Phragmites australis (common reed) has generally been regarded as a weed to be controlled. This paper shows that Phragmites-dominated vegetation provides important non-habitat ecosystem services  in proportion to its biomass, and many habitat functions for other organisms that vary depending on characteristics of the vegetation and surrounding landscape. Phragmites has both detrimental and beneficial functions; therefore decision-makers must clarify their management goals and understand the local situation. Extensive dense Phragmites may be managed to optimize ecosystem services by partial removal of biomass for a bioenergy feedstock.In North America,  Phragmites australis (common reed) is widespread in North America, with native and non-native haplotypes. Many ecologists and wetland managers have considered P. australis a weed with little value to the native biota or human society. I document important ecosystem services of Phragmites including support for many common and rare species of plants and animals. This paper is based on an extensive review of the ecology and natural history literature, discussions with field workers, and observations in 13 US states and one Canadian province during the past 40 years. Phragmites sequesters nutrients, heavy metals and carbon, builds and stabilizes soils, and creates self-maintaining vegetation in urban and industrial areas where many plants do not thrive. These non-habitat ecosystem services are proportional to biomass and productivity. Phragmites was widely used by Native Americans for many purposes; the most important current direct use is for the treatment of wastes. Most of the knowledge of non-habitat ecosystem services is based on studies of P. australis haplotype M (an Old World haplotype). Phragmites also has habitat functions for many organisms. These functions depend on the characteristics of the landscape, habitat, Phragmites stand, species using Phragmites and life history element. The functions that Phragmites provides for many species are optimal at lower levels of Phragmites biomass and extent of stands. Old World Phragmites, contrary to many published statements, as well as North American native Phragmites, provide valuable ecosystem services including products for human use and habitat functions for other organisms. Phragmites stands may need management  to create or maintain suitable habitat for desired species of animals and plants. Phragmites australis  is widespread in North America (Phragmites was found in coprolites of the extinct Nothrotheriops shastensis (Shasta ground sloth) in an Arizona cave  are 1–4+ m tall. Peak aboveground biomass in well-developed stands of the non-native haplotype M in the northeastern states can be 730–3700 g dry weight (dw) m−2 and exceeds the aboveground biomass of co-occurring marsh plants  in decreasing order in native Phragmites, Old World Phragmites and Spartina, and estimated that as much as 47 % of Phragmites nitrogen demand could be satisfied by DON. Phragmites is effective in taking up nitrogen from the soil, and due to the greater biomass of Phragmites relative to co-occurring plants, aboveground standing stocks of nitrogen may be 2–3 times higher in Phragmites stands , especially exposed bottoms of abandoned beaver ponds, are also suitable for the establishment of Old World Phragmites .Invasibility due to human alteration of hydrology, water quality, soils and vegetation plays an important role in the spread of haplotype M in North America  and one Canadian province (Manitoba), as well as three countries in Europe  and one in Africa (Botswana). In this paper, all observations are from North America unless identified otherwise. I refer to Phragmites stands or patches as ‘reedbeds’. In comparing the biota of reedbeds to alternate habitats, I have used abundance (density) of individual species and species richness because those metrics are most commonly available in the literature.This paper is based on an extensive review of the ecology and natural history literature, discussions with many biologists and naturalists, 40 years of qualitative field observations and a series of quantitative field studies. I have studied Phragmites: non-habitat services, and habitat functions or biodiversity support.The body of this paper addresses two categories of ecosystem service provided by Phragmites are listed in Table Non-habitat ecosystem services (i.e. services other than biodiversity support) provided by Phragmites services shown in Table Most of the Phragmites builds and stabilizes tidal marsh soils, and stores carbon in litter and soils more effectively than Spartina spp.  and other small nekton (l nekton .Phragmites for roof thatch and other products in North America (Table Phragmites for decoration in and outside the house is common. Phragmites is rarely planted in gardens or for landscaping (but see Cortaderia (pampas grass) and Miscanthus  are often planted for ornament. Other uses of harvested Phragmites material  in this respect, and does not require the energy and fertilizer inputs that switchgrass does . We are studying Phragmites fuel pellets developed by François Nsenga , and the potential to produce pellets from Phragmites combined with other cellulosic waste products. Additionally, Phragmites (perhaps combined with other organic wastes) should be a good feedstock for methane generation by anaerobic digestion. Phragmites in Sweden for fuel pellets or other solid biofuels.The rapid growth and regrowth after cutting, and high level of biomass production, of Phragmites leaves was twice that from S. alterniflora (smooth cordgrass) leaves in a New Jersey tidal marsh , a native, generalist feeder, heavily grazing Phragmites leaf blades where it grew sparsely among Calamagrostis canadensis (bluejoint grass), but not in the adjoining dense Phragmites stands  that is sessile beneath lower leaf sheaths may be widespread and abundant, at least in Old World Phragmites. −2 in a freshwater tidal marsh on the Hudson River. I have frequently seen songbirds opening leaf sheaths and consuming the scale insects, especially in winter, in the northeastern states. Birds also commonly peck holes in Phragmites internodes and eat insects living within.The non-native sap-feeding Hyalopterus pruni  is widespread and abundant in North America  in winter; it is a pest of prune (Prunus domestica) orchards in California ( America . This aplifornia . AlthougOndatra zibethicus (common muskrat) is the most important native vertebrate consumer of Phragmites. Muskrats feed on young shoots and rhizomes, and also cut mature culms for lodge construction. Several studies in different regions of North America have found Phragmites ranking from high to low among other plant species in the muskrat diet  and Scirpus  was associated with Phragmites . Castor canadensis (American beaver) also uses Phragmites for construction and perhaps eats it as well, but possibly less so than the muskrat.rat diet . Muskratbulrush; . For exal states ; in Marys found’ ; and feersh type . Nonetheragmites , and musntly low . MuskratSylvilagus spp. (cottontail rabbits) at times cut many Phragmites shoots for food (Sylvilagus floridanus (eastern cottontail) in experimental Phragmites plots in Rhode Island. I found extensive clipping by S. floridanus at a lakeside wet meadow in Rockland County, New York, in 2011. In 2006 I observed much use of Phragmites stands  by S. cf. audubonii (desert cottontail) in the Southwest. Domestic livestock  graze Phragmites, especially young shoots in spring, and have caused Phragmites declines in some cases (Phragmites is common. Odocoileus virginianus (white-tailed deer) may graze Phragmites in Louisiana but it is not a major food (Branta canadensis (Canada goose) grazes Phragmites leaf blades, especially in urban marshes of the New York City area, but does not seem to do much damage . Chen caerulescens (snow goose) feeds on Phragmites rhizomes in Gulf Coast marshes  provides food as well. Fungi and other microbes growing on decomposing wetland plants support detritivorous invertebrates  and Impatiens capensis (orange jewelweed) in fresh water, and Atriplex prostrata  in brackish water. Occasional individuals of larger woody or suffrutescent species such as Sambucus nigra ssp. canadensis (common elderberry), Ailanthus altissima (tree-of-heaven), or Hibiscus moscheutos  may also occur; in some cases these plants may have been present before reedbed development. Betula pumila (swamp birch), a shrub or small tree, was present in a Massachusetts fen before Phragmites colonization, and when Phragmites was removed, B. pumila grew taller . Similarly, Taxodium distichum  and Cephalanthus occidentalis (buttonbush) planted in a created non-tidal wetland in Beltsville, Maryland, persisted despite colonization by a dense stand of Phragmites . Phragmites than in Lythrum salicaria (purple loosestrife) or Typha. Reedbeds in which Phragmites highly dominant, or sparse with other species admixed. For example, in September 2000, I found 18 species of associated vascular plants  in the interior of a reedbed that had been harvested annually and occasionally burned in the New Jersey Meadowlands . These associated species were sparse and occurred just outside the most recently harvested area. Reedbeds that are sparse, deeply flooded, or subject to high hydrodynamic energy  may support a greater diversity of vascular plants in edges. The occurrence of rare vascular plants and mosses in the interiors or edges of reedbeds under some circumstances suggests that Phragmites is facilitating the associated species by ameliorating harsh environmental conditions. Some of the cases I have observed are in relatively high-energy (wave-washed) tidal shores where sparse reedbeds appeared to be physically sheltering smaller plants of other species or maintaining favourable substrates against wave erosion. At Jamaica Bay Wildlife Refuge in New York City, Platanthera lacera (ragged fringed orchid), a regionally rare species, was found beneath mixed upland stands of Phragmites and Betula populifolia (grey birch), and nowhere else . On the Hudson River, three rare native species, Limosella subulata (mudwort) and Lilaeopsis chinensis (eastern lilaeopsis) in brackish tidal wetlands, and Cardamine longii (Long's bittercress) in fresh-tidal wetlands, occur in reedbed edges where the Phragmites may be facilitating these small plants by providing physical shelter, stabilizing the sediments, or oxygenating the soil  occasionally parasitizes Phragmites; all other vines are non-parasitic. Certain robust woody vines that ordinarily use woody plants or permanent structures such as fences for support evidently are able to reach from old overwintered Phragmites culms to new shoots of the current year. I have documented >30 species of vines, half native and half non-native, using Phragmites as the host . Vines modify reedbed architecture and provide additional food resources for animals.Vines, both woody and herbaceous species, use Phragmites where it grows sparsely and the substrate is wet but not long-flooded. A rare species in New York, the moss Philonotis muhlenbergii, was found beneath Phragmites on a Hudson River island (Phragmites and Typha in an Ohio marsh (Diverse mosses and a few liverworts occur beneath reedbed edges and interiors on soil or culm bases (r island . Algae cio marsh .Reedbeds may retain ice and remain cooler than their surroundings in spring (Phragmites compared with other wetland herbs is a resource for certain species. Although the nests of Ammodramus maritimus (seaside sparrow) were placed low in native graminoids in Massachusetts, the birds most often sang from Phragmites or a shrub [Iva frutescens (marsh-elder); Phragmites located at higher substrate elevations in or near marshes, and perhaps the robust nature of the reedbed itself, can provide shelter from higher than normal tides or floods, as evidenced by nesting Larus atricilla (laughing gull) in New Jersey  nested in the edges between Phragmites and Scholochloa festucacea (whitetop grass). Phragmites was the most abundant plant in the vicinity of five nests (Particular features of reedbeds attract birds in many instances. Anatinae (dabbling ducks) loafed on cattle-trampled reedbeds at the Delta Marshes, Manitoba . Small, ve nests .Phragmites support of amphibians and reptiles, although various species have been found in reedbeds (Table Storeria dekayi dekayi (northern brown snake) individuals have been found beneath small piles of recently cut Phragmites culms in a non-tidal marsh restoration site in New York City .Few data are available regarding ds Table . Under cPhragmites culm, leaf, or inflorescence material in their nests. Common muskrat and American beaver use culm and rhizome material in lodge construction. No information is available comparing Phragmites with alternate materials. Muskrat and beaver lodge construction may disperse living fragments of rhizome or culm base because some of the nest material remains wet.Many birds use Phragmites often provide a buffer between human activities or cattle grazing and wetland wildlife  were anchored in reedbeds to provide shelter for the nests  nested in a narrow fringe of Phragmites at the upland edge of a brackish tidal marsh, and foraged in the adjacent S. alterniflora at a slightly lower elevation in the marsh , Ardsley, NY, pers. comm.). In marshes of the Hudson River and the New Jersey Meadowlands, larvae of Poanes viator  feed on Phragmites leaves in the reedbeds, and the adults fly out of the reedbeds to feed on flower nectar of L. salicaria (purple loosestrife), Nepeta cataria (catnip), and other plants.Mobile animals, such as birds, many mammals, and strongly flying insects, commonly use combinations of habitats to acquire all the resources they need. A reedbed can support one type of activity by a species while an adjacent or nearby alternate habitat can support another type of activity. In Marshlands Sanctuary (New York), Phragmites and alternate habitats  or taxon richness of invertebrates, fishes, and birds in s Tables –5. DensiPhragmites and S. alterniflora (or Typha) marshes or less dense in the Phragmites; in some cases the Phragmites marshes studied were tide restricted. However, the results for a small, abundant, and ecologically important tidal marsh fish Fundulus heteroclitus (mummichog) are different. Adult mummichogs are typically equally abundant in Phragmites and alternate plant communities, and spawn in both communities. Larval and small juvenile mummichogs are consistently less abundant in Phragmites. Phragmites because of sparser prey resources. Although Phragmites compared with Typha, this difference was apparently not related to benthic macroinvertebrate density or taxon richness. F. heteroclitus from Phragmites compared with S. alterniflora. F. heteroclitus were healthier, as indicated by several morphological and physiological metrics, in tidally restored marshes with less Phragmites compared with tidally restricted marshes dominated by Phragmites in Rhode Island.Table Phragmites dominated. Comparisons of fish assemblages in untreated Phragmites and herbicide-treated Phragmites have yielded variable results , Ontario, but a lower abundance in Phragmites compared with the alternate habitats. Also at Long Point, Phragmites overgrowing and detrimentally shading nest sites of freshwater turtles during incubation.Phragmites, although this information is distributed unevenly by taxon, season, geographic region, and habitat (Table Phragmites habitat. Examples include Sterna hirundo (common tern) nesting in offshore reedbeds in Lake Poygan, Wisconsin , Oxyura jamaicensis (ruddy duck) and Fulica americana (American coot) nesting only in reedbeds in New Jersey (Kane Leucophaeus pipixcan (Franklin's gull) at Bear River Migratory Bird Refuge in Utah , Ammodramus caudacutus , and A. maritimus (seaside sparrow), nested in the short graminoid meadows  of the high salt marsh . Of six studies of non-breeding birds, there were about 13 instances of species that were more abundant in reedbeds and three instances of species more abundant in the alternate habitat. These numbers suggest that reedbeds offer more functions to non-breeding birds (e.g. cover for roosting and escape from predators), but the fact that >75 species of North American birds have been reported to be breeding in Phragmites-dominated habitat  breeds only in association with Phragmites reedbeds  and the non-native Mus musculus (house mouse) frequented reedbeds in a Connecticut estuary, whereas Microtus pennsylvanicus (meadow vole) was more common in Spartina patens marsh  hiding in reedbeds. In other cases, Phragmites appears detrimental: rapidly colonizing and shading turtle nesting sites, displacing the short graminoid community of high salt marsh on the northeastern coast, and supporting fewer young F. heteroclitus than in S. alterniflora-dominated wetlands. If it were possible to replace the Phragmites with fully functioning alternate habitats, would there be a real benefit to these species? Does the presence of reedbeds decrease the overall population of F. heteroclitus? The absence or scarcity of a species in a habitat does not necessarily mean that the habitat quality is poor  and Egretta caerulea (little blue heron) to be greater in woody vegetation and nestling survival of E. caerulea greater in woody vegetation, whereas the hatching success of Bubulcus ibis (cattle egret) was greater in reedbeds, and nestling survival of E. thula and B. ibis did not differ between habitats. is poor . We needPhragmites is more highly dominant provide shelter from weather and predators to arthropods, small birds, and other small organisms, but may be too dense or shady for small plants or larger animals. However, large birds such as Circus cyaneus (northern harrier), Ardeidae (herons) and Threskiornithidae (ibises) can roost or nest on top of reedbeds with some degree of culm lodging. Large animals, such as O. virginianus (white-tailed deer), are sometimes able to break trails through dense reedbeds. Other Phragmites characteristics that shape its habitat functions include mats of lodged culms that animals rest on or under, hollow internodes of broken dead culms that shelter spiders, and the soil-stabilizing ability that apparently attracts Castor canadensis and O. zibethicus to build lodges. Some organisms are associated with high-biomass reedbeds whereas others are associated with low-biomass  reedbeds.What makes a reedbed attractive to other organisms? The tall, dense masses of leafy culms where Phragmites for particular biodiversity goals. It appears that extensive, dense beds of tall reeds support fewer species of breeding birds in the northeastern states than do small reedbeds, reedbeds with an admixture of other herbaceous or woody plants, sparse reedbeds and reedbeds in which patches of Phragmites are interspersed with pools or clearings  in mine-associated wetlands was concentrated along reedbed edges and where reedbeds were interspersed with open water and abundant Lemna (duckweed)  nested on mats of lodged culms  and extrinsic  variables may affect the suitability of  habitat b, 2010. Phragmites haplotypes. Native haplotypes of P. australis tend to grow more sparsely with an admixture of other plants, compared with Old World Phragmites . Differences in insect use of the subspecies were addressed by So far, there have been few studies comparing biodiversity support of different Phragmites. There are many native and non-native species that occur in association with reedbeds. Some of these species are common in reedbeds, and some prefer reedbed edges while others also occur in reedbed interiors. In certain cases, mobile animals are clearly selecting reedbeds in landscapes containing alternate communities; roosting songbirds may be the best example. Because Phragmites (at least Old World Phragmites) tends to form dense stands with large amounts of live and dead biomass, many other vascular plants may not do well beneath the Phragmites canopies. In some cases, larger animals may have difficulty moving through reedbeds. None of these characteristics is unique to Phragmites; dense, low-diversity, high-biomass stands of Typha, Scirpus, tall Carex (sedge) species and other robust colonial marsh plants are similar in many respects.The data summarized from many studies Tables –5 indicaPhragmites is affected by many other non-human organisms; animals eat it, gall it, collect it for nest material and trample on it; taller plants shade it; fungi infect it; beavers flood it; and vines weigh it down. These interactions rarely seem to have a large impact. Probably the most common large effect of other organisms is due to Ondatra (muskrat) activities in cutting and excavating rhizomes and culm bases for food and lodge construction. Beaver activities may create habitat for Phragmites on abandoned dams and the bottoms of drawn-down abandoned ponds, but may also inhibit or kill Phragmites by flooding it. Although in many respects the reedbeds of today are relatively unaffected by the activities of other organisms, three types of interaction are worth noting: (i) sublethal effects that may alter productivity, reedbed architecture or other aspects of Phragmites; (ii) effects of prehistoric megafauna that may have been greater than animal effects seen now; and (iii) changing biotic interactions including the establishment of non-native species or increases in species already here.Phragmites, it is not generally regulated by insect herbivory  with high water levels and wind waves apparently caused recession of reedbeds in Kearny Marsh West in the Meadowlands in the early 2000s . Muskrats, possibly in combination with insects or unidentified factors, fragmented a reedbed in South Glebe Marsh at Jug Bay Wetlands Sanctuary on the freshwater tidal Patuxent River in Maryland, and a few years later a vigorous but floristically diverse floating reedbed had developed at this site . In the fen meadows of upper Moore Brook, Salisbury, Connecticut, Phragmites colonizing Carex meadows was alternately inhibited or facilitated by increases or decreases, respectively, in water levels caused by changes in beaver activity .Although many insects, non-native and native, feed on erbivory . HoweverNothrotheriops shastensis  fed intensively on Phragmites at an Arizona locality 40 000 years ago  ate P. australis in Russia (Castoroides spp. (giant beavers) and many species of Equidae (horses), as well as Holocene mammals once much more abundant than now, such as Bison bison (American bison), may also have eaten Phragmites, as modern relatives do  the species uses Phragmites as a result of exploratory behaviour or accident; (ii) Phragmites provides a low-quality resource where better habitat is not available, or is occupied by spillover (population pressure) from a better habitat that is saturated; (iii) a species is adapted to use non-native Phragmites because of pre-adaptation to native Phragmites or other tall graminoids; (iv) a species is an ecological generalist whose ‘partner’ range includes Phragmites; or (v) there has been recent evolutionary adaptation to increasingly widespread, abundant, robust, productive Old World Phragmites . Possibilities (iii) and (v) would result from fitness advantages gained by e.g. refuge from predation, harsh weather, human disturbance or another stressor. A species that encounters Phragmites by chance (option i) may eventually develop a more intimate relationship with Phragmites.There are several possible explanations for use of Old World Phragmites can provide substantial ecosystem services, as well as being a pest, it requires a management approach that is tailored to individual sites and sets of local management goals  species. In the case of Phragmites, I propose that the general management goal be the support of biodiversity through conservation of important species, balanced with promoting the ecosystem services and human uses provided by reedbeds. Specific goals should be set only after thorough biological surveys and realistic assessment of the long-term sustainability of any management action. Below I discuss problems with proposed and currently used management techniques and Phragmites research, and suggest future research directions.Because nt goals . An apprPhragmites  and any other Phragmites-dependent insects of western North America. The potential for loss of biodiversity is illustrated by the recent description of a new species of fly from native Phragmites in New York , and most often the chemicals used have been glyphosate or one of its formulations. These herbicides have engendered genetic resistance in a number of weed species, and there is toxicological research indicating endocrine disruption, mutagenicity and carcinogenicity in animals . Prescribed livestock grazing, although often effective for managing habitat for the endangered bog turtle  birds and other wildlife. Observer trails, and call playback used for surveying birds, can alter the behaviour of animals and cause them to move out of, or into, the reedbeds. These problems could be addressed through the use of small-scale remote sensing, including remote audio or video recording, camera traps, and possibly miniature remotely controlled aircraft  have not been measured. Most studies have focused on relatively well-known groups of organisms  that may not represent ecological relationships of Phragmites with other taxa or guilds . Comparisons between biotas of Phragmites and alternate communities have almost always been based on population density (or catch-per-effort) or species richness, metrics that may not capture critical habitat functions of Phragmites for the most important species.Studies of Tamarix  as the breeding habitat for an endangered bird, Empidonax traillii extimus , diet, behaviour, reproduction and fitness. Phragmites on terrestrial vertebrates of tidal marshes. Studies should include designs that examine responses of biota to experimental management of reedbeds, including partial removal of Phragmites biomass.Important environmental and stand variables should be measured or described as appropriate. In addition to breeding activities, the roosting and foraging activities of birds in various seasons need study. Other important groups needing study, in addition to fishes, estuarine invertebrates and herbivorous insects, include vascular plants, bryophytes, algae, mammals, reptiles, amphibians, terrestrial molluscs, butterflies, odonates (dragonflies and damselflies) and spiders. Species of conservation concern should receive priority attention, along with economically important species and keystone species or ecological engineers. Comparisons between Phragmites, and Phragmites-dominated habitats, support many ecosystem services and diverse native and non-native biota. Studies comparing the density of individuals or the numbers of taxa (species) in reedbeds and alternate habitats show variable results. Reedbeds apparently support fewer individuals or taxa of certain kinds of invertebrates, fishes and birds, such as early life stages of the mummichog, three species of high salt marsh breeding birds, and muskrat, than do alternate habitats.Phragmites. Other important considerations include the rare species supported by reedbeds; the habitat functions of reedbeds for roosting, escape from predators and shelter from floods and other extreme conditions; the ability of Phragmites to vegetate urban habitats and derelict lands without human inputs; and other non-habitat ecological services provided by Phragmites. Given the severe changes in American landscapes and biotas resulting from land use, alteration of hydrology and chemistry, and climate change, concepts of the purity of native communities may not be practical for application to abundant, widespread, long-present non-native taxa such as Old World Phragmites. These arguments do not contravene controlling Phragmites where it is clearly a threat to important elements of biodiversity.Top-ranked food preferences, and relative density or taxon richness of breeding birds, monophagous herbivores and other groups, are not the only currency by which to judge Phragmites in wastewater management will continue to be important if it is not affected by biocontrol. Phragmites has good potential for bioenergy. The use of Phragmites fibre for paper, insulation and industrial materials should be explored. Given the new information presented here, we should look at Phragmites management as an optimization: how can we manage to increase and make use of the valuable ecosystem services provided by the plant, while reducing the harm that it causes in certain situations?The use of Phragmites Symposium of the 2011 Society of Wetland Scientists conference was partly funded by a grant from AoB PLANTS to the Smithsonian Institution, and by a donation to Hudsonia from the Kraus Dunne family. Previously, my research on Phragmites and its habitats has been funded by the Geraldine R. Dodge Foundation, Max and Victoria Dreyfus Foundation, Hudson River Foundation, Geoffrey C. Hughes Foundation, Metropolitan Conservation Alliance, New York City Environmental Fund, New York State Department of Environmental Conservation—Hudson River Estuary Program and Hudson River National Estuarine Research Reserve, and Westchester Community Foundation .My participation in the Phragmites fuel pellets; TechnoPhrag also offers Phragmites management services. Hudsonia also collaborates with Jason Tesauro Consulting LLC on biological survey and habitat management projects; in other projects this company manages Phragmites by means of prescribed livestock grazing. Hudsonia and the author do not have financial relationships either with entities that sell herbicides, mowing machinery or other supplies or equipment used for managing vegetation, nor with entities involved in research and development on biological control.Hudsonia is collaborating with TechnoPhrag, Inc.  on a study of


Dicentrarchus labrax L.) would be a viable way to counteract the chronic inflammation present in farmed fish. The authors observed that, in supplemented fish, interleukins 1β and 6 were significantly decreased, whereas splenic interferon γ levels were increased. Concomitantly, a reduction in the number of spleen macrophages compared with control fish was detected. These results open up new perspectives for the use of antioxidants in farmed fish and might contribute to a more sustainable aqua culture.Oxidative stress, the imbalance between reactive oxygen species (ROS) formation and enzymatic and nonenzymatic antioxidants, is involved in the pathogenesis and progression of many malignant, degenerative, and ageing-associated diseases. Most importantly, the chronic low grade inflammation associated with metabolic syndrome is characterized by a chronic oxidative stress condition and increased levels of cytokines. T. Magrone et al. investigated if polyphenol supplementation of farmed sea bass (α), nitric oxide (NO), and sperm abnormalities and concurrently induced a decrease in testicular superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and zinc levels. Furthermore, their results suggests that Spirulina platensis preparations may represent a potential therapeutic option to protect testicular tissue from arsenic toxicity. In particular, the improved antioxidant status of testicular tissues as a result of Spirulina platensis treatment can be deduced from the determined elevated levels of testicular SOD, CAT, zinc, and GSH and from the decrease in MDA in the Spirulina platensis + arsenic group as compared to the arsenic group.Inflammation and oxidative stress are also induced by various exogenous agents and are therefore major components that not only determine the toxicity of such agents in somatic cells but also potentially affect the teratogenicity of reproductive cells. S. AE Bashandy et al. reported that increased arsenic levels significantly increased testicular malondialdehyde (MDA), tumour necrosis factor alpha (TNF- Alhagi Maurorum (camel thorn plant) improved glucose levels, the lipid profile, and hepatic function in a rat model of diabetes. Moreover, treatment of diabetic rats with Alhagi Maurorum extracts improved the antioxidant status of hepatic tissues by increasing GSH levels and the activities of SOD, glutathione peroxidases (GPx), and glutathione transferase (GST) compared with the control group.In the study by S. A. Sheweita et al., the extracts of the medicinal plantNext to their direct antioxidative properties, polyphenols can act as oxidants in some conditions, inducing redox-sensitive genes such as antioxidant enzymes. J. Marinic and coworkers found in a model of liver resection and intraperitoneal therapy that the higher liver regeneration induced by olive oil polyphenol extracts was preceded by an initial decrease of GSH and an increase of thiobarbituric acid reactive substances during the first 3 hours after hepatectomy, associated with the induction of GST, SOD, and CAT.In the defence against ROS, both enzymatic and nonenzymatic antioxidants produced by cells and the low molecular weight molecules absorbed from food stuffs play vital roles in maintaining cellular homeostasis. S. Brundu and collaborators focused their study on the development of a reversed-phase HPLC method for the analysis of cysteine and reduced glutathione in biological samples from mice. Given the established and pivotal role of glutathione in many cellular functions, its determination in the assessment of oxidative stress is quite relevant. In particular, the authors validated their method in samples of diverse tissue origin, including spleen, lymph node, brain, and pancreas according to strict US and European standards. Cichorium intybus L. on Caco-2 cells in an in vitro monolayers model. Their results show that, at low concentrations, the polyphenol fractions indeed show antioxidative effects, but at higher concentrations they rapidly become cytotoxic. This effect is characterized by increased tight-junction permeability, epithelium abnormalities, and loss of plasma membrane integrity. The authors further confirm that the protective effect by polyphenol extracts from chicories occurs via the interaction with the mucopolysaccharide complexes in the glycocalyx.Despite the fact that an increasing body of evidence suggests that natural functional compounds have bioremedial properties and might consequently be beneficial to human health, clinical evidence remains turbid. Since bioavailability is a key factor that determines if a component is taken up and transported to tissues and cells, not surprisingly, a significant research effort focuses on determining compound bioavailability in humans. X. Guo et al. reported results from a 5-year study that was conducted within the framework of the PREDIMED trial on subjects with high cardiovascular risk. In this study urinary total polyphenol excretion (TPE) was inversely associated with a number of clinical cardiovascular risk factors, namely, plasma glucose and triglycerides concentrations and systolic blood pressure. These results suggest that TPE could be useful as a marker of compliance in intervention studies with foods with high-polyphenol content. On the other hand, polyphenols can also exert their bioactivity without reaching the systemic circulation. Such poorly absorbable antioxidants primarily exert their protective effect against oxidative stress at the interface between the gastrointestinal lumen and gastrointestinal lining. As such, these antioxidants might be attractive therapeutics against oxidative damage-induced gastrointestinal diseases. E. Azzini and collaborators studied the effect of polyphenol-rich extracts fromOxidative stress markers are important tools to assess both the redox status of subjects and the health-enhancing effects of antioxidants in humans. However, there is a lack of consensus, analytical validation, standardization, and reproducibility regarding many oxidative stress markers, evaluation models, and antioxidant assays. I. Peluso et al. investigated the relationship between the Peroxidation of Leukocytes Index Ratio (PLIR) and the increasingly studied postprandial metabolic stress. For this, in a pilot clinical trial with a functional cookie containing dark chocolate and pre- and probiotics, they measured PLIR in lymphocyte, monocytes, and granulocytes. The results of the investigation show that the determination of this parameter in healthy subjects may present some limitations during the postprandial period, probably due to the increase in uric acid.14C]-tyramine oxidation, whereas measurements with the radiochemical method using [14C]-benzylamine clearly indicated that resveratrol did not inhibit human semicarbazide-sensitive AO (SSAO). Therefore, when measuring MAO or SSAO inhibition by antioxidants, the verification of the putative interaction of these agents with hydrogen peroxide or chromogenic mixture should carefully accompany testing.In a study performed with samples of human subcutaneous abdominal adipose depots, C. Carpéné and coworkers illustrated that some phenolic compounds did not clearly block amine oxidases (AO) activities, whereas they impaired the interaction between hydrogen peroxide and the chromogenic mixture in fluorometric assays, which could be misinterpreted as an AO inhibition. Only resveratrol and quercetin partially impaired monoamine oxidases- (MAO-) dependent [ in vitro studies that evaluate the effects of natural functional compounds in relation to oxidative stress. Both measurement and interpretation are far from straightforward and there is a desperate need for standardization, especially since decades of research still leave a murky picture without clear definites regarding the bioremedial effects of supplemented antioxidants. This significantly hinders clinical trials and introduction of such compounds in a routine clinical setting. Nonetheless, we sincerely hope that this special issue contributes to shedding some light on the meaning of oxidative stress markers and the bioremedial capacity of natural functional components in experimental models and human studies.The manuscripts in this special issue show that caution must be taken when interpreting human, animal, or


Some parent feeding practices have been linked to disordered eating and higher BMIs in children. Relatively little research has examined factors that influence parent feeding practices. The aim of this study was to identify relationships between the parent feeding practices that have been linked to unhealthy eating patterns in children, and parent body image, eating attitudes, behaviours, and knowledge. Participants were 326 parents of pre-school children from Victoria (97.5% mothers). Parents completed measures of parent body dissatisfaction, body image knowledge, dieting behaviours, and parent feeding practices of their child closest to four years old . Knowledge scores were inversely associated with a number of negative feeding practices, including instrumental feeding, and with the frequency of parents reporting negative behavioural intentions to brief vignettes reflecting appearance-based stigma. Parent weight and shape concerns were positively associated with restrictive feeding practices, including restricting high-fat foods in their pre-schooler. Parent dieting was positively related to restricting and controlling feeding practices. Given that such parent feeding practices are associated with long-term risk of weight gain and disordered eating in children, these findings highlight the need for prevention interventions for parents of pre-schoolers.Parental Roles in Prevention and Support stream of the 2014 ANZAED Conference.This abstract was presented in the


Asthma affects over 300 million people worldwide and its prevalence continues to rise. It is typically characterised by intermittent symptoms of breathlessness, cough and wheeze punctuated with asthma attacks together with variable airflow obstruction, which are more frequent and persistent in severe disease . UnderpiAirway inflammation in asthma is typically eosinophilic in association with allergic sensitisation, particularly in those with early onset disease . AllergeOur understanding of granulocyte trafficking has underpinned the development of several biologic and small molecule therapies targeting granulocyte recruitment and survival in asthma including anti-IL5, anti-CRTh2, anti-CCR3, and anti-CXCR2 . It is tTo address this challenge Lukawska and colleagues report in this issue of EBioMedicine a small proof-of-concept study of real time, differential tracking of human eosinophil and neutrophil migration in 12 atopic asthmatics following allergen challenge . This isIn vivo real time tracking of granulocytes has immediate impact upon early phase clinical development as it can be incorporated into model systems to explore the effects of therapies upon granulocyte migration. However, with an increasing number of potential targets understanding their relative importance in different model systems and ultimately in specific patient subgroups is critical and is the drive towards stratified medicine. One approach to begin to dissect this complexity is multi-scale computational modelling, which might provide some important insights and become key in drug development and clinical decisions (in silico. Intervention studies can then inform, validate and further extend these models to improve their clinical utility. This parallel approach of in silico modelling with in vivo experimental approaches that closely reflect the disease will inform asthma mechanisms and improve a stratified approach to therapy. Therefore, understanding the dynamics of the traffic control system in asthma to direct granulocytes to their airway destination continues to be an important focus of research.ecisions . These mCEB has received grants and consultancy from AstraZeneca/MedImmune, GlaxoSmithKline, Novartis, Roche/Genentech, Almirall, Chiesi, and Boehringer-Ingelheim.


The pathophysiology of this entity is multifactorial; systemic, cellular,and extracellular mechanisms have been described, including maldistribution of coronaryblood flow, myocardial injury, complement-triggered (C5a) myocyte contractile failure,cytokine-induced neutrophil activation , dysregulation of calcium handling, and cytopathic hypoxia due tomitochondrial dysfunction.,4 whereas otherforms of myocardial dysfunction have been often overlooked. These variants include leftventricular diastolic dysfunction-8 and right ventriculardysfunction,,10 which have different treatment options and prognosticimplications. Interestingly, all types of myocardial dysfunction can be present inisolation or in combination and can be fully reversible with resolution of criticalillness.,11Cardiovascular compromise is a central component of multiple organ dysfunction syndrome,an often fatal consequence of severe sepsis and septic shock. There is a sizable body ofwork on left ventricular systolic dysfunction in sepsis, TDI is anechocardiographic technique based on measurements of myocardial velocities, which are low frequency,high-amplitude signals filtered from conventional Doppler imaging.It is particularly useful as a measureof ventricular relaxation and ventricular filling pressures. The significance of diastolic dysfunction wasrecently highlighted by studies that demonstrated that TDI might be prognosticallyuseful in the general intensive care unit (ICU) population.,16-22With the use of tissue Doppler imaging (TDI), a technique that has gained acceptanceamongst cardiologists and intensivists for the evaluation of diastolic function, it hasbecome evident that diastolic dysfunction is indeed common in critically illpatients.Revista Brasileira de Terapia Intensiva, aninteresting, single-center prospective cohort study confirmed the importance ofdiastolic dysfunction in patients with severe sepsis and septic shock. The authorsstudied 53 patients with the aim of assessing the prevalence of myocardial dysfunctionboth at ICU admission and one week later and also of evaluating the impact of leftventricular systolic and diastolic dysfunction on ICU mortality.In this issue of the A detailed echocardiographic examination was performed within 48 hours of ICU admissionand 7-10 days later, which included M-mode, two-dimension, and Doppler echocardiography.Systolic and diastolic function, including TDI, as well as right ventricular assessmentwith tricuspid annular plane systolic excursion, were carefully evaluated by a singlecardiologist specialized in echocardiography.The authors found an alarmingly high prevalence of diastolic dysfunction of 84% in thegroup of septic patients, a finding that remained unaltered in the follow-upechocardiography performed one week later. This high prevalence might be related to theage range (74 ± 13 years) of patients included. However, we cannot exclude thepossibility of overestimation due to selection bias because only 25% of eligiblepatients entered the study with a comparable number of patients being lost to follow-up.Additionally, although tempting, we cannot ascribe all the echocardiographic findings toseptic cardiomyopathy. Diastolic dysfunction could as well be a premorbid condition inthe sample of elderly patients studied, a hypothesis supported by the lack of resolutionof echocardiographic findings in the follow-up exam. the importanceof this previously overlooked variant of myocardial compromise. The E/e' ratio, one ofthe TDI measures used to define diastolic dysfunction, was the only echocardiographicmeasurement independently associated with death even after adjusting for age and diseaseseverity. Interestingly, systolic dysfunction was not a predictor of death. Thesefindings highlight the need to perform thorough echocardiographic evaluations inpatients with sepsis and septic shock.Another relevant finding was the association of diastolic dysfunction with mortality,confirmingThe Unbearable Lightness of Being, Milan Kundera wasright to acknowledge the powerful predictive ability of the heart: "When the heartspeaks, the mind finds it indecent to object".In his famous work


The academic researches and clinical applications in recent years found interest in induced pluripotent stem cells (iPSCs-) based regenerative medicine due to their pluripotency able to differentiate into any cell types in the body without using embryo. However, it is limited in generating iPSCs from adult somatic cells and use of these cells due to the low stem cell potency and donor site morbidity. In biomedical applications, particularly, dental tissue-derived iPSCs have been getting attention as a type of alternative sources for regenerating damaged tissues due to high potential of stem cell characteristics, easy accessibility and attainment, and their ectomesenchymal origin, which allow them to have potential for nerve, vessel, and dental tissue regeneration. This paper will cover the overview of dental tissue-derived iPSCs and their application with their advantages and drawbacks. Induced pluripotent stem cells (iPSCs) are a type of pluripotent stem cells that can be generated directly from adult somatic cells. In 2006, iPSCs with properties similar to embryonic stem cells (ESCs) could be generated from mouse fibroblasts by simultaneously transducing four exogenous OSKM genes  . In 2007Despite their promise, iPSCs generation from human fibroblast is limited in the clinical application due to lack of accessibility . PatientIn addition, iPSCs possess a potential for treating such genetically oriented disorders using availability of disease-specific iPSCs from the patient, which are available to investigate disease-specific treatments . AlthougiPSC technology was established on the basis of numerous findings. There were three major streams of research that led researchers to the production of iPSCs. The first stream was reprogramming by nuclear transfer by John Gurdon in 1962, which reported success of generating tadpoles from unfertilized eggs that had received a nucleus from the intestinal epithelium cells of adult frogs . More th Drosophila transcription factor (Antennapedia) was revealed to induce the formation of legs instead of antennae when ectopically expressed [The second stream was related to the discovery of a “master” transcription factor. Many researchers began to search for a “master” regulator to determine cell fate or reprogram various cell lineages. In 1987, axpressed  and a maxpressed . These rThe third stream is about ESCs. Since the first generation of mouse ESCs , researcCombining the first two streams of research led Yamanaka's group to hypothesize that a combination of multiple factors in oocytes or ESCs was needed to reprogram somatic cells back into the embryonic state and they designed experiments to identify that combination of the genes among 24 candidates genes and found combination of four master factors which are determined as OSKM genes. With information about the culture conditions that are needed to culture pluripotent cells, researchers have been then able to identify generated iPSCs.First success of inducing iPSCs used retroviral infection method to efficiently transport OSKM genes inside fibroblast . Four ye Sendai virus (SeV) vectors replicating the form of negative-sense single-stranded RNA in the cytoplasm of infected cells, double-stranded microRNAs (miRNAs), PiggyBac transposition, and cell penetrating peptide fused proteins have been suggested as viral-integration-free iPSCs generation method [ Sendai virus are now routinely used in many laboratories due to their simplicity and reproducibility but there are still hurdle regarding low efficiency of the process, which showed less efficiency than typical iPSCs generating process which is transfecting fibroblasts with retroviruses or lentiviruses [β-amino esters, polyketal nanoparticle, calcium phosphate nanoparticle, and polyamidoamine nanoparticles based nonviral transfection have been performed for generating iPSCs with high efficiency [Many trials to generate viral-transgene-free iPSCs have been performed. These methods using cDNA included plasmid, synthesized modified mRNAs,n method –32. Amoniviruses . Therefoficiency –38. Exteficiency . In addificiency , 41. UnfDental tissue-derived adult stem cells, such as dental pulp stem cells, periodontal ligament stem cells, dental follicle stem cells, stem cells from apical papilla, and stem cells from human exfoliated deciduous teeth have lots of advantages. One of them might be their ease of isolation from extracted third molars or deciduous teeth. For this reason, they can be used for regenerative therapies, but their sources and populations are very limited. Alternatively, iPSCs have been highlighted as a next regenerative cell source since their cell sources are rich and they are very proliferative. Among many types of iPSCs depending on cell origin, dental tissue-derived iPSCs are able to be readily produced from easily assessable dental tissues. With the advance in cell extraction technology from tissue, iPSCs can be generated from readily available dental tissue sources, such as oral mucosa, gingival tissue, and dental tissue-derived stem cell, mentioned above , 43. AmoAs another advantage, dental tissue-derived iPSCs are reproducible compared to dental tissue-derived stem cells which are not able to guarantee the reproducibility of regenerative potency in clinic due to their limitedly attainable stem cell incorporated dental tissue. This reproducibility is able to be provided for clinical application of dental tissue-derived iPSCs in regenerative medicine.The other advantage of dental tissue-derived iPSCs in regenerative medicine is to maintain epigenetic memory of the source tissue according to previously reported studies. The epigenetic memory induces preferential lineage-specific differentiation of iPSCs, which means that generated iPSCs will preferentially differentiate back to the original cell type , 44, 45.The major advantage of dental tissue-derived iPSCs over ESCs cells is that dental tissue-derived iPSCs can be derived from a patient's own dental tissue, thereby preventing immune rejection after transplantation and the ethical concerns regarding the use of ESCs . AdditioThe most arising problems using iPSCs in regenerative medicine may be safety concerns. Dental tissue-derived iPSCs cannot escape these issues. All iPSCs have genomic instability and a big rate of tumorigenicity in vivo , 49. TheSome issues about risks of infectious diseases and unwanted immunogenicity from animals have been raised regarding current iPSCs generating protocols. Current protocols use reagents of animal origin  that carry the potential risks of infectious diseases and unwanted immunogenicity, which is associated with a variety of quality control and safety issues . Exact cAlthough iPSCs can be generated simply and reproducibly, generating efficiency into iPSCs from donor cells remains very low (≈0.01%) using fibroblasts. Generation efficiency of iPSCs could be increased 4–10 times greater (≈0.1%) than fibroblasts when using dental derived tissues such as DPSCs, stem cells from shed primary teeth or extracted permanent teeth, and stem cells from human exfoliated deciduous teeth. But these generating efficiency from dental tissue is still low for scalable regenerative medicine. Along with the complicity of process and long generating time (≈2 weeks), low efficiency of dental tissue-derived iPSCs will induce spending much time in proliferating them, transferring into target site, and generating regenerative biomolecules from iPSCs cultured media, which may cause missing ideal treatment period for regeneration.Despite drawbacks associated with dental tissue-derived iPSCs, the potential that iPSCs have demonstrated for regenerative medicine and genetic disorders demands further research to minimize these remedial hazards. Therefore, the establishment of a safe and efficient process for generating iPSCs is required for regenerative application along with a better understanding of the biology of cellular reprogramming.Dental tissue-derived iPSCs are able to be generated by various somatic dental tissues or stem cells like DPSCs. DPSCs are retained in the soft living tissue inside the tooth, which is considered as a very special tissue. Dental pulp is a specific tissue originating from ectomesenchyme possessing similar properties of mesenchyme which is a precursor of mesodermal cells  and neural crest cells and is enclosed into a dental cavity surrounded by mineralized dentin. DPSCs have been applied in biomedical regeneration due to their promising potential to differentiate into a variety of other cell types including myocardiocytes to repair damaged cardiac tissue, neuron to generate nerve and brain tissue, myocytes to repair muscle, osteocytes to generate bone, and chondrocytes to generate cartilage –56. OwinDPSC-derived iPSCs can successfully differentiate into neuroectodermal lineage neuron-like cells, which resemble neurons both morphologically and functionally and could be used for neuron regeneration , 46, 57.+ EPCs differentiation conditions, DPSC-derived iPSCs showed higher efficiency in differentiation into functional endothelial and smooth muscle cells than normal iPSCs from fibroblasts. The angiogenic and neovasculogenic activities were confirmed in mouse models of hind-limb ischemia and myocardial infarction after transplantation, resulting in a promising strategy for patient-specific EPC therapies and disease modeling, particularly for ischemic vascular diseases. As a type of promising regenerative precursors, EPCs differentiated from iPSCs can be used as novel ingredients for the patient-specific EPC therapies [Bhattacharjee et al. reported the generation of DPSC-derived iPSCs using only two nononcogenic factors (Oct4 and Sox2) and their feasibility as substrates for endothelial progenitor cells (EPCs) . Under cherapies –63. EvenIn recent years, regenerative medicine has been focusing on a new strategy over dental tissue-derived stem cells to regenerate teeth for tooth replacement. With the rapid development of iPSCs technology, dental tissue-derived iPSCs can serve as a novel nonodontogenic stem cell source for a tissue-engineered tooth-like structure . To explDespite substantial progress in researches on dental tissue-derived iPSCs, significant challenges must be addressed for reaching clinical application. It is evident that dental tissue-derived iPSCs could be of use in neuron, blood vessel, and teeth regeneration due to highly accessible attainment, reproducibility, capability of self-renewal and large-scale expansion, less immune rejection, avoidance of ethical controversy, and differentiation toward all the three germ layers, especially neuron and vessel. However, the generation of functional teeth using these cells will almost certainly remain elusive in the foreseeable future due to low efficiency in their generation and possibilities of risks of genomic instability, tumorigenicity, infectious diseases, and unwanted immunogenicity. To conclude, this review confirms a potential that dental tissue-derived iPSCs and their derivatives contribute to enhancing the regeneration of nerve, vessel, and dental tissues; however, further studies are required to evaluate efficacy and safety prior to human clinical trials.


Staphylococcus, Bacillus, Listeria, and Clostridium. Although not currently used in human medicine, nisin is already employed commercially as an anti-mastitis product in the veterinary field. Recently we have used bioengineering strategies to enhance the activity of nisin against several high profile targets, including multi-drug resistant clinical pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) and also against staphylococci and streptococci associated with bovine mastitis. However, newly emerging pathogens such as methicillin resistant Staphylococcus pseudintermedius (MRSP) pose a significant threat in terms of veterinary health and as a reservoir for antibiotic resistance determinants. In this study we created a nisin derivative with enhanced antimicrobial activity against S. pseudintermedius. In addition, the novel nisin derivative exhibits an enhanced ability to impair biofilm formation and to reduce the density of established biofilms. The activities of this peptide represent a significant improvement over that of the wild-type nisin peptide and merit further investigation with a view to their use to treat S. pseudintermedius infections.Antibiotic resistance and the shortage of novel antimicrobials are among the biggest challenges facing society. One of the major factors contributing to resistance is the use of frontline clinical antibiotics in veterinary practice. In order to properly manage dwindling antibiotic resources, we must identify antimicrobials that are specifically targeted to veterinary applications. Nisin is a member of the lantibiotic family of antimicrobial peptides that exhibit potent antibacterial activity against many gram-positive bacteria, including human and animal pathogens such as  Staphylococcus pseudintermedius (MRSP) has emerged over the last decade as a critically important, opportunistic canine pathogen responsible for skin, soft tissue, and surgical site infections  that were found to possess superior antimicrobial activity against some non-pathogenic strains, in addition to showing an enhanced capacity to inhibit the outgrowth of spores of subtilis . Interessition 4 . Recentlsition 4 . AlthougThe opportunity also exists to combine nisin I4V with other antimicrobial agents, including naturally derived compounds and currently utilized antibiotics, with a view to identifying synergistic anti-biofilm combinations. From a commercial perspective, it is notable that neither Nisin A nor any other lantibiotic is currently employed commercially as a clinical antimicrobial. Its potential with respect to clinical applications is strengthened by laboratory based experiments highlighting its activity against human pathogens, including multi-drug resistant strains ,52. NisiS. pseudintermedius biofilm, which may have future applications as a stand-alone treatment or in combination with antibiotics for the elimination of problematic biofilms and associated infections.In conclusion, we have demonstrated the superior capacity of a bioengineered nisin derivative to prevent biofilm formation as well as reduce the density of an established


Dictyostelium discoideum has proven to be an excellent model system for studying these networks and a body of evidence has indicated that RasG and RasC, members of the Ras GTPase subfamily function as key chemotaxis regulators. However, recent evidence has been presented indicating that Ras signaling is not important for Dictyostelium chemotaxis. In this study, we have reexamined the role of Ras proteins in folate chemotaxis and then, having re-established the importance of Ras for this process, identified the parts of the RasG protein molecule that are involved.Signaling pathways linking receptor activation to actin reorganization and pseudopod dynamics during chemotaxis are arranged in complex networks. rasG-C- cells grown in association with a bacterial food source were capable of positive chemotaxis, only when their initial position was comparatively close to the folate source. In contrast, cells grown in axenic medium orientate randomly regardless of their distance to the micropipette. Folate chemotaxis is restored in rasG-C- cells by exogenous expression of protein chimeras containing either N- or C- terminal halves of the RasG protein.A direct comparison of folate chemotaxis methodologies revealed that Dictyostelium chemotaxis were the result of differing experimental methodologies. Both axenic and bacterially grown cells require RasG for optimal folate chemotaxis, particularly in weak gradients. In strong gradients, the requirement for RasG is relaxed, but only in bacterially grown cells. Both N- and C- terminal portions of the RasG protein are important for folate chemotaxis, suggesting that there are functionally important amino acids outside the well established switch I and switch II interaction surfaces.Conflicting data regarding the importance of Ras to  Directional cell movement is important throughout the life cycle of multicellular organisms, from axon guidance during embryogenesis to wound healing in adults ,2. UnderDictyostelium discoideum, is dependent on directional cell movement. In the growth phase, amoebae are attracted to folate released from their bacterial prey .Click here for file


Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states. Depression and schizophrenia are associated with deficits in motivation and enjoyment, which have been collectively termed anhedonia by some authors . ClinicaRecently it has been suggested that in both schizophrenia and depression, the aspects of reward processing that relate to reward receipt may be relatively spared, whereas anticipatory and motivational aspects of reward processing may be more dysfunctional and may be closely linked to negative symptoms/depression . HoweverThis still leaves open the question as to whether response to reward receipt, especially unexpected reward receipt, is normal in these disorders , and 21 healthy volunteers took part in the study . All schTo assess anhedonia we used the Snaith Hamilton Pleasure Scale (SHAPS), a validated self-report measure . See A Siemens Trio Tim operating at 3T was used to collect imaging data. Gradient-echo T2*-weighted echo planar images depicting BOLD contrast were acquired from 32 noncontiguous oblique axial planes to minimize signal drop-out in ventral regions. TR=2 s; echo time=30 ms; flip angle=78; voxel size=3.14 × 3.14 × 3.75 mmAn event-related analysis in FSL software was used to identify neural responses at the time of the unexpected win. We used a single statistical linear regression model with four explanatory variables and their temporal derivatives: (a) anticipation phase ; (b) win outcome ; (c) near-miss outcomes ; (d) full-miss outcomes . A near-miss outcome is where the play icon finishes adjacent to, but not on, the payline; near-miss outcomes have been shown to evoke neural responses different to other misses  and conducted post hoc comparisons across groups. Regression analyses at the whole-brain level in FSL were used to investigate relationships between brain activation and the post-scan subjective ratings of motivation and pleasure.As our hypotheses concerned brain activation in response to unexpected reward, an ‘unexpected reward receipt' contrast was investigated, formed by the contrast of win outcomes p<0.05 .Imaging comparisons were cluster thresholded using the FSL tool easythresh, using a family-wise error (FWE) correction at Groups did not differ in age, gender, handedness, years of education, IQ, or ethnicity .Patients with depression had higher SHAPS anhedonia scores than healthy controls and patients with schizophrenia. Patients with schizophrenia had higher SHAPS anhedonia scores compared with controls .p=0.843).The three groups did not differ on a visual analog measure of how much they valued 50 pence (answer to question ‘how often do you pick up a 50 pence coin when you see it in the street' p=0.11).There were no differences in the number of wins according to group, reflecting the pseudo-randomized nature of the paradigm . In this measure of liking there was a marginal difference between schizophrenia participants  and controls , and no difference between schizophrenia and depression participants .Participants with depression reported significantly lower liking of the feeling of winning money than controls . Controls scored higher than schizophrenia patients on this measure with marginal statistical significance . There was no significant difference between depression and schizophrenia on this motivational measure . One control had missing data on this measure.In response to the question ‘When the second picture matched the chosen picture you won money. Did this make you want to play more?', there was a significantly higher score in controls  than depression patients , and in the schizophrenia group . SHAPS anhedonia also negatively predicted the pleasure ratings after a win in the whole sample .vs full-loss outcome.We evaluated activation associated with unexpected reward receipt using the contrast of a win outcome x=−8, y=10, z=2; Z-score=9.28; There was a highly significant brain response in a widespread cortico-striatal network including the striatum, orbitofrontal cortex and medial prefrontal cortex. The maximum significance was located in left caudate  showed reduced activation in schizophrenia (compared with depression and controls) but there were no differences here between depression and controls  suggest that the group differences were secondary to reduced patient responses to unexpected reward receipt rather than differences in full-miss activation (Our results are based on the contrast of unexpected reward receipt tivation .p<0.05 corrected) with the post-scan rating of motivation to keep playing the task after a win in a medial prefrontal cluster situated in the anterior cingulate and paracingulate gyrus and bilateral medial superior frontal gyrus . Activation in this region was not significantly associated with SHAPS total score. No associations were found between unexpected reward receipt and the hedonic feeling of winning money at p<0.05 corrected.In a regression analysis in which we pooled all participants and, importantly, adjusted for group effects by modeling group means, brain activation during receipt of unexpected reward was positively associated  without learning confounds. The task we used, which had not been employed before in samples with mental illness, elicited activation to unexpected reward receipt in the classic reward network including striatum, orbitofrontal cortex, and medial prefrontal cortex, and yielded insights into relationships between brain activation and subjective experience during the experiment. We demonstrated that brain responses to unexpected rewards are suppressed in a similar way in both schizophrenia and depression in several regions previously implicated in the pathology of both of these disorders, including the orbitofrontal cortex, ventral striatum, thalamus, and insular cortex. However, there were also areas of deficit unique to schizophrenia, such as the posterior lateral parietal cortex. When we examined relationships between brain activation and task-related emotional reports, we found intriguing associations between medial prefrontal unexpected reward receipt responses and motivational state that could help explain aspects of clinical anhedonia.Our results indicated reduced activation to the receipt of an unexpected reward in overlapping regions in schizophrenia and depression: the orbitofrontal cortex, ventral striatum, thalamus, and inferior and middle temporal gyri had reduced activation in both disorders. There is a previous report of reduced ventral striatal reward receipt responses in unmedicated depression participants . A varieBecause not all patients with schizophrenia or depression have difficulties in motivation and enjoyment, patient heterogeneity may also contribute to variability of the results in the existing literature. Our results, in a study where all patients had at least some degree of anhedonia, indicate that striatal, insular, thalamic, temporal cortex, and orbitofrontal cortex processing of unexpected rewards may be abnormal in both schizophrenia and depression, which may impact on hedonic experience, the ability to learn reward-cue relationships and the generation of motivational states.One previous study compared reward prediction error responses in participants with depression, participants with schizophrenia and controls ; this cluster overlapped with the medial prefrontal cluster in which schizophrenia participants showed lower activation than controls and depression, and depression participants showed lower activation than controls, when receiving an unexpected reward. This evidence of an association between brain response to unexpected reward receipt and motivation, rather than pleasure, adds complexity and nuance to models of reward processing that parse pleasure and motivation into separable psychological processes with distinct neural components. However, a full-model should take account of how unexpected reward-related responses influences future behavior through motivation. Although SHAPS scores were associated with task-related measures of motivation, and brain activation in the medial prefrontal cortex was associated with task-related motivation, there was no direct association between brain activation and SHAPS scores, suggesting that medial prefrontal activation may be indirectly associated with anhedonic symptoms via its association with task-related motivation. Our results suggest that medial prefrontal and anterior cingulate activation to unexpected reward receipt may be a mechanism that enables the brain to update the motivational state to reinforce actions that maximize future reward.et al (2009) who found that putamen and gustatory cortex responses to sweet liquid rewards predicted clinical avolition as measured by the SANS. Our findings extend those of Waltz et al (2009) to relationships between reward receipt and motivation to the medial prefrontal and anterior cingulate cortices, key regions in processing reward information and in goal-directed behavior . We show that the activity in these regions is reduced in schizophrenia compared with controls during unexpected reward receipt, that the degree of reward receipt related activation in this area is associated with the degree of motivation to continue playing a game, and that the degree of motivation to continue playing in our experiment relates to severity of anhedonia in schizophrenia.vs unmedicated depressed participants and no associations between brain activity and dose of medication, it is not likely that medication completely explains the reward processing group differences observed in our study, though we recognize that studies in patients not taking medication are required to confirm our results. We note that there have been some previous studies documenting altered striatal reward prediction error signaling in unmedicated schizophrenia patients , could reflect either activity due to reward value or reward prediction error, hence inferences should be drawn accordingly.The task we used delivered unpredictable rewards, and as such rewards were surprising (and hence associated with positive reward prediction error). The activity formed by our contrast of interest  pooled a large number of patients with depression, schizophrenia, ADHD, mania, and alcohol dependence, who had all previously taken part in separate case-control studies using a reward anticipation task, and found evidence of right ventral striatal dysfunction linked to depressive symptom severity across diagnostic categories. This finding, and our results indicating shared areas of reward-related pathophysiology across disorders, are highly relevant to the RDoC initiative, and are supportive of its dimensional approach to psychopathology. RDoC aims to increase research that validates new cross-diagnostic dimensions that will ultimately inform future diagnostic systems , suggesting a possible causal pathway between brain activity, immediate measures of motivation, and longer-term levels of anhedonia.Dr Robbins has received research support from or served as a consultant to Cambridge Cognition, Eli Lilly, GlaxoSmithKline, and Lundbeck. Dr Clark has served as a consultant to Cambridge Cognition; the Centre for Gambling Research at UBC was funded by the Province of BC government and the British Columbia Lottery Corporation. Dr Ziauddeen has been jointly funded by the Wellcome Trust and GlaxoSmithKline on the Translational Medicine and Therapeutics programme. Professor Fletcher has received funds from GlaxoSmithKline for consultation services and from Astra Zeneca for a lecture. Drs Segarra, Metastasio, Spencer, Dudas, Arrondo, and Murray and Mr Reinders have no financial interests to disclose.


Filoviridae family of negative-sense RNA viruses. Since its identification in 1976, sporadic outbreaks have occurred in Central Africa. The 2014 outbreak in West Africa provides evidence that EBOV is emerging into new geographic regions. While previous outbreaks have been confined to small areas, the most recent outbreak is atypically widespread with over 25,000 people infected. Evidence from the limited-sequence studies that have been published suggests that the outbreak resulted from a single reservoir-to-human transmission event and subsequent human-to-human spread [Ebola virus (EBOV) belongs to the Infection is initiated by virions entering dendritic cells, macrophages, and, perhaps, hepatocytes . Virus rThe uniquely shaped filamentous particles made by filoviruses are surrounded by an envelope acquired during virion budding from the plasma membrane . Recent The cell surface interactions of filoviruses differ from other characterized enveloped virus/cell surface receptor interactions in that amino acid residues of EBOV GP are not thought to interact with a cell surface receptor. Instead, these viruses bind to target cells through two types of relatively non-specific receptors: C-type lectins (CLECs) that interact with glycans on EBOV GP and PtdSer receptors that interact with the viral envelope PtdSer . CLECs  is a lysosomal receptor for Lassa virus, suggesting this endosomal mechanism of fusion control may be broader than previously appreciated .Despite the progress over the past five years in understanding EBOV entry, many critical questions remain unanswered. For instance, how does PtdSer become enriched on the outer leaflet of enveloped virus membranes? Do virion interactions with CLECs, TIM proteins, or TAM/Gas6 complexes mediate direct internalization of virions into endosomes? If TIM proteins do directly mediate virus internalization, mechanistically, how is this accomplished since some TIM molecules are not thought to signal? Alternatively, do these receptors solely accumulate virions on the surface of cells? If so, is there a yet unidentified cell-surface receptor that is required for EBOV internalization? If PtdSer receptors do directly mediate EBOV internalization, do the different receptors mediate internalization through the same endosomal pathway and into the same endosomal compartment? For those filoviruses that do not require Cathepsin B and L, what endosomal proteases are responsible for their GP processing? What is the role of NPC1? Does NPC1 binding directly lead to EBOV fusion? If so, why are additional proteolysis events required and what protease(s) in which vesicular compartment mediate this second processing step? Finally, in terms of the big picture, what selective advantages are there for enveloped viruses such as filoviruses to use relatively non-specific, low-affinity mechanisms for internalization? Certainly, a growing body of evidence suggests that there must be advantages. These might include a breadth of tropism that would otherwise not be available to enveloped viruses. Further, using these entry mechanisms protects critical RBD and fusion residues from neutralizing antibodies by limiting extracellular exposure of these GP elements; in the current entry model for filoviruses, these sequences are solely exposed late within the endosomal/lysosomal compartments. A better understanding of these paradigm-shifting findings could provide additional drug targets to complement the current repertoire of Ebola virus antivirals in development. No doubt, the continued pursuit of answers to these questions by a number of groups will provide significant insights into both EBOV and, more broadly, virus biology.


The emergence of new novel therapeutic agents which directly target molecules that are uniquely or abnormally expressed in cancer cells  has changed dramatically the treatment of cancer in recent years. The clinical benefit associated with these agents is typically limited to a subset of treated patients, who in many cases are defined by a specific genomic mutations and expression lesion within their tumor cells. All these new therapy modalities represent new challenges to radiologists as their mechanism of action and side effect profiles differ from conventional chemotherapy agents. In this article we will discuss radiological patterns of response to molecular targeted therapies MTT in lung cancer, typical and atypical radiological responses of targeted molecular therapy for other intra thoracic malignancies, cardiopulmonary toxicity and other side effects of molecular targeted therapy MTT in the thorax. The emergence of novel therapeutic agents that directly target molecules that are uniquely or abnormally expressed in cancer cells  has changed dramatically the treatment of cancer in recent years. The cliThe role of MTT is to reduce or inhibit proliferative activity in cancer cells and block intracellular signaling pathways, blocking specific enzymes responsible for cancer growth and proliferation. Among these important MTT agents approved by the US Food and Drug Administration (FDA) are imatinib mesylate (Gleevec®), approved to treat gastrointestinal stromal tumor, trastuzumab (Herceptin®), approved to treat certain types of breast cancer as well as some types of gastric or gastroesophageal junction adenocarcinomas, and everolimus (Afinitor®), approved to treat patients with advanced kidney cancer whose disease has progressed after treatment with other therapies. In the highly vascular metastatic tumors hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC), successful response to anti-angiogenic therapy has been associated with the use of sunitinib (Sutent®) and sorafenib (Nexavar®), respectively. The response is assessed by decreased tumor size, decreased tumor attenuation, and tumor necrosis on the post-therapy contrast-enhanced computed tomography (CT) studies.First-line chemotherapy for lung cancer often includes a platinum-based drug (cisplatin or carboplatin) in combination with another FDA-approved chemotherapy drug . HoweverMany factors that correlate with favorable response occur in patients with particular clinical characteristics, such as a higher frequency of EGFR mutations (which themselves appear to be closely associated with higher likelihood of response to EGFR inhibitors) among Asians vs. non-Asians, women vs. men, never-smokers vs. current or prior smokers, and/or patients with adenocarcinomas vs. squamous histology tumors. New devRadiological assessment of response to treatment in lung cancer can be further divided into typical and atypical patterns of response. Typical patterns of response include: A) decrease in tumor size, B) decrease in vascularity (e.g. anti-angiogenic agent effect), C) presence of cavitary changes within the mass, and D) decrease in metabolism when F18fluorodeoxyglucose (FDG)- positron emission tomography (PET)/CT is used to evaluate treatment response. Atypical patterns of response include: A) increase in the size of a mass with decreased tracer uptake, B) presence of intralesional and/or perilesional hemorrhage with stable or increased size of the mass.A. Decrease in tumor sizeHistopathology is often used as the reference standard for assessing the response to primary chemotherapy in lung cancer. However, there is no single definition of a histopathologic response, and response criteria vary among studies. Most commonly, a pathologic complete response is defined by the absence of residual invasive tumor,9. OtherIn radiology, is generally accepted that a decrease in tumor size correlates with treatment effect; as a result, imaging was adopted for lesion measurement in the World Health Organization (WHO) criteria in 1979. However, because of some limitations of the WHO criteria, the Response Evaluation Criteria in Solid Tumors (RECIST) was introduced in 2000. Subsequently in October 2008 at the 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics  a New Response Evaluation Criteria in Solid Tumors: Revised RECIST Guidelines (version 1.1) was adopted [Table Both WHO and RECIST make use of anatomic imaging, predominantly CT, to obtain measurements of reference tumor lesions before and after treatment for response assessment and follow-up. However, functional imaging such as dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), perfusion CT and PET imaging have been found to be more useful than morphological changes in the assessment of tumor response. GoudarzB. Decrease in tumor vascularityTumor vascularity can be assessed by measuring blood flow kinetics using dynamic contrast enhancement either with dual energy CT or perfusional MRI. Subjective evaluation using changes in tumor attenuation and tumor vascularization, in addition to changes in tumor size, is considered a good way to evaluate response by computed tomography Figure . MeasuriC. CavitationCavitation has been commonly associated with squamous subtypes and can be seen occasionally in adenocarcinoma. Bevacizumab (Avastin) is a humanized monoclonal antibody against vascular endothelial growth factor (VEGF) that has been associated with cavitation in primary and metastatic lung cancer. Trials of VEGF inhibitors have shown that responding lesions frequently exhibit marked central cavitation. It has D. Decreased metabolismFrequently, there is a discrepancy between the anatomic appearance and the metabolic activity of the tumor during evaluation of response to anti-angiogenic drugs. Changes in tumor size do not necessarily correlate with changes in tumor viability and outcome. TherefoHicks et al evaluateA. Increase in the size of a mass with decreased metabolismThe overall increase in size and decrease in tracer uptake in a mass is a phenomenon that has been extensively described in gastrointestinal stromal tumor treated with imatinib mesylate (Gleevec), reflecting therapy response. In our B. Presence of intralesional and/or perilesional hemorrhage with stable or increased size of the mass.The discovery of the correlation of EGFR mutations and response to EGFR TKI therapy has demonstrated that molecular typing of tumors to guide therapy selection for lung cancer is possible. Prospective trials will need to validate the feasibility and efficacy of selecting therapy based on tumor molecular profiles. Also, numerous molecularly targeted agents are in clinical development, and future studies will need to identify molecular and clinical tools to guide the use of these agents, particularly in combination with current therapies such as surgery, radiation, cytotoxic chemotherapy, and other targeted therapies.The use of surgical specimens to identify EGFR mutations obtained is invasive, expensive, and increases morbidity and mortality. Alternatively, prior reports on EGFR mutation analysis in nonsurgical materials such as biopsy specimens, pleural effusions, and serum have noted problems of contamination by non-target normal cells within the samples-32. CT-gAntineoplastic agent-induced pulmonary toxicity is complex and a diagnosis of exclusion. SimilarOther causes of respiratory failure, including pneumonia, cardiogenic pulmonary edema, and diffuse alveolar hemorrhage, should be excluded. These conditions are not easily differentiated based on clinical presentation and radiographic findings. Furthermore, as patients usually receive multiple antineoplastic agents, it is usually difficult to identify the culprit agent.The clinical and radiologic manifestations of these drugs generally reflect the underlying histopathologic processes and include diffuse alveolar damage (DAD), interstitial pneumonitis, cryptogenic organizing pneumonia (COP), eosinophilic pneumonia, obliterative bronchiolitis, pulmonary hemorrhage, edema, hypertension, or veno-occlusive disease. Intra-thoracic and extra pulmonary side effects of these drugs include skin thickening, pleural effusions and thromboembolism.DAD is a common manifestation of drug-induced lung injury that results from necrosis of type II pneumocytes and alveolar endothelial cells. DAD is Drugs that may cause DAD include gefitinib, an oral EGFR tyrosine kinase inhibitor that is active against NSCLC, ovarian, colon, head and neck, and breast cancers. Gefitinib-induced lung toxicity usually occurs within the first 90 days of treatment. Interstitial pneumonitis, alveolar hemorrhage, and pulmonary fibrosis have been described-43.ChestInterstitial pneumonitis is characterized by areas of scattered expansion of the interstitium by inflammatory cells, mild interstitial fibrosis, and reactive hyperplastic type II pneumocytes. New tarErlotinib (Tarceva) is indicated for the treatment of patients with locally advanced or metastatic NSCLC. Vahid and Esmaili describeTrastuzumab is a humanized monoclonal antibody that selectively binds to the human EGFR (HER)-2 protein, indicated for the treatment of metastatic breast cancers with over expression of HER-2 protein. The incidence of trastuzumab-induced pneumonitis is 0.4 to 0.6%. Trastuzumab-induced pneumonitis may present with rapidly progressive pulmonary infiltrates and respiratory failure. Infusion-related symptoms, including hypotension, angioedema, bronchospasm, dyspnea, fever, chills, and urticaria, have been reported to occur in about 15% of patients. Severe episodes of hypotension, bronchospasm, and hypoxemia were also observed-49.Temsirolimus is a rapamycin analog that is active against renal cell carcinoma, endometrial carcinoma, breast cancer, glioblastoma multiforme, and gastrointestinal neuroendocrine tumors. Interstitial pneumonitis is a non–dose-dependent complication of temsirolimus. Interstitial pneumonitis has been reported in 1 to 36% of patients and the onset of pneumonitis usually takes place within 16 weeks (range 2 to 16 weeks) after temsirolimus treatment,51.Everolimus is an mTOR inhibitor that has been used as an investigational antineoplastic agent . Although clinical data in patients with malignancy are sparse, there have been previous reports of interstitial pneumonitis with everolimus in heart transplant recipients.Rituximab was first approved for the treatment of low-grade follicular lymphoma, and is now also approved for high-grade lymphomas, while it has also been used in other hematological diseases. The mechanism of action targets CD20+ B lymphocytes. Although rituximab-induced lung injury is rare, it has been well documented-56.Interstitial pneumonitis has been reported with rituximab monotherapy, thus proving the potential of this agent for lung injury. In all cases lung toxicity resolved after steroid treatment, with no late sequelae. Nevertheless, it should be mentioned that concomitant administration of steroids may not prevent the occurrence of pneumonitis.Radiological findings on chest radiographs in interstitial pneumonitis usually show diffuse heterogeneous opacities throughout both lungs. Areas of consolidation may also be present Figure . Early hCOP is a nonspecific histopathologic pattern of lung injury characterized by the proliferation of immature fibroblastic plugs within the respiratory bronchioles, alveolar ducts, and adjacent alveolar spaces. AffecteTrastuzumab treatment has been reported to be a causative agent of COP. Infusion-related symptoms, including hypotension, angioedema, bronchospasm, dyspnea, fever, chills, and urticaria, have been reported to occur in about 15% of patients.Chest radiographs demonstrate bilateral scattered heterogeneous and homogeneous opacities, which are typically peripheral in distribution and are equally distributed between the upper and lower lobes. CT often shows associated poorly defined nodular areas of consolidation, centrilobular nodules and “tree-in-bud opacities”, and bronchial dilatation. The patEosinophilic pneumonia is characterized by alveolar septal thickening and infiltration by eosinophils, lymphocytes, and plasma cells. CausatiDiffuse pulmonary hemorrhage is an uncommon complication with former chemotherapy regimens, but has become more common with the introduction of new MTT and anti-angiogenic agents. Pulmonary hemorrhage and hemoptysis have been reported in 2.3% of patients with nonsquamous NSCLC on bevacizumab (Avastin) therapy-63. SeveThe pathogenesis of antineoplastic agent-induced pulmonary edema is poorly understood and has been suggested to be due to direct injury to pneumocytes  or the alveolar capillary endothelium and the subsequent release of cytokines, which induce pulmonary edema due to leaky capillaries. Drugs that may lead to increased permeability and subsequent edema include imatinib, dasatinib and rituximab.Imatinib is a potent tyrosine kinase inhibitor, which is mainly used in the treatment of chronic myelogenous leukemia (CML) and is also effective in patients with gastrointestinal stromal tumor (GIST). Although most cases of imatinib-induced pulmonary adverse events have been reported in patients with CML, there have been cases of dyspnea during imatinib therapy, most often related to fluid retention and pulmonary edema.Dasatinib is a potent inhibitor of SRC/ABL kinase inhibitor used in the treatment of CML in patients who had disease resistant to or who could not tolerate imatinib. A studyPulmonary complications are uncommon and are usually associated with a fluid retention syndrome. The manifestations from the lungs are pleural effusions and pulmonary edema,68 seen VEGF antagonism could cause decreased matrix deposition in the supporting layers of vessels; therefore, the final picture of anti-VEGF therapy might consist of increased frequency of thrombotic events, as a result of tissue factor activation secondary to the exposure of the subendothelial collagen.In a randomized phase II study evaluating the efficacy and safety of bevacizumab in patients with previously untreated advanced colorectal cancer,69,70, vMore recently, two small molecules blocking the VEGF receptor (VEGFR) have shown promising results in the treatment of renal cell carcinoma and gastrointestinal stromal tumors (GISTs): sorafenib , approved by the FDA in 2005 as a second-line treatment for advanced renal cell carcinoma after cytokine failure, and sunitinib , approved in 2006 for patients with GIST previously treated with imatinib and for advanced renal cell carcinoma as a first-line treatment. Both of these agents have been strongly associated with thromboembolic events.Cardiac toxicity is one major concern related to trastuzumab administration. In 2002New imaging modalities are available to assess treatment response. PET have the ability to assess tissue viability more precisely than CT and detect metastatic lesions that would have been missed on conventional imaging. Other functional imaging techniques, such as dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perfusion CT imaging, have been found to be more useful than morphological changes in the assessment of tumor response, although not frequently used in most institutions.With the discovery and introduction of new MTT agents, the treatment for a wide variety of cancers has been revolutionized. As these treatments become increasingly recognized as therapeutic options, physicians who interpret imaging studies should be aware of different patterns of response and possible side effects of these new MTT agents.The authors declare that they have no competing interests.FFS is responsible for drafting the first and subsequent versions of the manuscript, as well as editing and collection of images and figures. AS (Andrew Smith) is responsible for editing the subsequent versions of the manuscript, as well as legends of the figures. JJ is Responsible for editing the multiple subsequent versions of the manuscript. CJ is Responsible for drafting the first and subsequent versions of the manuscript, as well as editing and collection of images and figures. KO is Responsible for drafting the first and subsequent versions of the manuscript, as well as editing and collection of images and figures. CA edited the manuscript and provided figures and legends. AS (Atul Shinagare) is responsible for drafting the first and subsequent versions of the manuscript, as well as editing and collection of images and figures. Responsible for drafting the subsequent versions of the manuscript, as well as collection of images and edition of the figures. All authors read and approved the final manuscript.