This letter advises the imminent formation of the Companion Animal Parasites Council for the Tropics (CAPCT). The CAPCT consists of region-specific  experts comprising academics, veterinarians, parasitologists, physicians and allied industry partners that will work together to inform, guide and develop best-practice recommendations for the optimal diagnosis, treatment and control of companion animal parasites in the tropics, with the aim of protecting the health of pets and that of the public. Nanophyetus salmincola in the Pacific Northwest of the United States and Canada and Heterobilharzia americana, the cause of canine schistosomiasis in south-eastern United States, information and guidelines are highly region-specific. Whenever possible to do so, the guidelines put forward by experts of CAPC and ESCCAP are evidence-based, extracted from comprehensive well-resourced epidemiological and clinical-based studies and updated frequently to cover the latest research.Both the European Scientific Council of Companion Animal Parasites (ESCCAP) and the Companion Animal Parasite Council (CAPC) in the United States are independent, non-profit making organisations consisting of experts in the field of parasitology and public health from across Europe and the United States, respectively. Initially convened in 2002 (CAPC) and 2005 (ESCCAP), the role of these organisations is to develop recommendations for the optimal treatment and control of companion animal parasites with the aim of protecting the health of pets and the health of the public by reducing the risk of zoonotic parasite transmission. The websites comprehensively present the life cycles, diseases, diagnosis, control, prevalence and distribution maps of a wide variety of endoparasites and ectoparasites of dogs and cats. In so doing, the guidelines aim to increase awareness and educate practicing veterinarians and public health professionals of the most relevant parasites within each region and provide guidance for specific best-practice procedures to protect pets and the public from parasitic infections. For the majority of globally distributed parasites that the recommendations for the geographic regions CAPC and ESCCAP represent, there is overlap, owing to commonalities in mode of transmission and risks of exposure of the respective parasites to pets and humans. For others that are restricted geographically, for example the trematode http://data.worldbank.org/about/country-and-lending-groups). Transmission of parasites is therefore particularly high in these less-industrialized nations. In addition, the demographics of dog and cat populations in these respective regions and countries are far from being comparable to Europe or North America. The co-existence of true companion animals with semi-domesticated and stray animals alike, contribute to the challenge of parasite control programmes. Veterinary awareness and treatment of animals may be lacking and environmental and sanitary conditions conducive for their transmission [Toxocara, Ancylostoma and Echinococcus. The diseases caused by these parasites are recognised by the WHO/FAO/OIE as ‘neglected zoonotic diseases’ that form under the umbrella of ‘neglected tropical diseases’ . Their strategic control requires the application of integrated, multidisciplinary input involving both veterinarians as well as public health practitioners. The term “neglected” highlights diseases that affect mainly poor and marginalised populations in low-resource settings that receive little attention in terms of investment in research towards their surveillance, treatment and control [A plethora of arguments stand in favour of developing companion animal parasite prevention and best-practice guidelines for the regions spanning Southeast Asia, the Pacific Islands, Northern Australia, South Asia (including India), Latin America and Africa, otherwise known as the ‘tropics’, the geographical area between the Equator and the Tropics of Cancer and Capricorn. The region is predominantly characterised by hot, humid weather, but also includes other climatic zones, namely the seasonally dry tropics, mountainous and less commonly, arid zones. These climatic conditions support a diverse range of pathogens and vectors of medical and veterinary importance, whose transmission and geographical distribution are closely linked to regional temperature, rainfall, humidity and soil type. The wet tropics in particular, favour an unrivalled animal and plant biodiversity. The high burden of disease transmission is exacerbated by the fact that despite varied economic, political and social histories, almost all of the tropical countries remain underdeveloped with the majority being classified as low to middle income countries by The World Bank . Toxocariasis is an important zoonosis that may manifest as visceral larva migrans, ocular larva migrans, or as non-specific, mild symptoms referred to as ‘covert’ or ‘common’ toxocariasis. Toxocariasis has been shown through seroprevalence studies to be especially prevalent among children from socio-economically disadvantaged populations [Toxocara eggs are capable of surviving for several years in optimal environments [For example, the higher infection pressure of parasites within the tropics, as distinct from cooler climes, can be demonstrated using ulations , especiaulations . Seropreulations ; 49 % inulations ; betweenulations , 9 and aulations . This isulations , 6.6 % iulations , 0–4.2 %ulations  and 8.6 ulations . Toxocarronments  and therDioctophyme renale, the giant kidney worm of dogs is endemic , patients may not be appropriately diagnosed or treated if veterinarians fail to consider the parasite as a differential cause of chronic dysuria and haematuria and occasionally, peritonitis. In Southeast Asia, control of Clonorchis sinensis and Opsithorchis viverrine relies on educating owners not to provide their animal access to raw fish. For others, differences in pre-patent period may also have important implications on timing of anthelmintic administration. Ancylostoma ceylanicum for example, has emerged as the dominant species of hookworm infecting dogs and cats in the Asia Pacific region with a reported prevalence of between 35 and 72 % in India [A. ceylanicum in dogs and cats is its relatively short pre-patent period of only 14 days compared with other major helminths [For other parasites, that are more restricted in distribution, knowledge about their impact as an agent of veterinary or human disease relies largely on local research and knowledge. The prevalence of these parasites may depend solely on the distribution of region-specific intermediate hosts (vectors) or be strongly influenced by sylvatic factors or anthroponotic behaviours and therefore necessitate more specific guidelines for their diagnosis and control. For example, in areas where in India , 17, 92 in India , 52 % inin India , 69–77 %in India , 21, andin India . In addiin India . A specielminths . In heavDirofilaria immitis from the relatively benign subcutaneous nodule worm, Dirofilaria repens in areas where these filarial worms are co-endemic is critical for companion animal veterinarians. For example, in Vietnam, northern India and Thailand, veterinarians must be vigilant in their choice of antigen test kit for detecting heartworm infection and with correctly identifying microfilaria in blood films; and combining these with the individual’s clinical presentation and ancillary test results, prior to making a definitive diagnosis of heartworm disease. Furthermore, in many of these heartworm-endemic countries , the compound melarsomine (registered as an adulticide), is either unavailable or rarely utilised as part of the heartworm treatment regime. Instead, ‘slow kill’, using macrocyclic lactones only, a method strongly discouraged by the American Heartworm Society (https://heartwormsociety.org), is routinely practiced throughout the tropics. “Slow kill” is not only ineffective, but leads to the selection of macrocyclic lactone resistant sub-populations of heartworms [The importance of distinguishing artworms .https://www.avma.org, 2012; http://www.fediaf.org, 2010). In contrast, three quarters of the dog population in developing regions of the tropics may be classified as stray or free-roaming community dogs. These may equate to as high as 1 dog to 5 people in Kathmandu, Nepal and Bali, Indonesia; 1 dog to 4 people in the Philippines and Bolivia and 1 dog to 3 people in rural Mexico [http://www.euromonitor.com/pet-care, 2014). Similar trends were recorded for the Philippines (+38 %), Venezuela (+30 %), Argentina (+20 %) and Brazil (+14.3 %). In these regions, the rapidly urbanising middle class appear to be working more, earning more and living in city apartments sharing close relationships with pet dogs. The close human-animal bond has undoubted mental and physical benefits [Companion animal populations can be divided into two major categories - pets (owned and supervised) and strays. Strays may be further classified according to their dependence on humans, namely unowned free-roaming , and owned free-roaming (community dogs) . In the l Mexico . These al Mexico . For exaThe benefits of economic growth and affluence also place an increasingly higher expectation and demand on veterinary practitioners by animal owners for improved standards of service in healthcare for their pets, and protection of their family from acquiring zoonoses. In developing nations, veterinarians are deemed at the forefront when managing the risk of zoonotic diseases . The proToxocara spp. in puppies, which consists of de-worming with appropriate anthelmintics at 2 weekly intervals until 8 weeks of age, and monthly thereafter. These recommended ‘intervals’ vary according to country. For instance, in Vietnam, Philippines and Malaysia veterinarians often de-worm puppies at 4, 8 and 12 weeks of age, followed by 2 to 4 times annually. Recommended de-worming intervals also vary according to local manufacturers’ guidelines, the perceived ‘risk’ of parasite infection by the veterinarian, their knowledge of the parasite’s life cycle and its clinical and zoonotic significance. In much of the tropics, resources to fund studies to address these issues are limited. Nevertheless, the past decade has seen a moderate increase in the published literature of research associated with companion animal parasites in tropical countries. Much of this has been focused on the surveillance and control of diseases that are zoonotic , rather than aiming to improve health standards of the animals themselves. There is, therefore, a significant gap in our knowledge about the significance and distribution of clinically important parasitic diseases of dogs and cats in much of the tropics. Furthermore, the average veterinarian’s ability to access relevant and up-to-date information about these diseases for their region is also a major factor that limits their ability to translate the research into everyday practice.Recently, region-specific guidelines for immunization of dogs and cats were published by the World Small Animal Veterinary Association Vaccination Guideline Group . The repThe combination of warmer climate, enhanced parasite life cycles, poor environmental sanitation and higher environmental contamination rates lead to significantly increased infection pressure for all animals and potentially pose a serious risk to the public. This risk extends to pets that are inadequately treated as puppies and adults, even if ‘occasionally’ walked outdoors. It is the opinion of the authors that there needs to be questions raised about the appropriateness of ‘standard’ parasite prevention protocols currently advocated by most companion animal clinicians in the tropics and a paradigm shift in the thinking of veterinarians with regard to treating dogs and cats.We propose formation of the Companion Animal Parasites Council for the Tropics (CAPCT). The CAPCT will consist of regional  experts comprising academic veterinarians, parasitologists, physicians and allied industry partners that will work together to inform, guide and make best-practice recommendations for the diagnosis, treatment and control of companion animal parasites in the tropics, with the aim of protecting animal and human health. The organization will seek input through close collaboration with the practicing veterinarians, medical and public health professions, regional government and non-for-profit bodies. In addition to biannual meetings, the Council will organize veterinary and public outreach events in each region to facilitate transfer of knowledge through local lectures, workshops, symposia within local conferences and webinars to primary stakeholders such as veterinarians and breeders. General and region-specific recommendations for the treatment and control of companion animal parasites will be developed and made available through a dedicated, freely accessible website.


There are some unsolvable fundamental questions, such as cell type classification, neural circuit tracing and neurovascular coupling, though great progresses are being made in neuroscience. Because of the structural features of neurons and neural circuits, the solution of these questions needs us to break through the current technology of neuroanatomy for acquiring the exactly fine morphology of neuron and vessels and tracing long-distant circuit at axonal resolution in the whole brain of mammals. Combined with fast-developing labeling techniques, efficient whole-brain optical imaging technology emerging at the right moment presents a huge potential in the structure and function research of specific-function neuron and neural circuit. In this review, we summarize brain-wide optical tomography techniques, review the progress on visible brain neuronal/vascular networks benefit from these novel techniques, and prospect the future technical development. The brain is the most sophisticated, complex and significant organ in the bodies of humans and other higher organisms. The brain is the seat of action and cognition; however, its function is hindered by various neurological and mental diseases. Thus far, the structure and functions of the mammalian brain remain largely unknown. Elucidating the structure and functions of the brain is one of the most challenging research subjects since the Human Genome Project  techniques for the brain-wide optical tomography and the matchable labeling for neuronal/vascular networks; and (2) application of brain-wide labeling and optical imaging, which include neuronal morphology, long-distance projection of the specific labeled neurons, and cytoarchitecture and vascular networks. Challenges are also discussed in the final part of prospectives.in vivo tissue. To study neural circuits spanning vast volumes, these conventional methods have to be improved to label the whole brain or tissue uniformly. Luo’s group modified the Golgi-Cox , serial two-photon tomography (STP) and micro-optical sectioning tomography (MOST).Dodt et al. combined LSIM  method, combining laser tissue ablation by amplified ultrashort laser pulses with two-photon excitation imaging by unamplified pulses   , which features a knife-collimator assembly of providing illumination as well as the means to cut individual sections of tissue  of a whole mouse brain with micrometer resolution , STP (by TissueVision) and MOST (by OeBio)]. Developments in whole-brain optical imaging will open a new chapter in neuroscience research.The brain’s complexity is exemplified by its variety of neuronal cell types Huang, . DiffereThe diversity of neuronal subtypes is first reflected in their morphology. Whether in different brain areas or in the same brain area, the vast variation in neuronal morphologies provides an abundance of natural distinctions that facilitate neuron classification. Criteria for the classification of neuron subtypes remain in dispute  technology and magnetic resonance imaging (MRI), the brain-wide live imaging and localization of large vessels have been achieved at 20 μm isotropic resolution (Dorr et al., In recent years, brain-wide optical tomography has been well developed, promoting the acquisition of neural anatomical information at single-neuron resolution. However, much remains to be explored in the complicated brain. Additionally, rodent models have obvious limitations in terms of understanding the advanced functions and dysfunctions of the human brain and the corresponding drug research. We are sure that non-human primates are better models to deal with the question, and even humans. Therefore, future studies must be conducted in a systematic and multi-disciplinary way and must include sample labeling and imaging techniques, as well as methods for processing big image data.Optical labeling and imaging techniques that enable the fine structural characterization of neuronal networks from a large volume of brain tissue with high accuracy and efficiency still present a challenge. During the imaging process, the somas of marked neurons emit much more light than their axons and dendrites. To reduce the influence of the high intensity of light coming from the soma, the neuron must be marked sparsely, while the axons and the dendrites must contain stable, high-intensity fluorescence. Then the precious signal must remain strong until all digitized intensity distribution is recorded. Meanwhile, developing sectioning and imaging techniques with better SNR and spatial resolution is urgently needed. The resolution of whole-brain optical imaging technology should be improved from one μm to several hundred nms and may even break the optical diffraction limit. Moreover, to study the decimeter-sized primate brain, available effective specific labeling techniques, such as CLARITY (Chung et al., With the increasing imaging resolution and sample volume, massive amounts of data are being obtained at an unprecedented rate, exceeding the processing capability of current hardware and software technologies, which have contributed to the increasing problem of “big data”. The 3D mouse brain data set in Li et al.  is 8 TB Establishing more effective research strategies is a necessity, in addition to considering the scientists, research facilities, and methods and techniques devoted to this area. Referring to the Human Genome Project, international cooperation under the guidance of the roadmap presents an important alternative to independent project teams. The Allen Institute for Brain Science in the USA has already made many beneficial attempts, starting in 2003. In addition, the integration and application of current knowledge is another area that should be a focus (Akil et al., The neuroscience boom is well underway. How are neural circuits organized? How are they interconnected? How many types of neurons exist in the brain? These questions can be addressed by the interdisciplinary cooperation between researchers in the fields of neuroscience, optics, engineering, chemistry, computer science and statistics.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.


Long non-coding RNAs (lncRNAs) are important regulators of gene expression that influence almost every step in the life cycle of genes, from transcription to mRNA splicing, RNA decay, and translation. Besides their participation to normal physiology, lncRNA expression and function have been already associated to cancer development and progression. Here, we review the functional role and mechanisms of action of lncRNAs in normal hematopoiesis and how their misregulation may be implicated in the development of blood cell cancer, such as leukemia. In the last decade, the family of regulatory RNAs has undergone a sudden expansion with the discovery and the functional characterization of long non-coding RNAs (lncRNAs). LncRNAs generally indicate ribonucleic molecules longer than 200 nucleotides without defined open reading frames. To date, the number of human lncRNAs is in the range of ~10,000 transcripts and, for some of them, the involvement in important regulatory circuits of gene expression has been identified .In the last few years, a large amount of sequence data have been generated, which allowed the identification of thousands of lncRNAs expressed in different cell types and stages of development . DiffereSeveral lncRNAs have been already found in the development of blood cells, even if the majority has not yet been functionally characterized. One of the first to be identified was the Eosinophil Granule Ontogeny lncRNA EGO . This noProfiling of lncRNA expression during differentiation of monocytes into dendritic cells (DCs) identified lnc-DC . Lnc-DC + T-cells identified 29 lncRNAs specific for these lymphocytes, and, more importantly, 21 out of them were modulated during memory T-cell differentiation, 81 during lymphocyte activation, and 4 during both transitions. A more comprehensive analysis of lncRNA expression during T-cell development was performed from 42 different T-cell types at various developmental and differentiation stages by using RNA-seq  is generally characterized by mutations that activate the NOTCH1 signaling . The lncA microarray analysis of lncRNAs from chronic myeloid leukemia (CML) with Bcr–Abl translocation identified the Beta Globin Locus 3 (BGL3) lncRNA . This lnAnother lncRNA involved in acute myeloid leukemia (AML) is IRAIN , which iThe well-known X-inactive specific transcript Xist lncRNA, an important regulator of X-chromosome inactivation in mammals, is aberrantly expressed in different human cancer, including leukemia . Xist prLong non-coding RNAs have been profiled from patients with citogenetically normal (CN) AML . DistincIn the next future, we will witness a comprehensive identification and functional analyzes of lncRNAs expressed during all stages of hematopoiesis and in multiple species, which will contribute to better defining the role of these molecules in blood cell development. Thus, it seems safe to predict that many new functional lncRNAs will be identified. Furthermore, lncRNAs might have diagnostic applications, with changes in their expression already associated with different classes of leukemia, regardless of function.in cis, are present in only few copies per cell and might not be considered in functional studies. Moreover, different functions might be active in different cells and at different developmental stages. LncRNAs can be very long, even several thousand nucleotides, which fold in complex three-dimensional structures to act as molecular scaffolds. Indeed, a single lncRNA molecule might carry out a large number of functions within the cells by interacting and cooperate with different cell-specific interactors (both proteins and nucleic acids) or by localizing in specific compartments. A large amount of sequence data have been generated in last few years, which already allowed the identification of thousands of lncRNAs expressed in different stages of hematopoietic development but most studies merely identify functional lncRNAs without explaining how these molecules act within the cell. This has further generated the need to develop new experimental tools to identify and analyze lncRNA mechanisms of action. Furthermore, targeted deletion studies in primary cells, or animal models when applicable, will be necessary to assess the specific functions of lncRNAs involved in normal and malignant hematopoiesis.It is very likely that the established molecular circuitries known to control blood cell differentiation will need to be reevaluated in the light of the contribution of this complex class of non-coding transcripts. However, the identification of functional molecules and, above all, the mechanisms by which they can regulate gene expression is still challenging for the field. Many lncRNAs, especially those acting Another important aspect to consider is the fact that, despite the advantages of RNA-seq in terms of sensitivity and accessibility, the assembly of transcript models from short reads is still limited and the bioinformatic tools utilized often provide different outcomes from same raw data. Therein, the lists of lncRNAs identified in different studies from the same cell type do not always coincide. In the next future, the development of technologies for long reads sequencing that minimize the bioinformatic assembly of novel transcripts will be of great help to standardize and unify the many different existing lists of lncRNAs.In conclusion, similarly to the most famous microRNAs, lncRNAs will become subject of several studies in normal and malignant hematopoiesis that, hopefully, will help to determine the therapeutic significance of lncRNAs in leukemia.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.


The neural crest and somites, progenitors of the peripheral nervous system and of skeletal tissues, respectively, beautifully illustrate the significance of EMT to the above processes. Ongoing studies progressively elucidate the gene networks underlying EMT in each system, highlighting the similarities and differences between them. Knowledge of the mechanistic logic of this normal ontogenetic process should provide important insights to the understanding of pathological conditions such as cancer metastasis, which shares some common molecular themes.Epithelial-to-mesenchymal transition (EMT) is a central process during embryonic development that affects selected progenitor cells of all three germ layers. In addition to driving the onset of cellular migrations and subsequent tissue morphogenesis, the dynamic conversions of epithelium into mesenchyme and  In vertebrates, epithelium and mesenchyme are basic tissue phenotypes. Epithelial–mesenchymal transitions (EMT) and the reverse process, mesenchymal–epithelial transitions (MET) are critical for development of many tissues and organs in the embryo. Epithelial and mesenchymal cells differ in phenotype as well as function. Epithelial cells are closely connected to each other by tight junctions, gap junctions and adherens junctions, have an apico-basal polarity characterized by polarization of their actin cytoskeleton and a basal lamina at their basal surface. Mesenchymal cells, on the other hand, lack this polarization, have a spindle-shaped morphology and interact with each other only through focal points . Neural At the population level, both NC and somites are multipotent and yield a rich assortment of derivatives. The vertebrate NC is the source of neurons, glia and Schwann cells of the peripheral nervous system . It also generates pigment cells of the skin, chromaffin cells in the adrenal gland, and additional endocrine derivatives ,3. The NAnother salient organizational feature of vertebrate embryos is the segmental organization of the paraxial mesoderm closely aligned on both sides of the axial organs, the NT and notochord, and medially localized with respect to the intermediate and lateral plate mesoderms. Laid down during gastrulation, the unsegmented mesoderm progressively epithelializes via a process of MET and subdivides to generate somites. These are transient sphere-like structures that set the basis for the segmental organization of skeletal derivatives, as well as that of peripheral ganglia and nerves ,9,10,11.Several characteristics are shared by both systems. For instance, the dorsal region of the NT that generates NC cells and the paraxial mesoderm-derived somites are composed of pseudostratified epithelia in which progenitor cells undergo interkinetic nuclear migration and exhibit typical patterns of cell proliferation ,17,18. SComparable processes take place in the DM, which is composed of four contiguous lips and a central sheet. Whereas the lips produce myocytes over a few days while remaining epithelial, the central sheet completely dissociates to produce dermis and mitotic progenitors ,24,25,26An additional common feature is the existence of long and short-range cellular migrations that follow initial EMT. For instance, studies performed in avian embryos revealed that NC progenitors that form sympathetic ganglia migrate a long distance from the dorsal NT toward the dorsal aorta, and then along the aorta for a length of three consecutive somites rostral and caudal vis-à-vis their exit point in the NT . A similLikewise, the ventrolateral lip of the DM at brachial and lumbosacral levels of a variety of species undergoes EMT and Pax3/7-positive progenitors migrate a long way into the limb primordia to generate the appendicular muscles . In addiAltogether, NC and dorsal somite progenitors share many similar traits during both epithelial and mesenchymal states. Nevertheless, heterogeneity in EMT patterns and migratory behavior are apparent within each system along the axis and at various stages. Undoubtedly, in both systems, EMT is a prerequisite and a driver for further cell migrations, events that are essential for proper morphogenesis. Since the above ectodermal and mesodermal progenitors yield a rich variety of derivatives, a fundamental question is whether the epithelia of origin are composed of naïve precursors or, alternatively, of fate-restricted cells. In the former case, one would postulate that cell fate decisions occur during migration or at the homing sites thus imposing the search for responsible mechanisms that operate after EMT. In the latter event, research should focus on mechanisms operating within the epithelium itself that would account for the emergence of an early heterogeneity. Hence, the epithelial–mesenchymal status of these early precursors may directly or indirectly be associated with the acquisition of final cell identities, as discussed elsewhere .A significant body of evidence, primarily stemming from avian embryos, relates the onset of NC migration in the trunk with somitogenesis and subsequent somite dissociation ,37. At tWnt1 transcription and Wnt-dependent canonical signaling, triggers EMT of NC progenitors and the consequent onset of cell migration [noggin transcription and activity that correlates with somite development. Downregulation of noggin progressively relieves inhibition of BMP and allows NC EMT ,104etc. Having the knowledge of conservation of upstream signaling pathways, of downstream genes coding for transcription factors and of effectors leading to changes in apico-basal polarity, cell adhesion, cell motility and extracellular matrix assembly, we are now able to build functional networks that underlie EMT in different biological systems and compare them between normal and diseased states.in vivo analysis when compared for instance to that performed in isolated tissues or explants. In addition, many effector proteins exhibit a heterogeneous subcellular distribution , imposing the need for a careful planning of experiments that considers this spatial and temporal dynamics both in single cells and at the level of whole tissue behavior.Since cell–cell interactions mediate the availability and duration of responsiveness to ligands, great importance should be given to the tissular context used for investigation, as significant changes (and thus different interpretations) may stem from complex More generally, translating insights on EMT and MET processes from development biology to pathological states will advance the field and help realize its full potential in drug discovery, preclinical models of human disease, and ultimately clinical applications.


Milk is synthesized by mammary epithelial cells of lactating mammals. The synthetic capacity of the mammary gland depends largely on the number and efficiency of functional mammary epithelial cells. Structural development of the mammary gland occurs during fetal growth, prepubertal and post-pubertal periods, pregnancy, and lactation under the control of various hormones  in a species- and stage-dependent manner. Milk is essential for the growth, development, and health of neonates. Amino acids (AA), present in both free and peptide-bound forms, are the most abundant organic nutrients in the milk of farm animals. Uptake of AA from the arterial blood of the lactating dam is the ultimate source of proteins  and bioactive nitrogenous metabolites in milk. Results of recent studies indicate extensive catabolism of branched-chain AA  and arginine to synthesize glutamate, glutamine, alanine, aspartate, asparagine, proline, and polyamines. The formation of polypeptides from AA is regulated not only by hormones  and the rate of blood flow across the lactating mammary gland, but also by concentrations of AA, lipids, glucose, vitamins and minerals in the maternal plasma, as well as the activation of the mechanistic  target rapamycin signaling by certain AA . Knowledge of AA utilization (including metabolism) by mammary epithelial cells will enhance our fundamental understanding of lactation biology and has important implications for improving the efficiency of livestock production worldwide. Milk consists of water, protein, lipids, carbohydrates (mainly lactose), minerals and vitamins, and is the secretory product of mammary epithelial cells (MEC) in all lactating mammals –62 Tabl. The mamMilk is essential for the growth, development, and health of mammalian neonates. In livestock species , milk production is a limiting factor for maximum preweaning growth and survival of offspring , 64, 66.Mammals have a highly developed brain and complex body systems . It usuaMilk composition varies among species Table  or breedA variety of causes, including low birth weight and inadequate provision of milk, lead to high pre-weaning mortality and poor performance of livestock neonates . For exaA sow must produce 18–20 kg milk/d to nurse a litter of 9 piglets, so that the neonates will have enough energy and protein to grow at a rate comparable to artificially-reared piglets of the same age . In pigsThe pig is an animal model widely used in studies of lactation biology . Sows haAA are building blocks of proteins that regulate metabolic pathways for whole body homeostasis . LactatiThe overall pathway of BCAA catabolism in the lactating mammary gland is depicted in Fig. The BCAA-derived BCKA undergoes oxidative decarboxylation by the mitochondrial BCKA dehydrogenase complex (BCKAD) . This ende novo synthesis of glutamate and glutamine helps to explain the high abundance of these two AA in both free and peptide-bound forms in milk , in the regulation of protein synthesis in animal cells has been well defined . ProteinDuring lactation, constitutive proteins are actively synthesized by cells of the mammary gland that may account for 40 to 70 % of total mammary protein synthesis . In lactMilk is of supreme importance to survival, proper development, and dynamic growth of the neonate. Furthermore, lactation is an integral component of the highly successful reproductive strategy of mammalian species. In fact, development of the mammary gland, which is affected by the provision of AA, is closely linked to the reproductive cycle of all mammalian species. The synthetic capacity of the mammary gland depends largely on the number and efficiency of functional MEC and directly correlates with subsequent growth of suckling neonates. In the lactating mammary gland, BCAA are extensively transaminated with α-ketoglutarate to produce glutamate and BCKA, with glutamate being an essential substrate for synthesis of several AA . Moreover, some of the BCAA carbons are either oxidized to provide ATP in mitochondria or utilized for lipid synthesis in the cytosol. Leucine, glutamine and arginine stimulate the mTOR cell signaling pathway to enhance protein synthesis and milk production. At present, there is a paucity of information about the metabolism of AA other than BCAA and arginine in the lactating mammary tissue or MEC. For example, it is unknown whether a severe deficiency of glycine in the milk of species   results


Tumor drug resistance is the leading cause of chemotherapy treatment failure. One of the more relevant mechanisms is represented by multidrug resistance (MDR) that leads to a reduced cellular accumulation of drugs due to increased efflux out of cells by the overexpression of several ATP-dependent efflux pumps or transporters. These proteins belong to the ATP-binding cassette (ABC) family and the most studied of them is P-glycoprotein (P-gp). Interestingly, P-gp acts as an efflux pump for various structurally unrelated anticancer agents , 2.in vitro MDR tumor models, and describe potential strategies to overcome MDR.The aim of this issue, that includes nine contributes, is to highlight mechanistic aspects of the P-gp functions, provide information on the development of Sharom  highlighOn the other hand, Fu  introducMcDermott et al.  provide Until now, the scientific history of MDR-reversing strategies has been characterized by a repeated series of failures: indeed, the pharmacological inhibitors of the ABC transporters, such as P-gp, MDR-related proteins (MRPs), breast cancer resistance proteins (BCRP), have not reached the sufficient specificity and efficacy to be translated into the clinical practice.Recently, however, the design of ABC transporters inhibitors has been progressively more refined, e.g., the creation of small libraries of compounds starting from versatile scaffolds or the use of dual effect drugs or multitarget drugs  can increase the selectivity and potency of transporter inhibitors and modulators, as described in the topic of Zinzi et al. . AlthougA second approach to improve the selectivity of chemosensitizing agents against MDR cells is the use of nanoparticles, for the active targeting of chemotherapeutic drugs, chemosensitizing agents or siRNA within the resistant tumor as proposed in this topic by Conde et al. . SeveralCancer stem cells (CSCs) exhibit several mechanisms of resistance against anticancer drugs that are mainly represented by the expression of ABC transporters and activation of different signaling pathways . Thus, compounds able to modulate MDR on CSC membranes could induce cytotoxicity in these cells, as described by Zinzi et al. .Two models have been suggested to explain the connection between MDR and CSCs: the “original” MDR model according to which, after exposure to the chemotherapeutic agent, only CSCs expressing ABC transporters repopulate the tumor, and the “acquired” MDR model according to which after chemotherapy, only CSCs survive and this population of survival cells, after mutations, originates new and more aggressive drug-resistant cell phenotypes. Thus, the combination of CSC targeting agents with novel or conventional cytotoxic drugs could lead to a potentiated effect. An innovative multimodal strategy, i.e., an approach in which specific CSC targeting drugs exert simultaneously the ability to circumvent tumor drug resistance (by ABC transporter modulation) and to exert cytotoxic activity toward CSCs and the corresponding differentiated tumor cells, may be hypothesized.Targeting ABC transporters is a challenge not only limited to tumors cells but it also involves the tumor microenvironment in specific districts: as demonstrated in this topic by Adkins et al., breast cancer cells metastasizing within central nervous system are rich of P-gp and are surrounded by a complex vasculature expressing P-gp as well . This siin vitro drug-resistant tumor models, the understanding of the ABC transporter functions, the use of medicinal chemistry, the production of new nanomaterials, the analysis of the biochemical features of MDR cells, and the management of clinical trials. Such multidisciplinary approach is mandatory to open new perspectives against chemoresistant tumors.This topic has reviewed pharmacological strategies to overcome MDR. Fighting MDR involves multiple skills and know-how, including the ability to develop suitable 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.


Atherosclerosis is a multifactorial, multistep disorder of large- and medium-sized arteries involving, in addition to age, gender and menopausal status, a complex interplay between lifestyle and genetic risk factors. Atherosclerosis usually begins with the diffusion and retention of atherogenic lipoproteins into the subendothelial space of the artery wall where they become oxidized by local enzymes and accumulate, leading to the formation of a cushion called atheroma or atheromatous or fibrofatty plaque, composed of a mixture of macrophages, lymphocytes, smooth muscle cells (SMCs), cholesterol cleft, necrotic debris, and lipid-laden foam cells. The pathogenesis of atherosclerosis still remains incompletely understood but emerging evidence suggests that it may involve multiple cellular events, including endothelial cell (EC) dysfunction, inflammation, proliferation of vascular SMCs, matrix (ECM) alteration, and neovascularization. Actually, a growing body of evidence indicates that autophagy along with the chronic and acute overproduction of reactive oxygen species (ROS) is integral to the development and progression of the disease and may represent fruitful avenues for biological investigation and for the identification of new therapeutic targets. In this review, we give an overview of ROS and autophagy in atherosclerosis as background to understand their potential role in this vascular disease.  Reactive oxygen (ROS) and nitrogen species (RNS) are highly reactive molecules, either endogenously produced during normal metabolism in the body or exogenously introduced by the environment. Among these classes of molecules, those deriving from ROS have great biological impact because they are endogenously produced and can damage virtually all classes of macromolecules at high concentrations . ROS areThe key initiating event in atherogenesis is actually considered the disruption of endothelial cell homeostasis which upsets the balance between vasoconstriction and vasodilation and initiates an inflammatory tissue cascade both directly, by promoting the infiltration of inflammatory cells into the vessel wall, and indirectly, through the induction of cytokines and other inflammatory mediators, that ultimately leads to the structural and functional manifestations of the disease , 20. IntNADPH oxidases were first described in the membrane of “professional” phagocytic cells of the immune system, where the high levels of ROS actively participate in host defense mediating the killing of ingested pathogens . More re−/− mice, the most widely studied animal model of the disease. These mice are hypercholesterolemic and spontaneously develop atherosclerotic plaques along their aorta and major arterial branches thereof. Among all the NADPH members, Nox1 has received the most attention mainly because it can be activated and regulated by many physiological and pathological stimuli, such as AngII and PDGF. It is assumed, although not yet documented in human lesions, that elevated Nox1 expression might have an active role in the pathogenesis of atherosclerosis [(−/−) Nox1(−/y)] compared to the ApoE-null animals . Im. Im95].  plaques –100. TheThe involvement of oxidative stress in atherosclerosis development is well established. As already mentioned above, oxidative stress can be defined as an excessive amount of oxygen radicals inside and/or outside the cell, which is the net result of an imbalance between the production and neutralization of ROS. An increasing number of studies have consistently demonstrated that oxidative stress is of major importance in atherogenesis, especially for its participation in the oxidation of LDL . Indeed,Several lines of evidence indicate that ROS are the upstream modulators of autophagy and that oxidative stress coupled with defective autophagy may play a fundamental role in regulating atherosclerotic plaque development. The general consensus is that basal autophagy can protect plaque cells against oxidative stress by degrading damaged intracellular material and promoting cell survival. In contrast to basal autophagy, excessive stimulation of autophagy in SMCs and/or ECs may cause autophagic cell death, leading to reduced synthesis of collagen, thinning of the fibrous cap, plaque destabilization, lesional thrombosis, and acute clinical events. However, despite all the valuable knowledge gained in recent years, further work is still necessary to determine the importance of this phenomenon in human atherosclerotic plaque and to identify the critical regulatory networks that could serve as targets for preventive and therapeutic interventions. We need to understand how ROS and autophagy are induced in atherosclerotic lesions, the regulation processes governing their crosstalk and their mechanism of action, and how they could influence the biology of the plaque.


Background. To evaluate the correlation of fundus autofluorescence (FAF) with indocyanine green angiography (ICGA) in patients with various posterior uveitis disorders. Methods. Interventional case series including 23 eyes of 15 patients with diagnosis of a specific type of retinochoroiditis, such as acute posterior multifocal placoid pigment epitheliopathy (APMPPE), serpiginous-like choroiditis, multifocal choroiditis (MFC), Harada disease, and syphilitic retinochoroiditis. Also, some cases with undefined retinochoroiditis were included. FAF and ICGA were performed and correlated at baseline and during follow-up after treatment. Results. In ICGA, early hypofluorescence was found to be the hallmark of acute choroidal inflammation, resolving in later stages and remaining in the late phase in areas with retinal pigment epithelium (RPE) damage. Poorly defined hyperautofluorescent areas correlated with acute choroidal lesions. Hypoautofluorescent delineation suggested the initiation of RPE healing processes, correlating well with the late phase of ICGA and delineating the RPE damage. Early hyperautofluorescence with late hypofluorescence in ICGA indicated the presence of primary RPE involvement. Conclusion. FAF contributes to the interpretation of RPE disease and may be a useful tool for the follow-up of progressive inflammatory disorders. Comparative evaluation of FAF and ICGA allows a characterization of the sequence of inflammatory events and the level of tissue affected. Posterior uveitis is a general classification term, which includes various inflammatory disorders, affecting primarily the retina, the choroid, or both. In cases of multilevel involvement, discrimination of the initially or exclusively affected tissue allows a more precise classification into retinitis, choroiditis, or retinochoroiditis. Diagnosis and follow-up of posterior uveitis patients have evolved significantly with the advances in imaging technology, such as indocyanine green angiography (ICGA) and fundus autofluorescence (FAF). These imaging tools are complementary to the standard evaluation with fundoscopy and fluorescein angiography (FA) , 2.Retinal inflammatory diseases, manifesting mainly as vasculitis or necrotic retinitis, such as Behcet uveitis, ocular toxoplasmosis, and herpes-associated acute retinal necrosis, can be easily suspected or even detected during fundoscopic examination. In cases of suspected retinal vasculitis or secondary induced ischemia, FA is a very useful tool for the clinical diagnosis –7. HowevIn the last years, noninvasive FAF imaging has been introduced into the ophthalmological clinical practice, providing for the first time a qualitative measure of the status of RPE layer in terms of function and structure , 13. ThiIn an attempt to optimize diagnostic procedures, there is a need to identify the most informative and least invasive clinical protocol for the evaluation of posterior uveitis. To our knowledge, there is no published study to date exploring the correlation between ICGA and FAF in patients with different forms of posterior uveitis. This analysis may provide a better understanding of the diagnostic potential of noninvasive FAF imaging. In the current study, our aim was to investigate if the combined-mode imaging (ICGA+FAF) could provide useful additional information contributing to the diagnosis, follow-up, and treatment optimization in posterior uveitis.This study is an interventional case series conducted at the Department of Ocular Immunology and Inflammation of “G. Gennimatas” General Hospital in Athens, Greece. Informed consent was obtained from all participants. All procedures were done in adherence to the tenets of Declaration of Helsinki. The study was approved by the institutional ethics committee.All patients included in the study either were new referrals, with symptoms or signs of posterior segment inflammation, or were already diagnosed with uveitis, with a follow-up performed in our department. At baseline, all patients had a complete ophthalmological examination, including biomicroscopy and fundoscopy. In addition, FAF exam, ICGA, and FA were performed. A standardized ICGA protocol for posterior uveitis was followed , using tPharmacological treatment was prescribed when necessary. During the follow-up, FAF and ICGA examinations were repeated when the signs of acute inflammation subsided as a result of treatment or due to a self-limiting clinical course. Direct comparison was performed between baseline and follow-up images obtained with both FAF and ICGA to investigate the presence of clinically relevant correlations of the results obtained with the two imaging technologies. Likewise, the level of affected tissue at baseline and during follow-up was evaluated. The clinical course of each disease and its anatomic and functional impact on the eye structures were also documented.23 eyes of 15 patients with various types of posterior uveitis were included. Specific diagnosis was done based on the results of FAF, ICGA, OCT, and FA imaging in most of cases . All casDiscrete contiguous hypofluorescent areas of the posterior pole are characteristic of acute disease in ICGA. In our series, two different angiographic patterns were observed in different areas. In the first one, profoundly dark hypofluorescent patches appeared in the early phase of the ICGA exam and persisted throughout the complete sequence of the exam. In the other pattern, hypofluorescent areas appeared mainly in the late phase Figures .FAF imaging revealed well-defined lesions with stippled autofluorescence in the core and hyperautofluorescent (hyper-AF) borders, which were partially surrounded by hypoautofluorescent (hypo-AF) halos . These FIn the convalescent stage, the early phase hypofluorescent areas (seen acutely) seemed to have faded away in ICGA. On the other hand, late phase hypofluorescence remained unchanged. Correlation between FAF and late phase ICGA seemed to be much stronger in the convalescent compared to the acute stage in all cases. Figures .Four eyes of 4 patients with serpiginous-like choroiditis, in the presence of a positive Mantoux and Quantiferon gold test, were included. In the acute stage, ICGA revealed profoundly dark hypofluorescent areas during the complete sequence that surrounded areas of hyperfluorescence in a serpiginous or centrifugal pattern Figures . FAF imaIn the convalescent stage, the majority of early-acute hypofluorescent areas became invisible in ICGA after treatment application. There was an agreement between the late phase of ICGA and FAF images. Furthermore, a clearly defined hypo-AF rim delineated the periphery of the whole AF lesions, which seemed to have undergone a peripheral expansion compared to baseline Figures .In MFC, ICGA revealed multiple hypofluorescent spots which became more obvious and numerous in the late phase. These findings in the late phase of ICGA correlated well with hypo-AF lesions on FAF Figures . On furtIn the active/acute stage of the disease, ICGA revealed the presence of small hypofluorescent areas in the early phase that changed to a diffuse mottled hypofluorescence in the late phase. The latter largely corresponded with the diffuse hyper-AF area in the posterior pole as seen on FAF. SD-OCT showed a disruption of RPE and outer retina Figures .After finishing the appropriate treatment, a resolution of hypofluorescence in ICGA and hyper-AF in FAF was observed that was accompanied with the disappearance of inflammatory signs and gains in visual acuity Figures .In the acute stage of the disease, ICGA showed hypofluorescent dots in the early phase that were converted into hyperfluorescent spots in the mid and late phase. Large circular or oval areas of hypofluorescence  were found to be surrounded by hotspots. Figures . FAF imaTwo cases were classified as full-thickness inflammation of choroid and retina in the macular area. Their common characteristic was a significant macular hypofluorescence in ICGA that was compatible with choroidal ischemia Figures . FAF shoAs previously commented, there are specific diagnostic tools available in clinical practice, to evaluate the inflammatory disease of the posterior segment of the eye. These tools include standard methods, such as FA and ICGA, OCT, and the novel technology FAF, which is being increasingly utilized as a noninvasive imaging procedure in the field of uveitis. FAF imaging is based on the special fluorescence properties of various molecules found in ocular fundus collectively called “fluorophores.” These molecules can be excited by electromagnetic energy (light) to a higher energy level and then return to their previous state by emitting light of higher wavelength. The major source of autofluorescence in human fundus is lipofuscin. This term describes a heterogeneous group of fluorophores which are found in the RPE cells and are the end product of incomplete lysosomal digestion of phagocytosed photoreceptor outer segments. Increased fundus autofluorescence is observed with aging but also in pathologic conditions whereas decreased autofluorescence is noted in RPE atrophy and/or due to signal attenuation from other pigments , 29. In Most of cases included in our series were classified under the general term WDS that represents a wide spectrum of diseases, such as APMPEE, serpiginous choroiditis, and MCP. These conditions, despite the variability of the clinical manifestations, may share common pathophysiologic mechanisms. Recently, choriocapillaris inflammation and secondary ischemia have been proposed as the initial events in WDS. However, it remains controversial if the inflammatory sequence originates in other neighboring structures such as the RPE, as was initially hypothesized . A compaIn our APMPPE cases, ICGA provided better imaging of the disturbances occurring in the choroidal circulation. Acute inflammation of choriocapillaris layer with secondary ischemia is the initial event followed by a reperfusion state at a later, convalescent stage. ICGA allowed us to obtain a precise mapping of these stages that coexisted in discrete geographic areas at the posterior pole, in the form of multiple, polymorphous, and asynchronous patches. The analysis of the correlation between ICGA and FAF allowed us to obtain an accurate evaluation of the inflammatory impact occurring at the RPE level, in terms of time and extent. Well-defined FAF findings were apparent only in areas of reperfused choriocapillaris, suggesting an established RPE damage. In contrast, minimal, ill-defined, hyper-AF spots with fluffy margins correlated with areas of acute choriocapillaris inflammation, which imply that there was not remarkable initial RPE involvement at the time of primary disturbance in the choroidal circulation.During the convalescent stage, lesions in the late phase of ICGA and FAF presented a remarkable similarity in size and shape. According to these outcomes, both FAF and late phase ICGA seemed to delineate the whole area of functionally impaired RPE, remaining after the resolution of acute inflammation. FAF imaging had the additional advantage of providing more information on the evolution and age of lesions. Nevertheless, OCT imaging, used in a complementary fashion, can further detect functional and structural alterations of the outer retina induced by the ischemia of underlying choriocapillaris. Overall, the area of initial choriocapillaris damage seemed to be much more extensive than the final RPE involvement, considering that not all acute lesions observed in ICGA were transformed into an abnormal FAF signal in the subacute or convalescent stage. Obviously, the size of the acutely ischemic areas at the choriocapillaris level may be the critical factor for the conversion of ischemia into an established RPE damage. Relatively small ischemic lesions were found to fade away in the follow-up, not affecting the overlying RPE Figures .Acute choriocapillaris inflammation may be the initial site of the pathological process in tubercular serpiginous-like choroiditis as well. In our series, FAF clearly identified the area of established RPE damage that corresponded with the reperfused choriocapillaris layer underneath. Likewise, hyper-AF margins were shown to be an indicator of an active underlying choroidal inflammation. Similar evidence has been recently reported by Gupta et al. in a series of serpiginous-like cases with associated tubercular infection . In the Regarding MCP, the analysis of the correlation between the two imaging modalities, ICGA and FAF, did not show any significant discrepancy in the findings at the inner-choroid and RPE level, as observed in the acute stage of the previous entities evaluated. In this condition, FAF was found to provide a better and more precise imaging of the RPE involvement than ICGA or fundoscopy in the form of hypo-AF spots scattered in the posterior pole. As choroidal structures seemed to be minimally affected, ICGA did not reveal significant findings in the early phase. ICGA was demonstrated to be inferior to FAF in the imaging of defects, even in its late phase. Indeed, the superiority of FAF over ICGA was observed to be even more significant in cases with exacerbations. In these cases, new hyper-AF spots in sites of previously normal background AF were confirmed to be indicative of a progression of the disease . AccordiIn ASPPC, the primary inflammation in the posterior pole has been postulated to be of infectious origin at the RPE/outer retina with a placoid pattern . In our In the group of disorders classified as stromal choroiditis, a granulomatous inflammation within the choroidal stroma targeting the choroidal melanocytes has been proposed to be the underlying pathophysiologic mechanism . Harada In conclusion, the evaluation of the correlation of FAF and ICGA can provide clinically relevant and complementary information about the timing and extent of RPE involvement compared to inner-choroid structures in disorders of the choroid-RPE complex.


In Uganda maternal and neonatal mortality remains high due to a number of factors, including poor quality of care at health facilities.This paper describes the experience of building capacity for maternal and newborn care at a district hospital and lower-level health facilities in eastern Uganda within the existing system parameters and a robust community outreach programme.This health system strengthening study, part of the Uganda Newborn Study (UNEST), aimed to increase frontline health worker capacity through district-led training, support supervision, and mentoring at one district hospital and 19 lower-level facilities. A once-off supply of essential medicines and equipment was provided to address immediate critical gaps. Health workers were empowered to requisition subsequent supplies through use of district resources. Minimal infrastructure adjustments were provided. Quantitative data collection was done within routine process monitoring and qualitative data were collected during support supervision visits. We use the World Health Organization Health System Building Blocks to describe the process of district-led health facility strengthening.Seventy two per cent of eligible health workers were trained. The mean post-training knowledge score was 68% compared to 32% in the pre-training test, and 80% 1 year later. Health worker skills and competencies in care of high-risk babies improved following support supervision and mentoring. Health facility deliveries increased from 3,151 to 4,115 (a 30% increase) in 2 years. Of 547 preterm babies admitted to the newly introduced kangaroo mother care (KMC) unit, 85% were discharged alive to continue KMC at home. There was a non-significant declining trend for in-hospital neonatal deaths across the 2-year study period. While equipment levels remained high after initial improvement efforts, maintaining supply of even the most basic medications was a challenge, with less than 40% of health facilities reporting no stock-outs.Health system strengthening for care at birth and the newborn period is possible even in low-resource settings and can be associated with improved utilisation and outcomes. Through a participatory process with wide engagement, training, and improvements to support supervision and logistics, health workers were able to change behaviours and practices for maternal and newborn care. Local solutions are needed to ensure sustainability of medical commodities. Neonatal conditions contribute approximately 10% to the global burden of disease, more than three times that of HIV . While dThe importance of an integrated continuum of care from pre-pregnancy through childhood across levels of service delivery from household to hospital is well known . HoweverThe Uganda Newborn Study (UNEST) was conceived to adapt a community care package for maternal and newborn health and evaluate its effect on maternal and newborn care outcomes in order to inform policy and scale-up in Uganda. When formative research revealed that poor-quality health facility care was the second leading reason for newborn deaths , it was Within Ugandan policy, one general hospital is supposed to serve approximately 500,000 people, while health sub-districts administer lower-level health facilities, including health centre (HC) levels II, III, and IV.; Level II HCs are small, outpatient-only units which can provide a first dose of antibiotics to sick newborns and referrals; level III HCs conduct births, manage newborn illness, and provide laboratory services; and Level IV HCs function as small hospitals, which should be equipped for emergency obstetric care. Private and faith-based organisations own 41% of hospitals and 22% of lower-level HCs. Private not-for-profit facilities receive government subsidies to expand care to rural areas .Integration of the targeted interventions into a health system is difficult and complex, especially in a weak health system . Yet, stThe study was nested within the UNEST randomised control trial whose details and results are described elsewhere , 14. BriFor the health systems strengthening component, 20 health facilities within the district were targeted from 2009 through 2011, including one hospital, one HC IV, six HC III, and twelve HC II, capturing both public and private health facilities. The health facilities catered to clients from both control and intervention areas, as well as outside of the study districts. For example, the catchment population of the hospital is approximately 1.5 million. The intervention was implemented together with district and Ministry of Health leadership to identify gaps in service delivery and to make changes which would improve the responsiveness of the health system to maternal and newborn complications.We describe and analyse the health system changes according to the WHO Health System Building Blocks, including health workforce, service delivery, health information systems, equipment and supplies, with leadership and finance combined . QuantitAn additional data capture form on service utilisation and care of the sick newborn babies and preterm babies using kangaroo mother care (KMC) was developed for use at the hospital. Key indicators collected included availability of basic essential medicines and equipment ; and availability of essential medicines . Data on the number of deliveries, stillbirths, neonatal deaths, patients discharged, as well as health worker training and turnover were collected. In instances where routine data were incomplete, stock cards were used to complete the section on medicines. Data were entered into Microsoft Excel spreadsheets and checked for completeness, then exported to Epidata version 3.1 for descriptive analysis.As part of the quarterly process monitoring, qualitative data were also collected. The study team documented implementation experiences and contextual factors and events  that might influence study outcomes. Field notes and reports from the support supervision and mentorship visits were reviewed on a quarterly basis. These activities were the basis for information on performance of service providers.Health workers at the targeted facilities were identified and their level of formal training documented. With involvement of facility administration and district leadership, frontline workers attended in-service refresher training in obstetric and newborn care, modified for the level of service delivery. Four training sessions were conducted between July 2009 and June 2010. Each training session lasted 6 days and used an integrated training maternal and newborn manual developed by the study team, reviewed by members of national midwifery, obstetric and paediatric professional associations, and endorsed by local stakeholders and the Ministry of Health. The training package addressed the major causes of maternal and newborn deaths and morbidity in Uganda. Modules included goal-oriented antenatal care, managing maternal complications, infection prevention, managing normal labour and partograph use, neonatal resuscitation, care of the sick newborn, and extra care for the small baby using KMC. Knowledge tests were given before and after training, as well as after 1 year of implementation. In addition, training in maternal and perinatal mortality auditing was provided according to Ministry of Health guidelines .In order to improve service delivery, the organisation of wards and patient flow were examined for critical bottlenecks. Interventions involved the redesigning and reorganisation of space to cater for labour management and newborn care. Screens were introduced for privacy in the labour ward. In the hospital, space was specifically designated for KMC by screening off two beds and placing posters and job aids on the walls. Later, with district buy-in, a modest special care neonatal unit was built adjacent to the labour and delivery ward to care for high-risk newborns.Support supervision and mentoring was also a key component of improving service delivery. Teams of national-level and district-based health workers carried out quarterly outreach visits to facilities that were conducting deliveries. The co-opted mentoring team comprised a paediatrician, an obstetrician, a midwife, and district technical officers. The supervision visits included assessment of skills, support for problem solving with frontline staff to identify gaps and solutions, and development and review of health facility work plans. In initial outreach visits, an assessment of the physical layout of the sites was done with recommendations for reorganisation, if needed. Maternal and perinatal death review committees were established with the expectation of biweekly meetings. The minutes were reviewed during supervision visits. Newly introduced interventions, such as neonatal resuscitation using bag and mask, KMC, and treatment of neonatal sepsis, were given particular attention during mentorship visits.Sensitisation meetings were held with health administration officials at different levels to highlight maternal and newborn care needs and the importance of timely procurement and dispatch of supplies. Health facility in-charges and district health teams were engaged to ensure future supplies are provided for through the routine channels. A once-off supply of essential medicines, medical supplies, and equipment was provided as a catalyst to address immediate gaps. Supplies included delivery beds, Ambu bags, newborn-size masks, bulb syringes, nasal prongs, cannulas, and oxygen concentrators. Partographs and standard management protocols and guidelines were printed and distributed targeting major causes and solutions of neonatal morbidity and mortality.The status of the patient charts and registers was assessed at baseline. File folders for inpatient care in maternity and paediatric wards approved by the Ministry of Health were reintroduced to standardise record-keeping and to facilitate data availability for the audit sessions. Where lacking, registers and summary sheets were printed and provided. At the hospital, new registers were developed and provided for the KMC unit, the neonatal special care unit, and the neonatal room on the paediatric ward. Forms for maternal death notification and maternal and perinatal mortality audit were also provided. During support supervision, health workers and records staff were consulted about the completeness and accuracy of the information collected. The HMIS data were extracted on a quarterly basis by the support supervision team.Sensitisation of district leaders, CHWs, and various stakeholders on the importance of maternal and newborn health was an early intervention milestone, with the assumption that local buy-in was crucial. Managers at health units were encouraged to prioritise procurement of basic supplies for obstetric and newborn care, and were given strategies to avoid stock-outs, support for annual budgeting, and training on quality improvement. The identification and development of local champions was a key strategy. Individuals were identified during early trainings and later involved in the co-opted mentorship teams, learning visits, trainings, reviews, and dissemination activities.Amongst the facilities assessed, all offered antenatal care, well-baby checkups, and served as a point of contact for sick newborns. Fourteen of the facilities (70%) conducted deliveries. Although current Ugandan policy only mandates delivery services at level III HCs and above, it was found that half of the level II HCs were also conducting deliveries. Only the hospital had facilities for admission and treatment with antibiotics for sick neonates.During the implementation period, there was an increase in the number of deliveries conducted at health facilities within the study period, from 3,151 at the beginning of the intervention in the second half of 2009, to about 4,115 deliveries (an increase of 30%) at the end of the study . DespiteOver the 2-year implementation period, four in-service training sessions were conducted. Overall, 72% (105/146) of targeted health providers were trained . The majResults from pre-training and post-training tests demonstrated improvement in knowledge of maternal and newborn care. The mean pre-training score was 32% compared to a post-training score of 68%. After 1 year of implementation, the mean score was 80%. While skill retention was not systematically assessed, this was documented in supervision notes. Supervision reports also revealed that health workers, midwives in particular, gained confidence and skills in inserting intravenous cannulas for medicines and dextrose, as well as nasogastric tubes for feeding preterm babies expressed breast milk, and for conducting neonatal resuscitation. In terms of identifying and supporting champions, most facilities had specific staff that took up more responsibility and had more enthusiasm for the relatively novel area of newborn care, and used their time to mobilise and train others.Infrastructural improvements, particularly the creation of a KMC unit, transformed service delivery (Box 1). While at baseline there were no additional services available for small babies at the hospital or HCs, by the end of the study, 547 preterm babies had been cared for in a KMC unit. Of those admitted to the hospital's KMC unit, 85% were discharged alive, with less than 2% of admissions requiring referral to higher-level care. Three-quarters of mother–baby pairs completed KMC follow-up to ‘graduate’ from the service. A substantial proportion (13%) of women admitted to KMC self-discharged against medical advice. Attempts were made to follow-up these cases in the community, and where possible they were linked to a lower-level health facility for continued care. Other infrastructural adjustments, such as the partitioning of the paediatric ward to allocate space for newborns, resulted in neonates being seen as needing special care apart from maternity and older child services. Differences between public and private facilities were observed, with the practice of essential newborn care services slightly higher in public facilities .Box 1When KMC was first being introduced at the hospital, during a supervision visit, the mentorship team found a woman admitted to the maternity ward who had delivered premature twins by caesarean section 6 days prior. The babies were weak, hypothermic, and were being fed glucose water. Their mother had painful, engorged breasts and remained weak following surgery.The supervision team counselled the health workers to admit the mother and babies to the KMC unit. The mother was supported to express breast milk while nasogastric tubes were passed for feeding the babies. The health workers were instructed on how to calculate feeds and do daily routine monitoring, including weighing. The grandmother and the mother of the twins were counselled on carrying the babies skin-to-skin while the mother regained strength and could take over the skin-to-skin care. The mother and twins were discharged after 3 weeks, and came back for weekly reviews.Treatment protocols on admission, feeding, monitoring, and discharge were developed and posted on the walls of the KMC unit. A motivated midwife was identified to champion KMC amongst staff and mothers and to serve as a point person for the mentorship team. While this single-champion strategy was successful as a short-term solution, high turnover amongst staff means that a broader leadership or steering team for KMC is beneficial.Supervision visits and learning opportunities were well utilised. Based on competencies observed during supervision visits, staffing adjustments were made by the district health team. Supervision visits lasted 3 days each, with half a day spent at each lower-level HC and 1 full day at the hospital. Exchange visits were provided for hospital staff at the national referral hospital and a general hospital in the capital city of Kampala for additional mentorship. Despite widespread national and local support for the mortality review process, this was not well taken up by facility staff and administration, citing competing demands and excessive workload. Fear of blame for specific failures in care might also have been a reason for discontinuation.At the level IV HC and hospital, less than half of the essential equipment was available and/or functional at baseline, with level II and III HCs functioning better for supplies, with 70% being available. Following the initial procurement and distribution of supplies to health facilities, these levels were maintained and even increased in the level IV HC and hospital. Still, only 80% of level II and III HCs had the basic equipment necessary by the end of the implementation period. Due to increasing demand for services and despite support for procurement, stock-outs of essential medicines were common throughout the implementation period and remained below 40%. This was more pronounced in the level IV HC and hospital compared to the lower-level health facilities, both due to increasing demand and budgetary constraints of the ‘pull’ procurement system.The availability and quality of health information improved dramatically over the course of the implementation. Whereas at baseline there were very few indicators captured within the routine system for neonates, outcome data became readily available and were requested by administrators and district leaders through the HMIS. Partograph use and completeness, documentation of weight, feeding, and treatments received all increased. The completeness and accuracy of inpatient and outpatient register documentation improved along with individual patient charts, although these were dependent on continued availability of stationery after the initial seed stock was consumed.Creating linkages among the health workers, community leaders, and district officials was an important part of ensuring continuity of care from the provider side. Health workers met with CHWs on a monthly basis at the health facility, and once a month they accompanied CHWs on home visits. Through community meetings, challenges at community level and health facility were discussed and raised with leadership, for example, the lack of housing available for health facility staff (Box 2). Managers were key drivers of all of the quality improvement processes employed. However, some of the major health systems bottlenecks  were outside of the control of local managers.Box 2According to national policy, level III HCs should be able to perform normal deliveries. However, at baseline, it was identified that one HC III had two midwives on its staff but was lacking all basic equipment, including a delivery bed, clean delivery kits, and a surface for resuscitation. Most of the women in the sub-county were delivering at home or at the home of a traditional birth attendant due to the long distance to the next nearest facility.Upon initiation of UNEST, the HC III received an initial seed stock of supplies, equipment, and essential medicines. Through mentorship visits, the maternity ward was reorganised for efficiency. Staff received support for using equipment and documenting care. While the number of births in the facility steadily increased, the ability to provide around-the-clock services was constrained given the lack of accommodation for midwives at or near the facility. Upon discussion with sub-county leaders and the district health team, it was agreed that housing would be donated by the community and constructed and provided onsite.The health systems strengthening efforts in this study reflect the limited material input possible within the existing district structure. The selected interventions were identified together with the Ministry of Health, district health team, and local experts, and were within the confines of the Uganda National Minimum Health Service Package. The number of deliveries with a trained, equipped birth attendant increased, with substantial improvements in the care provided to sick and preterm babies, particularly in public sector facilities. A strategy involving simple structural improvements, in-service training opportunities, effective team-based mentoring, and improved documentation has the potential to strengthen the capacity of the providers to care for vulnerable newborn babies. However, the shortage of essential drugs and supplies remains a major bottleneck in the system.Simple partitioning within the delivery, postnatal and paediatric wards to provide a designated space for newborns likely contributed to improved awareness of newborn care in the community. Interviews with mothers and health providers demonstrated increased confidence in the services they were receiving and providing . The ratin situ training is likely to further improve health worker skills, as demonstrated in Tanzania (Based on feedback following trainings, the in-service training was well accepted. The increase in provider knowledge 1 year after training reflects the importance of mentorship visits and support supervision. Increased frequency of Tanzania . Recent The equipment and medicines provided reflect only the most basic supplies necessary to provide maternal and newborn care. Yet, after the initial catalytic supply, the availability of medicines was erratic. While equipment levels were higher throughout the study period, there were also issues around maintenance and replacement. While administrative officials were encouraged to prioritise procurement, more effort is needed to improve budgeting and governance structures and to engage with the central medical stores to ensure that these are available. With an increasing volume of births in an area of high fertility, accurate planning for the quantity of necessary commodities is essential. Factors such as the availability of accommodation for service providers and the lack of ambulances and other emergency transport services were identified, but are largely beyond the ability of the study to address in the short term.There are several limitations to this study. First, although data were compiled by study researchers, they were collected within routine systems. Improving data collection was one of the interventions targeted through supervision visits, which may present bias. In addition, the study did not assess the quality of care provided, nor were health worker skills observed and evaluated systematically. While health facility strengthening was introduced alongside the randomised community-based package, it is not likely that the increase in awareness of and demand for services was solely related to the community intervention, given that the catchment area for the facilities, particularly the hospital, is well beyond the implementation districts. The reasons for the increase in utilisation of services are multifactorial, but it is possible that the intervention contributed to this increase as well as to the overall quality of services provided to families.Finally, given that there was little prior experience with maternal and newborn care services, the quality improvement interventions were introduced stepwise, which may have limited their effect, because there was a limited time period for the new services to take hold and be implemented together. An independent examination of mortality effect and impact on neonatal outcomes would be beneficial to supplement routine data and highlight potential gaps in measurement.Improving awareness of and demand for maternal and newborn care services at community level necessitates engagement with health facilities in order to ensure services are available and of sufficient quality. Even amongst higher-level health facilities, availability and quality of maternal and newborn care was low or non-existent. Basic health system strengthening was feasible in this low-resource setting, mostly within existing resources. Alignment with the Ugandan minimum health service package and the national standards for newborn health care demonstrates the potential for replication in other districts. Local leadership support, particularly engaging key champions and ensuring buy-in from frontline health providers, is required from the outset. However, addressing quality of care bottlenecks is a significant challenge and further innovative solutions are needed for resource constrained settings in order to save the lives of mothers and babies and help them thrive.


The TFCC consists of triangular fibrocartilage (TFC), meniscus homologue, ulnolunate ligament, ulnotriquetral ligament, radioulnar ligament, and sheath floor of the extensor carpi ulnaris (ECU). The TFCC functions as a stabilizer of the ulnocarpal and DRU joints, load distributor between ulna and ulnar carpus and introduces smooth forearm rotation. The TFCC is a hammock-like shape supporting and surrounding the ulnar carpus, with the strong and nearly vertical anchor to the ulnar fovea, i.e. the RUL. During forearm rotation, the radius, the carpus and distal surface of the TFCC rotate over the ulnar head, thus simple twisting of the RUL occurs at its foveal attachment. The main stabilizer of this tiny joint is the proximal component of the TFCC, the radioulnar ligament (RUL). Central attaching fibers of the RUL at the fovea indicate isometric pattern during forearm rotation, while eccentric fibers at the fovea and base of the styloid indicate changes in length, dorsal indicates longer length in pronation, while palmar indicates longer in supination. When the RUL is torn, instability of the DRUJ occurs. The greater the tear of the RUL be, the greater instability of the DRUJ indicates. When the RUL is ruptured at the fovea, the RUL must be introduced into the central lesion of the fovea of the ulna. Classical Palmer 1B peripheral lesion also demonstrates moderate DRUJ instability, because this lesion is close to the RUL. Other traumatic lesions on the TFCC, such as Palmer 1A and 1D tear, did not indicate DRUJ instability.Diagnosis of DRUJ instability due to TFCC tear is achieved by physical examination, such as DRUJ ballottement test, arthrogram, MRI and arthroscopy. Image diagnosis is useful, however arthroscopy is a gold standard for diagnosis as well as treatment of the TFCC lesions. DRUJ arthroscopy, recently introduced arthroscopic technique, provides direct visualization of fovea lesion, where the RUL attaches.Treatments of TFCC lesions are depending on the tear site. Palmer 1B lesion is easily treated by arthroscopic capsular repair. Debridement is useful for palmer 1A or 1D tear. We also prefer to shorten the ulna, when there were degenerative changes on the TFC  or with ulnar positive variance. Treatment options for DRUJ instability due to TFCC foveal avulsion are arthroscopic and open repair of the TFCC to the fovea for acute or sub-acute cases and reconstruction of the TFCC using ECU half-slip tendon or PL tendon for chronic TFCC injuries. Ulnar shortening procedure can be useful for partial avulsion of the RUL either dorsal or palmar, but not for complete avulsion of the TFCC at the fovea. Arthroscopic partial resection of the TFCC can no longer indicated for unstable DRUJ, because it does not introduce stabilization of the DRUJ.


Glucocorticoids released from the adrenal gland in response to stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis induce activity in the cellular reduction-oxidation (redox) system. The redox system is a ubiquitous chemical mechanism allowing the transfer of electrons between donor/acceptors and target molecules during oxidative phosphorylation while simultaneously maintaining the overall cellular environment in a reduced state. The objective of this review is to present an overview of the current literature discussing the link between HPA axis-derived glucocorticoids and increased oxidative stress, particularly focussing on the redox changes observed in the hippocampus following glucocorticoid exposure. However, these transitional metal ions can also undergo reactions resulting in the production of hydroxyl radicals (Rovira et al., Outside the mitochondrion, there are three major processes responsible for the production of free radicals, principally in the form of reactive oxygen and nitrogen species. The first process involves the production of hydrogen peroxide as a by-product of fatty acid catabolism by peroxisomes (Ames et al., S-transferase, thioredoxin-1, and heme oxygenase-1 through their antioxidant response element (Rushmore et al., In order to neutralize ROS, cells use a suite of enzymatic and non-enzymatic antioxidants, ultimately attempting to neutralize the radical by reduction to water. In the typical ROS reduction cascade, SOD is the top-tier antioxidant, catalyzing the dismutation of this radical to hydrogen peroxide. This is achieved through the transfer of electrons across the catalytic metal core of the enzymes to reduce the superoxide radicals. In mammals, the two main isoforms of SOD are the copper, zinc-SOD which are found throughout most cell compartments, and the manganese-SOD that is specific for mitochondria. Catalase enzymes are centered around an iron-containing ferriheme group that acts as the transition metal during the reduction of hydrogen peroxide. Access to this active site is fairly specific as the channel opening is narrow and does not allow the passage of large molecules. High concentrations of superoxide anions are able to inactivate catalase by oxidizing the heme group in the active site. To prevent this, catalase binds NADPH to maintain this group in the reduced state (Nordberg and Arner, Although there is a general negative connotation associated with ROS production, they have important cellular functions under normal physiological conditions. Even low levels of the extremely reactive hydroxyl radical have been shown to activate guanylate cyclase, stimulating the production of a cGMP second messenger cascade (Mittal and Murad, Increased secretion of adrenal glucocorticoids following physical and/or psychological stress exposure subsequently liberates glucose through gluconeogenesis, glycogenolysis, and lipolysis (Teague et al., in vivo evidence that administration of exogenous corticosterone over a 14 day period increases hippocampal oxidative indicators including lipid peroxidation and protein carbonyls, while the enzymatic antioxidants SOD, catalase, and glutathione peroxidase activities are all decreased (Sato et al., in vivo studies have shown that both corticosterone administration and restraint stress for 21 days induce an overall decrease in GSH in addition to SOD, catalase, glutathione transferase, and glutathione reductase activities in whole brain, liver, and heart tissues (Zafir and Banu, Glucocorticoids induce neuronal oxidative stress directly through enhanced mitochondrial respiration and oxidative phosphorylation. This was demonstrated clearly in a study by Du et al. , showingInterestingly, ROS attenuate the glucocorticoid-induced down-regulation of pro-opiomelanocortin in pituitary corticotrophs, thereby promoting an increase in HPA axis activity via reduced negative feedback (Asaba et al., Although oxidative stress and elevated glucocorticoids are both observed in a number of chronic pathologies, the delineation between physiological function and pathological insult is complex and remains unclear. In particular, the role of ROS in neuron-neuron and neuron-glia interactions is an area that requires attention. Based on the observations of increased gliogenesis in the presence of high levels of glucocorticoids, the mobility of ROS in the extracellular space, and the relative paucity of neuronal endogenous antioxidants, we suggest that glia may be playing an active role in response to neuronal oxidative stress. This may have important implications for neurodegenerative conditions involving redox-sensitive regions such as the hippocampus. These observations highlight that maintenance of a balanced redox state is critical for normal cellular homeostatic function and relies heavily on hormonal cues from the neuroendocrine stress system.Author Jereme G. Spiers managed the literature searches and wrote the first draft of the manuscript. Author Hsiao-Jou Cortina Chen produced the graphic and revised the manuscript. Author Conrad Sernia and Nickolas A. Lavidis critically revised the manuscript. All authors have approved the final version of the manuscript for journal submission.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.


Movement is planned and coordinated by the brain and carried out by contracting muscles acting on specific joints. Motor commands initiated in the brain travel through descending pathways in the spinal cord to effector motor neurons before reaching target muscles. Damage to these pathways by spinal cord injury (SCI) can result in paralysis below the injury level. However, the planning and coordination centers of the brain, as well as peripheral nerves and the muscles that they act upon, remain functional. Neuroprosthetic devices can restore motor function following SCI by direct electrical stimulation of the neuromuscular system. Unfortunately, conventional neuroprosthetic techniques are limited by a myriad of factors that include, but are not limited to, a lack of characterization of non-linear input/output system dynamics, mechanical coupling, limited number of degrees of freedom, high power consumption, large device size, and rapid onset of muscle fatigue. Wireless multi-channel closed-loop neuroprostheses that integrate command signals from the brain with sensor-based feedback from the environment and the system's state offer the possibility of increasing device performance, ultimately improving quality of life for people with SCI. In this manuscript, we review neuroprosthetic technology for improving functional restoration following SCI and describe brain-machine interfaces suitable for control of neuroprosthetic systems with multiple degrees of freedom. Additionally, we discuss novel stimulation paradigms that can improve synergy with higher planning centers and improve fatigue-resistant activation of paralyzed muscles. In the near future, integration of these technologies will provide SCI survivors with versatile closed-loop neuroprosthetic systems for restoring function to paralyzed muscles. Approximately 300,000 individuals in the United States, and more than 2.5 million individuals worldwide, are affected by traumatic spinal cord injury (SCI)  to the spinal cord Rowland, . Damage Most spinal cord injuries do not completely sever the spinal cord  , stimulating electrodes are implanted within the ventral gray matter of the spinal cord  are neural interface systems that can record, analyze, and decode brain signals . 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.


Drug abuse in juveniles is one of the most serious problems which lead to different physical, social and educational damages and outcomes.The aim of the present study is to predict the addiction Potential in youths by their early maladaptive schemas.The research sample included students of the University of Sistan and Baluchistan, Zahedan, Iran, with average age of 19-24 years. Participants were 260 undergraduate students (159 girls and 101 boys) that were selected by probability proportional cluster random sampling. The instruments were the Addiction Potential Scale (APS) and Early Maladaptive Schemas SQ-SF (short form questionnaires).The result showed that there are positive and significant relationships among early maladaptive schemas include Disconnection/ Rejection, Impaired autonomy / Performance, Impaired Limits, Other-Directedness and Over vigilance / Inhibition, and addiction Potential. Also, results of regression showed the highest Addiction Potential predicted by the following schemas: Disconnection / Rejection, impaired autonomy and performance other-Directedness.Therefore, Addiction Potential is one of the areas which can be used in planning and preventive activities, through identifying the groups with Early Maladaptive Schemas. Addiction is a physical, mental, social and psychic disease where various pre-addiction factors play a basic role in its formation . "AddictAlso, the results showed that drug users apply Disconnection/Rejection schemas . A studyTherefore, the disability in coping with stress and this belief that using drugs will have desirable outcomes are the basis for addiction potential . AccordiThe aim of the present study is to predict the Addiction Potential according to the Early Maladaptive Schemas in youths.The method of this research is descriptive and correlation type. The Statistical population consisted of students in year 2011-2012 in the University of Sistan and Baluchestan. The sample was comprised of 260 subjects  that were selected using the proportional cluster method. Age range of the subjects was from 19 to 25 years. The data was analyzed by Pearson Correlation and Stepwise regression.1. Addiction Potential Scale (APS): Inventory of Addiction Potential Scale (APS) was used to evaluate the addiction potential. The APS subscale of Weed et al.  consiste2. Young Schema Questionnaire–Short Form : The YSQ-SF consists of 75 items assessing 16 early maladaptive schemas. Each scale consists of five items rated on a six-point scale. A description of the 16 scales is provided below: Disconnection/Rejection ; Impaired autonomy/Performance ; Impaired Limits ; Other Directedness ; and Over vigilance/Inhibition  , 24.Descriptive results of this research are presented below. Results are presented according to the research questions posed below:1) Is there a relationship between addiction potential and Early Maladaptive Schemas areas among the youth? The result of Pearson correlation shows that there are positive relationship among the addiction potential and all of the five areas of early maladaptive schemas . These relations were significant at 0.01.2) Which one of the early maladaptive schema areas is a stronger predictor of addiction potential among the youth? The results in Early maladaptive schemas play an important role in the mentality, feelings and performance of people or the way they communicate with each other . Early mAccording to the results of the current study, there is a significantly positive relationship among the five areas of early maladaptive schemas: Disconnection/Rejection, impaired autonomy and performance, Impaired Limits, Other-Directedness and Over vigilance/Inhibition, and the addiction potential. In this context, the schemas Disconnection/Rejection, impaired autonomy and performance, and Other-Directedness had the highest prediction of the addiction potential variances. Accordingly, we can infer that people with addiction potential has early maladaptive schemas. Some of the studies have pointed to the correlation between early maladaptive schemas and drug dependence , 25, andMoreover, the regression results indicated that maladaptive schemas in Disconnection/Rejection area are the strongest predictors for addiction potential. Similarly, researchers showed that early maladaptive schemas, especially in areas of Disconnection/Rejection schemas, impaired autonomy and performance, and other directions play an important role in the prediction of addiction -20. CognIt can be concluded that the strategies to prevent the addiction potential need to achieve adaptive schemas. From the applied point of view, instruction for positive and adaptive schemas creates better feelings and capability in people, and enables them to better cope with problems. In addition, addiction potential is one of the areas which can be used in preventive planning. Moreover, it is useful to identify the groups with high tendency towards addiction and creating suitable preventive and therapeutic strategies. Ball and Young cited that therapeutic schema plays an important role in successful addiction treatment .According to the age limit of subjects in this study, generalization of the present results to other age groups should be made cautiously.