Google Scholar, eligible studies were identified. The collected outcome was a global measurement of improvement of 1) tinnitus, 2) vertigo, and 3) tinnitus combined with vertigo. For the meta-analysis, IPD were collected from the papers and/or from the authors. IPD were analyzed with logistic regression analysis while accounting for study clustering. RESULTS Thirty-five studies (572 patients) were included. The level of evidence provided by these studies was low. In 28% of patients with tinnitus and 32% of patients with vertigo, complete relief following MVD was reported. Patients with both tinnitus and vertigo had complete relief in 62% of cases. In 11% of patients, ≥ 1 complications were reported. Meta-analysis of IPD (165 patients) demonstrated that patients with both tinnitus and vertigo had a higher chance of success (OR 3.8, 95% CI 1.45-10.10) than patients with tinnitus alone. No other variables were significantly related to success. CONCLUSIONS Due to low success rates, MVD cannot be considered as a standard treatment method for tinnitus or vertigo. Moreover, a substantial complication rate was found. However, patients with combined symptoms had a higher chance of success. When combined symptoms occur, it is more likely that an NVC is the underlying pathology and MVD might be appropriate. Due to the low level of evidence in the included studies, this conclusion must be taken with caution. Further validation is necessary to evaluate whether patients with combined symptoms are indeed better candidates for MVD.

PMID: 27911239 [PubMed - as supplied by publisher]

http://ift.tt/2glrzAX

Patient- versus physician-reported facial disability in vestibular schwannoma: an international cross-sectional study.

Patient- versus physician-reported facial disability in vestibular schwannoma: an international cross-sectional study.

J Neurosurg. 2016 Dec 02;:1-10

Authors: Tveiten ØV, Carlson ML, Goplen F, Myrseth E, Driscoll CL, Mahesparan R, Link MJ, Lund-Johansen M

Abstract
OBJECTIVE Patient-reported outcomes are increasingly used in studies of vestibular schwannoma (VS); however, few studies have examined self-evaluated facial nerve function and its relation to physician-reported outcomes. The primary objective of this study was to compare patient self-evaluations of facial disability with physician-evaluated facial nerve status and with self-evaluations of a healthy control group. The second objective was to provide insight into the controversial subject of the optimal initial management of small- and medium-sized VSs; consequently, the authors compared patient-reported facial nerve disability following treatment via observation (OBS), Gamma Knife surgery (GKS), or microsurgery (MS). Lastly, the authors sought to identify risk factors for facial nerve dysfunction following treatment for small- and medium-sized VSs. METHODS All patients with a VS 3 cm or smaller that was singly treated with OBS, GKS, or MS at either of 2 independent treatment centers between 1998 and 2008 were retrospectively identified. Longitudinal facial nerve measures and clinical data, including facial nerve evaluation according to the House-Brackmann (HB) grading system, were extracted from existing VS databases. Supplementing the objective data were Facial Disability Index (FDI) scores, which were obtained via survey of patients a mean of 7.7 years after initial treatment. RESULTS The response rate among the 682 eligible patients was 79%; thus, data from a total of 539 patients were analyzed. One hundred forty-eight patients had been managed by OBS, 247 with GKS, and 144 with MS. Patients who underwent microsurgery had larger tumors and were younger than those who underwent OBS or GKS. Overall, facial nerve outcomes were satisfactory following treatment, with more than 90% of patients having HB Grade I function at the last clinical follow-up. Treatment was the major risk factor for facial nerve dysfunction. Almost one-fifth of the patients treated with MS had an objective decline in facial nerve function, whereas only 2% in the GKS group and 0% in the OBS cohort had a decline. The physical subscale of the FDI in the VS patients was highly associated with HB grade; however, the social/well-being subscale of the FDI was not. Thus, any social disability caused by facial palsy was not detectable by use of this questionnaire. CONCLUSIONS The majority of patients with small- and medium-sized VSs attain excellent long-term facial nerve function and low facial nerve disability regardless of treatment modality. Tumor size and microsurgical treatment are risk factors for facial nerve dysfunction and self-reported disability. The FDI questionnaire is sensitive to the physical but not the social impairment associated with facial dysfunction.

PMID: 27911236 [PubMed - as supplied by publisher]

http://ift.tt/2gzy5ad

Oral Squamous Cell Carcinoma: Current Treatment Strategies and Nanotechnology-Based Approaches for Prevention and Therapy.

Oral Squamous Cell Carcinoma: Current Treatment Strategies and Nanotechnology-Based Approaches for Prevention and Therapy.

Crit Rev Ther Drug Carrier Syst. 2016;33(4):363-400

Authors: Gharat SA, Momin M, Bhavsar C

Abstract
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer; it involves damage to oral epithelial cells due to accumulation of multiple genetic mutations in the cells. OSCC remains major cause of morbidity and mortality in patients with head and neck cancers. Tobacco, smoking, alcohol consumption alone or with chewing tobacco, and betel quid are potential carcinogens contributing to the high occurrence of OSCC. Current treatment modalities for OSCC like chemoradiotherapy, surgery, EGFR inhibitors and COX-2 inhibitors, and photodynamic therapy have led to the major problems related to non-specific cell death. Nanoengineered systems offer solutions to these problems that not only minimize the major drawbacks of nonspecific cell death but also maximize the efficacy of the cancer therapeutic agents. Various efficacious nanotechnology-based carrier systems are being widely investigated for their potential in OSCC treatment: polymeric nanoparticles, polymeric micelles, nanoemulsions and layered nanoemulsions, nanoliposomes, solid lipid nanoparticles and nanolipid carriers, cyclodextrin complexes, hydrogels, metallic nanoparticles, nanocarbon tubes, and receptor mediated drug delivery systems. We highlight the etiology, line of the treatment and chemopreventive measures related to OSCC. We focus on data available in the research carried out worldwide in past 15 years related to the management of OSCC.

PMID: 27910740 [PubMed - in process]

http://ift.tt/2glABh9

Institutional experience in the treatment of colorectal liver metastases with stereotactic body radiation therapy

Publication date: Available online 2 December 2016
Source:Reports of Practical Oncology & Radiotherapy
Author(s): Alejandra Méndez Romero, Fatma Keskin-Cambay, Rob M. van Os, Joost J. Nuyttens, Ben J.M. Heijmen, Jan N.M. IJzermans, Cornelis Verhoef
AimTo investigate whether the impact of dose escalation in our patient population represented an improvement in local control without increasing treatment related toxicity.Materials and methodsA cohort of consecutive patients with colorectal liver metastases treated with stereotactic body radiation therapy (SBRT) between December 2002 and December 2013 were eligible for this study. Inclusion criteria were a Karnofsky performance status ≥80% and, according to the multidisciplinary tumor board, ineligibility for surgery or radiofrequency ablation. Exclusion criteria were a lesion size >6cm, more than 3 metastases, and treatment delivered with other fractionation scheme than 3 times 12.5Gy or 16.75Gy prescribed at the 65–67% isodose. To analyze local control, CT or MRI scans were acquired during follow-up. Toxicity was scored using the Common Toxicity Criteria Adverse Events v4.0.ResultsA total of 40 patients with 55 colorectal liver metastases were included in this study. We delivered 37.5Gy to 32 lesions, and 50.25Gy to 23 lesions. Median follow-up was 26 and 25 months for these two groups. Local control at 2 and 3 years was 74 and 66% in the low dose group while 90 and 81% was reached in the high dose group. No significant difference in local control between the two dose fractionation schemes could be found. Grade 3 toxicity was limited and was not increased in the high dose group.ConclusionsSBRT for colorectal liver metastases offers a high chance of local control at long term. High irradiation doses may contribute to enhance this effect without increasing toxicity.



http://ift.tt/2gzr74R

Irbesartan ameliorates hyperlipidemia and liver steatosis in type 2 diabetic db/db mice via stimulating PPAR-γ, AMPK/Akt/mTOR signaling and autophagy

Publication date: January 2017
Source:International Immunopharmacology, Volume 42
Author(s): Juan Zhong, Wangqiu Gong, Lu Lu, Jing Chen, Zibin Lu, HongYu Li, Wenting Liu, Yangyang Liu, Mingqing Wang, Rong Hu, Haibo Long, Lianbo Wei
Irbesartan (Irb), a unique subset of angiotensin II receptor blockers (ARBs) with PPAR-γ activation function, has been reported to play a role in renal dysfunction, glucose metabolism, and abnormal lipid profile in diabetic animal models and humans. However, the underlying mechanisms that improve hyperlipidemia and liver steatosis are unclear. This study investigated the effects of Irb on lipid metabolism and hepatic steatosis using the spontaneous type 2 diabetic db/db mouse model. The results demonstrated body and liver weight, food consumption, lipid content in serum and liver tissue, and liver dysfunction as well as hepatic steatosis were increased in db/db mice compared with db/m mice, whereas the increases were reversed by Irb treatment. Moreover, Irb administration resulted in an increase in LC3BII as well as the LC3BII/I ratio through activating PPAR-γ and p-AMPK and inhibiting p-Akt and p-mTOR, thereby inducing autophagy in the db/db mouse liver. Therefore, our findings suggest that Irb can ameliorate hyperlipidemia and liver steatosis by upregulating the expression of PPAR-γ, activating the AMPK/Akt/mTOR signaling pathway and inducing liver autophagy.



http://ift.tt/2gzsErI

Not All Patients with Critical Limb Ischaemia Require Revascularisation

Publication date: Available online 2 December 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): T.B. Santema, R.M. Stoekenbroek, J. van Loon, M.J.W. Koelemay, D.T. Ubbink
ObjectivesInternational guidelines recommend revascularisation as the preferred treatment for patients with critical limb ischaemia (CLI). Most contemporary research focuses on the outcome of invasive procedures for CLI, but little is known about the outcome of conservative management. Amputation free survival (AFS) and overall survival (OS) was investigated in patients with CLI who did or did not receive revascularisation, and characteristics associated with clinical outcomes were explored.MethodsThis was a retrospective cohort study of consecutive patients with chronic CLI between 2010 and 2014 in a Dutch university hospital. CLI was defined as the presence of ischaemic rest pain or tissue loss in conjunction with an absolute systolic ankle pressure < 50 mmHg or a toe pressure < 30 mmHg. Patients were divided into invasive (revascularisation within 6 weeks), deferred invasive (revascularisation after 6 weeks), or permanently conservative treatment groups. Univariable and multivariable survival analyses were used to identify factors associated with AFS and OS.ResultsThe majority (66.7%; N = 96) of the identified 144 patients with CLI (mean age 71.2 years; median follow-up 99 weeks) underwent revascularisation within 6 weeks of diagnosis. Deferred invasive treatment was provided in 18.1% (N = 26) patients and 22 patients (15.3%) were treated permanently conservatively. AFS and OS did not differ significantly between the three groups (Breslow–Wilcoxon p = .16 for AFS and p = .09 for OS). Age, chronic obstructive pulmonary disease (COPD), and heart disease were significant independent predictors of AFS. Age, COPD, and hypertension were significant independent predictors of OS. Treatment was not a significant predictor of either AFS or OS.ConclusionsNot all patients with CLI require revascularisation to achieve an AFS that is similar to patients undergoing revascularisation, although the efficacy of conservative versus invasive treatment in CLI patients is still unclear. Further prospective studies should determine subgroups of patients in whom revascularisation may be omitted.



http://ift.tt/2h5mmku

Randomised Controlled Trial: Potential Benefit of a Footplate Neuromuscular Electrical Stimulation Device in Patients with Chronic Venous Disease

Publication date: Available online 2 December 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): R. Ravikumar, K.J. Williams, A. Babber, T.R.A. Lane, H.M. Moore, A.H. Davies
ObjectivesChronic venous disease (CVD) is common, affecting a quarter of the population. Current conservative methods of treatment aim to prevent progression of disease by reducing ambulatory venous pressure. Neuromuscular electrical stimulation (NMES) refers to the use of electrical impulses to elicit muscle contraction. This pilot randomised controlled trial investigates the effect of a footplate NMES device (REVITIVE) on venous flow parameters, limb oedema, and quality of life outcome measures in patients with CVD.MethodsTwenty-two patients with Clinical Etiological Anatomical and Pathophysiological (CEAP) clinical class C2–C4 venous disease were randomised to receive a sham or test device. The recommended duration of use was for 30 minutes daily for 6 weeks. Venous flow parameters (duplex ultrasound), limb volume (optoelectric volumeter), and quality of life outcome measures were measured at baseline and after 6 weeks.ResultsThe mean age of participants was 62 years, body mass index 28.6, with a 15:7 female preponderance. There was a significant difference in the percentage change in femoral vein flow parameters (from baseline) between the test and sham group while using the device (Week 0 time-averaged mean velocity 102.4% vs. −9.1%, p < .0001; volume flow 107.9% vs. −3.7%, p < .0001; peak velocity 377.7% vs. −6.7%, p < .0001). Limb volume was observed to increase significantly in the sham group (2.0% at Week 0 and 1.2% at Week 6; p < .01). This was prevented in the test group (+0.8% at Week 0 and 1.0% at Week 6; p = .06). There was a significant difference in the Aberdeen Varicose Vein Questionnaire between the two groups over the 6 weeks.ConclusionsThis trial demonstrated a significant difference in venous flow parameters and prevention of orthostatic limb oedema with NMES. There was a positive effect on quality of life. Larger studies are required to determine the clinical significance of this in patients with venous disease.



http://ift.tt/2gT9YBh

Renal Artery Stenosis in Patients with Peripheral Artery Disease: Prevalence, Risk Factors and Long-term Prognosis

Publication date: Available online 2 December 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): V. Aboyans, I. Desormais, J. Magne, G. Morange, D. Mohty, P. Lacroix
Objective/BackgroundThe objective was to determine the prevalence and clinical determinants of renal artery stenosis (RAS) in patients undergoing digital subtraction angiography (DSA) for the assessment of peripheral artery disease (PAD), and to evaluate its prognostic significance.MethodsAll DSAs performed from January 2000 to January 2006 were retrospectively reviewed for assessment of PAD in patients naive for any prior revascularisation of lower-limb arteries. All DSA studies were read by two senior physicians blinded to outcome, and consensus was reached in cases of disagreement. RAS was defined as the presence of ≥50% stenosis in either renal artery. Patients' electronic medical files were systematically reviewed and follow-up was completed by contact with family physicians until January 2014. The primary outcome was composite, including death, peripheral revascularisation, or any limb amputation. Secondary outcomes were all-cause mortality, and another composite, including death and non-fatal myocardial infarction or stroke or coronary or carotid revascularisation.ResultsIn total, 400 consecutive patients having a first DSA of lower extremities, two thirds of whom were for critical limb ischaemia, were studied. Thirteen patients were excluded owing to poor renal artery imaging. RAS was detected in 57 patients (14%). Only two factors were independently and significantly associated with RAS in multivariate analysis: diffuse PAD (involving both proximal and distal segments [odds ratio {OR} 3.50, 95% confidence interval {CI} 1.16–10.54; p = .026]) and decreased glomerular filtration rate (OR 0.55 per 30 mL/minute/1.73 m², 95% CI 0.41–0.75; p < .001). During follow-up (mean ± SD 62 ± 47 months), 25% experienced limb amputation and 54% died. In multivariate analysis, no significant association was found between RAS and primary outcome (hazard ratio 0.80; 95% CI 0.57–1.10). No significant association was found with secondary outcomes.ConclusionIncidental RAS is frequent (14%) among patients with PAD undergoing lower extremity imaging. No difference in outcome in patients with RAS versus those without RAS was seen. Larger studies are necessary to draw definite conclusions.



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Sacotomy if All Else Fails?

Publication date: Available online 2 December 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): M. Elkawafi, U.J. Kirkpatrick




http://ift.tt/2gT9E5t

A Novel Technique for Bifurcated Bovine Plus Omniflow Aortic Graft Reconstruction

Publication date: Available online 2 December 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): P.W. Stather, A.Q. Howard




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Management of Tissue Ischemia in Mastectomy Skin Flaps: Algorithm Integrating SPY Angiography and Topical Nitroglycerin

Summary: Tissue ischemia can be managed in several different ways based on the cause of the perfusion defect, including topical nitroglycerin or surgical intervention. However, there are times when tissue perfusion is questioned and clinical examination is unable to determine definitively the cause of ischemic tissue and whether it will survive. In this technique article, we describe our comprehensive algorithm for the management of tissue ischemia in mastectomy skin flaps, which can be applied to other plastic surgery procedures by integrating SPY angiography and topical nitroglycerin.

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Histone deacetylase inhibitors deplete myeloid-derived suppressor cells induced by 4T1 mammary tumors in vivo and in vitro

Abstract

Myeloid-derived suppressor cells (MDSC) have been identified as a population of immature myeloid cells that suppress anti-tumor immunity. MDSC are increased in tumor-bearing hosts; thus, depletion of MDSC may enhance anti-tumor immunity. Histone deacetylase inhibitors (HDACi) are chemical agents that are primarily used against hematologic malignancies. The ability of these agents to modulate anticancer immunity has recently been extensively studied. However, the effect of HDACi on MDSC has remained largely unexplored. In the present study, we provide the first demonstration that HDACi treatment decreases MDSC accumulation in the spleen, blood and tumor bed but increases the proportion of T cells (particularly the frequency of IFN-γ- or perforin-producing CD8⁺ T cells) in BALB/C mice with 4T1 mammary tumors. In addition, HDACi exposure of bone marrow (BM) cells significantly eliminated the MDSC population induced by GM-CSF or the tumor burden in vitro, which was further demonstrated as functionally important to relieve the inhibitory effect of MDSC-enriched BM cells on T cell proliferation. Mechanistically, HDACi increased the apoptosis of Gr-1⁺ cells (almost MDSC) compared with that of Gr-1⁻ cells, which was abrogated by the ROS scavenger N-acetylcysteine, suggesting that the HDACi-induced increase in MDSC apoptosis due to increased intracellular ROS might partially account for the observed depletion of MDSC. These findings suggest that the elimination of MDSC using an HDACi may contribute to the overall anti-tumor properties of these agents, highlighting a novel property of HDACi as potent MDSC-targeting agents, which may be used to enhance the efficacy of immunotherapeutic regimens.

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Bathing and Associated Treatments in Atopic Dermatitis

Abstract

Atopic dermatitis is one of the most common complaints presenting to dermatologists, and patients typically inquire as to appropriate bathing recommendations. Although many dermatologists, allergists, and primary-care practitioners provide explicit bathing instructions, recommendations regarding frequency of bathing, duration of bathing, and timing related to emollient and medication application relative to bathing vary widely. Conflicting and vague guidelines stem from knowledge related to the disparate effects of water on skin, as well as a dearth of studies, especially randomized controlled trials, evaluating the effects of water and bathing on the skin of patients with atopic dermatitis. We critically review the literature related to bathing and associated atopic dermatitis treatments, such as wet wraps, bleach baths, bath additives, and balneotherapy. We aim to provide readers with a comprehensive understanding of the impact of water and related therapies on atopic dermatitis as well as recommendations based upon the published data.

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iTRAQ-based quantitative proteomic analysis of midgut in silkworm infected with Bombyx mori cytoplasmic polyhedrosis virus

Publication date: 30 January 2017
Source:Journal of Proteomics, Volume 152
Author(s): Kun Gao, Xiang-yuan Deng, Meng-ke Shang, Guang-xing Qin, Cheng-xiang Hou, Xi-jie Guo
Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) specifically infects the epithelial cells in the midgut of silkworm and causes them to death, which negatively affects the sericulture industry. In order to determine the midgut response at the protein levels to the virus infection, differential proteomes of the silkworm midgut responsive to BmCPV infection were identified with isobaric tags for relative and absolute quantitation (iTRAQ) labeling followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). 193, 408, 189 differentially expressed proteins (DEPs) were reliably quantified by iTRAQ analysis in the midgut of BmCPV-infected and control larvae at 24, 48, 72h post infection (hpi) respectively. KEGG enrichment analysis showed that Oxidative phosphorylation, amyotrophic lateral sclerosis, Toll-like receptor signaling pathway, steroid hormone biosynthesis were the significant pathways (Q value≤0.05) both at 24 and 48hpi. qRT-PCR was used to further verify gene transcription of 30 DEPs from iTRAQ, showing that the regulations of 24 genes at the transcript level were consistent with those at the proteomic level. Moreover, the cluster analysis of the three time groups showed that there were seven co-regulated DEPs including BGIBMGA002620-PA, which was a putative p62/sequestosome-1 protein in silkworm. It was upregulated at both the mRNA level and the proteomic level and may play an important role in regulating the autophagy and apoptosis (especially apoptosis) induced by BmCPV infection. This was the first report using an iTRAQ approach to analyze proteomes of the silkworm midgut against BmCPV infection, which contributes to understanding the defense mechanisms of silkworm midgut to virus infection.SignificanceThe domesticated silkworm, Bombyx mori, is renowned for silk production as well as being a traditional lepidopteron model insect served as a subject for morphological, genetic, physiological, and developmental studies. Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) specifically infects the epithelial cells in the midgut of silkworm and causes the silkworm to death, which negatively affects the sericulture industry. Studies on insect antiviral immunity and on interactive mechanisms between host cells and BmCPV are in their infancy and remain insufficient. In order to obtain an overall view of silkworm response to BmCPV infection, we performed a proteomic analysis of the midgut of silkworm responses to BmCPV infection by iTRAQ. This was the first report using an iTRAQ approach to analyze proteomes of the silkworm midgut against BmCPV infection, which contributes to understanding the defense mechanisms of silkworm midgut to virus infection.

Graphical abstract

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A glimpse into the modulation of post-translational modifications of human-colonizing bacteria

Publication date: 30 January 2017
Source:Journal of Proteomics, Volume 152
Author(s): Paulo André Dias Bastos, João Pinto da Costa, Rui Vitorino
Protein post-translational modifications (PTMs) are a key bacterial feature that holds the capability to modulate protein function and responses to environmental cues. Until recently, their role in the regulation of prokaryotic systems has been largely neglected. However, the latest developments in mass spectrometry-based proteomics have allowed an unparalleled identification and quantification of proteins and peptides that undergo PTMs in bacteria, including in species which directly or indirectly affect human health. Herein, we address this issue by carrying out the largest and most comprehensive global pooling and comparison of PTM peptides and proteins from bacterial species performed to date. Data was collected from 91 studies relating to PTM bacterial peptides or proteins identified by mass spectrometry-based methods. The present analysis revealed that there was a considerable overlap between PTMs across species, especially between acetylation and other PTMs, particularly succinylation. Phylogenetically closer species may present more overlapping phosphoproteomes, but environmental triggers also contribute to this proximity. PTMs among bacteria were found to be extremely versatile and diverse, meaning that the same protein may undergo a wide variety of different modifications across several species, but it could also suffer different modifications within the same species.

Graphical abstract

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Profiling and identification of new proteins involved in brain ischemia using MALDI-imaging-mass-spectrometry

Publication date: 30 January 2017
Source:Journal of Proteomics, Volume 152
Author(s): Víctor Llombart, Sebastián Alejandro Trejo, Sílvia Bronsoms, Anna Morancho, Ma Feifei, Júlia Faura, Teresa García-Berrocoso, Alba Simats, Anna Rosell, Francesc Canals, Mar Hernández-Guillamón, Joan Montaner
The identification of proteins involved in brain ischemia might allow the discovery of putative biomarkers or therapeutic targets for ischemic stroke. Our aim is to study the distribution of proteins within mouse brain after an ischemic insult using MALDI imaging-mass-spectrometry and to identify relevant proteins involved in brain damage. We occluded the middle cerebral artery of C57BL/6J mice. Brain slices were analyzed by MALDI-TOF and infarct (IC) and contralateral (CL) regions were compared using ClinProTools. The ion distribution maps of relevant m/z values were obtained by FlexImagin3.0. Protein identification was conducted through a bottom-up approach consisting on complementary sample fractionation methods. Some identifications were confirmed by immunohistochemistry and western blot. We identified 102 m/z values with different abundances between IC and CL (p<0.05), from which 21 m/z peaks were selected as more relevant. Thirteen of them were found increased in the infarct region and 4 m/z values showed AUC>90% between IC and CL. Identification analyses confirmed altered expressions of ATP5i, COX6C and UMP-CMP kinase in IC compared to CL.Biological significanceUsing MALDI-IMS we identified for the first time new proteins that might be involved in brain ischemia representing potential diagnostic biomarkers or target molecules for neurological recovery.

Graphical abstract

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Plant pathogens but not antagonists change in soil fungal communities across a land abandonment gradient in a Mediterranean landscape

Publication date: January 2017
Source:Acta Oecologica, Volume 78
Author(s): L. Bosso, F. Lacatena, R. Varlese, S. Nocerino, G. Cristinzio, D. Russo
We assessed whether the presence and abundance of plant pathogens and antagonists change in soil fungal communities along a land abandonment gradient. The study was carried out in the Cilento area (Southern Italy) at a site with three different habitats found along a land abandonment gradient: agricultural land, Mediterranean shrubland and woodland. For all microbiological substrates the colony forming units were about 3.1 × 10⁶ g⁻¹ soil for agricultural land and about 1.1 × 10⁶ g⁻¹ soil for Mediterranean shrubland and woodland. We found the following genera in all habitats: Cladosporium, Mortierella, Penicillium and Trichoderma. In agricultural land, the significantly most abundant fungus genera were Aspergillus, Fusarium, Cylindrocarpon and Nectria; in Mediterranean shrubland, Rhizopus and Trichoderma; and in woodland, Bionectria, Mortierella, Cladosporium, Diplodia, Paecilomyces, Penicillium and Trichoderma. We found a total of 8, 8 and 9 species of fungal antagonist, and 16, 6 and 6 species of fungal plant pathogens in agricultural land, Mediterranean shrubland and woodland respectively. Fungal plant pathogens decreased significantly over a land abandonment gradient, while we no found significant differences among fungal antagonists in the three habitats. We conclude that a decrease in the number of fungal pathogen species occurs when formerly cultivated areas are abandoned. On the other hand, fungal antagonists seem not to be affected by this process.



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Autoimmune Cardiotoxicity of Cancer Immunotherapy

Publication date: Available online 2 December 2016
Source:Trends in Immunology
Author(s): Feixiong Cheng, Joseph Loscalzo
Contemporary immunotherapies (e.g., immune checkpoint inhibitors), which enhance the immune response to cancer cells, improve clinical outcomes in several malignancies. A recent study reported the cases of two patients with metastatic melanoma who developed fatal myocarditis during ipilimumab and nivolumab combination immunotherapy; these examples highlight the risk of unbridled activation of the immune system.



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