Background. This review identifies the content of virtual visits in community nursing services to older adults and explores the manner in which service users and the nurses use virtual visits. Design. An integrative literature review. Method. Data collection comprised a literature search in three databases: Cinahl, Medline, and PubMed. In addition, a manual search of reference lists and expert consultation were performed. A total of 12 articles met the inclusion criteria. The articles were reviewed in terms of study characteristics, service content and utilization, and patient and health care provider experience. Results. Our review shows that in most studies the service is delivered on a daily basis and in combination with in-person visits. The findings suggest that older home-dwelling patients can benefit from virtual visits in terms of enhanced social inclusion and medication compliance. Service users and their nurses found virtual visits satisfactory and suitable for care delivery in home care to the elderly. Evidence for cost-saving benefits of virtual visits was not found. Conclusions. The findings can inform the planning of virtual visits in home health care as a complementary service to in-person visits, in order to meet the increasingly complex needs of older adults living at home. According to the United Nations , developEuropean countries are not alone in facing these challenges. In the USA, home care for the elderly is based on efforts of family caregivers , and con virtual visits includes the use of real-time audio-visual communication devices, in this review acknowledged as videoconference by the use of videophones, personal computers/laptops, or the TV screen  elderly OR old OR aged OR senior OR frail elderly [AND] home care OR home care service OR home-based care OR community health service OR community dwelling. The terms videoconferencing, telehealth, ehealth, aged, and elderly are MeSH words in the PubMed database, while home care, home care services, videoconferencing, telehealth, and telecommunications are Cinahl headings. In addition to the literature searches in the electronic databases, reference lists of both the included studies and of previously published reviews on the subject were examined for eligible studies. Reference tracking was conducted by consulting a telehealth expert.A literature search was carried out prior to the integrative review. The literature search was performed in the electronic databases Cinahl, Medline, and PubMed for papers published between January 2003 and April 2013. The following search terms were used:Titles, abstracts, and full-text articles were read independently by the two authors (AMLH and MS). Consensus was reached in cases of uncertainty or disagreement on a study's eligibility. Studies included in the review were written in English, had been subject to peer review, and were published in scientific journals and focused on virtual visits as part of home care health services for the elderly. Thirty-two full-text articles were assessed for eligibility. Of these, 12 were included in the review. The search strategy and selection process are presented in a flow diagram in Excluded studies did not meet the inclusion criteria and focused on either the use of audio-visual communication between elderly living in a nursing home and family members or the use of videoconferencing for communication between service providers only, videoconferencing as a peer-driven intervention, videoconferencing as part of cancer, palliative or mental health care, or videoconferencing between the patient and his or her physician's office. study characteristics, service content and utilization, patient experience, and health care provider experience  . In addiPerforming an integrative review allowed for the inclusion of studies with substantial methodological diversity. Although considered a strength of integrative reviews by contributing to a broader perspective on the studied phenomenon, we acknowledge that sampling and comparison of heterogeneous studies might lead to the possibility of biased conclusions . The resThe review identified virtual visits as having the clear advantages of enhanced social inclusion and less loneliness for the elderly patient and also providing support and guidance in the patient's self-management of medication. Both service categories could help postpone admission to long-term facilities or the need for substantial in-home care. However, the studies in this review do not provide strong evidence for cost savings of virtual visits as part of elderly home health care services. Thus, the review does not support the claim that virtual visits can be more than a supplement to traditional in-person home care visits.The fact that both patients and nurses, in general, found the technology satisfactory might be attributable to the most frequent service models applied in the studied reviews, combining virtual visits with ordinary in-person visits. The literature shows a duality in using technology in the home care services, warning against eliminating in-home visits because of the advantage of virtual visits , 14. ThiWe believe that this review could inform both administrators and clinicians working in community health care services on how virtual visits can be integrated into home care services for older adults. Moreover, the review can inform further development and implementation of virtual visits in a home health care context.


In fact the use of MSCs, and their secretome, become a strong candidate to be used as a therapeutic tool for CNS applications, namely by triggering the endogenous proliferation and differentiation of neural progenitors, among other mechanisms. Quite interestingly it was recently revealed that MSCs could be found in the human brain, in the vicinity of capillaries. In the present review we highlight how MSCs and NSCs in the neurogenic niches interact. Furthermore, we propose directions on this field and explore the future therapeutic possibilities that may arise from the combination/interaction of MSCs and NSCs.Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) share few characteristics apart from self-renewal and multipotency. In fact, the neurogenic and osteogenic stem cell niches derive from two distinct embryonary structures; while the later originates from the mesoderm, as all the connective tissues do, the first derives from the ectoderm. Therefore, it is highly unlikely that stem cells isolated from one niche could form terminally differentiated cells from the other. Additionally, these two niches are associated to tissues/systems  that have markedly different needs and display diverse functions within the human body. Nevertheless they do share common features. For instance, the differentiation of both NSCs and MSCs is intimately associated with the bone morphogenetic protein family. Moreover, both NSCs and MSCs secrete a panel of common growth factors, such as nerve growth factor (NGF), glial derived neurotrophic factor (GDNF), and brain derived neurotrophic factor (BDNF), among others. But it is not the features they share but the interaction between them that seem most important, and worth exploring; namely, it has already been shown that there are mutually beneficially effects when these cell types are co-cultured  Injury and disease within the central nervous system (CNS) frequently induce chronic and acute insults leading to irreversible processes of neuronal cell death. Understanding how neurogenesis can be modulated, either through drugs or interaction with other cell types, and neural progenitors recruited to the site of injury, is of the utmost importance for the development of novel strategies that may impact the current state of the art. In recent years it has become evident that a population with a non-neural phenotype known for their role in the osteogenic niche, mesenchymal stem cells (MSCs), is able to regulate important phenomena within the CNS, including neural progenitor cells proliferation and differentiation. This quite unexpected and surprising function of MSCs brought closer the neurogenic and osteogenic niches, and prompted a new field of research that aims at understanding their interaction, and how both may impact on CNS regenerative medicine as we know it. Having this in mind the objective of the present paper is to review the most relevant advances in this field. It will first give an overview of neurogenic niches and how neurogenesis is regulated within them, then give an introduction to the osteogenic niches and MSCs, and end with a review on the most important works on the interactions between MSCs, neurogenic niches and disease models within the CNS.Neuroanatomists have long believed Cajal’s assumptions on the immutability of the CNS. This dogma has been challenged due to growing evidence that endow the brain with considerable regenerative potential and neuroplastic capacity, essential to promote brain homeostasis , described to be multipotent stem cells , is the site of the adult brain where neurogenesis is most intense. In rodents, the SEZ is seldom described as a thin layer of cells located below the ependymal layer that lines the lateral walls of the lateral ventricles, but it also extends to the dorsal and medial ventricular walls  that, as indicated above, form a monolayer that outlines the ventricular wall. These cells constitute a physical barrier that diminishes the direct and free exchange of molecules between the CSF and brain parenchyma , demonstrating that this transcription network is maintained postnatally  in the adult SEZ is topographically heterogeneous and this might be bound to transcriptional regulation. In fact, the expression of distinct transcription factors in both overlapping and non-overlapping regions of the SEZ is described. Similarly to the SGZ, some of these transcription factors were correlated with the SEZ embryonic origin  instruct distinct neurogenic phases and ultimately the cellular fate. Many of the mechanisms regulating NSCs proliferation and neurogenesis during embryonic development, appear to be conserved in adulthood, and both intrinsic and extrinsic factors important for embryonic neurogenesis are also involved in the regulation of neurogenesis in the adult brain , available data, both from animal models and human patient related studies, indicates that the immunomodulatory properties of the secretome of MSCs regulate the immune/oligodendrogenic niches. For instance Wang et al.  revealedOn other hand, in disorders such as PD, Ischemic Stroke (IS) and Glioblastoma Multiforme (GBM) it is believed that the action of MSCs goes beyond the neuro-immunomodulation, and in fact, some of the reported benefits may be closely related with their direct interaction with the neurogenic niches. Due to the nature and objectives of this review, this topic will be further explored in the following section.pars compacta (SNpc) within the mesostriatal/nigrostriatal pathway  and interferon γ (INF γ). Moreover, their presence also revert the loss of nigral DAergic neurons and striatal fibers  to neural cells , but also acts as inflammation and immune response modulators. Moreover, recent reports have shown that besides soluble growth factors and cytokines, MSCs also secrete microvesicles and exosomes containing mRNAs and/or miRNAs (microRNAs), which are believed to mediate cell-to-cell communication and act as reparative agents  stem cells. The most unique and critical feature of stem cells that renders them as attractive tools for cancer therapy is their intrinsic capacity to migrate towards pathologic tissues, including malignant tumors. Indeed, this selective cancer-tropism has been shown for various stem cell types, including embryonic, hematopoietic, mesenchymal, neural, endothelial, and experimentally-induced stem cells , PI-103 , and lanatoside C (a cardiac glycoside), resulted in synergistic therapeutic effects, emphasizing the potential clinical value of sensitizing glioma cells to TRAIL-induced NSC-mediated cell death , a cytokine that promotes apoptosis by binding to death receptors commonly present in the cellular membrane of tumor cells. These engineered NSCs can track tumor cells and deliver sTRAIL to glioma cells NSCs have also been genetically modified to express and secrete IL-12, a cytokine that does not act directly in tumor cells, but is involved in the enhancement of T-cell-mediated antitumor immune responses. Using intracranial glioma mice models, Ehtesham et al. showed that IL-12-secreting NSCs injected directly in the tumor significantly prolong the survival of mice  in combination with the pro-drug ganciclovir (GCV), based on the HSV-tk-mediated phosphorylation of inert GCV into a cytotoxic product that kills HSV-tk-positive cells and neighboring cells . Taking advantage of the tumor-tropism of stem cells, many recent studies have explored the incorporation of HSV-tk into NSCs, MSCs, and bone marrow-derived progenitor cells as therapeutic strategies for glioma, showing promising results  and antibodies  to glioma cells in vivo. The recent literature on this topic is very promising, but a concerted and integrated effort in this field will still be crucial to definitely pave the way to better treat patients, most likely integrating the rational use of particular stem cell-based approaches to act synergistically in concert with surgery, radiation and chemotherapy.In conclusion, a wide variety of stem cells hold great promise as novel therapeutic tools for the treatment of therapy-insensitive malignant brain gliomas. Some hallmarks of these cells that are critical for this purpose include their high tumor-trophic migration and tracking capacity, peculiar immunosuppressive properties, and easy genetic manipulation for cargo delivery. Nonetheless, inherently to its innovative nature and similarly to other experimental glioma therapies attempted in the past, several issues will certainly need to be addressed in order to translate these promising pre-clinical findings into clinically-relevant therapies for patients. Some of the obstacles that may be envisaged include the proper selection of the best stem cell type/origin, choice of the most appropriate cargo for each tumor type or personalized to specific patients, optimization of administration routes and dosing, evaluation of the long-term cell fate of engrafted stem cells , and development of real-time imaging systems for therapeutic stem cells It is now evident that cells derived from the osteogenic and neurogenic niches present important interactions that may impact the future development of CNS related therapies. As discussed in the present review there is robust evidence showing that MSCs and their secretome are able to modulate the action of neurogenic niches and neural progenitors. Their usage was shown to promote the functional recovery of animal models of PD and stroke, as well as the application of novel paradigms for glioblastoma therapies. Nevertheless, it is still a largely unexplored field, with many questions yet to be addressed. For instance, are the traditional growth factors the main mediators of the actions promoted by the MSCs secretome; or, instead, do MSCs-derived unknown neuroregulatory molecules modulate such actions? Can we modulate the tropism that these cells display towards gliobastomas? So far, most of the studies focused on the action of MSCs towards the neurogenic niches, namely NSCs. However, few address if and how the neurogenic niches, and within them NSCs, modulate the action of MSCs. In fact a bidirectional communication between both cell types is most likely to occur. The answer to this and other questions will be important to further define this field in the future, and its impact in future CNS regenerative strategies.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.


Objective: A review is made of the immediate or immediate postoperative bleeding complications in dental implants, with a view to identifying the areas of greatest bleeding risk, the causes of bleeding, the length of the implants associated with bleeding, the most frequently implicated blood vessels, and the treatments used to resolve these complications.Material and Methods: A Medline (PubMed) and Embase search was made of articles on immediate bleeding complications in dental implants published in English up until May 2014. Inclusion criteria: studies in humans subjects with severe bleeding immediately secondary to implant placement, which reported the time until the hemorrhage, the implant lenght, the possible cause of bleeding and the treatment. Exclusion criteria: patients receiving anticoagulation treatment.Results: Fifteen articles met the inclusion criteria. The area with the largest number of bleeding complications corresponded to the mandibular canine. The cause of bleeding was lingual cortical bone perforation during implant placement, with damage to the sublingual artery. The implants associated with bleeding were those measuring 15 mm in length or more. Management focused on securing the airway (with intubation or tracheostomy if necessary), with bleeding control.Conclusions: It’s important to pay special attention when the implants are placed in the mandibular anterior zone, especially if long implants are used. The most frequently cause of bleeding was the perforation of the lingual plate. Treatment involves securing the airway, with bleeding control. Key words:Hemorrhage, complications, immediate, bleeding, dental implants. Complications in dental implant surgery are infrequent and normally self-limiting, causing the technique to become an almost routine procedure. However, immediate bleeding complications have been described which although infrequent, may prove serious, particularly in the floor of the mouth. Some cases can even be life-threatening, requiring emergency treatment on an in-hospital basis -3.The branches of the sublingual and sub mental arteries that irrigate the lingual zone of the mandible are located close to the lingual cortical plate. This implies an increased risk of bleeding if the lingual cortical bone is damaged during drilling or implant placement. Profuse bleeding is less common in the upper jaw, and only one article to date has reported important bleeding following maxillary sinus lift surgery with immediate implant placement .Adequate planning of surgery is required, with thorough knowledge of the anatomical features of the surgical zone, and the use of complementary techniques such as cone-beam computed tomography (CBCT), in order to avoid possible risk situations. Despite such precautions, however, some patients are at an increased risk of bleeding due to physiological anatomical variants . Two revThe present study reviews the literature on immediate or immediate postoperative bleeding complications in dental implants, with a view to identifying the areas of greatest bleeding risk, the causes of bleeding (including the implicated arteries), the length of the implants associated with bleeding, and the treatments provided.- Study search strategiesThe review was based on the following question: Is implant length and location associated to important bleeding risk during or immediately after implant placement? A Medline (PubMed) and Embase search was made of articles on immediate bleeding complications in dental implants published in English up until May 2014. The following key words were used: “(hemorrhag* OR bleeding) AND complications) AND dental implants”, “hemorrhag* AND complications AND pterygoid”. The search was completed with a review of the references cited by the identified articles, in order to generate additional studies not identified by the online search. Important bleeding complications were defined as bleeding requiring hospital admission. The reviewers (JB and DP) individually analyzed the titles of the articles, with application of the inclusion and exclusion criteria (defined below) in order to identify the publications to be included in the systematic review. The reviewers then performed a new selection of articles after analyzing the abstracts of those manuscripts that had been selected according to title. Lastly, a full-text review was made. Article inclusion was decided by consensus in the event of disagreement between the reviewers. The Mendeley Desktop reference manager  was used.- Inclusion and exclusion criteriaThe following search inclusion criteria were used:  articlesAfter analyzing the articles, the reviewers collected the following information from each publication: Number of patients, Age, Artery causing bleeding, Position of the implant causing bleeding, Time from implant bed drilling to bleeding, Length of the implant and treatment provided.A total of 486 articles were identified. After reviewing the abstracts and eliminating duplicities, this number was reduced to 28 publications, of which 13 were excluded because they failed to meet the inclusion criteria: one article was published in German, 11 could not be retrieved as the full-length article, and one failed to produce all the information required for inclusion Fig. . The meaImmediate bleeding complications were most often observed in the mandibular canine region (6 cases) -11,13-15The possible cause of bleeding was only specified in 7 of the case series included in the review ,11,13,14Gauze was applied to the bleeding zone under manual pressure ,13,14,16After securing the airway, Drainage of the hematoma was also carried out ,13,15-18We identified only one case of serious bleeding of the upper jaw in the context of immediate dental implant placement following indirect sinus lift surgery. Treatment consisted of the application of gauze to the bleeding zone, but this was not enough to stop the bleeding. A window was opened in the lateral wall of the maxillary sinus using the Caldwell-Luc technique, with cauterization of the posterior superior alveolar artery . None ofet al.  ,8-12,18 - Cause of bleeding.et al. . Treatment involves securing the airway, with bleeding control. The use of short implants is advised in the anterior mandibular sector, in order to avoid the risk of important bleeding complications.


The cholesterol pathway is an essential biochemical process aimed at the synthesis of bioactive molecules involved in multiple crucial cellular functions. The end products of this pathway are sterols, such as cholesterol, which are essential components of cell membranes, precursors of steroid hormones, bile acids and other molecules such as ubiquinone. Several diseases are caused by defects in this metabolic pathway: the most severe forms of which cause neurological involvement (psychomotor retardation and cerebellar ataxia) as a result of a variety of cellular impairments, including mitochondrial dysfunction. These pathologies are induced by convergent mechanisms in which the mitochondrial unit plays a pivotal role contributing to defective apoptosis, autophagy and mitophagy processes. Unraveling these mechanisms would contribute to the development of effective drug treatments for these disorders. In addition, the development of biochemical models could have a substantial impact on the understanding of the mechanism of action of drugs that act on this pathway in multifactor disorders. In this review we will focus in particular on inhibitors of cholesterol synthesis, mitochondria-targeted drugs and inhibitors of the inflammasome. The cholesterol pathway (CP), also called the mevalonate pathway, is a crucial metabolic process that leads to the synthesis of cholesterol and other biomolecules such as steroidal hormones and isoprenoids. These essential bioactive molecules play an important role in multiple cellular processes, including intracellular signaling, gene expression, protein modification, cell growth/differentiation, cytoskeletal dynamics and stability, mitochondrial function and cell membrane structure ,2.The CP is promoted by a molecule of acetyl-CoA and its thiolase (Acetoacetyl-CoA), using the 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) synthase, to synthesize HMG-CoA. HMG-CoA reductase (HMGCR) then converts HMG-CoA to mevalonate (MVA), which is further metabolized to Isopentenyl-5-pyrophosphate (IPP) and its isomer Dimethyllallyl-pyrophosphate (DMAPP). At this point, Farnesyl pyrophosphate (FPP) synthase catalyzes a sequential reaction to generate mevalonate-derived isoprenoids, such as FPP and geranylgeranyl pyrophosphate (GGPP) ,2,3.For the synthesis of cholesterol, two molecules of FPP are converted by squalene synthase to the linear hydrocarbon molecule squalene, which is cyclized to the first sterol intermediate, lanosterol, and then converted, through a series of reactions, to cholesterol.N-glycosylation (dolichols), mitochondrial electron transport chain function (ubiquinone), and free radical scavenging  benzamide), which was developed to limit the infarct size following myocardial ischemia–reperfusion in a mouse model, proved to be highly effective [The interest elicited by the effectiveness of this new class of drugs is supported by a growing body of data. Following the synthesis of compounds such as glyburide , which wffective .Several studies have described how the oxidative damage of mitochondria and the activation of inflammasomes can interact to determine defects of the CP. Targeting these two mechanisms would be relevant both to curing rare disorders of cholesterol biosynthesis and to the treatment of metabolic and degenerative disorders. Although considerable evidence, deriving from cellular and animal models, is available, much remains to be understood about the real potential of inflammasome inhibitors in the clinical setting. The crucial fact remains that cholesterol is tightly regulated by positive and negative feedback mechanisms that may affect different cell types and functions in different ways.For example, consistent data show that shortage of geranygeranyiol can lead to inflammation by reducing prenylation of membrane bound GTP-binding proteins of the Rab and Rac family, with consequent activation of the inflammasome ,139,140.Furthermore, the regulation of the CP may vary greatly depending on the cell type. CP plays an essential role in liver metabolism and in the production of biliary acids. In monocytes, the main function of the CP is probably to modulate the activity of membrane bound proteins or regulate cell membrane composition. Therefore, it is difficult to predict how pharmaceutical interventions on this pathway may influence the various functions of the different cells types and organs.For the same reasons, it is hard to predict what the long term consequences of treatments that reduce the inflammatory response and hyper-protect mitochondria could be. Further studies addressing these questions in preclinical settings are needed. In the meantime, randomized controlled trials will definitely clarify the preventive and curative potential of these novel therapeutic strategies on neurodegenerative and cardiovascular inflammatory disorders.


Superior mesenteric artery (SMA) syndrome arises from a reduction in the angle formed between the SMA and the aorta, thereby compressing the third portion of the duodenum. This phenomenon may be caused by a number of factors, one of which being acute weight loss. We report a case of a female patient presenting with abdominal pain and vomiting who developed superior mesenteric artery (SMA) syndrome as a result of rapid weight loss, thought to be secondary to amphetamine abuse. This association can often be overlooked and, to our knowledge, has not been previously reported. The superior mesenteric artery (SMA) syndrome, also known as Cast Syndrome, Mesenteric Root Syndrome, or Wilke's disease, is a rare cause of mechanical small intestinal obstruction and classically associated with rapid weight loss. SMA syndrome stems from compression on the third portion of the duodenum, resulting from the acute angle created between the superior mesenteric artery and the aorta, as caused by paucity of mesenteric and retroperitoneal fat pads. An illustration of this concept can be seen in The patient being presented is a 30-year-old Asian-American female with a past medical history significant for Attention Deficit Hyperactivity Disorder (ADHD) and bipolar disorder and is prescribed a daily regimen of 10 mg amphetamine/dextroamphetamine. She presented with right upper quadrant and epigastric pain of 5 days' duration. The pain was described as sharp, constant, and exacerbated by eating. It was associated with bilious, nonbloody vomiting, nausea, anorexia, and a thirty-pound weight loss over a time period of two months. The patient stated that she was under a significant amount of stress and she recently increased the dosage of her amphetamine/dextroamphetamine, the exact amount of which she was not able to specify. Examination revealed cachexia (BMI of 15.6) and right upper quadrant tenderness upon palpation. Abdominal CT scan  revealedLocated in the retroperitoneum, the third portion of the duodenum runs through the acute angle created by the aorta and its branching artery known as the superior mesenteric artery , 6. The The FDA approves the use of amphetamines for indications such as ADHD and narcolepsy; however, the off-label use and abuse of these drugs have grown to become a dangerous epidemic in the United States in recent years, most notably amongst young, college-aged individuals. Amphetamine abuse may involve acquisition from illicit sources or manipulation of legal doses, which we suspect led to our patient's rapid weight loss and SMA syndrome. Amphetamine abuse may be difficult to recognize, and a patient's history is oftentimes withheld. Therefore, when presented with a patient complaining of abdominal symptoms mimicking small bowel obstruction in the setting of rapid weight loss, one should consider the diagnosis of amphetamine-induced weight loss causing SMA syndrome.


With increasing use of clinical breast MRI and a plethora of novel techniques and sequences for lesion characterisation, a standardised approach to lesion description and reporting is increasingly important. This facilitates meaningful research and audit, particularly in the context of multicentre studies.th edition of the BI-RADS lexicon, with revision of the MRI section including addition of new descriptors, modification of others and deletion of some that were rarely helpful in practice, such as ‘stippled’ enhancement [To this end the American College of Radiology has recently published the 5ancement . CategorThe lexicon highlights the importance of a structured report, including the indication, scan technique, salient findings and critically, an overall assessment with a clear recommendation for further management. This approach has been validated in a number of studies correlating the assessment category with histopathological findings and/or long-term follow-up ,3.Use of a standardised lexicon, modified in the light of available evidence, has obviated some of the interpretative challenges of breast MRI. Use of supplemental diffusion weighted imaging may also be helpful . NonetheMost importantly, it should be remembered that to date, despite the recognised superiority of breast MRI over any other modality for breast cancer detection and local staging, there is no hard evidence for improved patient outcomes. Two randomised controlled trials and seven comparative cohort studies have not shown any benefit for preoperative MRI in terms of re-excision rates; rather, there is a trend to higher mastectomy rates . No convThis workshop will provide an update on the BI-RADS lexicon and indications for breast MRI, with expert tuition in hands-on analysis of case studies.


Plant–microbe interactions are omnipresent in terrestrial ecosystems and central to understand processes of individual growth, community assembly, and biogeochemical cycling. Plants and microbes interact above and below ground, and such interactions could theoretically include all combinations of positive , negative , or neutral effects. Many plant pathogenic and symbiotic microbes produce specialized structures that invade plant cells, but remain enveloped by plant-derived membranes. These intimate contacts between plant and microbial structures drive either bidirectional flows of nutrients as symbiotic  or unidirectional flows as in pathogenic interactions. Whatever the biotrophic context (symbiotic vs. pathogenic), nutrients must pass several membrane barriers and the apoplastic interface before their assimilation by plant or microbial cells. Plant and microbial cells must be “re-programmed,” which includes differentiation and polarization of membrane transport functions to take up, to transfer or to exchange nutrients between partners of the biotrophic interaction. However, the mechanisms underlying the functioning and the dynamics of the transportome  at the biotrophic interface are still poorly understood. The transportome is a key player in nutrient uptake and exchange mechanisms and its regulation pattern is essential in determining the outcome of plant fungal interactions and in adapting to environmental changes.Availability, uptake, and exchange of nutrients in biotrophic interactions will drive plant growth and modulate biomass allocation, that are central to plant yield, a major outcome, in the context of high biomass production. In a long term approach, unraveling those biotrophic transportomes and their underlying mechanism will be extremely useful in (i) the prediction of plant–microbes ecological niches, (ii) plant diagnosis , (iii) our understanding of microbial ecology and evolution of function, (iv) the development and implementation of environmentally and sustainably agro-ecosystems for crop production, (v) the identification of natural routes to the cycling and sequestration of carbon in terrestrial environments, and (vi) the ecosystem response to climate change , and (v) also the metabolic patterns of how plants and microbes interact at the biotrophic interface is unknown, suggesting that the key transporter genes need to be elucidated from model organism. Regarding the availability of plant and microbial genomes, only several transporters involved in biotrophic interactions were characterized: mycorrhizal symbiosis , root nodule symbiosis , actinorhizal symbiosis , and pathogenic interaction (amino-acid nutrition: Struck). Moreover, only few recent studies are about such characterization: metal transporters , an ammonium transporter , phosphate transporters  in the mutualistic fungus Rhizophagus irregularis forming arbuscular mycorrhizas, an aquaporin . Increasing applications and improvements of methodologies could complete classical transporter characterization and give a better detection and resolution of the functioning of biotrophic interfaces: transcripts and proteins by laser capture microdissection technology . These recent technological achievements in model plants associated to microbial consortia will facilitate comprehensive identification of the key nutrient transporters involved in biotrophic  interactions. The functioning of some of these transporters  could be evolutionary linked in plant–mutualistic  that could influence microbial nutritional/trophic transportome. Soils, minerals, and leaves represent specific microbial habitats influencing and controlling the establishment of microbial communities, but also the expression of transport-related genes Johnson, .PC and DW have co-edited the topic and co-prepared the editorial.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 handling Editor declared a shared affiliation, though no other collaboration, with one of the authors P-EC and states that the process nevertheless met the standards of a fair and objective review.


Ectocarpus to develop novel DNA-based sex-markers for three commercially relevant kelps: Laminaria digitata, Undaria pinnatifida and Macrocystis pyrifera. Markers were designed within nine protein coding genes of Ectocarpus male and female (U/V) sex chromosomes and tested on gametophytes of the three kelp species. Seven primer pairs corresponding to three loci in the Ectocarpus SDR amplified sex-specific bands in the three kelp species, yielding at least one male and one female marker for each species. Our work has generated the first male sex-specific markers for L. digitata and U. pinnatifida, as well as the first sex markers developed for the genus Macrocystis. The markers and methodology presented here will not only facilitate seaweed breeding programs but also represent useful tools for population and demography studies and provide a means to investigate the evolution of sex determination across this largely understudied eukaryotic group.Sex discriminating genetic markers are commonly used to facilitate breeding programs in economically and ecologically important animal and plant species. However, despite their considerable economic and ecological value, the development of sex markers for kelp species has been very limited. In this study, we used the recently described sequence of the sex determining region (SDR) of the brown algal model  Brown algae (Phaeophyceae) are the dominant inhabitants of coastal environments and the major primary producers in these marine ecosystems. They are best known for forming kelp forests in shallow, rocky, cold water environments, especially in the northern Hemisphere. Subtidal kelp forests, together with their associated fauna and flora, are among the most diverse and productive ecosystems worldwide (reviewed in –3). The th February 2015) .,79.EctocL. digitata in Brittany [Lessonia nigrescens species complex for which changes in sex ratio was observed specifically in the populations where sister-species were in close contact [The sex markers developed in this study also have multiple applications for the analysis of the structure of wild kelp populations, allowing the detection and analysis of the life cycle variations in the field. For example, it will be possible to test the degree of parthenogenetic reproduction in marginal habitats at species range limits, a phenomenon that was recently described in populations of Brittany . The stu contact . The avaEctocarpus SDR genes were sex-linked in the kelp species, whereas the markers based on PAR genes that were tested failed to detect evidence of sex-specific alleles in kelps. This suggests that the SDR of Laminariales and Ectocarpales have shared ancestry, i.e, the sex-determination system originated more than 100 Mya, before the divergence of the two orders [The analyses carried out in this study provide the first evidence that sex chromosomes in two major brown algal orders, the Ectocarpales and the Laminariales, are derived from a common ancestral sex-determination system. All of the kelp sequences that were amplified using primers based on o orders . Howevero orders , and it L. digitata, U. pinnatifida and M. pyrifera. The markers are robust and easy to apply, because sex is determined simply by PCR-amplification of sex-specific DNA, visualized as bands on agarose gels. This is an advantage over alternatives such as microsatellite-based markers for example, which require the application of more sophisticated analyses to measure the exact size of the amplified product. Moreover, the three target kelp species were phylogenetically diverse, suggesting that the approach should be adaptable to a broad range of species within the Laminariales. The sex markers described here, and the general approach of developing sex markers based on Ectocarpus sex chromosome sequences, represent important new tools for seaweed breeding and biotechnology. They also have potential applications in natural population studies and in studies that aim at understanding the mechanisms and evolutionary principals underlying sex determination in brown algae.In this study we have developed novel DNA-based sex-markers for the three economically important kelp species, S1 Table(DOCX)Click here for additional data file.


Drosophila to humans. Interestingly, intestinal damage upon ingestion of chemicals or pathogenic bacteria leads to an inflammatory response in the Drosophila intestine, which promotes regeneration and predisposes to tumorigenesis. This regenerative inflammatory signaling culminates in proliferation and differentiation of ISCs that replenish the damaged intestinal cells and is regulated by the interplay of conserved cell-cell communication pathways, such as the JNK, JAK/STAT, Wnt/Wingless, Notch, InR, PVR, EGFR, and Hippo. These pathways are induced by signals emanating not only from the damaged intestinal epithelial cells, but also from neighboring tissues associated with the intestinal epithelium, such as the muscles and the trachea, or distant tissues, such as the wounded epidermis and the brain. Here we review tissue communication during homeostasis and regenerative inflammatory signaling in Drosophila focusing on the signals that emanate from non-intestinal epithelial tissues to ensure intestinal integrity.The intestine, as a barrier epithelium, serves in the first line of defense against invading pathogens and damaging agents that enter the body via food ingestion. Maintenance of intestinal homeostasis is therefore key to organismal health. To maintain homeostasis, intestinal stem cells (ISCs) continuously replace lost or damaged intestinal epithelial cells in organisms ranging from  Drosophila intestine has evolved to an excellent model for studying signaling events that control intestinal homeostasis, which, when deregulated, can cause disease  and enteroendocrine cells (EEs), with absorptive and secretory properties, respectively, the transient enteroblasts (EBs), and the self-renewing intestinal stem cells (ISCs). The ISCs are evenly distributed in the epithelium, reside basally close to the BM and replenish lost cells continuously  activate a process of regenerative inflammatory signaling, whereby damaged cells produce inflammatory signals that trigger regenerative pathways to replace lost cells and maintain tissue integrity  mutant clones, which activate Wnt/Wg signaling, has uncovered a proliferative, not a self-renewal, role of Wg in the ISCs , instead of the temperature sensitive wg mutation that broadly removes wg   ligands that control these processes remains largely unknown. Two of the eight Drosophila insulin-like peptides, Dilp3 and Dilp7, are expressed in the intestine: Dilp7 is expressed in intestinal neurons and regulates intestinal physiology . Interestingly, expression of the Dpp ligand is found in tracheal cells and trachea-specific dpp RNAi knockdown leads to reduced BMP/Dpp activity in the intestinal epithelium concurrent with increased ISC proliferation suggesting that trachea-derived Dpp is necessary for midgut homeostasis by counteracting stress factors and protecting ECs from apoptosis  and is necessary and sufficient for the differentiation of specialized midgut ECs, the copper cells , the trachea (TGF-beta/Dpp) and the neurons . In mammals epithelial-mesenchymal interactions involving Hh, PDGF, and BMP signaling drive the modeling of the epithelium (Crosnier et al., Drosophila and mammals in intestinal homeostasis and regenerative inflammation. Clearly, studies in the Drosophila intestinal system will broaden our understanding of tissue communication in mammalian homeostasis.An emerging theme in intestinal regeneration of both 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.


Proteins are among the major constituents of a healthy and balanced human diet. Legumes have been serving as a human food-source for many centuries Imsande, . NotablyThough not done by the editors chapters discussed herein can be divided into two major groups. Comprising nine contributions, the first group gives insights into the legume stress responses. The second group, with eight contributions, highlights approaches for improving legume stress tolerance.Major insights into legume responses to a number of abiotic stresses including salinity, nutrient-deficiencies, pesticides, and temperature regimes are nicely overviewed. The impact of increasing soil salinity on legume crop health and productivity is particularly important, due to the sensitivity of legumes to salinity stress. Information related to leguminous crop genome sequences has also been well-summarized. The responses of legumes to nutrient deficiencies are elaborated, including their control measures with major micro and macro mineral nutrients. Osmotic stress is argued to be a factor impacting the legume–rhizobia symbiotic relationship by severely impairing nodule integrity and functioning. Two chapters are dedicated to discussion of the responses of chickpea (the third most important pulse crop) to major abiotic and biotic stresses. An overview is presented of chickpea responses to temperature regimes. The lack of simple and accurate screening procedures for screening parental genotypes and breeding populations for various abiotic stresses is advocated as a major bottleneck in the development of low temperature stress-tolerant chickpea. Contributions also provide details on the pesticide uptake, metabolism, persistence, and impacts in major leguminous crops. It is revealed that pesticides can severely impair biological nitrogen-fixation by impacting nodule formation and nitrogenase activity, causing oxidative stress, and damaging important components of the antioxidant defense system. Exploration of pesticide-tolerant bacterial strains is emphasized to improve legume–rhizobia association, and also to increase growth and performance of legume plants under pesticide stress.Under the second group of contributions, several chapters highlight the role of exogenous application of phytoprotectants  in the minimization of abiotic stress impacts on legumes. In particular, the use of biotechnological approaches is argued as a panacea for overcoming biotic and abiotic stress constraints in legumes. The need for development of safer and more effective methodologies for legume stress tolerance improvement is emphasized. The isolation of a sufficient number of stress resistance genes, understanding their accurate delivery and analyses methods, and comparative analyzing protein expression profiles and functional analyses are argued to be significant in this context. Molecular-genetic information is meager on the legume biology and also with nodule formation, and other vital processes like resistance, potential tolerance, and susceptibility to various stresses  in the regulation of a wide variety of physiological and stress responses in non-legume crops Zhang, . HoweverNotably, under field conditions, a number of biotic stresses can co-occur and modulate abiotic stress-impacts on plants, where interaction between these stress-types can yield positive (cross-tolerance) or negative outcomes (Atkinson and Urwin, Since a thorough understanding of plant stress responses and tolerance is essential, new dialogue will be provoked by this book leading to improved legume health under adverse conditions. In summary, this book is timely and a welcome addition to the literature. Researchers and Ph.D. students in the field of crop-biology/physiology, agronomy, and plant-breeding areas can be benefited with this book.http://onlinelibrary.wiley.com/book/10.1002/9781118917091.This book can be found at: NAA conceived the idea and wrote the paper.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Demodex mites and bacteria involved in bovine demodectic mange lesions and the normal flora inhabiting the skin of noninfected animals was investigated. Demodex bovis and D. ghanensis mites were isolated from the infected purulent material extracted from skin and meibomian gland lesions, respectively. The mites could not be demonstrated in skin brushings or impression smears from the eyes of noninfected cattle. Pathogenic bacteria (Staphylococcus aureus and Streptococcus pyogenes (Group A)) and opportunistic organisms  were isolated from skin lesions of demodectic mange, and Moraxella bovis and Staphylococcus aureus were isolated from meibomian gland lesions. Bacillus subtilis, Escherichia coli, Proteus vulgaris, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes (Group A) were isolated from skin brushings from noninfected cattle. The nature of association between Demodex mites and bacteria in demodectic mange lesions is synergistic and of equal significance. Pathogenic and opportunistic bacteria facilitated the establishment of Demodex mites in the lesions produced and provided an excellent microclimate for the mites to propagate and reproduce, resulting in severe and progressive disease. The “high-turnover” granulomatous reaction which characterized the histopathological changes proved that Demodex mites and associated bacteria were persistent and immunogenic.The nature of association between  Demodex bovis (Stiles 1892) [Demodex belongs to a very specialized group of mites which live in the hair follicles and sebaceous glands of various mammals and man, causing demodectic or follicular mange –5. Demods Stiles 892 [1, 4es 1892) , 7. Demodex mites in the infected purulent material extracted from nodules and pustules [The disease is characterized by the formation of papules, nodules, pustules, and cysts of varying sizes , 5, 8, 9pustules . Demodex mites in macerated or histological sections of the eyelids of clinically healthy cattle, while other workers [Meibomian gland demodicosis was reported by a few workers –17. Meib workers , 17, 21 The bacteria associated with the mites in demodectic mange lesions were regarded by some workers as secondary invaders , 9. SomeThe invasion of a host by pathogenic bacteria may be aided by the production of bacterial extracellular substances (invasins) which act against the host by breaking down primary or secondary defenses of the body , 25. SprStaphylococcus aureus and Streptococcus pyogenes were reported to produce a wide array of virulence factors in the form of exotoxins and enzymes that damaged host tissues; expressed many potential virulence factors such as surface proteins that promote colonization of host tissues; inhibit phagocytosis; provoke symptoms of disease; and possessed inherent and acquired resistance to antimicrobial agents [l agents –26.Moraxella bovis caused infectious bovine keratoconjunctivitis, a devastating ocular disease of cattle which occurs worldwide [ M. bovis was attributed to fimbriae, which allowed adherence of the organisms to the cornea, and during replication, haemolysin and other lytic enzymes were produced playing a significant role in virulence [orldwide . The orgirulence , 27–29.Pseudomonas aeruginosa caused a wide range of opportunistic infections. Pathogenic strains of P. aeruginosa produced a variety of toxins and enzymes which promote tissue invasion and damage [d damage , 25. Attd damage , 25.Trueperella pyogenes (Arcanobacterium pyogenes) is one of the most common opportunistic pathogens of domestic ruminants, capable of producing suppurative lesions in any organ or tissue in animals. In farm animals, especially ruminants, it is the most common bacteria found in infected wounds and abscesses [ A. pyogenes expressed several known and putative virulence factors required for adherence, subsequent colonization, and host tissue damage [bscesses , 31. A. e damage , 31.The pathology of the disease was described in different animals including man; in cattle , 32; in  Demodex mites in skin and meibomian gland lesions of demodectic mange. Studying the normal flora inhabiting the skin of normal noninfected cattle of the same herds is a crucial and prerequisite part of this investigation, as it represents an important integral part in the ecology of cattle skin. Moreover, the role played by bacteria in the severity and spread of the lesions of demodectic mange in relation to host parasite interactions is elucidated.Previous workers have undermined the role played by bacteria in demodectic mange lesions by simply regarding them as secondary invaders. The current study is probably the first encounter on the nature of association of bacteria and Demodex mites and bacteria involved in the lesions of demodectic mange. Purulent infected material was extracted from skin and meibomian gland lesions using sterile techniques. Each specimen of infected material was divided into two parts. The first part of each specimen was kept in a sterile Bijou bottle and refrigerated for bacteriological investigations. The second part was kept in other Bijou bottles containing equal volumes of glycerol and ethanol for parasitological examination. Two sets of impression smears and swabs from the eyes of noninfected cattle were also collected and refrigerated. Bacteriological and parasitological investigations were also conducted on each of 200 specimens of skin brushings collected from noninfected cattle belonging to the same infected herds using a coarse brush. Skin biopsy specimens were collected from the infected and noninfected cattle following the technique described by Abu-Samra [Three hundred cattle with skin and eye lesions suggestive of demodectic mange and 50 noninfected cattle belonging to the same herds were clinically examined and sampled to study the nature of association betweenbu-Samra . After bTwo milliliters of sterile nutrient broth was added to the refrigerated infected material and skin brushings in each bottle, and two drops of sterile nutrient broth were placed on the swabs from the eyes of noninfected animals. The contents of the bottles were thoroughly mixed using a mechanical shaker. The procedures adopted for the preparation of culture media and media for biochemical tests were according to standard methods and techniques described by Barrow and Feltham . Each ofA small piece from each specimen of the infected purulent material was crushed between two microscope slides. Another piece from each specimen and a small amount of each specimen of skin brushings was placed in the middle of a microscope slide, a drop of 20 percent potassium hydroxide was added, and the preparations were gently heated and covered with coverslips. The two preparations were examined under the microscope. Individual mites were isolated and identified following the technique described by Abu-Samra et al. .μm prior to staining with Haematoxylin and Eosin stain and examined following standard methods and techniques described by Bancroft and Harry [The biopsy and necropsy specimens were processed, embedded in paraffin wax, and sectioned at 5 nd Harry .Five forms of skin lesions were recognized. They were papules, nodules and papules, nodules and few pustules , pustuleThemeibomian gland lesions were characterized by swelling of the eyelids, lacrimation, hyperaemia, and congestion of the mucous membranes, and in extreme cases by purulent exudation, swelling, and closure of the eyelids. Both eyelids showed 2–4 purulent nodules of 3-4 mm in diameter arranged in a linear fashion . InspectControl noninfected cattle had no visible or palpable lesions after careful examination of the skin and eyes.Skin Lesions. Culture of the 300 specimens of infected purulent material , and Trueperella (Arcanobacterium) pyogenes . These pathogenic organisms produced an array of invasins (toxins and enzymes) that break down primary and secondary defenses and produced allergic reactions causing severe irritation and pruritus resulting in scratching, rubbing, licking, or gnawing at the affected areas of the skin and eyes. This produced more inflammation, wounds, and damage of the affected areas in the skin and meibomian glands. The reaction became more severe as the result of invasion of the devitalized structures in the skin and meibomian glands by commensal and opportunistic pathogens . These organisms also possessed an array of virulence factors, invaded damaged tissues, and produced a suppurative reaction. Thus, the bacteria had created a suitable microclimate for the establishment and rapid replication of Demodex bovis and D. ghanensis mites in the skin and meibomian gland lesions, respectively. Maximum distension of the hair follicles with mites, bacteria, pus, secretions, and excretions resulted in the transformation of the hair follicles to cylindrical or saccular bladder-like cysts  were isolated from the infected purulent material extracted from skin lesions of infected cattle and from skin brushings from noninfected cattle. These bacteria had probably chosen the skin surface as a natural habitat, were intestinal flora existing in the animals' surroundings as reported by some workers [ workers , 24, 25, workers , 42, 43. workers  who enumPseudomonas aeruginosa and Trueperella (Arcanobacterium) pyogenes were only isolated from skin lesions of demodectic mange and were not isolated from skin brushings of noninfected cattle. The former organism usually infected damaged tissues or tissues with reduced immunity, while the latter is one of the most common opportunistic pathogens of domestic ruminants capable of producing suppurative lesions in any organ or tissue in farm animals. Many workers [ workers , 30, 31 Moraxella bovis and Staphylococcus aureus were isolated from the infected material extracted from meibomian gland lesions. However, these organisms could not be demonstrated in impression smears or isolated in swab cultures from the eyes of noninfected cattle. This proved that the two organisms did not exist as natural inhabitants of the eyes of noninfected cattle. Moraxella bovis is an opportunistic pathogen whose virulence is influenced by both host and environmental factors. Moraxella bovis might have been acquired from the animals' surroundings being contaminated by ocular discharges from cattle infected with infectious keratoconjunctivitis, while Staphylococcus aureus might have been acquired from the skin when the animals scratched or rubbed their irritated eyes against their bodies. Moraxella bovis was reported to be of high morbidity (80%), reaching epizootic proportions when transmission agents  became available [β-haemolysin toxins which lysed the corneal epithelial cells, and secreted cytotoxic toxin and pathogenic fibrinolysin, phosphatase, hyaluronidase, and aminopeptidases.vailable . The patvailable –29, 44 wD. bovis and D. ghanensis) from the same specimens was probably due to the chitinous exoskeleton of these mites making them resilient and resistant and would take a longer time to be destroyed, engulfed, and digested by the macrophages and giant cells.Failure to isolate bacteria from 48 specimens (16%) of purulent material extracted from skin lesions of demodectic mange and from 90 specimens (41.3%) of purulent material extracted from meibomian gland lesions was probably due to the destruction of the bacteria by the degenerative and reparative reaction of the high turn-over granulomatous reaction . The isolation of the mites , thus establishing the phenomenon of synhospitality.The isolation of only workers , 48, 49  Demodex mites and associated bacteria were both persistent and immunogenic producing severe, progressive, and generalized disease as was observed in natural field cases. These findings were in agreement with other workers [In both skin and meibomian gland lesions, the histopathological changes seen were compatible with cell-mediated immunity. This was in agreement with the report of a previous investigator  who repo workers , 52 who  Demodex mites and bacteria in demodectic mange lesions is synergistic and of equal significance. Most of the bacteria involved in the lesions possessed an array of virulence factors (toxins and enzymes) causing severe skin and meibomian gland deterioration and damage facilitating the establishment of Demodex mites in the lesions produced and provided an excellent microclimate for the mites to propagate and reproduce, resulting in a severe and progressive disease as observed in natural field cases. Furthermore, the “high-turnover” granulomatous reaction which characterized the histopathological changes proved that Demodex mites and associated primary pathogenic bacteria are both persistent and immunogenic.It was concluded that the nature of association between


Considering the pivotal role that creative ideas play in human societies, and creativity's contribution to multiple aspects of human life, understanding the cognitive components underlying creativity has become increasingly fundamental. Since the Five-Stages Model of the creative process proposed by Wallas , creativZedelius and Schooler); imagination of activities over a long period of time, relevant especially for actual creative achievements in science and writing ; as well as ‘looking at nothing’ and blinking behaviors, that do not necessarily involve visual imagery . In addition, we explored the relationships between different creative objects' production and artistic drawings with different mental imaging processes .In the present Frontiers in Cognition Research Topic 11 novel publications were collected: 8 Original Research Articles, 1 Review, and 2 Perspective Articles. From the beginning, the Research Topic was planned as a collection of studies exploring the relationships between creativity and mental imagery. Mental imagery is a representational medium for providing researchers access to thoughts, symbolization, and combination of elements, possibly facilitating the emergence of new ideas and creativity. In this direction, different aspects of mental imagery were considered which could increase or explain the emergence of creativity: daydreaming styles ; or the relationships between flexibility of divergent thinking (the number of categories encompassing the relevant responses) and attentive processing . Interestingly, the relationships between convergent thinking involving insight and intelligence , and working memory updating . In addition, neural correlates of creativity were investigated. Chavez highlighted the key role of brain areas involved in motor imagery on highly creative individuals, whereas Boccia et al. showed that general creativity relies on multi-componential neural networks supporting executive functions, whereas domain-specific creativity  roughly depends on different functional specialized brain regions.We also collected studies that investigated distinct and peculiar aspects of creativity and its cognitive components, such as: the equal-odds rule of divergent thinking, also known as the relationships between fluency (the number of responses) and creativity as assessed by independent judges (Jankowska and Karwowski), aimed at assessing three components of creative imagination: vividness of imagery, originality of responses, and transformative imagery ability; and the Artistic Creativity Domains Compendium (Lunke and Meier), aimed at measuring artistic creativity in visual arts, performing arts, literature and music.Finally, two different tests recently developed have been reported: the Test of Creative Imagery Abilities  might help to better understand the cognitive and neural correlates of creativity and the relationships among creativity and other cognitive domains, such as mental imagery, attention, and problem solving. We hope that the papers included in this Research Topic can help to stimulate more studies on these topics and in increasing research in the field of creativity.MP: Planned the topic and edited the most of papers included in the topic. LaP: Edited some papers included in the topic. RN: Edited some papers included in the topic. LiP: Edited some papers included in the topic. CS: Edited some papers included in the topic. CG: Edited some papers included in the topic.This work was supported by NIH [grant number T32 NS047987] to CS.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.


Although the mechanism of dry eye disease is not clearly understood, it is certain that inflammation and the immune response play a major role in determining the health of the ocular surface in dry eye patients. Accurate ocular surface characterization during the early stages of dry eye disease is critical for successful treatment, because there exists no single standard, objective test to diagnose the early phase of dry eye disease. The treatment target should be direct to prevent the perpetuation of chronic inflammation and immune responses. Numerous studies have categorized dry eye disease as an autoimmune-related inflammatory disease. However, relatively little is known about how innate immune mechanisms act following a local insult, why some patients are particularly vulnerable, and why local inflammation fails to resolve in these patients. Within this review, particular attention will be given to the very early events and corresponding defense mechanism in dry eye disease. The transition from innate to adaptive immunity will also be discussed. The tear film, lacrimal glands, corneal and conjunctival epithelia, and meibomian glands constitute a lacrimal function unit (LFU) that serves to preserve the health of the ocular surface. The components of the LFU work together to maintain homeostasis despite internal and external insults , 2. Dry The immune reaction comprises innate and adapted immunity, which differ vastly in terms of methodology as well as objective. Recent research has examined how the innate immune system influences adaptive immune responses . UnderstIn DED, a chronic inflammatory reaction is generated at the ocular surface, accompanied by the destruction of epithelial tight junctions and finally sloughing of the surface epithelia . The epiCorneal and conjunctival epithelial and epithelial-associated Langerhans cells are known to express a range of both toll-like receptors (TLR) and NOD-like receptors (NLR). The TLR and NLR pathways are the primary route by which host cells detect the presence of foreign invaders. The responses triggered include the production of cytokines, chemokines, and antimicrobial peptides. Increasing the expression of TLR or NLR may prevent the risk of infection but may also lead to inflammation. There is some evidence that TLR expression is modulated at the ocular surface in DED. In an experimental DED model, TLR2-4 and TLR9 expression was increased at the ocular surface and lacrimal glands .The rate of epithelial turnover is increased in DED, with viable corneal surface cells shed by classical apotosis , 12. DeaLactoferrin, which is secreted by acinar cells of the lacrimal glands, has anti-inflammatory, anti-cancer, and immune-modulating properties. Lysozyme, another secretory protein from acinar cells in the main lacrimal gland and conjunctival accessory lacrimal glands, attacks the cell walls of bacteria. The levels of lactoferrin and lysozyme are reported to be decreased in the tear fluid of DED patients , 16. TheMucins keep the ocular surface moist and protect it from external stimuli, and the induction of mucin from the ocular surface may facilitate the stability of the tear film . Mucins + NK cells that are activated in response to DS-induced stress signals. This suggest that the triggering immune response in DED pathology.Very recently, Desiccating stress-induced chemokine expression in the epithelium was shown to be dependent on upregulation of NKG2D/RAE-1 and release of IFN-γ in experimental DED . UpregulEnvironmental triggers may also contribute to the initiation and perpetuation of the disease. The activation of innate immunity results in antigen presentation, T-cell activation, and the release of pro-inflammatory cytokines . These cImmune-mediated inflammatory disease (IMID) is associated with various conditions. While the exact etiology is undefined, both genetic and environmental factors play an important role in its pathogenesis. Recently, genome-wide association studies (GWASs) using millions of nucleotide polymorphisms as genomic markers and non-synonymous single nucleotide polymorphisms (nsSNP) have identified loci involved in IMID susceptibility . MurakamThe inflammatory response can resolve insults to the tissue and restore homeostasis . HoweverThis review presents the current evidences for the role of innate immunity and an interface between innate and adaptive immunity in early DED Table . AlthougDisruptions to the primary ocular barrier (innate immunity) in DED would be expected to allow for pathogen invasion. However, there has been little evidence published to connect microbial keratitis and DED. This may imply that DED patients have stronger innate immunity to ocular surface damage and infection. It is also possible that changes in the expression of TLRs, innate immune molecules (secretory proteins), and mucins in DED may represent a compromised innate immune response. Failure of the innate response could trigger an adaptive immune response. Clinical and basic science research to accurately evaluate innate and adaptive immunity in DED are necessary because none of the hypothesis itself only  can definite in the pathogenesis of DED. The diagnosis of DED, especially in its early stages, has been hampered in clinical settings. Future research should focus on techniques to detect the early signs (innate immunity) in DED patients, and to facilitate the resolution of local inflammation at the ocular surface in order to prevent progression to chronic disease (adaptive immunity). To date, western DED researchers  have focused on inflammation and the immune response, while Asian researchers  have focused on the corneal epithelium.Within this review, we discussed the early events and defense mechanism of DED. The current knowledge might be the tip of an iceberg and further studies relating pathogenesis must be sought. By understanding the mechanisms of early event of immune dysfunction through basic science and translational research, potential drug targets can be identified.


When dental implants are malpositioned in relation to the adjacent teeth and alveolar bone or in an excessive buccal or lingual position, the final prosthesis rehabilitation impairs the peri-implant health of the gingival tissues and the aesthetics of the patient. Thus, the purpose of this case was to report and discuss a multidisciplinary protocol for the treatment of a compromised maxillary tooth in a patient with an abscess in his right central incisor due to an excessive buccal implant position. The patient presented with an implant-supported provisional restoration on his right maxillary central incisor and a traumatic injury in his left central incisor. The treatment protocol consisted in (i) abutment substitution to compensate the incorrect angulation of the implant, (ii) clinical crown lengthening, (iii) atraumatic extraction of the left central incisor, and (iv) immediate implant placement. Finally, (v) a custom abutment was fabricated to obtain a harmonious gingival contour around the prosthetic crown. In conclusion, when implants are incorrectly positioned in relation to the adjacent teeth, associated with soft-tissue defects, the challenge to create a harmonious mucogingival contours may be achieved with an interdisciplinary approach and with the placement of an appropriate custom abutment. One of the main challenges in esthetic dentistry is the preservation and reproduction of the natural mucogingival architecture surrounding the malpositioned implants in the anterior maxilla, especially when the patient presents a high lip line . There aPreferably, implants should be installed parallel to each other and to adjacent teeth and be aligned vertically with axial forces. However, when implants are incorrectly angled or improperly positioned and soft-tissue defects exist, conventional abutments cannot be used; therefore the use of custom angled abutments is required . FurtherSome studies suggest that angled abutments result in increased stress on supporting implants, adjacent bone, and the prosthesis . On the Thus, given the need to correct small angles and customize the connection between the implant and prosthesis, the aim of this paper was to report a case of an esthetic and functional anterior maxillary rehabilitation using periodontal surgery and custom abutments to correct the implant positioning. Moreover, the clinical implications of the use of angled abutments were discussed.A 57-year-old Caucasian man presented to the Department of Periodontology, School of Dentistry at Araraquara, Sao Paulo, Brazil, with an implant-supported provisional restoration on the maxillary right central incisor. The patient had no significant medical history and denied use of alcohol. He had sustained a traumatic injury involving his left maxillary central incisor, which had been treated endodontically and restored with a core and a crown. The main patient complaint was the uneven gingival level with consequent increasing of crown length in the right maxillary central incisor Figures .Clinical examination showed an abscess in the right maxillary central incisor mainly caused by the cement retention Figures  and due The periapical radiography revealed endodontic treatment in his left maxillary central and lateral incisors, root resorption of left maxillary central incisor, periapical lesion in his left lateral incisor, and the presence of a dental implant in his right maxillary central incisor with a prefabricated titanium abutment  maintaining a fixed provisional restoration . Also, tPrior to the prosthetic rehabilitation, a longitudinal root fracture in the left central incisor was observed; thus, an atraumatic extraction of this tooth was performed under local anesthesia  followedThe implant was placed 3 mm below the bone crest and in a more palatine position, allowing a minimal distance of 2 mm from the buccal cortical bone . PrimaryA CeraOne abutment  was installed immediately after the implant installation . ThereafAfter four months, the EsthetiCone and CeraOne abutments were removed in order to make a cast. From this cast, the custom UCLA abutments overcast with cobalt-chromium were prepared. One commonly used method to mitigate the poor appearance of peri-implant tissue caused by cobalt-chromium metal is to alter the metallic color using the application of porcelain on the component. Therefore, Ivoclar press ceramic was applied to obtain better aesthetic results on the pillars Figures . The copUsually, the use of parallel abutments to elaborate an implant-supported prosthesis instead of abutments is preferred. However, there are cases where it is not possible to place an implant in an ideal tridimensional position without additional surgical procedures –16. ThusSuccessful anterior esthetic of a single-crown restoration is achieved when the crown color matches the neighboring teeth, the peri-implant tissue contours simulate the gingiva around the crown, and the peri-implant tissue matches the patient natural color. In this particular case, we chose the UCLA abutment. This component has been indicated in some cases, including (i) implants positioned in the same gingival level; (ii) angled implants; (iii) presence of small interocclusal space; (iv) or if the final prosthesis cost is a preponderant factor . Using UIn this particular case, the patient presented with a deep peri-implant area and an angled implant, which contributed to the esthetics commitment. In relation to the implant position, the scientific literature is contradictory about the problems caused by angled abutments. In 2008, Kao et al.  observedAnother treatment option is the use of CAD/CAM technology. CAD/CAM allows the creation of duplicate abutments, whereby two precisely shaped abutments of similar or dissimilar materials can be fabricated from the same computer file. A crown that is fabricated for one of these abutments will fit the other, despite any material differences. However, this treatment alternative is still restrictive in developing countries due to the high cost to the patient . AnotherPassive adaptation between the abutment and the implant and between the crown and the abutment prevents the onset of the inflammatory process that causes peri-implantitis. Interventions prior to the complete healing process in response to patient demands may result in unpredictable soft-tissue manifestations. This outcome may include an inadequate zone of attached gingiva, as well as the compression of the soft tissue surrounding the abutment from an overlying provisional prosthesis . AchieviIn conclusion, when implants are incorrectly positioned in relation to the adjacent teeth, associated with soft-tissue defects, the challenge to create a harmonious mucogingival contours may be achieved with an interdisciplinary approach and with the placement of an appropriate custom abutment.


Mycobacterium tuberculosis (Mtb) facilitated a shift to target-based approaches to drug design but these efforts have proven largely unsuccessful. More recently, regulated gene expression systems that enable dose-dependent modulation of gene expression have been applied in target validation to evaluate the requirement of individual genes for the growth of Mtb both in vitro and in vivo. Notably, these systems can also provide a measure of the extent to which putative targets must be depleted in order to manifest a growth inhibitory phenotype. Additionally, the successful implementation of Mtb strains engineered to under-express specific molecular targets in whole-cell screens has enabled the simultaneous identification of cell-permeant inhibitors with defined mechanisms of action. Here, we review the application of tetracycline-regulated gene expression systems in the validation of novel drug targets in Mtb, highlighting both the strengths and limitations associated with this approach to target validation.Although efforts to identify novel therapies for the treatment of tuberculosis have led to the identification of several promising drug candidates, the identification of high-quality hits from conventional whole-cell screens remains disappointingly low. The elucidation of the genome sequence of  Mycobacterium tuberculosis (Mtb) resistant to rifampicin and isoniazid, defined as multidrug-resistant (MDR), continue to emerge, with an estimated 480,000 cases of MDR-TB identified in 2013  remains a major global health crisis, with 9 million new cases and 1.5 million deaths attributable to this disease in 2013 . The tre in 2013 . The morf action . This neMtb in vitro. This approach has been considerably more successful  of compound libraries or by structure-guided drug design . While tccessful , and ledccessful , the firccessful ; delamanccessful ; and PA-ccessful . Importaccessful . Howeverccessful  or if thccessful .Mtb, specifically in the context of target validation. We highlight the technical advancements that have been made, and describe the application of conditional mutants of Mtb in the validation of novel drug targets, and in target-based whole-cell screening (TB-WCS), in which phenotypic and target-based approaches are combined to identify target- and pathway-selective compounds with whole-cell activity.A fundamental requirement of a desirable antimicrobial drug target is that it should have an essential, and preferably non-redundant, function in growth and pathogenesis of the organism. The study of  essential gene function in bacteria has been revolutionized by the development of regulated gene expression systems, which enable the expression of a target gene to be controlled in a manner that depends upon the level of an inducer. A number of such systems have been developed for use in mycobacteria, and have been employed to investigate the roles of a wide variety of genes essential and conditionally essential for bacillary growth, physiology, and metabolism . In thisM. leprae from the acetamide-inducible promoter of Mycobacterium smegmatis ; these have been reviewed elsewhere  located within the promoter of tetA, encoding the Tet-exporting protein, thereby suppressing tetA expression . The dynamic range of the Tet-ON system can be expanded further by expression of TetR from either a strong promoter or an intermediate-strength promoter to generate hypomorphs in the Tet-ONS and Tet-ONM configurations, respectively. This increases the flexibility of the system, enabling dose-dependent regulation of genes with widely differing levels of expression. Since the removal of ATc can be difficult to achieve in some experimental settings, the manipulation of Tet-dependent hypomorphs was greatly simplified by the development of a modified “Tet-OFF” system, which utilizes a mutated, “reverse” TetR (revTetR) that binds to tetO only in the presence of ATc . The regulatory capacity of both Tet-ON and Tet-OFF systems in mycobacteria has been enhanced by codon optimization of the genes encoding TetR and revTetR to allow increased expression in Mtb  ligase  involved in decaprenyl-phospho-D-arabinofuranose (DPA) biosynthesis in Mtb , resulted in a decline in bacillary load in the lungs and spleens of mice, indicating a role for the proteasome in both growth and persistence of Mtb in vivo (Mtb genes for growth during different phases of infection (Table 2), simultaneously providing genetic validation of many of these as potential drug targets. Although perhaps not of direct relevance to the physiology of Mtb itself, it is worth noting that the selective inhibition of mitochondrial protein translation by Tets can lead to altered transcriptional profiles in eukaryotic cell lines and has minor effects on physiological fitness in mice . Given increasing evidence suggesting that targets requiring incomplete inhibition in order to confer a lethal phenotype may be more valuable , when grown on acetate, most likely reflecting a significantly lower level of icl1 expression by the Tet-regulated promoter than the native (fatty-acid-inducible) promoter  resulted in depletion of PanK protein to below the limit of detection, growth of Mtb in liquid culture and in vivo was not impeded , the enzyme that catalyzes the first, and rate-limiting, step in the conversion of pantothenate (vitamin B5) into CoA , has attin vitro , and des impeded . A similin vitro . Likewis in mice , >95% deb growth . These rtype Mtb . HoweverMtb  synthetase PrsA, exhibited the most profound growth inhibitory effects, with depletion of each resulting in a loss of Mtb viability in vitro and in macrophages. While the cidality associated with transcriptional silencing of drpE1 and ubiA in vitro was shown to occur as a result of induction of cell lysis, silencing of prsA resulted in reduced viability through cell implosion, without lysis occurring. Interestingly, although cell death occurred more slowly upon depletion of UbiA or PrsA than DprE1, the decrease in nucleic acid and protein synthesis observed as a consequence of PrsA depletion suggested that the bactericidal effects of PrsA inhibition are likely to be pleiotropic, thus identifying this enzyme as another promising a target in the DPA pathway. However, in an exciting new development, DprE1 was shown to occupy an extracytoplasmic location in Mtb, suggesting that cellular localization may be a major determinant of the vulnerability of DprE1 to chemical inhibition, accounting for the potency of the many inhibitors that act on this target . Using this system, dose-dependent Tet-regulated depletion of RpoB was achieved by insertion of a DAS+4 tag at the 3′ end of the rpoB gene, which encodes the target of the first-line anti-TB drug, rifampicin. Importantly, targeted degradation of RpoB had the same bactericidal effect on Msm as treatment with rifampicin.To overcome the limitations associated with using promoter replacement mutants for target depletion by transcriptional silencing, powerful new methods have been devised to enable regulated protein degradation in mycobacteria as an alternative approach . Althougin vitro  and duriin vitro , mediateD-cycloserine; dihydrofolate reductase (DHFR), the target of trimethoprim; InhA, the target of isoniazid; and KasA, the target of thiolactomycin – on the growth and viability of Msm  biosynthesis . Upon addition of the ATc inducer, transcription of sspB proceeds, leading to Clp-mediated proteolysis of the DAS+4-tagged target protein and simultaneous transcriptional silencing of the target gene through binding of revTetR to the Tet-regulated promoter . The biological utility of the DUC system was confirmed by generating a BioA-DUC mutant, which showed faster kinetics of killing than achievable by transcriptional silencing or targeted proteolysis alone and also resulted in the reduced emergence of suppressors that were no longer inducer-responsive (Table 1) in combination with SspB-mediated Clp proteolysis, was used to confirm the essentiality of the transketolase, Tkt, for growth of Mtb both in vitro and in macrophages . The rationale underlying this approach is that a reduction in the concentration of a target may render the cell hypersensitive to inhibitors that act on that target. Firstly, hypomorphs can be applied in drug susceptibility testing of individual compounds to provide biological confirmation of target specificity. The utility of TB-WCS for confirming target specificity in azinones , which aazinones . Subsequproaches ; PanC . The feasibility of TB-WCS as a tool for identifying novel antibacterial agents was first demonstrated by the discovery of the type II fatty acid synthesis (FASII) inhibitor, platensimycin, which showed enhanced activity against Staphylococcus aureus isolates in which fabF transcript was conditionally depleted by antisense-mediated interference (Mtb (panC hypomorph was screened against a ∼14,000-compound library which led to the identification of a series of flavones that displayed increased potency against PanC-depleted cells relative to wildtype Mtb. It was subsequently shown that these compounds do not directly inhibit PanC, despite the fact that pantothenate – the product of the PanC enzyme – rescued Mtb from the toxic effects of the compounds (Target-based whole-cell screening has also found application in enabling the direct identification of novel, cell-permeable inhibitory scaffolds with whole-cell activity against defined targets or pathways through screening of large compound libraries. The hits may include inhibitors of non-catalytic sites in an enzyme target. They may also include chemotypes that would escape detection in screens against wildtype cells by virtue of their weak inhibitory activity, thus increasing the availability of chemical matter for lead identification (rference . Althougrference , it has nce (Mtb . In the ompounds . This reompounds . In the icl1 resulted in Tet-dependent growth impairment of Mtb on acetate as the sole carbon source and hypersensitivity to 3-NP, but had no effect on growth of 3-NP susceptibility when cultured on glucose.In addition to this potential complication, there are a number of other issues that should be taken into account when considering the use of TB-WCS for hit identification in TB drug discovery. Firstly, it is critical to monitor and confirm stability of the hypomorph during the course of the phenotypic screen as the emergence of suppressors that are no longer inducer-dependent will compromise the screen. Secondly, as highlighted recently , an alteMtb, whose sequestration in remote lesion compartments in the human host likely accounts for the lack of correlation observed between plasma pharmacokinetics and drug efficacy (Mtb has the potential to overcome these limitations in that the transcriptional level of the target is maintained no modification of the expressed protein is required (While the utility of hypomorphs in TB drug discovery has been convincingly demonstrated, variability between individual targets can sometimes make data interpretation difficult. Furthermore, the concept of genetic validation is predicated on the assumption that a perturbation in the cellular concentration of a target by transcriptional silencing or proteolytic degradation is a reasonable surrogate for the inhibitory effect of a chemical inhibitor of the target’s function. In reality, the genetic vs. chemical vulnerability of a target may differ considerably as a result of a variety of factors . These iefficacy . The latefficacy  has the efficacy , this aprequired .E. coli (Msm (Msm did not phenocopy treatment with trimethoprim (The potential disconnect between depletion of a target by genetic means and its pharmacologic inhibition is perhaps best illustrated in the case of DHFR, the target of the folate biosynthesis inhibitor, trimethoprim. Although overexpression of DHFR in both E. coli  and Msm oli (Msm  was showethoprim . One posethoprim  suggestiMtb, remarkable progress has been made in this area. Hypomorphs provide an effective means of genetically validating novel drug targets, of comparing selected mutants in terms of vulnerability and of evaluating the downstream consequences of loss of target function. However, other factors such as cellular localization and druggability, which are critically important in determining target access by small molecule inhibitors, must also be taken into account when ranking and prioritizing novel drug targets, particularly in a pathway context. The implementation of regulated protein degradation systems and DUC genetic switches provide enhanced stringency while simultaneously enabling more rapid kinetics of inactivation, thus providing a powerful means of validating new drug targets. The increasing accessibility of ‘omics approaches offer exciting prospects for combining metabolomic and proteomic analyses with genetic approaches for target validation, which, when coupled with live-cell imaging of bacilli undergoing target depletion or drug treatment, have the potential to provide key insights into the global effects that disruption of an essential cellular function can have upon bacterial metabolism and physiology. Whether the systems reviewed here have a role in validating targets in animal models other than mice, which more accurately recapitulate the pathology of human disease, remains to be seen. Nonetheless, the encouraging results obtained to date, suggest that conditional mutants are set to play an increasingly important role in early stage TB drug discovery.Given that less than a decade ago there were no robust genetic switches available for regulation of gene expression in 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 ribosome is an ancient ribonucleoprotein machine universally responsible for catalyzing protein synthesis. Within eukaryotic cells, mitochondria contain their own ribosomes (mitoribosomes), which are highly modified ribosomes of bacterial descent, specialized for the synthesis of a handful of proteins, all essential for the biogenesis of the oxidative phosphorylation system. With high-resolution cryo-EM structures of the mitoribosome becoming recently available, the attention is geared towards understanding the mitoribosome biogenetic process and its compartmentalization.Spatial compartmentalization is essential for cytoplasmic ribosome biogenesis. Within the nucleus, the membrane-less nucleolus is organized around the chromosomal regions that contain the ribosomal RNAs (rRNA) genes, and is the site of rRNA transcription and processing, and of ribosome assembly. Nascent rRNA transcripts move away from the DNA template and are detected first in the fibrillar and later in the granular nucleolar components. Subsequently, pre-ribosomal particles are released from the nucleolus to undergo sequential maturation in the nucleoplasm and cytoplasm before they acquire translation competence. Within mitochondria, the genome (mtDNA) and proteins involved in mtDNA maintenance, replication and transcription, form a nucleoprotein complex known as the mitochondrial nucleoid. Hundreds of nucleoids are present per cell, each containing 1-5 mtDNA molecules. Recent data has indicated that the assembly of mitochondrial ribosomes occurs near the nucleoid –5. We haThe stages of mitoribosome biogenesis occurring at the nucleoid or at the mitochondriolus are a source of current debate in the field. Formaldehyde cross-linking performed to determine the nucleoid proteins that are in close contact with the mtDNA, led to a model for a layered structure of nucleoids in which replication and transcription occur in the central core, whereas RNA processing and translation may occur in the peripheral region. Affinity purification of known mammalian nucleoid components followed by mass spectrometry identified proteins involved in mtDNA metabolism and additionally many mitoribosome proteins (MRPs) and translation factors, indicating an intimate association among nucleoids, components of the mitochondrial translation machinery and foci containing ribonucleoprotein complexes. Supporting this view, the absence of MPV17L2, a protein required for mitoribosome assembly whose stability depends on mtDNA, induces the trapping of mitoribosome small subunit (mtSSU) proteins in enlarged nucleoids . This haThe RNA granules or mitochondrioli contain the core protein component GRSF1, required for mtSSU biogenesis -4, RNA pThe overlapping pool of proteins associated with either nucleoids or RNA granules reflects their proximity and the lack of membranous boundaries sealing these compartments. Their functional and physical dynamics is highlighted by the observation that approximately 10-15% of RNA granules co-localize with nucleoids, probably reflecting active transcription sites , 3, 7. AWhat is the precise composition and structure of the mitochondriolus, how molecular confinement is achieved within this membrane-free compartment, and at which point of maturation mitoribosomal subunits are released from the mitochondriolus and become translationally active are some of the questions that warrant future investigations.


An awareness and complete knowledge of the immunopathogenesis of renal disorders is mandatory. This is important not only for classifying disease, but in fact an effective management can only be planned according to the etiopathogenesis involved in the disease which is essential for the benefit of the patient.Majority of renal diseases, especially those involving the glomeruli and blood vessels, are caused by immune mediated injury. Either systemic or local abnormal immune responses are known to cause renal pathology. The abnormality may be due to hyperactive or a deficient immune system ,2. The aOur immune system is broadly divided into innate and adaptive immune systems. The cells of the innate immunity are polymorph nuclear leucocytes, monocytes/macrophages, natural killer cells and dendritic cells. Numerous molecules are involved in the innate immune response network such as complement proteins, C-reactive proteins and other acute phase proteins, receptors for pathogen associated molecular patterns (PAMPs), enzymes and cytokines. The adaptive immune system mainly includes T and B lymphocytes, antibodies, cytokines and numerous transcription factors involved in differentiation and generation of specific immune response to damaging agents. The innate and adaptive immune responses are very well coordinated and tightly regulated. It is when this coordination and regulation fails, that diseases occur ,3,5,6.The urinary tract system bears the main burden of removing waste and maintaining homeostasis in the body ,6. VarioThe cells and the molecules of innate immune system have a major role in maintaining immune surveillance, providing protection to the urinary tract system against pathogens and other damaging factors . The immThe release of cytokines and chemokines upon ligation of PRRs leads to the recruitment of cells including phagocytes and lymphocytes to the area of injury. The neutrophils and monocytes cause injury due to the generation of reactive oxygen species upon excessive activation. The lymphocytes also participate in the damage by augmenting the immune response to cognate antigens ,12.The inflammasomes causing inflammation have a very important role in renal injury. NLRP3 inflammasomes can be stimulated by bacterial products, uric acids or apoptotic cell debris directly or indirectly by DAMPs. This, in turn, activates IL-1 converting enzyme leading to increased expression of IL-1 and inflammation . This isComplement activation is important not only for the elimination of uropathic pathogens but also for the removal of injurious immune complexes that cause damage to urinary tract system. The alternate and lectin pathways are the components of innate immune response armamentarium, while the classical pathway is activated by antigen-antibody complexes. The inefficient activation or ineffective control of this system is not only associated with severe UTI but also leads to renal injury due to excessive and uncontrolled inflammation. Excessive and/ or aberrant activation of any or all three complement pathways is seen in various GNs ,14. The The important role of antibodies and mediation of inflammation is very well known in causing GN. These may be autoantibodies against various local or systemically generated antigens. They can cause pathogenesis by directly binding to native or to localized antigens, or may get deposited in the form of antigen antibody complexes in various renal tissues. The ultimate activation of complement system, recruitment of inflammatory cells, surge of chemokines and cytokines all lead to renal injury .Hence, depending on the etiology and pathogenesis, the treatment strategies are better planned. These may include steroidal and non-steroidal anti-inflammatory drugs, anti-hypertensives, immunosuppressive drugs, biomolecules including monoclonal antibodies, plasmapheresis and others ,16,17.SA was the single author of this manuscript.The authors declared no competing interests.None.