Bacteria that reside in animal tissues and/or cells must acquire iron from their host. However, almost all of the host iron is sequestered in iron-containing compounds and proteins, the majority of which is found within heme molecules. Thus, likely iron sources for bacterial pathogens (and non-pathogenic symbionts) are free heme and heme-containing proteins. Furthermore, the cellular location of the bacterial within the host (intra or extracellular) influences the amount and nature of the iron containing compounds available for transport. The low level of free iron in the host, coupled with the presence of numerous different heme sources, has resulted in a wide range of high-affinity iron acquisition strategies within bacteria. However, since excess iron and heme are toxic to bacteria, expression of these acquisition systems is highly regulated. Precise expression in the correct host environment at the appropriate times enables heme iron acquisitions systems to contribute to the growth of bacterial pathogens within the host. This mini-review will highlight some of the recent findings in these areas for gram-negative pathogens. Borrelia burgdorferi, which uses manganese in place of iron  iron is poorly soluble in aerobic conditions at neutral pHs; however, ferrous (Fe2+) iron is much more soluble. Additionally, the host sequesters free iron in iron binding proteins  and in heme and hemoproteins to prevent iron toxicity and to withhold nutrients from pathogens, thereby limiting pathogen growth. Thus, free iron is not readily available to the bacterial pathogen inside the host. Pathogens have evolved numerous mechanisms to capture this limited supply of free iron and iron from host iron proteins. Since the type of iron available varies depending on the location of the pathogen within the human host and since pathogens occupy a wide variety of host niches, there is a diversity of iron acquisition mechanisms employed by both intracellular and extracellular pathogens. This mini-review focuses on acquisition of iron in gram-negative pathogens from one of the most abundant sources—host heme.Almost all living organisms require iron for growth. One notable exception is the Lyme disease pathogen, Approximately 70% of the iron in the human body is within heme, a heterocyclic organic ring called porphryin covalently bound to one ferrous iron atom  . Most commonly, there is direct uptake of heme by a cell surface receptor which binds heme or host hemoproteins. A variation of this method includes bipartite systems in which a lipoprotein facilitates heme or hemoproteins binding to the cell surface receptor  suggesting that there are other motifs for heme coordination in outer membrane heme transporters . Other species have one outer membrane receptor capable of binding to multiple hemoproteins , suggesting the recognition is at the level of the heme molecule  . Recently, new structural classes of HOs have been identified such as the “split-barrel fold class” in Helicobacter pylori (HugZ) and Campylobacter jejuni (ChuZ)  high-affinity heme iron acquisition is generally not needed and, thus, would be energetically wasteful and (2) excess iron is cytotoxic. One of the most common mechanisms of regulation of heme iron acquisition system expression by iron levels utilizes iron-responsive transcriptional regulators that repress transcription of high-affinity iron acquisition systems when iron is plentiful. The prototypical example is Fur (ferric uptake regulation). In the classical model of iron-repression, Fe-Fur binds to a DNA sequence called the Fur-box in promoters of many high-affinity iron acquisition genes. Fe-Fur occupation of the promoter prevents RNA polymerase binding, thereby repressing transcription. When iron levels decrease, the Fe-Fur equilibrium shifts, Apo-Fur cannot bind to the Fur-box, and transcription occurs [for review Carpenter et al. ]. DtxR a high-affBartonella quintana, transcription of the hut operon increases when heme concentrations are lower than required for optimal growth, but decreases at very high heme concentrations. The decrease in expression is predicted to be mediated by the heme-responsive Irr transcriptional regulator, which is only found in some alpha-proteobacteria  called HurI and its cognate anti-sigma factor HurR to modulate transcription of the bhuRSTUV heme uptake operon by heme though a mechanisms in which iron regulation and heme regulation converge. In low iron, Fur repression of hurIR is relieved; however, HurI is inactive because it is bound by HurR when heme is absent. Heme binding by BhuB alleviates HurR repression of HurI activity, and HurI can activate transcription of the bhuRSTUV operon.  because the pathogen is in a stable environment with low free iron and access to heme.E. coli heme mutants), and bioinformatic  approaches. Defining the role of each particular heme iron acquisition system in virulence is ongoing for many pathogens, but has been complicated by the presence of redundant systems in some pathogens and/or the use of certain systems in just one niche in the host. Thus, deletions of particular heme iron acquisition genes do not always show an effect in all animal models. It is clear, however that in many pathogens there is a role for some heme iron acquisition proteins, demonstrating the importance of heme for pathogenesis , genetic , suggesting potential for rapid spread of these genes via horizontal gene transfer (Wyckoff et al., Pathogens and their human hosts have evolved together, and as a consequence, there is a complex interplay between sequestration of iron from the pathogen by the host and elaboration of mechanism to capture that iron by the pathogen. From the host side, human hemoglobin is quite variable in amino acid sequence; thus, individuals may have differing susceptibility to pathogens due to differences in the ability of the pathogen to bind hemoglobin to access the heme (Pishchany and Skaar, Laura Runyen-Janecky conceived and wrote the entire manuscript.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The presence of melanocytes in the oral epithelium is a well-established fact, but their physiological functions are not well defined. Melanin provides protection from environmental stressors such as ultraviolet radiation and reactive oxygen species; and melanocytes function as stress-sensors having the capacity both to react to and to produce a variety of microenvironmental cytokines and growth factors, modulating immune, inflammatory and antibacterial responses. Melanocytes also act as neuroendocrine cells producing local neurotransmitters including acetylcholine, catecholamines and opioids, and hormones of the melanocortin system such as proopiomelanocortin, adrenocorticotropic hormone and α-melanocyte stimulating hormone, that participate in intracellular and in intercellular signalling pathways, thus contributing to tissue homeostasis.There is a wide range of normal variation in melanin pigmentation of the oral mucosa. In general, darker skinned persons more frequently have oral melanin pigmentation than light-skinned persons. Variations in oral physiological pigmentation are genetically determined unless associated with some underlying disease.In this article, we discuss some aspects of the biophysiology of oral melanocytes, of the functions of melanin, and of physiological oral pigmentation. While under physiological conditions the number of melanocytes in the oral epithelium is the same regardless of racial/ethnic origin, the colMelanocytes containing melanin are present in the basal cell layer of the epithelium even at those oral mucosal sites that show no visible signs of melanin pigmentation-7. Oral Melanocytes produce melanin in membrane-bound organelles termed melanosomes. Melanosomes have all the proteins and enzymes necessary for melanin biosynthesis, for maintaining the structure of the melanosome, and for the maturation of the immature pre-melanosome into a mature melanosome producing melanin,12. As tNon-physiological alterations in melanin pigmentation of the oral mucosa are related to genetic, metabolic, endocrine, chemical or physical factors, to infective agents and to inflammatory or neoplastic processes,9. It haMost of our knowledge about the regulation and biology of oral melanocytes is derived from data obtained from research on epidermal melanocytes which are histologically and ultra-structurally similar,16. HoweThe aim of this short review is to discuss some aspects of the biology and physiology of oral melanocytes, the function of melanin and critically to evaluate the concept of intraoral physiological pigmentation.Melanocytes are melanin-producing cells originating from the neural crest. During Melanocyte stem cells have the capacity for self-renewal and for differentiation and thus can maintain the population of mature melanocytes. In the epidermis, the melanocyte stem cells reside in the bulge region of hair follicles,20, but Epidermal melanocyte stem cells give rise to transient-amplifying melanocyte precursors that settle without the stem cell niche where they differentiate into mature melanin producing melanocytes,21-24. SIn the skin, migration of precursor melanocytes from the dermis to their final destination in the basal cell layer of the epithelium is mediated by c-Kit/SCF, endothelin 1 and 3, hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF). These precursor dermal melanocytes, as they pass through the basement membrane, express E-cadherin which later facilitates intercellular communication with neighbouring keratinocytes in the basal cell layer of the epithelium. The funMature melanocytes are elongated dendritic cells residing in the basal cell layer of the epithelium. They contain all the proteins required for melanin biosynthesis and for the structural maturation of melanosomes, includiIn the basal cell layer of the epithelium the ratio of melanocytes to keratinocytes ranges from 1:10 to 1:15via an array of paracrine-like biological mediators that they secrete, have the capacity to regulate melanocyte melanogenesis. It. It49]. The extent and intensity of physiological oral pigmentation increases with age,53, concThe global frequency of physiological oral pigmentation in different racial/ethnic groups is unknown; but it has been reported that about 95% of healthy black persons in the United States are affected; that pigmentation is more extensive in the anterior than in the posterior portion of the mouth; and that when the gingiva is affected the buccal/labial surfaces are more intensely pigmented than the lingual/palatal surfaces. It has Eighty to a hundred percent of Australian Aborigines have physiological oral pigmentation with equal gender distribution. By contMelanocytes can adjust and respond to biological, physical and chemical stimuli in their microenvironment, and can in turn generate physical and biochemical signals which may affect that microenvironment. Melanocytes have the capacity to mediate antimicrobial and immune responses and to act as neuroendocrine cells, and they produce melanin that provides protection from environmental stressors such as UV radiation, reactive oxygen species and free radicals. Why certain persons are more affected by physiological oral pigmentation is unknown, but certainly it occurs predominantly in darker skinned persons.Written informed consent was obtained for the publication of this report and any accompanying images.The authors declare that they have no competing interests.Concept of paper was devised by LF. LF, AM, RAGK, MA, YJ, and JL wrote the manuscript. The manuscript was critically revised by LF, RAGK and JL. All authors read and approved the manuscript.


Metabolic Engineering has undertaken a rapid transformation in the last ten years making real progress towards the production of a wide range of molecules and fine chemicals using a designed cellular host. However, the maximization of product yields through pathway optimization is a constant and central challenge of this field. Traditional methods used to improve the production of target compounds from engineered biosynthetic pathways in non-native hosts include: codon usage optimization, elimination of the accumulation of toxic intermediates or byproducts, enhanced production of rate-limiting enzymes, selection of appropriate promoter and ribosome binding sites, application of directed evolution of enzymes, and chassis re-circuit. Overall, these approaches tend to be specific for each engineering project rather than a systematic practice based on a more generalizable strategy. In this mini-review, we highlight some novel and extensive approaches and tools intended to address the improvement of a target product formation, founded in sophisticated principles such as dynamic control, pathway genes modularization, and flux modeling. The utilization of industrial biotechnology for the conversion of energy, chemicals and materials to value-added products is centuries-old. Traditional methods of strain development based on evolution, random mutagenesis, mating and selection strategies were successfully used for the optimization of production hosts. However, early applications of microbial production of chemicals were limited to native metabolites, such as amino acids, alcohols, organic acids, fatty acids or antibiotics. The foundational development of genetic and metabolic engineering made possible the production of a wide and diverse range of molecules including biofuels, pharmaceuticals, biopolymers, precursors and specialty chemicals . By defiEscherichia coli [E. coli enabled the conversion of 6dEB into the bioactive erythromycin analogs Ery C and Ery D. Further chassis optimization provided a robust proof of principle that mature erythromycin analogs can be efficiently produced in a single heterologous expression system [The potential of metabolic engineering could be exemplified by the early successful heterologous production of polyketide compounds. Polyketides are an important class of natural products with complex chemical structures widely used as antibiotics, immunosuppressant, antitumor, antifungal and antiparasitic agents . These bhia coli . This wahia coli , a polykhia coli . These rn system , 10.Nevertheless, metabolic engineering is not only restricted to “compound manufacture”. Nielsen J. grouped different examples of metabolic engineering into the following categories : 1) heteMaximization of product yields through pathway optimization is a central challenge for every metabolic engineering project . NaturalIn essence, pathway optimization is a multivariate problem and the answer of this challenge is not universal and depends on the pathway to be expressed, the compound to be produced, the host, the availability of genetic tools, and the substrates utilized. In this context, the ability of the metabolic engineer to identify potential bottlenecks and eliminate them is critical and has a decisive impact on project success. This mini-review will dig into the existing novel approaches intended to improve the efficiency of metabolite-compounds production in designed microbial cells.The simple overexpression of a biosynthetic pathway often is not enough to achieve high yield production of the desired compound. In this context, the depletion of essential cellular precursors  and the accumulation of intermediates can cause toxic effects on the host and lead therefore to a decrease in productivity –15. On tE. coli strain [tac promoter [E. coli [E. coli FadR transcription factor, capable of binding fatty acyl-CoA molecules, and on hybrid promoters created by the combination of FadR and LacI responsive elements [E. coli fatty acid biosynthetic pathway and a thioesterase, TesA, to produce free fatty acids. Module B is an ethanol biosynthetic pathway that converts pyruvate into ethanol. Module C contains an acyl-CoA synthase (FadD) and a wax-ester synthase (AtfA). AtfA condenses the fatty acyl-CoA product (generated from module A plus FadD activity) and ethanol (module B) to form FAEEs  an aollutant . A clearollutant . Future ad hoc for each new metabolic engineering project, making this discipline costly and very time-consuming [As we already mentioned, classical optimization of metabolic pathways is achieved by modification of promoters, RBS, codon composition, copy number, construction of operons, etc . Howeveronsuming .In order to achieve the same flexibility of chemical engineering for the production of structurally diverse molecules, metabolic engineering need to establish principles of systematization to achieve their goals in terms of production and optimization. An excellent application of this concept was applied to the design and development of engineered pathways for the production of terpenoid derived moieties.E. coli resulted in innovative and interesting advances not only for their particular yield improvement, but also because they laid down strategies capable to systematize metabolic engineering approaches, generating universal principles capable of been transferred to other pathways and/or hosts [Studies addressing the heterologous pathway optimization of isoprenoid-derived molecules on or hosts . Chronolor hosts .Artemisia annua, in E. coli [First, amorphadiene production was achieved by heterologous expression of the MVA pathway from yeast and a codon-optimized amorphadiene synthase gene from  E. coli . Althoug E. coli . Importa E. coli ; and theE. coli by expressing the native host MEP pathway, the geranylgeranyl diphosphate (GGPP) synthase and the taxadiene synthase. The MEP pathway has the advantage over the MEV pathway in being more balanced and efficient in producing isoprenoids from sugars. The MMME approach is based on grouping enzymes with similar turnovers in modules, and then doing a combinatorial screening varying the expression of the different modules. For this, operons are constructed and the toolbox of promoters, RBS and plasmid vector can be used to achieve different expression levels which will maximize the product titers of the system. The combinatorial approach can easily circumvent the non-linear interactions between enzymes in the pathway and offer the opportunity to broadly sample parameter space [E. coli MPE pathway, which generates IPP (isopentenyl pyrophosphate) and DMAPP ; and the “downstream module”, a GGPP synthase and taxadiene synthase biscistronic transcriptional unit. Thus, instead of dealing with six genes, the problem is reduced to two modules, considerably simplifying the system, making it more tractable and easy to handle. In this way, the carbon flux balance along the pathway is achieved by changing the expression levels (plasmid copy number or promoter strength) of each module, and doing a combinatorial screening of all the possible combinations  . They deer space . In thisinations . Using tDespite its outstanding medical and industrial relevance, the progress in metabolic engineering of this family of products is laying down the basis for systematization of metabolic engineering in general. Principles of codon-adjustment, identification of pathway bottlenecks and, more recently, modularization and combinatorial experimentation can be transferred and reused to perform the heterologous production of completely different products. These principles, together with the ever declining costs of DNA synthesis and sequencing, and the development of computational software for analyzing and predicting the behavior of these heterologous systems will lead microbial metabolic engineering to be a systematic and flexible tool for production of an expanding array of molecules for pharmaceutical and other industrial uses.The last two decades encompassed what is called “post-genomics era” of metabolic engineering, an overwhelming compendium of data coming from genomics, transcriptomics, proteomics and more recently, metabolomics fields. In this context, the paradigm of metabolic engineering has clearly shifted away from one focused in perturbing individual pathways, to one which considers cell reactions in their entirety, and which integrates metabolic (native and heterologous) pathways in a genome-scale metabolic network.in vivo conditions in order to maximize product formation [Metabolic engineering makes particular emphasis in the metabolic fluxes and their control under ormation . Since eormation . In the ormation , 33. Oncormation . By alteormation , 36.While it is generally accepted that microorganisms metabolism is suited to achieve optimal growth, this may not be the case of a mutant organism obtained under laboratory conditions. Frequently, when a mutation is introduced, the topology and flux distribution of a metabolic network is so perturbed that the mutant organism does not follow the optimal growth principle. In such cases, the objective of “minimization of metabolic adjustment” (MOMA) is better suited for predicting growth and product yields, since it is not based on an optimal growth objective function, but in the concept that the mutant metabolism remains initially as close as possible to the wild type optimum in terms of flux values . In thisin silico predict increasing product titers. For example, Brochado et al., have successfully improved vanillin production in yeast by knocking out genes of central carbon metabolism [in silico analysis of carbon metabolism in E. coli for redirecting carbon flux to malonyl-CoA, in order to optimize the synthesis of the flavanone naringenin [These two different approaches to analyze metabolic networks are frequently complementary, and understanding the general principles and the biological interpretation of each method provide an extremely powerful advantage to the metabolic engineer . Algorittabolism . More retabolism . Malonyltabolism , 42 and tabolism , and alstabolism . Since mtabolism . Many retabolism . Howeverringenin . They usIn silico simulation tools open the field of metabolic engineering possibilities that can be explored to circumvent the problems that arise when expressing a foreign pathway, contributing to accelerate the design cycle of metabolic engineering and leading to the cost-effective production of industrial and medical important molecules.Competition with native pathways and metabolites, accumulation of side products and consequent growth inhibition are only some of the possible effects that a heterologous pathway can have on cell metabolism. These examples are a clear demonstration of how metabolic networks and metabolic flux analysis can be used to identify non-trivial targets for genetic interventions that lead to further optimization of product titers. The rapid rate of fossil resources consumption has drawn the attention towards the development of an economy based on renewable biological raw materials. In this context, the term “Biorefineries” is used to describe biological entities capable of generating high value-aggregated directly from biomass, in an analogy with petroleum-based refineries . MetabolThe intersection of metabolic engineering with other emerging areas of systems and synthetic biology presents exciting opportunities to develop solutions to many of the global challenges we face nowadays. In particular, these disciplines will be of fundamental importance to promote sustainable energy, reduce the environmental impact of several industrial processes and to improve the cell factory production of natural and semisynthetic drugs that are currently synthesized at very low yields, hopefully having an impact in the costs and availability of medicines.


Primary melanoma of the lung is an extremely rare pathological entity and sparsely reported in the literature. A 68-year-old man was admitted with 3 months history of cough, sputum production, dyspnea, hemoptysis and chest pain. The chest radiography demonstrated bilateral mass lesion and thoracal computerized (CT) showed a bilateral tissu mass with left parietal invasion. Bronchoscopy revealed a large polypoidal tumor arising from the left lower lobe bronchus, histology at bronchial biopsy revealed a malignant melanoma. Surgical biopsy of the left parietal mass was confirmed by invasive malignant melanoma. Primary melanoma of the lung represents a rare pathological entity; careful interpretation of histopathological information in correlation with all other findings from clinical studies can establish a diagnosis. Melanoma is widely known as the most lethal of all skin cancers, and pulmonary metastases are the most common presentation of advanced disease . PrimaryA 68-year-old man was admitted with a 3 months history of cough, sputum production, dyspnea, hemoptysis, chest pain, and weight loss. Physical examination found a patient cachectic with a mass of right chest wall pain on palpation. The chest radiography demonstrated bilateral mass lesion  and thorTo exclude the possibility of metastasis from occult primary malignant melanoma, an extensive examination was carried out, the patient had no past history of skin tumor, and we could not find any skin, external ear, or ocular lesions. Gastrointestinal endoscopy, colonoscopy, and endoscopy of the nasal cavity were performed, and no possible primary tumor was detected. The final diagnosis was primary melanoma of the lung, the patient was given chemotherapy consisting of the docarbazinze, nimustine hydrochloride and vincristine, the patient died of tumor progression one month after first cycle of chemotherapy.Primary malignant melanoma of the lung is a very rare neoplasm; accounting for 0, 01% of all lung tumours. It is frequently endobronchial and manifest with symptoms of cough, hemoptysis, postobstructive pneumonia, or atelectasie. In 30% of the cases, primary malignant melanoma of the lung is an incidental finding on chest radiography . The proThese criteria should be revised with the advent of whole-body PET scan: in case of a single pulmonary uptake with histological confirmation of lung lesion, this association would increase the likelihood of diagnosis of primary malignant melanoma of the lung. The present case fulfils the aforementioned diagnostic criteria.Why should malignant melanoma develop in the bronchi when melanocytes are not apparently present in the normal respiratory tract? Normally, melanocytes migrate to the epidermis and the dermoepidermal junction of the skin, but they may migrate to the visceral during embryogenesis. this has been suggested for the oesophagus and the larynx and may be the case in lung too .The main differential diagnosis is melanocytic carcinoid tumour, melanotic paraganglioma, melanotic schwanoma and pulmonary metastasis of a malignant melanoma. Treatment of choice is surgical resection of the tumour with an oncologically adequate margin, the role of postoperatively adjuvant chemotherapy or radiotherapy either singly or in combination is not known, adjuvant interferon ? was also received on postoperatively .In most cases, patients with primary malignant melanoma of the lung had a poor prognosis, in some reports, the surgical approach with adjuvant chemotherapy /immunochemotherapy provided long-term survival . Our patPrimary malignant melanoma of the lung is exceptional: the diagnosis is based on old criteria, the advent of the PET scan will definitely change the attitude diagnosis but the prognosis is poor.


Antral follicular growth in the ovary is characterized by rapid expansion of granulosa cells accompanied by a rising complexity of their functionality. Within two weeks the number of human granulosa cells increases from less than 500,000 to more than 50 millions cells per follicle and differentiates into groups of cells with a variety of specialized functions involved in steroidogenesis, nursing the oocyte, and forming a functional syncitium. Both the rapid proliferation and different specialized functions of the granulosa cells can only be explained through the involvement of stem cells. However, luteinizing granulosa cells were believed to be terminally differentiated cells. Only recently, stem and progenitor cells with FSH-receptor activity were identified in populations of luteinizing granulosa cells obtained during oocyte collected for assisted reproduction. In the presence of the leukaemia-inhibiting factor (LIF), it was possible to culture a subpopulation of the luteinizing granulosa cells over prolonged time periods. Furthermore, when embedded in a matrix consisting of collagen type I, these cells continued to express the FSH receptor over prolonged time periods, developed globular formations that surrogated as follicle-like structures, providing a promising tool for reproductive biology. Ovarian follicular development is initiated from a pool of inactive primordial follicles. Each follicle contains a small nongrowing oocyte and a single layer of nondividing cells encapsulated by the follicular basal lamina . As partThe mammalian ovary produces mature oocytes capable of being fertilized and sustaining early embryonic development. Developmental competence of the oocyte correlates with follicular size, larger oocytes being more developmentally competent , 9. The There are three ovarian functional somatic cell types involved in folliculogenesis: (1) the ovarian surface epithelium that surrounds ovary, (2) the theca, and (3) the granulosa cells, which essentially reside within the avascular space of the ovarian follicle.Primordial follicles are not distributed uniformly in the ovary but are predominantly located in the ovarian cortex. The ovarian cortex is covered by a layer of irregularly shaped cells , commonlThe tunica albuginea is a thick fibrous subepithelial layer with cells embedded in connective tissue, which does not begin to form until the end of intrauterine life , 14. In Theca cells surround the developing follicle, form the two layers known as the theca externa and interna, and produce the androgens which are ultimately converted to estradiol by the GCs.During the final stages of follicular growth, GCs are at the centre of ovarian function, as they not only direct the growth of the oocytes thereby inhibiting meiotic progress but also produce and secrete the hormones which prepare such processes as ovulation and endometrial proliferation. The antral growth, the proliferation, differentiation, and function of GCs are initially controlled by the follicle-stimulating hormone (FSH) alone, later by both FSH and luteinizing hormone (LH). FSH targets its receptor (FSHR) and induces the maturation of ovarian follicles through proliferation of GCs; induction of the LH-receptor (LHR) and formation of a functional syncytium –23 whichThe membrana granulosa or follicular epithelium is more complex than most other epithelia for various reasons. At first it expands from a single to a multilayered epithelium, as the follicle grows. In the transition from a pre- to a postantral follicle, the shape of GC changes from nondividing flattened appearance to dividing cubical appearance. The epithelium also expands laterally with time, as the follicle enlarges. During the preovulatory phase the membrana granulosa becomes vascularised with capillaries sprouting from the surrounding theca interna. Finally, at ovulation GCs differentiate into luteal cells. It is the fate of 99% of all follicles to become atretic, and apoptosis among the GCs is one of the first indicators of follicular atresia , 9, 24.de novo from mesenchymal progenitor cells residing in the ovarian tunica albuginea. During differentiation into OSE cells the mesenchymal progenitor cells line either the ovarian surface or invaginated epithelial crypts. Mesenchymal progenitor cells would first contribute to the development of epithelial cells similar to granulosa cells, and these cells subsequently form epithelial nests descending into the deeper ovarian cortex. These cells may be a source of germ cells, which assemble together with nests of primitive granulosa cells to form primary follicles ..60].In contrast to the ongoing controversy with regard to the possibility of ongoing renewal of oogenesis in the ovary and the possible existence of oocyte-producing stem cells in the adult ovary, the existence of stem cells sustaining the other compartments of the ovary has long been neglected. Conventional thinking considers the ovarian follicle as an isolated structure, distinct both in space and time, either destined for early degeneration through atresia or for growth to a mature, Graafian follicle, ovulation, and formation of the corpus luteum. The cyclicity of follicular development, ovulation, and luteal function is seen as discrete phenomena, separated both in time and space. In recent years, however, experimental evidence has shed some doubt on this conventional thinking. Most notably, it has been demonstrated that mature and fully grown mouse oocytes are able to influence the development of preantral follicles in mouse ovaries , indicatin vitro invariably cease to proliferate already after two to three passages. Similar results have been obtained when culturing thecal cells. Recently, it has been shown that the four growth factors, bFGF, EGF, LIF, and IGF1, exhibited significant enhancing effects on colony growth of thecal cells, leading to the detection of thecal stem cells in the ovary [GCs cultured he ovary , 72.in vivo during growth of a follicle [A subpopulation of mural granulosa cells has now been demonstrated to contain cells with multipotent stem cells potential, as they express the stem cell marker Oct-4 . POU5F1 follicle  particulfollicle . The hypothesis for the presence of stem and progenitor cells in the granulosa was first postulated, when it was demonstrated that the granulosa possesses some marked similarities to other epithelia in the body , 67. Thein vitro. GCs, positive for FSHR but not for LHR, may either become dedifferentiated to the progenitor GCs or differentiate to luteinized GCs  of ovarian stem cells . The preIn addition to the granulosa cells FSHR/LHR subgroups the substantial subpopulations of long cultured granulosa cells were attained by expression of mesenchymal lineage marker CD117 (c-kit). The results differed within patients .GCs stained for both FSHR and CD117 (c-kit) established 3 populations: cells positive only for FSHR, cells positive for both markers, and cells negative for those markers. Our observation showed that women with good quality of oocytes and the one who got pregnant after the IVF therapy had higher amounts  of cultured GC positive for both CD117 and FSHR markers than a population only positive for FSHR or with none. However, correlation between the number of those cells among fertile and subfertile women failed to indicate any role with respect to the likelihood of successful pregnancy.c-Kit is the stem cell factor receptor and is expressed in human ovarian follicular development, and their interaction is required for the survival of follicles in long-term culture . c-Kit wTogether with the stem cells located in the theca , 81, thein vitro culture system may provide a promising technical tool for in vitro maturation of both human and animal ovarian follicles. Such culture systems can be used in reproductive toxicology, in drug targeting, and in assisted reproduction, respectively, breeding.In female mammals, the normal and physiological production of good quality gametes relies upon the highly controlled growth and differentiation of the surrounding ovarian follicle. GC proliferation is maintained throughout folliculogenesis, providing not only a specialized microenvironment but also nutrients for oocytes growth. GC multipotency and the use of granulosa stem and progenitor cells in the newly developed 3D


This review describes some of the recent developments in imaging aspects of pain in the periphery. It is now possible to image nerves in the cornea non-invasively, to image receptor level expression and inflammatory processes in injured tissue, to image nerves and alterations in nerve properties, to image astrocyte and glial roles in neuroinflammatory processes, and to image pain conduction functionally in the trigeminal ganglion. These advances will ultimately allow us to describe the pain pathway, from injury site to behavioral consequence, in a quantitative manner. Such a development could lead to diagnostics determining the source of pain , objective monitoring of treatment progression, and, hopefully, objective biomarkers of pain. Early work in the fields of neuroanatomy, neurophysiology, and clinical observations has provided a robust description of pain pathways. These pathways can now be evaluated with imaging to contribute to a more objective view of pain, where both the sensory and emotional experience may be assessed in health and disease. This review describes some recent advances in imaging of pain and inflammation-related processes below the level of the brain, that is, at the level of 1) the periphery; 2) the nerve; and 3) the nerve root. We discuss methods to measure neuroinflammation and future lines of inquiry linking peripheral markers to spine, brainstem, and brain functional imaging. An ultimate goal is a more mechanistic definition than the one currently offered by the International Association for the Study of Pain: “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”1Identifying active inflammatory pathology may be critical for adequate treatment. Further, precise measurement of inflammation may allow assessment of disease activity and assess the effect of therapeutic measures. Structural imaging methods such as computerized tomography (CT), magnetic resonance imaging (MRI), and ultrasound may detect large anatomical lesions and subtle swelling, but differentiating active disease from anatomical changes in healed tissue and/or normal variations is difficult. Two non-invasive imaging techniques, corneal confocal microscopy (CCM) and positron emission tomography (PET), may, however, provide insights into peripheral nerve function.The cornea is a window into free nerve fiber endings.in vivo with PET ligands directly, the technique may still inform us on the functional state of the inflammatory milieu and levels of receptor expression/occupancy. Due to changes in blood flow, vascular permeability, metabolism, white blood cell influx, and changes in the local chemical environment, many PET ligands accumulate at sites of peripheral inflammation.Although it is not currently possible to image nociceptors 67Gallium citrate, or autologous leukocytes labeled with indium-111 or technetium-99m.18F-fluorodeoxyglucose (FDG), thanks to its availability and its excellent properties in oncological imaging. It is a tracer for glucose metabolism, and its distribution is not specific to cancer cells but is also observed in inflammatory tissue, including macrophages, capillaries, and fibroblasts. FDG has been used to image inflammation processes and treatment monitoring in rheumatoid arthritis  receptor antagonist tracer is elbow .17 This Glia are the most abundant cells in the nervous system, and recent research has changed the perception of glia from being just supportive cells of neurons to being dynamic partners participating in brain metabolism and communication between neurons in health and in chronic pain.21Astrocytes are the most abundant brain cell type in terms of their number and volume, and they constitute 40% to 50% of all glial cells. Astrocyte reaction has been demonstrated in peripheral nerve injury and in tissue inflammation models. Peripheral chronic nerve lesion is associated with breakdown of the blood–spinal cord barrier permeability and activation of astrocytes.L-deprenyl (selegeline) is a selective irreversible MAO-B inhibitor that has been carbon-11-labeled, allowing for PET imaging of astrocyte activity.Microglia are the resident macrophages of the brain and spinal cord and thus act as the first and main form of active immune defense in the central nervous system. Microglia rapidly activate in response to a variety of pathological conditions, including nerve damage and persistent pain.de novo expression of cell surface markers or receptors, and migration to the site of injury.MAO-B expression occurs primarily in astrocytes, while TSPO expression occurs in activated microglia and to a lesser degree in active astrocytes. Compared with the microglial response to nerve injury, astrocyte proliferation begins relatively late and progresses slowly but is sustained for more than 5 months, a time-frame paralleling the development of chronic pain.High-resolution magnetic resonance neurography provides excellent visualization of peripheral nerves and may be an integral component in evaluating nerve injuries, supplementing electrodiagnostic (ED) studies, such as electromyography, nerve conduction studies, and quantitative neurosensory testing.41Functional imaging of the nerves and nerve roots has, to the best of our knowledge, not yet been achieved. The utility of structural and diffusion imaging of neuropathies is illustrated by a collection of prominent studies,Primary afferent nerves in the dorsal root ganglia convey pain information to the central nervous system. Both peripheral inflammation and nerve damage can lead to alterations in anatomy and function of neurons within the ganglion, alterations that contribute to persistent pain states.56Taken together, these studies demonstrate that, at least for cranial nerves, functional and diffusion MRI can provide mechanistic insight into pain processes at the interphase of the peripheral and central nervous system.18F-fluorodeoxyglucose. We found no studies demonstrating altered spinal PET ligand uptake in pain, but such an endeavor appears possible if there is massive peripheral signaling. FDG is routinely used in oncological staging, and a retrospective analysis of cancer pain patients might demonstrate elevated FDG uptake in corresponding segments of the spinal cord. Ideally, such a study would utilize high-resolution PET in combination with MR or CT to delineate the spinal cord cross-section in multiple voxels, allowing assessment of anterior and posterior segments, and possibly lateralization effects. To illustrate PET imaging of the spine, we present mean FDG standardized uptake values (SUV) obtained from two studies of 92 patientsThe metabolic rate of glucose increases in the spinal cord during nociceptive in-flow,Structural MRI is used routinely to assess spinal cord injuries, but due to the spine’s small cross-section, and noise sources such as motion, cerebrospinal fluid (CSF) pulsation, and magnetic susceptibility, functional imaging of the spine is technically challenging. Recent developments in MR sequences and post-processing have opened up the field, and it is possible to define structure and function with greater specificity.There are only a handful of studies that have attempted to relate peripheral alterations to CNS dysfunction. An excellent example of such an approach is determining the relationship between carpal tunnel nerve conduction velocity and regional gray matter alterations in the brain.67Functional MRI and machine-learning pattern recognition can be used to define neurologic signature of acute pain with high sensitivity and specificity.Clearly, the study of pain is and will remain a multidisciplinary field. Animal imaging of brain systems, reviewed by Borsook and Becerra,An increasing body of literature has implicated inflammation as a contributor to the initiation but also to the maintenance of chronic pain, whether it be an obvious inflammatory process produced by specific disease , following trauma , or other neuropathic conditions such as complex regional pain syndrome (CRPS). It seems increasingly clear that peripheral inflammation may produce central inflammatory processes.


Many examples of partnerships between academic and service settings were thoroughly described and best practices suggested, most often, however, without formal evaluation of outcomes. Nursing leaders in both settings have a long tradition of partnering with very little replicable evidence to support their efforts. It is critical that future initiatives evaluate the effectiveness of these partnerships, not only to ensure quality of patient outcomes but also to maximize efforts at building capacity for tomorrow's workforce.This integrative review summarizes currently available evidence on academic-service partnerships in the profession of nursing. More than 300 articles, published primarily in refereed journals, were accessed. Articles (110) were included in this review as they presented detailed and substantive information about any aspect of a nursing academic-service partnership. The majority were anecdotal in nature. Topics clustered around the following categories:  Report on the Future of Nursing [In November 2010, the Institute of Medicine (IOM) released its highly anticipated  Nursing , but now Nursing . A partnership is defined as an arrangement where parties agree to cooperate to advance their mutual interests . In the Ironically, the twentieth century transition from hospital based training to academically-based nursing education contributed inadvertently but substantially to the development of a wide chasm between academic and service sectors . The melnursing, nursing education partnerships, academic-service partnerships, academic-practice partnerships, and nursing education re-design. Consistent with the methodological approach [An extensive review of the literature was conducted to synthesize current knowledge about academic-service partnerships in nursing. No other published report on this topic was found. The review included both empirical and conceptual articles published from 1990 through 2010. Data collection consisted of a search of the Cochrane Library, CINAHL, and MEDLINE databases using the following keywords: approach , referenpre-requisites for successful partnerships, benefits of partnerships, types of partnership, and workforce development with its themes of academic-practice progression and educational re-design. Key points in each of these categories are described below. More than 300 citations were accessed. Of these, 110 met the criteria for inclusion, only nine of which reported on original research. Many examples of partnerships between academic and service settings were thoroughly described and best practices suggested, but most lacked formal evaluation of outcomes. An analysis of the main issues discussed in these articles clustered around the following categories: Many authors not only called for a recommitment to partnering but also identified key pre-requisites to developing and sustaining effective academic-service partnerships –34. TheyAccording to Bleich et al. , who areAcademic-service partnerships have been widely discussed in the literature. These include partnerships with hospitals, community health, and public health agencies, nursing homes, schools, and governmental agencies. From early on in nursing's history, the focus of these partnerships was directed toward providing care to specific populations, educating students and staff, producing research, and addressing workforce issues in nursing. Faculty practice models and centers for research are two examples of partnerships that developed in the mid-20th century. Today, in the early 21st century, the majority of academic-service partnerships are focused on building workforce capacity. Faculty practice models, first seen in the United States in the 1950s , 38, eme One model of faculty practice was the academic nursing center, housed in the university and staffed by faculty. These centers provided cost-effective care to their neighboring communities , 39, 40.While faculty practice had its early roots in academic nursing centers, other popular models allowed for joint appointments for both faculty in a practice setting and the practitioners in the university. In a critical review of 35 articles, Sawyer and colleagues  concludeThe many benefits to faculty practice for all partners, regardless of model employed, included cost effectiveness, good patient outcomes, positive student learning, increased research productivity, and faculty satisfaction –64. AddiWhile academic nursing centers and collaborative faculty practice collaborations were typically developed to provide patient care and student learning experiences, research collaborations between faculty and clinicians were often an unanticipated benefit. Development of partnerships for the primary purpose of advancing research and building an evidence-based practice began to emerge soon thereafter , 69–75. academic-practice progression and educational re-design. The majority of academic-service partnerships in the past decade have focused on building professional nurse workforce capacity . All of In 2008, the Nursing Executive Center , 78 publSeveral approaches have been described to address this gap in preparation to practice readiness. The most wellknown is the senior capstone experience where students work one-on-one with a clinical nurse to care for assigned patients , 80. RepAt the same time that the Nursing Executive Center published its reports, data were emerging on how faculty shortages across the country were limiting student capacity , 98. A mThe development of accelerated postbaccalaureate nursing education programs was an early attempt at increasing the nursing workforce. According to the AACN , today tSome of this educational re-design work was developed as a result of AACN's 2003 support to establish the University Health System Consortium . The conMacIntyre and colleagues  recommenDedicated education units (DEU) were designed as partnerships and resonate with the suggestions made by MacIntyre and colleagues. One of the first articles to describe the DEU came from Flinders University in Australia and was published in 1999 . A dedicThe development of the clinical nurse leader (CNL) role and supporting curriculum is another recent example of academic-service partnership that addresses the preparation-practice gap. The AACN proposed the CNL role in 2003 after consulting with an extensive group of leaders from a variety of settings across the healthcare delivery system. The CNL is a provider and a manager of care at the point of care to individuals and cohorts . The masAs is typical with the development of CNL programs, nursing leaders from three New Jersey healthcare organizations partnered with the College of New Jersey to develop their curriculum. They worked together to implement the program with representatives from both practice and the academic settings involved in teaching the students . A focusSmith and Dabbs  publisheWhile the literature is replete with descriptions of numerous academic-service partnerships that have developed over the past twenty years, objective evidence for the success of these relationships is limited at best. While much informal evaluation has occurred, very few of the innovations described have been formally studied. Generalizability of research published to date is limited by small, nonrepresentative samples in single locations followed over relatively short time periods. As academic and service partners move forward to design and implement changes to prepare the next generation of professional nurses for the realities of a changing healthcare delivery landscape, both process and outcome evaluations must be incorporated in the planning. Both research and quality improvement methodologies may be useful, depending on the proposed innovation. The key point is that measurement is essential to determine the short- and long-term effectiveness and the efficiency of these initiatives. We will need to know, for example, the kind and number of staff and faculty resources required to ensure success, and their associated costs. The effect on patient outcomes must also be considered, as well as staff and faculty outcomes, such as readiness for practice and effects on workloads, job satisfaction, recruitment, and retention. Despite the limitations of the extant literature, this integrative review has highlighted a number of successful or promising academic-service partnerships and associated benefits perceived by the innovators. Thought leaders have also described the prerequisites that should frame future partnerships. The IOM's call  is urgen


In recent times, food safety and security have generally remained basic human needs, therefore because of the largely unregulated nature of the Nigerian markets, coupled with the poor housing and feeding conditions to which animals are subjected in the abattoirs, a survey for assessing potential mycotoxin exposure through meat consumption was undertaken.Eighty Samples of meat boughtrandomly from 5 major markets distributed in 5 local government areas of Oyo state , Nigeria were analysed for contaminating mycoflora using the plate count and micromorphological methods, while aflatoxin detection and quantification was by Thin Layer Chromatography (TLC).Aspergillus, Penicilliu, Alternaria, Cladosporium, Fusarium, Neurospora, Rhizopus and yeast were identified. The predominant genus Aspergillus yielded 7 species while the potential toxicogenic fungi represented 38% of the isolated mycoflora. The genera requiring higher water activity for growth  were not obtained from the dried meat. Aflatoxins B1, B2, G1 and G2 were detected in all the samples analysed. The fresh samples with the exception of the total aflatoxin G (AFG) in kidney gave the highest mean concentrations for all aflatoxins, also an exceptionally high aflatoxin content was found in all the kidney samples.Mycological analysis of samples revealed a higher contamination level in the sun-dried samples. Eighteen fungi species belonging to 8 genera, namely, Aflatoxin detection in meat should be addressed urgently to avert the possible adverse health effects like aflatoxicosis, exacerbated malnutrition, suppression of growth and immunefunctions on consumers. Also the animal health inspectors should pay more attention to the feeding conditions of the animals on farm and the abattoirs. Meat refers to meat flesh, skeletal muscles, connective tissue or fat and others than meat flesh, including brain, heart, kidney, liver, pancreas, spleen, thymus, tongue and tripe that is used as food, excluding the bone and bone marrow and it contains high biological value protein and important micronutrients that are needed for good health throughout life . HoweverRaw materials for animal feeds are exposed to microbial contamination at the time of their cultivation, processing, storage and distribution, while chemical composition of food, properties of the outside environmental and specific growth requirements determine the type of microorganisms and the course of physico-chemical reaction in the contaminated food .In general, mycotoxin exposure is a critical problem in the hot and humid low income countries where poor methods of food handling and storage are common. In spite of occasional high profile incidents of acute poisoning outbreak, mycotoxins have not been widely prioritized from a public health perspective -4. HowevAlthough mycotoxin contamination of food commodities is a global problem, the developed world through the application of modern agricultural practices and legislatively regulated food processing and marketing system have greatly reduced exposure in these populations . The conMeat as a source of animal protein is consumed heavily in Nigeria and is also is recommended by nutritionists as a major source of protein for growing children, the convalescent, the expectant mothers and the aged. Therefore, the objective of this was to determine the various contaminating fungi on meat, assaying for mycotoxin residues and ascertaining the general safety of meat consumed in Northern and Eastern parts of Nigeria; in order to create awareness on the presence, concentrations and distributions of mycotoxins in meat. It could also form the scientific basis for promulgation of regulations important in the decision-making process to establish meaningful limits for mycotoxins in foods, most especially meat and meat products .Sample preparation, isolation, enumeration and identification of mycofloraFive major markets for bulk purchase and retail of foodstuffs and animal produce brought largely from the Northern and Eastern parts of Nigeria were selected for this study. The markets  distributed in 5 local government areas  are known for wide patronage by inhabitants of the South-western states. Ten samples each of fresh and sun-dried pieces of cow beef and edible organs  were purchased randomly from these markets. They were placed in labeled sterile polythene bags and then transferred immediately to the laboratory for mycological and mycotoxin residue analysis. Ten grams of sample was diluted with 90mL of physiological saline and homogenization was achieved using mortar and pestle. Two hundred microlitres (200Ll) of ten-fold serially diluted homogenized sample was inoculated onto potato dextrose agar (PDA) incorporated with antibiotics. Incubation was at 25 degrees Celsius for 3-5 days. Fungal enumeration was by plate count while mycoflora identification was by micromorphological characteristics .Extraction, detection and quantification of aflatoxins in meat samplesA thin layer chromatographic (TLC) method previously described by Oyero and Oyefolu, 2009 [Aspergillus, Alternaria, Fusarium, Cladosporium, Penicillium, Neurospora, Rhizopus and Yeast. Three of these  are potential mycotoxin producers  commonly found in animal tissues were found in varying concentrations. The fresh samples, with the exception of the total AFG  in kidney gave the highest mean concentrations for all the aflatoxins detected . This raThe determination of the level of fungal contaminants in the samples analysed revealed a high microbial load in the sun- dried meat. This may not be unconnected with the fact that during the sun drying process, meats are spread openly in the sun and on bare concrete floors, this often allow contamination by dust. However, the mycoflora on the fresh meat may have been derived from contaminants in water, air, floors and surroundings of the slaughter house, as well as the instruments used during the slaughtering and processing into table meat for sale. Also the situation of the meat processing plants, the slaughter of animals, insufficient cleaning and disinfestations of working areas, instruments and other equipmentcontributes greatly to meat contamination by toxigenic moulds .Aspergillus , Alternaria, Fusarium, Cladosporium, Rhizopus, Penicillium, Neurospora and Yeastgenera. The incidence of the various genera has been documented by several workers [Alternaria, Aspergillus, Cladosporium and Penicillium genera have been implicated as a cause of rhinitis and severe asthma [Fusarium and Penicillium species in systemic respiratory disease as well as opportunistic infections involving various body sitesby the Aspegillus and Rhizopus sp have been reported. The Aspergillus sp especially is particularly dangerous to the asthmatics and those with weakened immune systems [Fusarium, Alternaria and Yeast species from the dried meat samples however may be due to the fact that they require a moderately high moisture content of 22-23 % [The mycoflora of the meat were identified into the  workers ,13-17. T workers ,17-19. C workers . However workers . The pote asthma  while th systems -24. The  22-23 % . This reAflatoxins commonly associated with animal tissue  were found in all the samples analysed. In nature, several mycotoxins co-occur in contaminated commodity  and so tThe AFB1 and AFG1 detected in samples are proven human carcinogens and are thus classified as Group 1 carcinogens with AFB2 as Group 2B probable human carcinogens . DocumenThis study confirmed that meat generally sold in Nigeria are grossly contaminated by various fungi species including the potentially mycotoxigenic ones. The determination of aflatoxins though in acceptable concentrations should urgently be addressed with a view of ensuring the safety of the consumers.The authors declare no competing interests.AOBO was involved in study design, laboratory analysis of samples and wrote the initial draft of the manuscript; OGO lufunmilayo was involved in study conception, design, sample collection, laboratory analysis and writing of the final manuscript.


Hippocampal neuronal ensemble activity appears to play an important role in establishment of spatial and non-spatial episodic memories  and 2]..2]. In pFirstly, we measured the degree of rate-remapping, due to task-induced changes in population activity. The kolmogorov-smirnov distance between the empirical firing rate distribution of each single cell, collapsed in time and trial, and different null hypotheses, based on different assumptions on global remapping was computed. We also computed the correlation between pairs of population vectors taken from different times of each trial. These measures are independent of the relative magnitude of firing. Comparing the distributions of correlation values for entire set of population vectors between two trials, or two behaviorally different phases of each trial, provides an estimate of how much the ensemble code changes. When the rats experienced different phases of the task, however, the hippocampus encoded these changes robustly by changing the values of the components of the population vectors, without much, if any, change in the ensemble of recruited cells. Secondly, to see how presence of noise correlations may enhance coding property of the population, the performance of a non-linear classifier trained on few informative “single” cells was contrasted with a classifier trained on a) the complete set of cells and b) the principle components of the cell assembly. Thirdly, we applied trajectory-based activity classification of neural responses using Hidden Markov models, to segment the complete recording into a sequence of a few statistically discriminated hidden states, each correlated with different behavioral condition.


The aim of this study was to assess retrospectively the clinical presentation, management and outcome of three patients with isolated SMA dissection encountered at Okinawa Prefectural Chubu Hospital, Japan from 2005 to 2006, along with a review of the literature. We follow up the patient's clinical symptoms and the image by using enhanced dynamic CT at 1 week, 1 or 2 months, 6 months, and yearly after onset.We present three patients with acute abdominal pain due to spontaneous dissection of the superior mesenteric artery (SMA), who were treated by surgical revascularization or conservative management. Two patients underwent surgery because of signs or symptoms of intestinal ischemia and one patient elected conservative management. The SMA was repaired by bypass graft in two cases, and in one of these, the graft was occluded because of prominent native flow from the SMA. All patients were symptom free and there was no evidence of disease recurrence after a median follow-up of 4.3 years.Although the indications for surgery are still controversial, we should proceed with exploratory laparotomy if the patient has acute symptoms with suspicion of mesenteric ischemia. A non-operative approach for SMA dissection requires close follow-up abdominal CT, with a focus on the clinical signs of mesenteric ischemia and the vascular supply of the SMA, including collateral flow from the celiac artery and inferior mesenteric artery. Spontaneous dissection of the superior mesenteric artery (SMA) is not associated with aortic dissection, and is a rare but potentially fatal disease. It is now being reported more often, which is a reflection of the increased use of imaging techniques, such as multidetector row computed tomography (MDCT), multiplanar (MPR) imaging, reconstruction imaging, and CT angiography (CTA) -4. ThreeA 50-year-old man with an 8-day history of epigastric pain of acute onset was admitted. No associated symptoms of fever, nausea, constipation or diarrhea were present. He was previously healthy and had no remarkable medical history and trauma except for hypertension and appendectomy. On physical examination, mild tenderness and rebound tenderness over the epigastrium was observed, and no bruit was audible. Laboratory tests showed slightly elevated serum amylase and bilirubin. Therefore, we initially presumed that the patient had acute pancreatitis, but contrast-enhanced CT revealed isolated dissection of the SMA, in which the false lumen was thrombosed figure , and theA 46-year-old woman presented to the emergency department with acute abdominal pain, back pain and vomiting. She had a history of hyperthyroidism but did not have any cardiovascular risk factors or recent trauma. On physical examination, mild periumbilical tenderness without signs of peritonitis was observed. Laboratory tests and abdominal radiography were unremarkable. Contrast-enhanced CT of the SMA showed abnormal wall thickness and irregular diameter, with a double lumen. Isolated dissection of the SMA began from just after the orifice of the SMA and separated the SMA into two distinct lumina for 3 cm from the origin of the artery; the distal portion of the SMA showed signs of thrombosis and stenosis, with the true lumen being compressed by the false lumen figure . There wA 47-year-old man with a 5-day history of acute epigastric pain with radiation to the back was admitted. No associated symptoms of fever, nausea, constipation or diarrhea were present. He was previously healthy and had no cardiovascular risk factors and recent trauma. On physical examination, mild tenderness over the epigastrium without signs of peritonitis sign was observed, and no bruit was audible. Laboratory tests and abdominal radiography were unremarkable. Contrast-enhanced CT revealed a thin flap of the SMA, which began from just after the orifice of the SMA and separated the SMA into two distinct lumina; the resulting false lumen was thrombosed in the mid to distal portion of the SMA. Three-dimensionally reconstructed images demonstrated severe stenosis of the SMA, but no sign of bowel ischemia caused by prominent collateral flow from the celiac artery and inferior mesenteric artery figure . We chosSpontaneous dissection of the SMA is a rare condition and is not associated with aortic dissection. It was first described by Bauerfield in 1947 . HoweverThe etiology of the disease has not yet been established, but atherosclerosis, cystic medial necrosis, and fibromuscular dysplasia have been implicated, often associated with untreated hypertension . Solis eThe natural history of the disease is also unclear and depends on each case. Most patients present with acute epigastric pain, which is considered to be caused by the dissection itself or intestinal ischemia. Other common symptoms are nausea, vomiting, melena, and abdominal distention. These patients present acutely with symptom duration of <4 weeks . LaboratDiagnosis in the acute stage has become possible as a result of advances and increased use of imaging techniques such as MDCT, leading to MPR and reconstruction imaging, and CTA -4. DynamHowever, neither Sakamoto et al. nor Yun et al. have found a clear relationship between radiological appearance and clinical course. Abdominal color Doppler echo is also effective for following hemodynamic changes within the SMA, bowel movement, and signs of bowel ischemia, such as wall thickening and intestinal dilatation.Some treatment algorithms for management of spontaneous SMA dissection have been reported ,25,26. ASparks et al. have suggested that indications for surgery are increasing size of the aneurysmal dilatation of the SMA, luminal thrombosis, or persistent symptoms despite anticoagulation. Various procedures for surgical intervention have been reported -11, inclRecent minimally invasive techniques, such as percutaneous endovascular stent placement and intralesional thrombolytic therapy, could be useful in certain cases, especially in patients at high risk for surgery -18. HoweTable There is no consensus on the best treatment of spontaneous isolated dissection of the SMA. Although the indications for surgery are still controversial, we should proceed with exploratory laparotomy if the patient has acute symptoms with suspicion of mesenteric ischemia. A non-operative approach for SMA dissection requires close follow-up abdominal CT, with a focus on the clinical signs of mesenteric ischemia and the vascular supply of the SMA, including collateral flow from the celiac artery and inferior mesenteric artery.The authors declare that they have no competing interests.All authors except HT were involved in the preoperative and postoperative care of the patient. MK is the primary author and reviewed the case and the literature. HM and KM participated in the surgeries and provided editorial commentary. HT performed the angiography treatment. All authors conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors have read and approved the final manuscript.


The adult brain is in a continuous state of remodeling. This is nowhere more true than in the dentate gyrus, where competing forces such as neurodegeneration and neurogenesis dynamically modify neuronal connectivity, and can occur simultaneously. This plasticity of the adult nervous system is particularly important in the context of traumatic brain injury or deafferentation. In this review, we summarize a classic injury model, lesioning of the perforant path, which removes the main extrahippocampal input to the dentate gyrus. Early studies revealed that in response to deafferentation, axons of remaining fiber systems and dendrites of mature granule cells undergo lamina-specific changes, providing one of the first examples of structural plasticity in the adult brain. Given the increasing role of adult-generated new neurons in the function of the dentate gyrus, we also compare the response of newborn and mature granule cells following lesioning of the perforant path. These studies provide insights not only to plasticity in the dentate gyrus, but also to the response of neural circuits to brain injury. The ability of the mammalian brain to change with experience is perhaps its most important feature. At the organismal level, the positive (adaptive) benefits of experience-dependent changes underlie our abilities to learn, speak multiple languages, ride a bicycle and so on. However, equally important are enduring negative  effects that are associated with experience-dependent changes including benign habits as well as more disruptive conditions such as anxiety, post-traumatic stress, and drug addiction. In both cases, these changes are manifested at the level of circuits and individual neurons as a reordering of gene expression profiles, synaptic strength, and circuit connectivity. Reorganization reflects the adaptation of the network to a changing environment, either encoding new information or compensating for injury-induced degeneration. Reorganization following a brain injury inevitably perturbs the dynamic equilibrium, which can affect many aspects of neuronal structure and function including intrinsic neuronal properties, synaptic interactions, and connectivity within and between networks. The cellular and molecular landscape can impose limits on plasticity and regenerative capacity of the adult brain.A variety of injury models have been used to examine the response of the brain such as crush injuries to peripheral nerves, cortical stab wounds, and spinal cord injury (SCI) models. For example, SCI models have been extensively examined for factors that limit the growth of axons following damage or transection , surrounds the synapse  staining in the denervated zone Figure ,b. The wInterruption of the perforant path denervates one of the main inputs to the principal neurons in the adult dentate gyrus—the mature granule cells. These cells are part of the trisynaptic hippocampal circuit, with their dendrites receiving afferent input from the entorhinal cortex and other brain regions; and their axons forming the mossy fibers that synapse with pyramidal cells in CA3. The two subdivisions of the perforant path, medial and lateral, synapse with mature granule cell dendrites in the middle and outer molecular layers, respectively (Hjorth-Simonsen and Jeune, Post-lesion structural reorganization in the adult dentate gyrus is influenced by the post-injury dynamics of the extracellular environment. Reactive gliosis following perforant path lesion is both rapid and sustained, and is considered adaptive in this context. Gliosis serves to clear degenerating debris, to maintain laminar borders, and to aid reactive synaptogenesis in the deafferented region. For example, microglia proliferate and acquire reactive morphology within 3 days post-lesion and return to baseline by day 10 (Hailer et al., In summary, lesion of the perforant path eliminates the main excitatory input in the outer two-thirds of the dentate molecular layer, thus partially denervating dendrites of mature granule cells. This lesion illustrates both the potential for regeneration in the CNS, but also some of the limits. Within 2 weeks post-lesion, remaining afferent homo- and heterotypic systems can sprout, but the laminar borders largely limit reorganization of axons and synaptic terminals. Changes in the composition of the extracellular matrix, triggered by degenerating perforant path axons and reactive gliosis, are a major contributing factor in this regard.Plasticity of neuronal circuits occurs in the adult mammalian brain and is particularly intriguing in the form of adult neurogenesis (Lledo et al., Proliferation of newborn neurons in the dentate gyrus is highly sensitive to environmental and endogenous signals, such as learning, exercise, or severe stress (van Praag et al., Newly-differentiated neurons in the first 1–2 weeks post-mitosis (Kempermann et al., Although dendritic arbors are reduced in total length and complexity, 21-day-old granule cells in the adult mouse develop dendritic spines in the denervated zone. This is surprising because mice have no detectable entorhino-dentate projection from the contralateral hemisphere (van Groen et al., The perforant path model serves as an example of CNS plasticity that incorporates many features of the injury response. Neuroplasticity in the adult brain is a complex process that involves all aspects of the neural circuit—axonal sprouting and terminal bouton turnover, reorganization of dendrites and spines, activity-dependent modulation of synaptic strength, as well as adult neurogenesis. The dynamic nature of the adult brain gives hope for endogenous repair following injury, however, the limits of neuroplasticity must be recognized in order to optimize medical treatments. Following perforant path lesion, newborn neurons showed a greater degree of structural plasticity than mature granule cells by accommodating sprouting axons in the inner molecular layer. However, circuit-appropriate reinnervation of denervated targets is essential for functional recovery, and this aspect of recovery has yet to be fully explored. For example, following ischemic lesions, newborn neurons from the expanded ipsilateral SVZ can replenish cells lost in the striatum by migrating in chains toward the site of infarction, where they differentiate into medium spiny neurons (Arvidsson et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


A commentary onOne nose one brain: contribution of the main and accessory olfactory system to chemosensation6:46. doi: 10.3389/fnana.2012.00046by Mucignat, C., Redaelli, M., and Caretta, A. (2012). Front. Neuroanat. Current neurobiological evidence supports the synergic involvement of sensory organs in decoding complex environmental objects. The somewhat independent study of the anatomical and functional aspects of the major sensory systems has yielded a wealth of information on how environmental stimuli are decoded. Understanding the central integration that results in complex, behaviorally relevant objects, however, is still in its infancy. The same applies to chemical senses that act in concert to build representations of physiologically distinct objects which, in turn, motivate effective adaptive responses. The success of this chain of events is decisive for virtually all fundamental behaviors that lead to survival such as feeding, mating, fighting, or fleeing.A first approximation toward a holistic view of interrelated sensory senses is achieved by analyzing the molecular, developmental, and structural characteristics that underlie the function of each subsystem. In this broad context, the work by Mucignat-Caretta and coworkers describes the distinct, yet synergic, functions of the vomeronasal system and contrast them with other aspects of chemoreception associated with the face and its air-passages. This approach builds upon and challenges the early postulate regarding the functional dichotomy between the main and accessory olfactory systems, although the influence of endogenous axons  Figure  discoverMucignat-Caretta and collaborators discuss intra-species recognition in the context of the ontogenetic onset and development of both pheromone and volatile substance decoding and the central thesis of this comprehensive revision. That is, the overlapping of volatile odorant and pheromonal responses. Emphasis is given to the detection of chemical cues by classic and new  putative chemoreceptors.In précis, the present article by Mucignat-Caretta et al. offers a concise account highlighting the most influential work supporting the integrative processes that take place between the chemical senses associated with volatile and pheromonal perception.


Background: Climate change is projected to cause substantial increases in population movement in coming decades. Previous research has considered the likely causal influences and magnitude of such movements and the risks to national and international security. There has been little research on the consequences of climate-related migration and the health of people who move.Objectives: In this review, we explore the role that health impacts of climate change may play in population movements and then examine the health implications of three types of movements likely to be induced by climate change: forcible displacement by climate impacts, resettlement schemes, and migration as an adaptive response.Methods: This risk assessment draws on research into the health of refugees, migrants, and people in resettlement schemes as analogs of the likely health consequences of climate-related migration. Some account is taken of the possible modulation of those health risks by climate change.Discussion: Climate-change–related migration is likely to result in adverse health outcomes, both for displaced and for host populations, particularly in situations of forced migration. However, where migration and other mobility are used as adaptive strategies, health risks are likely to be minimized, and in some cases there will be health gains.Conclusions: Purposeful and timely policy interventions can facilitate the mobility of people, enhance well-being, and maximize social and economic development in both places of origin and places of destination. Nevertheless, the anticipated occurrence of substantial relocation of groups and communities will underscore the fundamental seriousness of human-induced climate change. Climate change is widely projected to cause substantial increases in the scale of human population movement in coming decades. Forecasts of the number of people who will move by around midcentury in response to the effects of climate change vary from tens of millions to 250 million people . There is now an overwhelming majority consensus among climate scientists that human-generated emissions of greenhouse gases are initiating climatic changes that are unprece-dented in human experience during the Holocene epoch. Human amplification of the natural “greenhouse effect” reflects the scale and intensity of energy use and economic activity that have arisen during the industrial era, along with the accompanying surge in human numbers and consumption levels (particularly in high-income countries), land use patterns, and food production activities over the past century . An incrClimate change poses risks to communities and livelihoods via impacts on ecosystem “goods and services,” loss of arable land, and increased severity and frequency of climate-related disasters . These iResearch on climate change and movement of people has been dominated by studies seeking to estimate likely population numbers, and the pathways by which movements might occur e.g., . EstimatMeanwhile, there has been little research on the impacts of climate-change–related migration on “everyday lives,” including health, humanitarian, and equity aspects . Yet, thThe dynamics of population movement, whether climate related or not, are complex and diverse. The core choices of migration include weighing the risks and benefits of staying versus moving, and the opportunities and constraints relating to the timing and destination of movements . Such moClimate change is amplifying the intensity and frequency of extreme weather events such as floods, heat waves, and extreme wind events . The relClimate change will also lead to slow-onset changes in climatic and environmental conditions  that contribute to loss of important environmental amenity and livelihoods . Slow-onClimate change will affect the safety and health of communities and populations globally. Most health impacts will be adverse and will occur via direct exposures  and less direct influences arising from disruptions to environmental, ecological, and social systems. Indeed, most of the impacts of climate change on physical, ecological, and social systems will affect human health via changes in food yields, freshwater flows and quality, stability of infectious disease patterns, air quality, social cohesion, and family income and livelihoods . The tenClimate change poses risks to food security via reductions in agricultural and fishery yields, especially in already food-insecure regions such as in sub-Saharan Africa and South Asia . ChangesClimate change will also influence the geographic range, seasonality, and incidence rate of various infectious diseases, such as malaria, diarrheal diseases, and cholera . There iIn response to the health and physical safety risks posed by climatic-environmental disasters, both acute and sustained, migration can be a survival strategy. Yet populations in low-income countries whose health is most at risk from climate change , and wheFamines are extreme health crises that cause people to move to avoid hunger and death . The sevHowever, migration is not necessarily an indicator of vulnerability: It can be an adaptive response by communities to cope with the effects of climate change . Indeed,Analysis of the complex paths by which climate change influences population movement can be facilitated by using a three-category typology : forced Forced displacement is likely to occur as environmental changes and extreme climate events undermine peoples’ ability to live in their places of residence. This displacement will typically be over short distances and may involve large-scale movements of people, most often within countries. The first subsection below considers the health implications of displacement, with reference to health outcomes among political and environmental refugees.There may be planned resettlement of large populations to reduce their exposure to climate impacts. These are likely to be at the scale of communities, resettled within countries. The second subsection focuses on the health implications of planned resettlement schemes, from which the evidence comes largely from large-scale resettlement for dams and environmental remediation.Migration is also likely in response to, or in anticipation of, climate-related impacts, and will likely be within countries and contribute to urbanization. The third sub-section addresses the health implications of climate--related migration, focusing particularly on those migrating to urban areas within -developing countries.Health implications of displacement. People displaced by climate-related processes and events will include those who have little choice because of loss of habitable land, extreme health risks, and deteriorating live-lihoods  2007]. After the 2004 Asian tsunami, one million people were initially displaced in Sri Lanka. In the immediate aftermath, there was an increased risk of water and food-borne disease outbreaks , disease related to overcrowding , and vector-borne disease  [World Health Organization (WHO) 2005]. Infectious disease outbreaks occur particularly in camps or settlements that are crowded, are poorly ventilated, and have inadequate shelter, water, sanitation, and access to immunization and health care facilities . The mosFood shortages, restricted access to food, and undernutrition are recurring problems for displaced people in low-income regions . Urban policy makers and services in low- and middle-income countries should therefore focus on improving environmental conditions and access to health services to improve health outcomes, including emerging health issues such as chronic noncommunicable diseases, among the urban poor . SpecifiThe health needs and outcomes of -climate-related displaced populations will depend on the nature of migration processes and the capacity of receiving communities and countries. There are many innovative policies and interventions that address health issues and access to health services for international immigrants, including migrant-focused health schemes, the European “Migrant-Friendly Hospitals” project, and refugee and migrant-focused health services (UNDP 2009; Finally, there is a heightened need for research and data collection systems that can capture information relating to population movements and migrant health indicators and needs. Data collection and research will be demanding, because displaced popu-lations can be difficult to reach as people move both within and across multiple geographic borders and through formal and informal “bureaucratic” regimes. Key roles for data collection systems and research are to identify ways of reducing vulnerability in climate-change–affected communities in order to reduce the likelihood of displacement and maintain good health, understand the risks to health during migration and resettlement processes among climate-affected populations, and identify and evaluate interventions and policies that will improve health outcomes among those who move. Such research can inform policy interventions, research, and public health practice with the goal of increasing the health and health equity among -climate-change–related migrant populations.If climate change continues on its current trajectory, then an increase in the numbers of displaced people over the coming decades is likely. Although the range and extent of health risks associated with future climate-related population movements cannot be clearly foreseen, the evidence of health outcomes of analogous movements of people indicates that health risks will predominate over health benefits. This, then, is an issue of considerable geopolitical, ethical, and economic importance.Planned resettlement and migration will usually be last resort options. However, effective policy must facilitate the mobility of people when it becomes necessary, thereby seeking to enhance well-being and maximize social and economic development in both the places of origin and destination . WhetherClimate change mitigation, through reduction of greenhouse gas concentrations, is the primary aim for governments and communities. A fuller understanding of the range of risks posed by climate change to human well-being and health, including the health of those involved in climate-related migration, could strengthen the resolve of the international community to take effective mitigation action to abate climate change. Yet, because climate change is already occurring and at least some future temperature changes are already “locked in,” adaptive strategies are also required to protect against increasing risks to human health and the adverse effects of climate-related migration and displacement. Through deep cuts in global greenhouse gas emissions, together with comprehensive socioecological adaptation strategies, adverse climate-related migration and health outcomes could be greatly reduced.


FMD is one of the major causes of economic loss of cloven-hoofed animals in the world today. The assessment of dominant genotype/lineage and prevalent trends and confirmation the presence of infection or vaccination not only provides scientific basis and first-hand information for appropriate control measure but also for disease eradication and regaining FMD free status following an outbreak. Although different biological and serological approaches are still applied to study this disease, ELISA test based on the distinct format, antigen type and specific antibody reinforce its predominance in different research areas of FMD, and this may replace the traditional methods in the near future. This review gives comprehensive insight on ELISA currently available for typing, antigenic analysis, vaccination status differentiation and surveillance vaccine purity and content at all stages of manufacture in FMDV. Besides, some viewpoint about the recent advances and trends of ELISA reagent for FMD are described here.More than 100 studies regarding ELISA method available for FMD diagnosis, antigenic analysis and monitor were thoroughly reviewed. We investigated previous sagacious results of these tests on their sensitivity, specificity.We found that in all ELISA formats for FMD, antibody-trapping and competitive ELISAs have high specificity and RT-PCR (oligoprobing) ELISA has extra sensitivity. A panel of monoclonal antibodies to different sites or monoclonal antibody in combination of antiserum is the most suitable combination of antibodies in ELISA for FMD. Even though from its beginning, 3ABC is proven to be best performance in many studies, no single NSP can differentiate infected from vaccinated animals with complete confidence. Meanwhile, recombinant antigens and peptide derived from FMDV NPs, and NSPs have been developed for use as an alternative to the inactivated virus antigen for security.There is a need of target protein, which accurately determines the susceptible animal status based on the simple, fast and reliable routine laboratory test. A further alternative based on virus-like particle  in combination of high throughput antibody technique (Phage antibody library/antibody microarray) may be the powerful ELISA diagnostic reagents in future. Foot and mouth disease(FMD) is a highly contagious and economically devastating disease of cloven-hoofed animals which hold a wide of the host spectrum such as cattle, pigs, sheep, goats, buffalo, deer, antelope and wild pigs and can severely constrain international trade of animals and animal products. FMD is caused by FMD virus (FMDV), a virus in the genus Aphthovirus within the family Picornaviridae . The genTypical Clinical signs of FMD are characterised by a vesicular condition of the feet, buccal mucosa, rhinarium and the mammary glands of the females. Therefore, FMD cannot be differentiated clinically from other vesicular diseases, such as vesicular stomatitis, swine vesicular disease and vesicular exanthema. As a result, laboratory diagnosis of suspected FMD cases became a matter of significance.Although methods based on virus isolation or the demonstration of FMD viral antigen or nucleic acid in samples of tissue or fluid or culture products is sufficient for a positive diagnosis, in general, the ELISA ,7 using A serotype-specific Mab-based antigen detection ELISA in use at the Istituto Zooprofilatico Sperimentale, Brescia, Italy , relies Currently, there is a little FMDV antigen detection test that employs the use of serotype-independent cross-reactive reagents. To aid improved diagnosis, Muller et al.  developeOwing the characteristics of quasispecies, natural isolate FMD viruses derived from different outbreaks showed much antigenic difference, which generally results in vaccine lacking effective protection against those FMD epidemic strains and even causing FMD outbreak. It is, therefore, an essential part of the epidemiological survey to assess regularly the antigenic characteristics of field isolates. Continuous monitoring of the antigenic relationship of field isolates in relation to the reference vaccine strain will provide an up to date knowledge about the efficacy of the vaccine virus in use and also has access to select the most suitable vaccine strains in case of emergency vaccination. Antigenic profiling by ELISA using panels of well-characterised MAbs  is suitaSince monoclonal antibodies define a specific region, a large number of viruses can be analyzed against a panel of Mab in a single test . Such stControl of FMD mainly encompasses vaccination and slaughter policy, particularly for the FMD-free countries, and slaughter policy is considered a fundamental measure. However, some restrictions from economic situation, social culture, geographical and natural environment limit this policy to be applied in a large-scale range in the endemic areas. Consequently, vaccination or the combination policy of vaccination and slaughter remain the most effective countermeasure against FMDV. Though different type of vaccine comprising subunit vaccine, peptide vaccine, DNA vaccine are developed, FMD inactivated vaccine still play a key role in control campaigns and eradication of FMD  in the m3D Protein 3D, also known as the virus infection associated antigen (VIAA) since antibodies to this antigen would be detected in serum from recovery animals [ animals , is the  animals  and resp animals .The antigenicity of 3D protein is highly conserved among all serotypes , holding3B Protein 3B, also known as VPg, is the viral genome-bound protein. It exists in three nonidentical copies and covalently bound to the 5' end of the genome and serves as a primer for virus genome replication [lication . Besideslication . An epitlication  to evalu3ABC The polypeptide 3ABC, playing an important role during the different stages of viral replication [lication -67, is plication -71. In olication ,72,73 walication  establislication  modifiedlication  establislication ,78.However, the NSPs expressed in E. coli and baculovirus expression systems may sometimes create problems in the interpretation of the results on account of non-specific reactions. Furthermore, the number of epitopes found on such a long recombinant protein may interfere with antibodies to other Picornaviruses ,79,80. MOther NSPs or NPs ELISAs based on other NSPs and NPs or assays using infection-specific epitopes of NSPs to remove cross reactivity are being explored [explored ,80,81. Mexplored . The funexplored ,86. Howeexplored , using aexplored  reportedUsually, the effectiveness or immunogenicity of the vaccine depends to a large extent on the content of 146S and the stability of these particles after virus inactivation procedures and formulation into vaccines. In the past, the most common method for the quantification of the FMD whole virus particle is either CsCl, or linear sucrose density centrifugation procedure , both ofFMD, which is an acute, contagious disease of cloven-hoofed animals, has caused huge economic losses since the finding and is still prevalent in many parts of the world. Though different approaches are used, the ELISA assay has been actively studied in terms of examination, variation, and diagnosis research of FMD. A preliminary study of ELISA was aimed at typing FMDV different serotype, and subsequent was used to identify antigen epitopes and evaluate the relationship or the variant degree between reference virus and isolated strains or circulating strains. Currently, ELISA was designed to exploit their potential in differentiating infected from vaccinated animals or carriers and quantitation virions during different stages of vaccine production, particularly in manufacture of pre-production, in-process and final products test. Although theoretically the detection of antibody to NSP's must indicate infection rather than vaccination, but in practice, antibody against NSPs also might be provoked by trace amounts of NSP's existed in commercial vaccines and multiple vaccinations. Therefore, currently no test has been fully validated. Whereas, a popular viewpoint from international NSP test validation at Brescia is that the usage of multi-NSP test will acquire the most suitable combination of tests and increase the efficiency of detection ,94. FurtRegardless of the target (antigens or serum), as the core reagent of ELISA, antibody, particularly a large number of monoclonal antibody against FMD virus different regions of SP and NSP was prepared -107. AccThe risk of virus release is the primary consideration for most researchers in the choice of virus antigen. To address this limitation, recombinant proteins and peptide derived from FMDV NPs and NSPs have been developed for alternative to whole-virus and inactivated virus antigen. However, the narrow antigenic epitopes harboring in such antigens have generally been insufficient to either afford solid protection of natural hosts or potent test. But empty capsids maintain continuous and discontinuous B-cell epitopes and T-cell epitopes presenting in authentic virions -114 and The authors declare that they have no competing interests.LNM contributed to the original draft of the manuscript, and approved the final version. JZ and HTC contributed to conception and design of the manuscript, and involved in revising the manuscript. JHZ and YZD helped to provide information and suggestion. YSL is the corresponding author. All authors read and approved the final manuscript.