A key systemic regulatory hormone is growth hormone (GH), which has a developmental role in virtually all tissues and organs. This review catalogs the impact of GH on tissue programming and how perturbations early in development influence GH function.Developmental programming of the fetus has consequences for physiologic responses in the offspring as an adult and, more recently, is implicated in the expression of altered phenotypes of future generations. Some phenotypes, such as fertility, bone strength, and adiposity are highly relevant to food animal production and  The fundamental role of normal fetal development is best exemplified by pattern formation in the embryo. “Programming” was a term coined in 1986 to reflect that events occurring c traits  and the c traits ,4. The iRecent data highlight that the metabolic environment experienced by the fetus influences phenotypic expression and disease susceptibility in later life ,6. SmallIgf-2 gene with the paternal copy as the sole source of IGF-2 during development and the maternally inherited copy silenced. It is hypothesized that the maternal and paternal expression are balanced to maximally promote fetal growth while preventing excessive depletion of the dam’s resources [Although not developmental programming, the most familiar illustration of developmental epigenetic imprinting is the insulin-like growth factor-2 (IGF-2) pathway. The methylation status differs between the paternally and maternally inherited esources . Anotheresources . The genesources  to regulesources .Importantly, developmental programming may have multigenerational consequences transmitted through epigenetic modifications of the genome. Transgenerational epigenetic programming was initially recognized as a result of malnourishment. The Dutch famine, sometimes referred to as the “Hunger winter”, is most often cited as the initial epidemiological human case study illustrating the impacts of nutritional stress upon both physical and behavioral traits in subsequent generations (reviewed in ). More rin utero [The accepted role of GH and the GH-IGF axis in tissue development is predominantly postnatal with other hormones assuming importance in utero . Yet GH in utero  and calvin utero ,24. Thesin utero .in utero growth restriction. Furthermore, adult height is correlated with placental GH expression. Genetic variation within the sequence of the placental-form of GH is significantly associated with mature height confirming that altered expression of GH in utero governs longitudinal bone growth potential [Evidence that fetal perturbations program GH signaling is also emerging. A common model used to define the role of GH in developmental programming is the neonate that experienced impaired fetal growth, specifically SGA infants, who are characterized by compromised bone growth and reduced body mass. Infants having low birth weights trend to lower circulating GH as young adults  indicatiotential . Immune otential  indicatiBirth weight and neonatal growth is predictive of adult circulating GH levels suggesting that the intrauterine environment programs GH secretion  or tissuin utero reduces birth weights of calves [in utero exerts long term consequences on the offspring possibly through alteration of maternal metabolic pathways and placental function.The role of GH in normal development was established decades ago through ablation studies and assessing the physiological consequences of the absence of GH. Additional models to characterize GH action elevate the hormone either through exogenous administration of GH, GH-transgene expression, or chemical compounds that induce GH. Elevated GH f calves , lambs [f calves , and rodf calves . In sheef calves . For rodf calves . Furtherf calves . Similarf calves . Ewes trf calves ,43. Takein utero growth inhibition and restore overall bone length [Elevated GH postnatally has significant effects on bone, muscle, and adipose. Human SGA infants given GH respond with increased bone growth velocity for the duration of GH treatment . In rodee length . GH exere length . Provisiin utero for lambs.Lambs given HMB during the first 3 postnatal weeks show elevated circulating levels of GH, IGF-1, and biochemical markers of bone turnover. However once the HMB treatment concludes, these indices all fall to control values indicating resistance to long term bone programming by HMB when provided postnatally . The faiThe enhanced gain accompanying elevated GH has a greater proportion of protein than normal tissue accrual in rodents. Rodent development is characterized by each unit of gain being composed of the same proportions of water, lipid, protein and ash across the entire growth phase, despite the speed of accrual . In contTherapeutic GH treatment of SGA children offers growth advantages as noted above, yet the elevated GH also reduces insulin sensitivity potentially increasing the risk of diabetes. Recent studies of children born SGA and treated with GH would suggest this is not a valid concern as they have normal insulin post-GH treatment . HoweverIn utero or postnatal exposure to elevated GH in a GH-transgenic mouse model increases adipose storage by increasing adipocyte hyperplasia, differentiation, and cellular lipid content [The role of GH in adipogenesis is complex.  content ,54,55. A content . Postnat content . This ne content .in utero [The interplay with leptin adds more complexity to the influence of GH on adipose. Leptin, synthesized by adipose cells, regulates energy metabolism (reviewed in ) and infin utero  with potEarly dysregulation of GH promotes adipogenesis which in turn elevates leptin that influences adipose function at later ages. Elevated GH in a GH-transgenic mouse model increases plasma leptin  while miStudies in multiple mammalian species demonstrate that aberrant programming of adult tissue response is associated with stress-induced glucocorticoid secretion during fetal and perinatal development. Maternal stress in humans is known to impact neurological circuitry of the offspring: infants have an increased risk of neuropsychiatric disease when the mother experienced psychological stress during the first trimester (reviewed in ). SimilaEarly research demonstrated that adult GH secretory patterns are influenced by perturbations during the perinatal period. For example, male rats normally express a high amplitude secretory pattern of GH whereas females have low amplitude pulses within a higher basal background. Transient manipulation of sex steroids in the neonatal period can modify the GH secretory pattern to that of the opposite sex . GlucocoMothers who are undernourished during pregnancy give birth to SGA infants and when adult those children exhibit adult-onset obesity, insulin resistance, hypertension, and metabolic dysfunction. Maternal nutritional deprivation stress also is implicated in intergenerational epigenetic programming to alter future generations’ growth and metabolic phenotypes. This phenomenon is suggested to account for the rising cases of human obesity, diabetes, and coronary disease (reviewed in ).Levels of placental GH found in maternal circulation are positively correlated with fetal birth weight and in times of maternal nutrient deprivation and SGA pregnancies, placental GH secretion is reduced . A recenAs noted above, there are generalized consequences of SGA on bone characteristics but SGA due to nutritional deprivation also programs bone through the GH- IGF axis. The necessity of adequate fetal and neonatal nutrition for normal bone growth and adult bone integrity was underscored by Eastell and Lambert in their review . In ratsAnother mechanism of nutritional programming on bone is by its effects on the formation of the embryonic skeletal anlage. Fetal and postnatal bone growth depends upon chondrocyte hypertrophy and hyperplasia. Fibroblast growth factors (FGF) and their cognate fibroblast growth factor receptors (FGFR) are key signaling molecules of chondrocyte function in developing bone. Activation of different FGFR family members both promote and inhibit chondrocyte proliferation . The FGFIn rats, restricting maternal dietary protein to induce intrauterine growth restriction enlarges abdominal adipose depots when animals are adult . The enlIntrauterine growth restricted babies, piglets, and rodent pups have reduced leptin at birth and then propensity for obesity at adulthood ; provisiPhysical stressors, often modeled with induced hypoxia, have been used to assess the epigenetic consequences of stress. Hypoxia-inducible factor 1 (HIF-1), induced under conditions of hypoxia to adapt to reduced oxygen supply, is also required for normal fetal tissue and skeletal development . The traGrowth hormone has a pivotal role in pre and postnatal development although its effects on intergenerational programming are as yet under studied. Given the plasticity of postnatal development, defining fetal and neonatal programming and the effect upon later phenotypes is important to maximize the expression of desirable traits in food animals. This is particularly important on the impact of more permanent epigenetic alterations of gene expression that may have future consequences. Historically, classical genetic selection has permitted extremely favorable phenotypic advances. The implementation of quantitative trait loci selection schemes for livestock based upon genomic signatures will accelerate genetic improvement. Overlaid upon genetic selection one must be mindful of the epigenetic programming that environmental perturbations can exert on future trait expression and how that may factor into selection schemes for agricultural livestock production in a changing environment. Better defined knowledge of the mechanisms of programming will facilitate incorporation of epigenetic factors into selection.


Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is trigeminal autonomic cephalalgias which is characterized by repetitive short lasting, severe attacks. Headache attacks are distribution of the ophtalmic and maxillary trigeminal divisions and associated with ipsilateral autonomic phenomena .A growing body of literature has focused on brain magnetic resonance imaging (MRI) evidence of neurovascular compression in these syndromes. There is some evidence supporting microvascular decompression of the trigeminal nerve in selected patients who have medically refractory SUNCT and a demonstrable ipsilateral aberrant vessel on magnetic resonance imaging (MRI). Here, we describe two cases concerning a 52-year-adult and a 69-year-elderly with short-lasting, recurrent headache combined with cranial autonomic features. Pain was described as excruciating, and was non-responsive to most traditional analgesic drugs. We report two patients of SUNCT syndrome with MRI cisternography and tractography findings of neurovascular compression. We performed MRI cisternography and tractography for delineates structural changes in the trigeminal nerve. Pain was completely relieved after surgery that microvascular decompression.We suggest that SUNCT patients with brain MRI should always be performed with a dedicated view to exclude neurovascular compression. In this case reports we performed MRI tractography delineates structural changes in the trigeminal nerve for SUNCT. MRI tractography is the first reports for SUNCT patients in the literature.


In the framework of better risks management in hospital environment and in perspective to improve quality and safety care, university hospital center Farhat Hached Sousse (Tunisia) has developed a medical device-vigilance system in order to monitor incidents or risks of incidents that may arise through using medical devices allowed-on in market.Our objective is to determine medical staff knowledge’s, attitudes and practices in university hospital center Farhat Hached Sousse (Tunisia) regarding medical device-vigilance system establishment.We conducted a descriptive study, type KAP , in December 2014, among all medical staff exercising at university hospital center Farhat Hached Sousse (Tunisia) who are in direct contact with medical devices. Measuring instrument used is a self-administered questionnaire, preestablished, and pretested. Seizure and data analysis was made by the SPSS software 20.0.More than half of participating physicians do not know, nor institution correspondent local )), neither existence of standardized form for reporting )). Concerning attitudes, majority of investigations )) shall notify interest of creating medical device-vigilance system. Participants in study report their desire to receive more information about medical device-vigilance system but they relate their desires to follow a training )).Our study highlights lack of information and training in field yet sensitive and heavily regulated. This needs to affirm medical nature relatively to medical device-vigilance by integrating it into health care professional’s curriculum study but also by strengthening awareness and communication around medical device-vigilance system. Success system’s functionality must be supported by promulgation laws and regulations and better organization of regulatory agencies.None declared.


Noma is a devastating ancient illness that causes severe facial disfigurement in >140,000 children every year mainly in Africa, South America and India. The cause of noma remains unknown but infection, oral hygiene and immune status likely all contributeEfforts have been deployed over the 2 past decades to identify microbial agents  responsible for nomaResearch in the field of microbial identification has benefited from dramatic technical improvements. Until the late 90’s culture based methods were predominantly used. More recently, culture-independent methods were used to identify bacteria in noma patients. We present three approaches used to study hundreds of gingival samples from noma patients and local control samples collected from villages near Zinder, Niger (Africa): large-scale cloning sequencing methods used at the beginning of 2000, high-density microarrays and high-throughput sequencing (HTS) devicesFusobacterium necrophorum as the causative agent of noma, while culture-independent methods identify higher levels of Fusobacteriales in healthy controls. Cloning-sequencing strategies identify disequilibrium in microbial communities from noma patients particularly in Fusobacteria, Prevotella intermedia and Peptostreptococcus genus abundance. This was also detected in studies using semi-quantitative microarrays. More recently, the utilization of HTS provided a detailed analysis of microbial flora in noma patients and identified Clostridiales, Bacteroidales, and Spirochaetales as indicators of noma. Our epidemiological investigations excluded the possible role of viruses such as cytomegalovirus or morbillivirus as possible significant contributor of noma diseaseCulture-based methods identified Although we identify a unique distribution and composition of microbial communities in noma wound sites compared to unaffected samples from the same mouths and healthy controls, the etiology of noma disease remains elusive. Future studies should include longitudinal sampling in high risk areas and detailed exploration of microbiota before and during development of lesionsNone declared.


Reviewing progress in the fabrication of diverse odorant and flavored sol-gels, shows us how different synthetic strategies are appropriate for practical application with important health and environmental benefits.Microencapsulation has become a hot topic in chemical research. Technology mainly used for control release and protection purposes. The sol-gel micro encapsulation approach for fragrance and aroma in porous silica-based materials leads to sustainable odorant and flavored materials with novel and unique beneficial properties. Sol-gel encapsulation of silica based micro particles considered economically cheap as capital investment in manufacturing is very low and environmentally friendly. Amorphous sol-gel SiO Encapsulation technology arouse as a sparkle in recent world accounting significant health and environmental benefits. Industry grow with wide range of applications in all fields specifically, Deodorants, food, oils, synthetic nitro and polycyclic musk's, detergents, cosmetics (perfumes), personal care , food (flavors), and home care (laundry and detergents) etc.  given by Avnir and co-workers in 1984. Simple addition or entrapment of organic molecules in inner porosity of silica used as matrix at the onset of sol-gel process can be shown as below in Equation (1) Where Extraction and GC analysis performed for aroma load show total mass of sol-gel powders best described by following Equation (4)mi = mass of the aroma component in the extraction sample, mW the mass of water, mSE the mass of dry silica subjected to extraction Aroma retention of different components i in matrix found by Equation (5)Where the subscript 0 stands for the initial conditions  and bergamot oil in different silica based microcapsules widely applied in perfumes  and octylmethoxycinnamate (OMC) used initially as sunscreen but show endocrine disruption and estrogenic activity .The SPF calculations obtained for each subject and represented in Table Oils also commonly used in perfumes, cosmetics, agriculture, and food due to aromatic properties. On the basis of origin and composition, properties of EOs can be changed by encapsulation using widely used technique called coacervation. Lemon, thyme, citronella, vanilla, menthol, eucalyptol, clove, peppermint are some of EOs used (Martins et al., Microscopy, a powerful tool used to analyze microcapsule morphology. For example: Thyme oil droplets encapsulated as spherical particles demonstrated by optical microscopy and cryogenic scanning electron microscopy confirms rough surface with some pinholes, pores, and cracks of microcapsules. Release of Thyme oil affected by film thickness and polymer concentration whereas diffusion not only affected by polymer membrane but also by type of oil used. Such difference occurs due to hydrophilic characteristic of the oil (Ashraf et al., Sol-gel encapsulation of silica based micro particles considered economically cheap as capital investment in manufacturing is very low and environmentally friendly. Stobber process (Stober et al., TEOS used as a cheap solvent therefore main cost of sol-gel encapsulation supposed only for labor. An overall value of sol-gel products in global market in 2006 estimated $1 billion with annual growth rate of 6.3% until 2011 as shown in Figure Positive impacts of silica based materials involving sol-gel encapsulation leading to sustainable fragrances on human health and environment apart from technical and economical feasibility are highly appreciated. Comparing synthetic perfumes which are highly poisonous causing neuromodulations in human neuroblastoma cells at extremely low concentration with EOs, being natural renewable shows multiple human health benefits. Double encapsulation of EOs first caged in β-cyclodextrin following silica encapsulation using water based route turning oil to more stabilized and resistant toward temperature, humidity, and light. Today commercialized water based products also present in tone scale in broad variety are available. In US 50 largest companies generate about 70% of revenue from this industry. This technology also enables to produce and stabilize costly active ingredients by enhancing precision and effectiveness of actions and delivered where needed in required amount. First leading Europe's chemical engineering company, sol-gel technology Ltd. constructed in 2001 installed a plant in Israel. Green technology since, 1990s grow with advancement in nanomaterial synthesis (Dahl et al., In this article, we have discussed and demonstrated encapsulation technique based on silica micro particles and its applications in different fields which offer improved products for the benefit of human beings and are environmentally friendly. Sol-gel encapsulation proves highly flexible technology that can be applied to multiple systems. Further innovation to this unique process may include isolation of incompatible compounds through their independent encapsulation within a common formulation. In order to check biological properties of encapsulated materials in food, agriculture and cosmetic industry, supplementary studies are still required.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.


Ischemia/reperfusion injury (IRI) and organ failure especially IRI-induced remote and multiple organ failure contribute significantly to postoperative mortality and morbidity, and reperfusion induced oxidative stress plays a critical role in this pathology , 2.Reactive oxygen species (ROS) induced vascular endothelial dysfunction plays an important role in the development of IRI in various organs. In this special issue, Q. Yang et al. reported that the otherwise cardiac protective polymerized hemoglobin, when used at high dose, failed to alleviate cardiac IRI due to induction of oxidative damage in coronary artery. On the other hand, natural herbal extracts such as Licochalcone B as reported by J. Han et al. in this special issue conferred protection against myocardial IRI through attenuating ischemia-reperfusion induced oxidative damage.The intravenous anesthetic propofol possesses antioxidant capacity and has been shown to attenuate IRI in patients undergoing cardiac surgery and in animal models of myocardial  and inte mitochondrial homeostasis play critical roles in Acute Organ Failure [ mitochondrial homeostasis alterations during these pathologies is largely unclear. In this special issue, S. Cao et al. provided genome-wide expression profiling of cardiomyocytes subjected to hypoxia-reoxygenation injury in an effort to uncover the roles of mitoKATP in energy homeostasis and its regulation.Disturbances of Failure  and in p Failure , while tWe hope that the original and review articles presented in this special issue, representing the current advances in the oxidative stress-mediated ischemia-reperfusion injury, with respect to their potential impact in cellular survival pathways and therapeutic strategies, will stimulate further exploration of this important area. Despite diversity, it is our belief that the articles comprised in this special issue could represent an important advancement and contribution to improve our knowledge of the mechanisms governing reperfusion injury.


Tissue microarrays (TMAs) have become a valuable resource for biomarker expression in translational research. Immunohistochemical (IHC) assessment of TMAs is the principal method for analysing large numbers of patient samples, but manual IHC assessment of TMAs remains a challenging and laborious task. With advances in image analysis, computer-generated analyses of TMAs have the potential to lessen the burden of expert pathologist review.In current commercial software computerised oestrogen receptor (ER) scoring relies on tumour localisation in the form of hand-drawn annotations. In this study, tumour localisation for ER scoring was evaluated comparing computer-generated segmentation masks with those of two specialist breast pathologists. Automatically and manually obtained segmentation masks were used to obtain IHC scores for thirty-two ER-stained invasive breast cancer TMA samples using FDA-approved IHC scoring software.κ=0.81) than between pathologists' masks (κ=0.91), this had little impact on computed IHC scores (Allred; Although pixel-level comparisons showed lower agreement between automated and manual segmentation masks (The proposed automated system provides consistent measurements thus ensuring standardisation, and shows promise for increasing IHC analysis of nuclear staining in TMAs from large clinical trials. With the improvements in clinical outcome in women treated for breast cancer such that 5 year survival now approaches 90% and 10 year survival 80%, adjuvant clinical trials require very large numbers of patients and tissue samples for biomarker studies to drive changes in clinical practice. Many such large clinical trials have moved towards generating tissue microarrays  staining or molecular analyses of a single TMA slide with representation from 20–40 patients and multiple samples per patient is an efficient use of human tissue, antibodies and laboratory processes, there remains the problem of skilled detection and assessment of biomarkers. Such reading of the biomarker status is laborious and time consuming, requiring expert assessment. Thus, there has been increasing attention paid to the potential for automated reading of breast TMA biomarker slides rather than relying on pathology review . HoweverIn previous studies comparing automated and manual IHC scores . Stained slides were scanned with lossy compression using an Aperio Scanscope XT  on a × 20 objective with the optical doubler in place . Each slide was then segmented into the individual constituent stained spots, each spot representing a section from a tissue core.Breast TMAs were generated, for research purposes, from primary, previously untreated breast cancers using excess tissues from routine clinical practice after written, informed consent from the donor patients. Ethical permission was granted by Tayside Tissue Bank, Dundee, UK, under delegated authority of the Tayside Local Research Ethics Committee. In brief, surgically resected primary breast cancer from otherwise unselected patients was fixed in buffered formalin, stored at controlled temperature (18–22 °C) overnight and processed to formalin-fixed paraffin-embedded blocks. Whole mount sections stained with Haematoxylin and Eosin were marked to highlight relevant invasive cancer or normal tissue to allow TMA generation of up to six 0.6 mm cores per cancer. TMAs were then constructed using a manual tissue arrayer . Four micron TMA sections were cut, mounted onto poly-Thirty-two uncompressed TIFF format images of TMA spots from thirty-two breast cancers were used. The perimeter of each spot was delineated and pixels exterior to this perimeter were excluded from subsequent analyses. Each spot image was ∼3000 pixels in diameter and contained invasive cancer.T) or non-tumour (N). Each spot took on average 23 min to annotate by each pathologist; however the task of annotating TMAs was spread over several days.Tumour regions in the TMA spots were manually segmented using Aperio Technologies Spectrum Software with TMA Lab and the Webscope interface (Aperio Technologies). Segmentation involved manually tracing the boundaries of invasive tumour regions on a Wacom Bamboo Fun tablet (model CTH-461) using the stylus for precision; the software tool displayed filled regions overlaid on the TMA spot images as they were annotated. Each spot was annotated independently by two specialist breast pathologists (pathologist A and pathologist B), resulting in two sets of tumour masks. Pixels in each mask were labelled as either tumour  assigned to each pixel. There are four possibilities when comparing a pixel's labels in two masks: , ,  and . However, there are qualitative differences between segmented regions that are not well captured by simply counting the numbers of pixels that fall into each of these four categories. Therefore, when comparing two segmentation masks, we categorised pixel label disagreements into three types as follows  were passed to the scoring algorithm. The Aperio IHC algorithm identifies nuclei automatically and outputs a staining intensity score (ranging from 0 to 3) and an estimate of the percentage of positively stained cells. From these measurements, IHC scores (Allred score and Quickscore) were computed for manually and automatically obtained segmentation masks. Comparisons are reported to assess the extent to which differences in these segmentations affected scoring.The FDA-approved Aperio IHC Nuclear Version 10 algorithm (Aperio Technologies) was used to estimate ER scores based on the segmentation masks obtained. Only regions labelled as tumour  and false negatives .In pixel-level comparison of manually hand-drawn segmentation masks, pathologists differed in their labelling of 9% of pixels . AutomatWhen distributions of agreements and disagreements were visualised , some vaIntensity scores and percentage of positive cells were measured by the Aperio IHC Nuclear algorithm (Aperio Technologies) when provided with segmented tumour regions. Percentage of positive ER cells computed by Aperio were also evaluated . Agreeme   and 0.92 (Quickscore) .This study addressed the need for automated interrogation of TMAs using ER nuclear staining of primary breast cancer as an exemplar. Although previous studies have shown that image analysis can increase workflow and reduce inter- and intra-observer variability . However determining the impact of pixel-level disagreements in clinical practice is challenging. Therefore in this study, a method of categorising disagreements was presented, given the intended usage of the application is IHC scoring. Proportion of disagreement types , equivalent to USCAP 1% cut-off, resulted in almost complete agreement between all reported segmentations. Using Quickscores (cut-off >3), two TMA spots were labelled as ER+ve from automated segmentations and the same spots labelled ER−ve from manually obtained segmentations. The remaining 30 spots, 20 ER+ve and 10 ER−ve, were in complete agreement across all segmentations. Generally there was an overall agreement in treatment decisions, however results varied between scoring systems and non-standardized cut-offs. These discrepancies suggest more work may be required before automation is applied for treatment decisions as suggested for studies comparing visual and automated assessment of Ki67 markers in breast cancers (Despite pixel-level disagreements averaging 16% , computeThe automated segmentation method sometimes had difficulty distinguishing ER−ve cancer cells from ER−ve healthy epithelial cells. Availability of a greater number of TMA spots containing both ER−ve cancer cells and ER−ve healthy epithelial cells, along with accurate annotations of those spots for training, is therefore likely to be of substantial benefit. Indeed, increased volumes of annotated spots for training to more fully represent a range of staining conditions, tissue structures and artefacts can potentially improve segmentation accuracy and further align automated analyses with those of specialist pathologists. The impact of using larger volumes of annotations during training can be usefully explored in future work.In summary, the use of automated annotations for scoring breast TMAs using the methods developed for and exemplified in this study concord closely with expert pathology reviews. 27% of pixel disagreements relate to minor misalignment of drawn tumour boundaries. Classification differences rarely resulted in a change of overall score that would be likely to change clinical management. Using the exemplar of nuclear ER staining, the methods of automated annotation employed here hold promise for reducing the expert pathology time required and speeding up analysis of IHC-stained TMAs from large data sets drawn from clinical trials.


The degree of genetic differentiation among populations experiencing high levels of gene flow is expected to be low for neutral genomic sites, but substantial divergence can occur in sites subject to directional selection. Studies of highly mobile marine fish populations provide an opportunity to investigate this kind of heterogeneous genomic differentiation, but most studies to this effect have focused on a relatively low number of genetic markers and/or few populations. Hence, the patterns and extent of genomic divergence in high-gene-flow marine fish populations remain poorly understood.Gasterosteus aculeatus) distributed across a steep salinity and temperature gradient in the Baltic Sea, by utilizing >30,000 single nucleotide polymorphisms obtained with a pooled RAD-seq approach. We found that genetic diversity and differentiation varied widely across the genome, and identified numerous fairly narrow genomic regions exhibiting signatures of both divergent and balancing selection. Evidence was uncovered for substantial genetic differentiation associated with both salinity and temperature gradients, and many candidate genes associated with local adaptation in the Baltic Sea were identified.We here investigated genome-wide patterns of genetic variability and differentiation in ten marine populations of three-spined stickleback  contains supplementary material, which is available to authorized users. While local adaptation is likely to be of commonplace occurrence, demonstrating its occurrence can be difficult and take substantial research efforts -3. TradiOutlier detection methods have become particularly popular in identifying population structuring and adaptive differentiation in marine fishes, which generally show very low levels of genetic differentiation in neutral marker genes -22 and iGasterosteus aculeatus; e.g.,  and log-transformed geographic distances separating sampling locations.To compare the patterns of genetic variability and differentiation in SNP markers with those in microsatellite markers, we retrieved data from 40 microsatellite loci genotyped for these same populations . A simplTo validate estimates of allelic frequency from the pool-seq data, we genotyped a subset of 30 SNPs from each of the individual fish used for the pooled DNA analyses using the iPlex Gold® assay on the MassARRAY® platform (Sequenom) system. This genotyping was performed by the Technology Centre of the Institute for Molecular Medicine Finland at the University of Helsinki. Allele frequencies from this data were estimated with a custom Perl script and compared to estimates from pooled data as obtained using the procedures above.Sequences underlying this study have been deposited in NCBI’s Sequence Read Archive and accession numbers are SRR1596320, SRR1596321, SRR1596322, SRR1596323, SRR1596324, SRR1596325, SRR1596326, SRR1596327, SRR1596328, and SRR1596329.


The International Federation of Gynecologists and Obstetricians (FIGO) has recently revised the staging of ovarian cancer . It inclThe standard of care for patients with newly diagnosed advanced ovarian cancer has been comprehensive staging laparotomy and primary optimal surgical cytoreduction followed by adjuvant chemotherapy. However, the use of neoadjuvant chemotherapy followed by interval debulking surgery (IDS) as a suitable alternative is supported by multicenter randomized controlled trials . ImagingCT is the primary imaging modality used to stage ovarian cancer. It is complimentary to surgical staging identifying possible sites of unsuspected disease such as pelvic peritoneum, paraaortic nodes, diaphragm and chest ,4. The t


A 27-year-old immigrant sought care for inflammatory nodular swelling lesions over the right arm extending upto the neck with axillary and cervical fistulas lasting for six months (A). His medical history was marked by a long forest stay due to conflicts in his homeland . A deep biopsy was made for infectious and histopathological examinations. Cultures were negative. Microscopy on hematoxylin and eosin stained sections showed nodular abscesses organized around multilobated grains showing Splendore-Hoeppli Phenomenon (B). Special stains  were positive. Thus, the histological diagnosis of actinomycetoma probably due to Nocardia was given. In addition, laboratory tests revealed an active hepatitis B infection. After consulting hepatologists, treatment with trimethoprim-sulfametoxazol was introduced, substituted by amoxicillin clavulanate for months with partial clinical response. The evolution was characterized by the reduction of right arm lesions but extension of the infection to the chest wall.


We urgently need new therapies to improve outcomes after cardiac arrest. Initial studies typically target surrogate endpoints, and these studies help to inform subsequent larger trials that are powered to measure more patient-orientated clinical outcomes such as survival. The competing risk of death and premature assessment of neurological prognosis pose significant challenges to measuring these surrogate endpoints after cardiac arrest. We urgently need new therapies to improve survival with good neurological outcomes after cardiac arrest . CardiacCritical Care, Donnino and colleagues present the results of a randomized controlled trial targeting one such surrogate endpoint, the reversal of shock after cardiac arrest [In this issue of c arrest . Specific arrest . The triHowever, some experts may offer other potential interpretations for the apparent lack of a biological effect, including timing of medication initiation or inclusion of patients without adrenal insufficiency. Another possible explanation is that many patients died before they could achieve shock reversal, rendering this surrogate endpoint unable to discriminate between responders and non-responders. Indeed, more than two-thirds (34/50) of patients died before hospital discharge, and it is unclear how many died before shock reversal . The resUsing a surrogate endpoint becomes even more problematic when it does not actually sit on the causal pathway. Ideally, a surrogate endpoint should have a clear relationship as an intermediate event occurring between the exposure of interest and the more meaningful clinical outcome , in thisCurrent evidence-based guidelines now recommend delaying neurological prognostication for at least 72 h after return of spontaneous circulation owing to the inaccuracy of clinical examinations performed before this time point . As a co


It is now well established that gut flora and chronic liver diseases are closely interrelated. This association is most evident at late stages of the disease: cirrhosis and impaired liver function are associated with intestinal bacterial overgrowth, small bowel dysmotility, increased gut permeability, and decreased immunological defenses, all of which promote bacterial translocation from the gut to the systemic circulation, leading to infections that in turn aggravate liver dysfunction in a vicious circle . For a lNAFLD encompasses a spectrum of hepatic pathology . Accumulation of triglycerides in hepatocytes (hepatic steatosis) is the most common liver phenotype in NAFLD. Some individuals with hepatic steatosis develop nonalcoholic steatohepatitis (NASH), a more severe type of liver damage characterized by hepatic inflammation and liver cell death. In some individuals with the NASH phenotype, liver regeneration cannot keep pace with the increased rate of hepatocyte death, and liver scarring (fibrosis) ensues. Over time, some of these individuals accumulate sufficient fibrosis to develop cirrhosis. Because cirrhosis dramatically increases the risk for both primary liver cancer and overall liver-related mortality, liver cirrhosis is the NAFLD phenotype that has the worst prognosis. Epidemiologic studies indicate that NAFLD is now the most common cause of liver disease in many countries, including the United States . It is eClostridium coccoides [The first evidence that gut dysbiosis might be involved in NAFLD pathogenesis was provided by a few cross-sectional studies that evaluated the association between gut microbiota and the liver phenotype in NAFLD patients. Using quantitative polymerase chain reaction (qPCR) for selected bacteria in a small cohort of 50 patients , Mouzaki et al. showed that NASH patients had decreased fecal Bacteroidetes and increased occoides . The negBlautia and Faecalibacterium genera. The increase in Proteobacteria was mainly explained by an increased abundance of Enterobacteriaceae, especially Escherichia, which was the only abundant genus within the whole bacteria domain exhibiting a significant difference between the obese and the NASH groups. Interestingly, Escherichia are known alcohol-producing bacteria, and serum alcohol concentration was significantly higher in NASH patients compared to obese or control groups.Zhu et al. screened the whole gut microbiota using 16S ribosomal RNA pyrosequencing in a pediatric cohort of 63 children that included 16 healthy controls, 25 obese subjects without known liver disease, and 22 patients with biopsy-proven NASH . They foThe Mouzaki and Zhu studies may seem quite conflicting, the first showing a decrease in Bacteroidetes and the second an increase. However, different populations were studied  using different approaches (qPCR versus pyrosequencing). Both works were also limited by small sample size. Thus, further studies including larger and well-characterized cohorts are required to better identify the associations between gut microbiota and the various liver phenotypes observed in NAFLD.Cross-sectional studies allow for the discovery of potential associations between liver phenotype and certain gut bacteria, but they cannot establish a causal link. By using gut microbiota manipulations, recent animal studies have demonstrated direct roles for gut microbiota in each liver lesion observed in NAFLD: steatosis, NASH, fibrosis, and liver cancer.Conventional C57BL/6J mice fed with a high-fat diet (HFD) for 16 weeks generally display liver steatosis, hyperglycemia, and systemic inflammation (responders), but some mice are nonresponders, developing no metabolic disorder with this dietary manipulation . To explInterindividual differences in the intestinal microbiome and severity of NASH, a more serious NAFLD phenotype, have also been linked. Targeted disruption of the NLRP3 or NLRP6 inflammasome altered the gut microbiota and was associated with enhanced colonic inflammation and NASH in mice fed methionine-choline-deficient-diets . By studGut microbiota can also promote liver fibrosis, a known risk factor for NAFLD-related cirrhosis. In a recent study, mice fed a HFD before bile duct ligation (BDL) developed more severe liver fibrosis than control mice that were fed a standard chow diet before BDL . HFD-relA recent study established a link between the gut microbiota and NAFLD-related hepatocellular carcinoma . NeonataThere are thousands of bacterial species in the gut, and they all display an incredibly wide range of metabolic functions. Now that we realize that gut microbiota modulate NAFLD-related pathophysiology, the challenge is to decipher the mechanisms by which they exacerbate NAFLD severity . As mentNAFLD is associated with a higher prevalence of gastro-oesophageal reflux  that reqIn summary, NAFLD is an extremely common, complex disease that results from interactions between susceptible polygenic backgrounds and environmental factors. Recent evidence has introduced gut microbiota as a new crucial player in this complex story. Deciphering the mechanisms linking gut microbiota to NAFLD and its severity will advance understanding of the disease’s pathogenesis, thereby identifying new therapeutic targets that will ultimately improve the outcome in patients with this disease.


Injury to the central nervous system (CNS) results in oligodendrocyte cell death and progressive demyelination. Demyelinated axons undergo considerable physiological changes and molecular reorganizations that collectively result in axonal dysfunction, degeneration and loss of sensory and motor functions. Endogenous adult oligodendrocyte precursor cells and neural stem/progenitor cells contribute to the replacement of oligodendrocytes, however, the extent and quality of endogenous remyelination is suboptimal. Emerging evidence indicates that optimal remyelination is restricted by multiple factors including (i) low levels of factors that promote oligodendrogenesis; (ii) cell death among newly generated oligodendrocytes, (iii) inhibitory factors in the post-injury milieu that impede remyelination, and (iv) deficient expression of key growth factors essential for proper re-construction of a highly organized myelin sheath. Considering these challenges, over the past several years, a number of cell-based strategies have been developed to optimize remyelination therapeutically. Outcomes of these basic and preclinical discoveries are promising and signify the importance of remyelination as a mechanism for improving functions in CNS injuries. In this review, we provide an overview on: (1) the precise organization of myelinated axons and the reciprocal axo-myelin interactions that warrant properly balanced physiological activities within the CNS; (2) underlying cause of demyelination and the structural and functional consequences of demyelination in axons following injury and disease; (3) the endogenous mechanisms of oligodendrocyte replacement; (4) the modulatory role of reactive astrocytes and inflammatory cells in remyelination; and (5) the current status of cell-based therapies for promoting remyelination. Careful elucidation of the cellular and molecular mechanisms of demyelination in the pathologic CNS is a key to better understanding the impact of remyelination for CNS repair. Cnp1, which encodes 2′,3′-cyclic nucleotide phosphodiesterase in oligodendrocytes, show no structural abnormality in myelin but develop axonal swelling and degeneration (Myelin is a cholesterol rich extension of oligodendrocytes and Schwann cells (SCs) plasma membrane, which serves as a specialized insulation sheath for axons in the nervous system. Myelin facilitates axon signal conduction through enabling “saltatory conduction” (see review by neration . These sneration . Survivaneration . ConsideOligodendrocyte precursor cells (OPCs) and neural stem/progenitor cells (NPCs) are two endogenous cell populations, capable of replacing lost oligodendrocytes and remyelinating spared axons following injury . DespiteShiverer mice that lack MBP demonstrate dysmyelinated axons associated with axonal dysfunction and motor impairments . Node of Ranvier is the gap between two adjacent myelin sheaths and contains high concentrations of voltage-dependent Na+ channels on the axonal membrane  and KCNQ K+ channels . Among these molecules, βIV-spectrin and ankyrin G play a major role in stabilizing the Nav channels at nodal region .In myelinated axons, node of Ranvier was characterized by the localization of voltage-gated sodium .Paranode is the adjacent segment to the node of Ranvier where myelin loops provide an anchor by tethering the myelin to the axonal membrane . Evidencmembrane . The parmembrane . Caspr imembrane . Caspr dmembrane  . Upon receiving of an action potential, Nav channels open, allowing an influx of Na+ into the axon causing depolarization. After each depolarization, Na+/K+ ATPase pumps, located at the juxtaparanodal and internodal regions, exchange axonal Na+ for extracellular K+ . Sodium channel redistribution causes an overall increase in Na+ influx during impulse conduction and increased demand for ATP during repolarization  . Inhibition of sodium channels and NCX has been shown to prevent axonal degeneration , a marker for axonal injury, whereas it is only expressed in 20% of axons, which are β-APP negative . Our investigations on dysmyelinated Shiverer mice and Long Evans Shaker (LES) rats elucidated the role of K+ channels in axonal function  and non-specific (4-AP) blockers improved axonal conductance; however, this effect was shown to be more dependent on a combination of subunits as a specific blocker of Kv1.1 failed to improve axonal conduction significantly  axons showed 2.2-fold increase in the size of stationary mitochondria sites and 47% increase in the velocity of motile mitochondria following demyelination  showed normal OPC proliferation, differentiation and initiation of myelination. However, these FGF receptor null animals demonstrated defective myelin thickening during postnatal period and remained defective throughout their adulthood  is another growth factor known to promote OPCs survival, migration, and differentiation into mature myelinating oligodendrocytes . Nrg-1 iCurrent evidence shows that remyelination is additionally limited by inhibitory modifications in the post-SCI niche caused by secondary injury mechanisms particularly in chronic SCI . Newly fin vitro and in vivo , Wnt signaling, and Semaphorin 3A (Sema3A) . LINGO-1Collectively, these findings demonstrate that endogenous remyelination was impeded by the inhibitory microenvironment following injury and activated astrocytes and microglia/macrophages seem to play pivotal roles in this inhibition. We will discuss recent studies on the role of resident glial cells and peripherally recruited immune cells in modulating oligodendrocyte replacement and remyelination following CNS injury.Astrocytes play critical role in several aspects of myelination in pathologic CNS including clearance of myelin debris, modulating the activity of oligodendrocytes, myelin maintenance, and renewal . Using aIntercellular connections between astrocytes and oligodendrocytes are critical for the proper physiology of oligodendrocytes. While there are no gap junctions between oligodendrocytes themselves, they are connected to astrocytes through gap junctions, which make oligodendrocytes indirectly interconnected . EvidencAstrocytes provide trophic support to oligodendrocytes by producing growth factors. In an ethidium bromide (EB) induced rat model of spinal cord demyelination, In vivo and in vitro observations have shown that CSPGs limit the ability of OPCs to migrate, mature and myelinate axons , a Toll-like receptor-4 (TLR-4) agonist, caused a significant increase in NG2feration . Interesferation . Of noteferation .Several mechanisms have been proposed for the positive role of macrophages in remyelination. Among the main proposed mechanisms are removal of myelin debris  and prodAltogether, evidence indicates that the type of immune response is a determining factor that can promote or inhibit remyelination in demyelinating CNS lesions , these studies have suggested that remyelination is a key mechanism in promoting functional recovery following SCI and demyelinating conditions . When we transplanted brain-derived NPCs into the spinal cord of subacutely injured rats, we found that survival and oligodendrocyte differentiation of NPCs was limited in the injury microenvironment . Similarly, in our rat SCI studies, evidence of NPC-derived remyelination was confirmed with immunoelectron microscopy against YFP expression in transplanted YFP-NPCs  in enhancing oligodendrocyte differentiation and maturation has been established in the CNS and PNS . GeneticAltogether, current evidence suggests that NPCs can be engineered to act as environmental modulators in addition to their role in cell replacement. This strategy presents a therapeutic avenue for improving microenvironment and optimizing the outcome of cell transplantation in CNS trauma and demyelinating diseases.Due to challenges with oligodendrocyte differentiation of NPCs, transplantation of differentiated glial-restricted precursors (GRP) and OPCs has been pursued in SCI and demyelinating conditions . Early sApplication of OPCs has also shown promising results in supporting remyelination. The potential of human ESC derived OPCs for remyelination has been evaluated in animal models of SCI and demyelination . These sOne important outcome of the Keirstead study was the inability of transplanted OPCs to remyelinate chronically demyelinated axons despite their survival and the capacity to differentiate into oligodendrocytes . This evEfficacy of transplanted OPCs has also been investigated in chronic demyelinating conditions. Transplantation of mouse ESC derived OPCs into a radiation induced rat model of cervical spinal cord demyelination 4 months after radiation therapy, showed successful survival, and migration of these cells toward the lesion and their capacity for oligodendrocyte remyelination . MoreoveIn addition to their role in replacing remyelinating oligodendrocytes, OPCs are known to enhance axo-neuronal growth and survival by producing growth factors such as brain derived neurotrophic factor (BDNF), IGF-1, glial derived growth factor (GDNF), neuregulins (NRGs), and neurotrophins  that potOlfactory ensheathing cells (OECs) have been extensively examined for their potential for remyelination after SCI and demyelinating lesions . OECs arStudies by Another study in nonhuman primate demonstrated the ability of OECs to remyelinate spinal cord axons following demyelination lesions . In thisSince SCs and OECs demonstrate similar characteristics, their behavior and response have been compared in demyelinated spinal cord in co-transplantation studies , 2014. IWhile extensive evidence suggests a direct role for OECs in axonal ensheathing and remyelinating, there are also some reports that have questioned their myelinating capability in SCI . Boyd etRegardless of their direct role in axonal remyelination, OECS are shown to recondition injury environment by producing a host of trophic factors including NGF, BDNF, and CNTF that can support endogenous repair . Studiesin vitro and in vivo studies using specific markers of OECs and SCs is required to specifically distinguish these two cell populations and confirm the myelinating capacity of OECs.Collectively, while application of OECs has shown promising results in experimental models of SCI and demyelination, the ability of OECs for CNS remyelination is still a matter of debate due to their similarities with SCs and potential contamination of OEC cultures with SCs. Further While cell translation is a promising approach for enhancing remyelination following injury, graft rejection due to the host immune reaction poses a major challenge to the success of cell-based therapies . SuccessGeneration of induced pluripotent stem cells (iPSCs) using autologous somatic cells has opened new avenues for developing clinically feasible cell transplantation approaches . Since tin vitro (Shiverer mice, human iPSC-derived OPCs integrated with the host neonatal brain tissue after transplantation, differentiated to MBP expressing oligodendrocytes, remyelinated the dysmyelinated Shiverer axons, and constructed the nodes of Ranvier (Shiverer mice exhibited increased lifespan (Remyelination has been considered as a mechanism underlying the functional improvement observed in iPSCs transplantation strategies . A recenin vitro . In immu Ranvier . No tumolifespan .Table 1, we have listed cell therapies that have been developed to promote oligodendrocytes replacement and remyelination after SCI and MS conditions.Taken together, emerging evidence shows the potential and feasibility of transplanting iPSCs derived NPCs and OPCs for promoting oligodendrocyte replacement and remyelination in demyelinating conditions such as MS and traumatic CNS injury. While promising, the risk of tumorigenicity and proper cell differentiation of this therapy have yet remained to be carefully investigated. In The myelin sheath is an essential component in the CNS and PNS that ensures rapid signal transduction in axons through the nervous system. Myelinated fibers show a highly specialized and organized structure at the node of Ranvier that is vital to their proper functioning. Damage to oligodendrocytes due to trauma or disease results in demyelination that causes aberrant localization and expression of ion channels associated with axonal dysfunction. Although considerable remyelination occurs spontaneously by endogenous CNS progenitor cells, the quality and extend of myelination is not optimal to restore structural and physiological properties of injured axons. Emerging research evidence has uncovered several mechanisms by which oligodendrocyte differentiation and remyelination are regulated within the microenvironment of injury. Inhibitory role of activated glial cells and insufficient expression of promoting factors are major limiting factors that impede remyelination. Over the past years, extensive research efforts have been made to therapeutically promote remyelination following CNS trauma or demyelinating disease. Outcomes of the recent pharmacological and cell-based therapies indicate the impact of remyelination as a mechanism for improving function after injury. Further investigations are needed to develop effective and feasible repair strategies with potential for clinical translation.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.


Hippocrates famously advised, “Let food be thy medicine and thy medicine be thy food.” Numerous plant-derived compounds are used as cancer therapeutics including antimitotics, topoisomerase inhibitors, and kinase inhibitors. Here we will review emerging evidence suggesting that diet derived small RNAs may be an inexpenisive, non-invasive and affordable way to deliver cancer treatments.RNA interference (RNAi), the use of short double-stranded RNA sequences to silence endogenous genes is emerging as the next generation of therapeutics. A well-designed RNAi molecule is able to differentially silence a mutated oncogene with just a single mutated base, leaving the wild-type unaffected. Further, due to the use of intrinsic cellular mechanisms for gene silencing, RNAi exerts an amplified stoichiometric effect, suppressing expression of thousands of mRNA transcripts per RNAi molecule. The challenge with the use of RNAi therapeutics remains their efficient uptake and transportation to target cells. Various delivery techniques are being investigated including viral delivery, engineered nanoparticles and modified nucleic acid chemistry. Each method faces a unique set of challenges including efficiency, safety, and immunogenicity. Utilization of therapeutics by the oral route promises low costs, minimal invasiveness, and high compliance, making this the holy grail of delivery methods.In 2012, a study demonstrated a dietary microRNA (miRNA) from rice was packaged and systemically circulated in consuming mice to silence a liver gene . Our worCells are known to release small vesicles (exosomes and microvesicles) from their membranes, packaging and protecting their contents . Though the biological role of these vesicles is still being explored, the packaging of specific subsets of cellular molecules suggests that exosomes function as mediators of systemic intercellular communication. Recent examples have also suggested that exosomes are able to cross barriers between species. Reports have described the detection of cow's milk-derived miRNAs in serum of the consumers at physiologically relevant concentrations . In mousC. elegans has been well described and transporters for these small RNAs characterized. Animal genomes contain sequences that are homologous to those responsible for the systemic RNAi effect seen in C. elegans. Could we impact dietary miRNA uptake by altering the localization and kinetics of these putative endogenous transporters? We favor a model where therapeutic plant-based miRNAs within the plant matrix display enhanced bioavailability compared to synthetic plant-based miRNAs. Scientists are in the process of expressing therapeutic miRNAs in crops plants to assess efficacy of these engineered foods fed to patients.The future of dietary miRNAs as therapeutics requires new tool development and mechanistic insights regarding uptake and delivery. Dietary miRNA studies are confounded by high variation and low copy number detection. These issues need to be addressed with judicious and standardized detection methods. Use of sensitive tissue sensors will help identify both the presence and functionality of low-level absorbed miRNAs. Dietary RNAi function in In addition, the milk-based approach to therapeutic miRNA delivery may prove especially useful in infants. The developing fetus and newborns may lack acquired ‘protective' mechanisms in the gut that deter small RNA uptake in adults. Perhaps nature has already provided an ideal mechanism for the safe and efficient delivery of next generation therapeutics, allowing us to rekindle the notion of using foods as medicine.


Stenting of conduit stenoses are more commonly reported[2].Although percutaneous placement of intravascular stents in congenital heart disease is a common practice, there are few reports regarding native right ventricular outflow tract (RVOT) stenting in children In the preoperative setting, palliation of significant cyanosis by balloon valvuloplasty or RVOT stenting has been advocated by some as a means for reducing symptomatic cyanosis in patients with severe annular hypoplasia. Improvement in antegrade flow is thought to simultaneously enhance pulmonary arterial growth by augmenting pulmonary blood flow. [3]. Most of transcatheter interventions for relieving RVOT were done for conduit stenosis. There are few reports about native RVOT stenting, and to the best of our knowledge there are very few reports on native RVOT stenting in tetralogy of fallot (TOF) with absent left pulmonary artery A 9-year-old child was admitted with cyanosis noted from birth with failure to thrive, cyanotic spells and worsening cyanosis. The patient had undergone central modified Blalock- Tausig (MBT) shunt and right MBT shunt at the ages of three and six respectively. At this admission the child weighed 17 kg, had severe systemic desaturation (<55%) and severe cyanosis, digital clubbing and a New York Heart Association (NYHA) classification of class IV. Clinical examination revealed unremarkable pulmonary examination and 3/6 systolic heart murmur at pulmonary focus.  EKG revealed normal sinus rhythm, right axis deviation and severe right ventricular hypertrophy (RVH). Echocardiography showed TOF anatomy, severe RVOT stenosis with 75 mmHg pressure gradient, RVH, abscent left pulmonary artery branch (LPA), non-functioning previous MBT shunts and major collateral arteries originating from descending aorta. On catheterization, both previous MBT shunts were occluded, the right pulmonary artery (RPA) was small with fairly acceptable arborization. Left lung was supplied by major collateral arteries originating from descending aorta and severe RVOT stenosis was present . RVOT st The arterial oxygen saturation rose to 83%. At six-month follow-up, his arterial oxygen saturation was maintained at above 80% and NYHA functional class was improved to class II. Palliative procedures for relieving RVOT stenosis include either surgical or transcatheter interventions. The indications for RVOT stenting are RV-to-PA conduit stenosis, residual infundibular stenosis after intracardiac repair, TOF with hypoplastic branch pulmonary arteries after palliative shunt surgery, pulmonary atresia after perforation of atretic segment, and RV hypertrophic cardiomyopathy and also as a bridge to surgery. RVOT stenting is also usually indicated in cases in those patients who are not amenable to total surgical repair. Our patient had absent LPA, small RPA and poor clinical condition. Thus, we carried out percutaneous RVOT stenting.RVOT stenting in such patients theoretically can lead to two major problems: overflow and edema of the right lung with resultant vasculopathy in the long term, and free pulmonary valve regurgitation with its consequences that include right ventricular dilatation and dysfunction. In our case, none of these complications occurred, because we chose the stent size with scrutiny and we did not sacrifice the pulmonary valve. Also we did not have complications such as stent migration, ventricular arrhythmias, collapse or fracture of the stent and recurrent stenosis during follow up. To our knowledge the patient has not undergone any curative operation by now. RVOT stenting provides an effective palliative modality for children with TOF and unfavorable pulmonary artery anatomy. Although re-stenosis can occur but it responds to re-dilatation.[4]. In conclusion native RVOT stenting is an effective and safe procedure in appropriately selected patients, especially in whom total correction is not possible. This procedure causes better growth of pulmonary artery branches, decreases right ventricular hypertrophy and increases left ventricular volume. Although many of these stents cannot be dilated to adult size, their efficacy in small infants and children in whom further surgery will ultimately be required is remarkable.  In high risk patients such as our patient with severe cyanosis and high hemoglobin level and blood viscosity, the RVOT stenting decreases perioperative morbidity and mortality


Impaired mucociliary clearance (MCC) is a hallmark of acquired chronic airway diseases like chronic bronchitis associated with chronic obstructive pulmonary disease (COPD) and asthma. This manifests as microbial colonization of the lung consequently leading to recurrent respiratory infections. People living with HIV demonstrate increased incidence of these chronic airway diseases. Bacterial pneumonia continues to be an important comorbidity in people living with HIV even though anti-retroviral therapy has succeeded in restoring CD4+ cell counts. People living with HIV demonstrate increased microbial colonization of the lower airways. The microbial flora is similar to that observed in diseases like cystic fibrosis and COPD suggesting that mucociliary dysfunction could be a contributing factor to the increased incidence of chronic airway diseases in people living with HIV. The three principal components of the MCC apparatus are, a mucus layer, ciliary beating, and a periciliary airway surface liquid (ASL) layer that facilitates ciliary beating. Cystic fibrosis transmembrane conductance regulator (CFTR) plays a pivotal role in regulating the periciliary ASL. HIV proteins can suppress all the components of the MCC apparatus by increasing mucus secretion and suppressing CFTR function. This can decrease ASL height leading to suppressed ciliary beating. The effects of HIV on MCC are exacerbated when combined with other aggravating factors like smoking or inhaled substance abuse, which by themselves can suppress one or more components of the MCC system. This review discusses the pathophysiological mechanisms that lead to MCC suppression in people living with HIV who also smoke tobacco or abuse illicit drugs. With the introduction of combination antiretroviral therapy (cART) dramatic declines in morbidity and mortality from HIV/AIDS have been seen  can directly regulate MCC and this is evident in diseases like primary ciliary dyskinesia where attenuated ciliary beating leads to cough, infection, and airway obstruction  and CBF activation rely on the common adenylate cyclase/cAMP/PKA pathway for activation making this pathway critical in maintenance of optimal MCC. HIV infection, environmental stimuli/pollutants like cigarette smoke and smoked substance abuse like crack cocaine, marijuana, methamphetamine can affect one or more components of the MCC system facilitating microbial colonization leading to recurrent lung infections and chronic airway diseases.CO (Diffusing capacity of the lung for carbon monoxide), and anatomic and radiographic emphysema , a significant proportion of HIV-infected individuals are cigarette smokers or smoked substance abusers . Almost 60% of People living with HIV are also smokers . Cocaine was also shown to suppress Cl− efflux in response to CFTR potentiators like β2-agonsits  and CBF depend on the adenylate cyclase/cAMP/PKA pathway. Hence therapeutics that potentiate this pathway can be used to restore MCC in HIV infected individuals and/or smoked substance abusers Figure . β2-adre van As, , activat van As, , and con van As, . AlternaNormal mucociliary function fails with dysfunction of any one of the major components of the MCC apparatus namely mucus production, ciliary beating, and ASL depth maintenance fail. Suppression of MCC leads to an inefficient clearance of pollutants, pathogens, and allergens. This leads to chronic inflammation and microbial colonization which manifests as chronic airway diseases like asthma, chronic bronchitis associated with COPD, and recurrent lung infections pervasive in HIV infected individuals and/or smoked substance abusers. Smoked substance abuse can suppress MCC independently and an underlying HIV infection can have an additive effect as each of these can suppress one or more components of MCC system. Under these conditions, therapeutics that can restore CFTR function or CBF can restore MCC and prevent microbial colonization consequently decreasing the incidence of pneumonia in People living with HIV.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.


V600BRAF mutant melanoma, but acquired resistance is almost universal. Early understanding of how melanomas acquire resistance to BRAFi via MAPK pathway reactivation has guided the development of specific BRAFi-anchored inhibitor combinations designed to overcome resistance. The first of these successful combinations has been between BRAF and MEK inhibitors. Combined BRAF/MEK targeted therapy improves upon BRAFi therapy but is still beset by acquired resistance. Thus, studying how melanomas escape from BRAFi and how these processes are similar or distinct from acquired resistance mechanisms to BRAFi+MEKi remains of the utmost importance to melanoma therapeutics. Recent whole-exome analysis of patient-paired melanoma samples obtained pre-BRAFi treatment and post-disease progression after initial responses have provided landscape genetic perspectives into the nature of tumor heterogeneity, clonal evolution, and core resistance pathways. This benchmark understanding is helping to guide and prioritize clinical studies of BRAFi-based combinations such as that between BRAFi and AKTi. Recent work on the genetic mechanisms of acquired BRAFi+MEKi resistance has shed key insights into the molecular limitations of this therapeutic approach but also novel therapeutic opportunities. Overall, genetic alterations affecting individual genes are not highly recurrent and collectively cannot account for a significant subset of clinical acquired resistance to BRAF or combined BRAF/MEK targeted therapies (MAPKi). Thus, understanding the entire spectrum of genetic and non-genetic mechanisms of acquired MAPKi resistance and the temporal continuum of these evolutionary processes promises to usher in a new era of personalized medicine for melanoma patients.BRAF inhibitors (BRAFi) elicit rapid antitumor responses in the majority of patients with


The existing clinical biomarkers for prostate cancer (PCa) are not ideal, since they cannot specifically differentiate between those patients who should be treated immediately and those who should avoid overtreatment. Current screening techniques lack specificity, and a decisive diagnosis of PCa is based on prostate biopsy. Although PCa screening is widely utilized nowadays, two-thirds of the biopsies performed are still unnecessary. Thus, the discovery of noninvasive PCa biomarkers remains an urgent unmet medical need. Once metastasized, there is still no curative therapy. A better understanding of sustained androgen receptor signalling in castration resistant prostate cancer (CRPC) has now led to the development of more effective therapies. We need a better understanding of the molecular and cellular aspects of prostate carcinogenesis and progression. Identification of cancer initiating cells and therapies against these populations is a promising way forward to fight this disease.


During the last decades research all over the world has highlighted the deleterious effects of pollution on respiratory health of adults and children. Nevertheless, air pollution still represents a significant threat to health. Children are more sensitive than adults to pollutants for several factors: increased respiration relative to body size; physiologic immaturity of respiratory and immunologic systems; low metabolic capacity; longer life expectancy.2), ozone (O3), sulfur dioxide (SO2), may provoke cytotoxic and functional damages in the airways through oxidative stress and inflammation. During the last decades the amount of pollutants from vehicular traffic has significantly increased, especially in urban areas. Recent epidemiological studies have shown that vehicular traffic represents the main source of outdoor pollutants and that it may increase the risk of respiratory outcomes  in children through short-term and long-term effects on airways, lung function and allergic sensitization [Several studies demonstrated an association between exposure to outdoor pollutants and respiratory diseases in childhood. Outdoor pollutants, such as nitrogen oxides (NOx), particulate (PM), carbon monoxide (CO), carbon dioxide . Indoor pollutants concentration depends on external environmental pollutants filtered inside buildings, pollutants generated inside buildings (domestic work) and pollutants generated by personal activities. Combustion products (tobacco smoke and wood burning), CO, CO2, volatile organic compounds (VOC), microbial agents , organic products  are the most important indoor pollutants. There is growing epidemiological evidence that indoor allergen exposure may contribute to the development of allergic respiratory symptoms, such wheezing, coughing and asthma in children [third-hand smoke’ (THS), represents a new concept in the field of tobacco control [Tobacco smoke is one of the environmental pollutants influencing morbidity and death rate in childhood as it is responsible for adverse health effects in both prenatal and postnatal life. Homes remain a site where children are dangerously exposed to environmental tobacco smoke (ETS). The combination of tobacco smoke pollutants which remain in an indoor environment, the so-called ‘ control .Children still need to be protected with strict air quality standards, in order to improve their respiratory health. Therefore, policies that ensure better air quality are strongly desirable all over the world.


Recent studies report promising results regarding extracorporeal magnetic separation-based blood purification for the rapid and selective removal of disease-causing compounds from whole blood. High molecular weight compounds, bacteria and cells can be eliminated from blood within minutes, hence offering novel treatment strategies for the management of intoxications and blood stream infections. However, risks associated with incomplete particle separation and the biological consequences of particles entering circulation remain largely unclear. This article discusses the promising future of magnetic separation-based purification while keeping important safety considerations in mind. The direct removal of disease-causing compounds is an inherently attractive treatment modality for a range of pathological conditions, including intoxications and blood stream infections . While lMagnetic separation-based blood purification is especially attractive for the removal of high molecular weight compounds, which are poorly removed by conventional (diffusion-based) blood purifications systems  Fig.  2]. The. The2]. 18 single particles). Magnetic measurements for ultrasensitive magnetic nanoparticle detection are now increasingly being explored, which would allow detection of off-target accumulation of nanomaterial and biodegradation of nanomaterials, which in turn could initiate acute and long-term effects such as tumorigenesis, fibrosis and toxic effects.When bringing magnetic blood purification processes closer to clinical evaluation, safety of operation becomes pivotal. Extracorporeal blood purification has been suggested previously to provide a possible alternative to direct in vivo application (injection) of magnetic nanoparticles and to prevent off-target accumulation of magnetic capturing agents (e.g. in the liver or lung). Recent studies have shown that the capturing efficiency of magnetic iron oxide nanoparticles is significantly decreased under clinically desirable blood flow rates, thereby potentially compromising the procedure’s efficiency and safety . Blood fOther important safety aspects include non-specific adsorption of blood constituents  as well as activation of inflammatory reactions in the blood compartment . Such poUnfortunately, there is an ever growing disequilibrium between manuscripts reporting on the synthesis of new nanomaterials and their promising applications and studies actually performing comprehensive risk evaluation of the synthesized materials . At presIn summary, extracorporeal magnetic separation-based blood purification is a promising strategy to rapidly and selectively remove high molecular weight compounds from blood. The technique has been successfully evaluated in vivo in experimental settings investigating the clinically relevant scenarios of intoxication and sepsis in rat models . However


Tissue-engineering technologies have progressed rapidly through last decades resulting in the manufacture of quite complex bioartificial tissues with potential use for human organ and tissue regeneration. The manufacture of avascular monolayered tissues such as simple squamous epithelia was initiated a few decades ago and is attracting increasing interest. Their relative morphostructural simplicity makes of their biomimetization a goal, which is currently accessible. The mesothelium is a simple squamous epithelium in nature and is the monolayered tissue lining the walls of large celomic cavities  and internal organs housed inside. Interestingly, mesothelial cells can be harvested in clinically relevant numbers from several anatomical sources and not less important, they also display high transdifferentiation capacities and are low immunogenic characteristics, which endow these cells with therapeutic interest. Their combination with a suitable scaffold  may allow the manufacture of tailored serosal membranes biomimetics with potential spanning a wide range of therapeutic applications, principally for the regeneration of simple squamous-like epithelia such as the visceral and parietal mesothelium vascular endothelium and corneal endothelium among others. Herein, we review recent research progresses in mesothelial cells biology and their clinical sources. We make a particular emphasis on reviewing the different types of biological scaffolds suitable for the manufacture of serosal mesothelial membranes biomimetics. Finally, we also review progresses made in mesothelial cells-based therapeutic applications and propose some possible future directions. Tissue engineering has emerged as a promising alternative to conventional medicine to achieve the healing and regeneration of human damaged tissues and organs. The manufacture of functionally optimal bioartificial tissues is an extremely complex process relying on a comprehensive stepwise combination of cells with scaffolds, extracellular matrices (ECM), and molecular signals. The achievement of such objective usually relies on the combination of advanced knowledge and skills from interdisciplinary specialists, making tissue engineering one of the most challenging fields of biomedical research.Elaborated bioartificial soft tissues and inclusively some bioartificial organs are under current experimental development and evaluation in laboratories  and the surface of celomic visceral organs  and water channels (aquaporins)  used in experimental animal models for human inflammatory diseases. Their protective effects was found to be largely attributed to their hypoimmunogenicity and capacity to regulate innate immune cells functions through secretion of soluble and membrane-bound factors with potent immunosuppressive and/or immunomodulatory activities .+ and CD8+ T lymphocytes (T cells), through their secretion of the immunosuppressor TGF-β  to harvest mesothelial cells. Due to its largest size, the abdominal cavity is the predominant anatomical source from where mesothelial cells are harvested. Specific peritoneal sources and isolation procedures are reviewed below.2. Like other visceral mesotheliums, the omental mesothelium displays a high cellularity and can provide around one million mesothelial cells from each square centimeter of omental tissue  could significantly improve their healing and reduce the score of peritoneal adhesions , which is the parietal mesothelium of the testicular cavity, has been identified as another reliable source of mesothelial cells  derived from plants or animals are highly sophisticated molecules that emerged from millions of years of natural evolution. They are usually endowed with desirable properties such as high degradability, excellent biocompatibility, and biomechanical properties such as elasticity, tensile strength, and transparency, which make them excellent candidate materials in biomedical engineering applications . We below review different types of biologic materials that have been previously proposed or used in tissue engineering of diverse types of simple squamous epithelia or related tissues  to generate scaffold with a desired form, porosity, and stiffness. Furthermore, and not less important, the polymer chitosan is particularly rich in chemical side groups, that allow covalent binding with other biomaterials to produce biodegradable biocomposites with increased strength and cell adhesion potential  is considered as a new bioengineering treasure by a majority of the biomedical community. Its outstanding biophysical and biochemical properties such as robustness, flexibility, biocompatibility, biodegradability, and processing properties have prompted a general interest for its use in tissue-engineering applications . The prBioartificial functionalized SF fibrous scaffolds have been yet applied for tissue engineering of vascular endothelium and corneal endothelium biomimetics , or scaffolds subjected to posterior treatments (cross-linking) to improve their mechanical properties, can however lose biological properties such as poor cells adhesion index and may require surface treatments with basement membrane proteins. In that sense, different tissue-engineering applications aimed at reproducing and fixing a synthetic basement membrane on top of biologic or synthetic scaffolds to improve adhesive and functional properties of their surface. As example, a study demonstrated that electrospun SF/polycaprolactone meshes posteriorly coated with major basement membrane proteins such as collagen IV, laminins, entactins, and proteoglycans could improve The cellular homogeneity and density achieved in a bioengineered mesothelium or in other types of simple squamous epithelial-like tissues are two critical parameters. The static cell-seeding technique, which basically consists in the manual pipetting of a concentrated cells suspension onto the scaffold, has been shown to be a convenient approach for the establishment of mesothelial cells layers , this “smart polymer” is capable of hydrophobic to hydrophilic reversible transition in response to temperature changes. By only decreasing the culture temperature below its lower critical solution temperature (LCST) that is around 32°C in pure water, PNIPAAm become hydrophobic, and consequently force the release of cells monolayer from the dishes  represents the main clinical strategy to prevent or reduce post-operative peritoneal adhesions .The development of new adhesion barriers remains however under current research due to the partial effectiveness of the commercially available adhesion barriers. A host of experimental approaches involving pharmacologic treatments and anti-adhesive polymers or molecules promoting endogenous mesothelialization are also under intense research  arterial grafts seeded with mesothelial cells however generated markedly divergent outcomes, suggesting that the adhesion capacity of mesothelial cells on this type of synthetic material is reduced and thus strongly influences their long-term patency . Thin membranes created from electrospun bombyx mori silk fibroin (BMSF) are transparent and were shown to support the growth of human corneal epithelial (HCE) cells  is made up of two types of synoviocytes: “phagocytic or absorptive” macrophage-like cells (Type A) and “secretory” fibroblast-like synoviocytes (Type B), these later accounting for around 80% of the total intimal cells Smith, . SynoviaInterestingly, a careful revision of the literature provides evidence of phenotypic similarities between fibroblast-like synoviocytes and mesothelial cells. Hence, both cellular phenotypes are mesodermal epithelial-like cells which display abundant microvilli on their apical membrane, a structural feature that is commonly found in cells secreting fluid Smith, . In addiThe evidence of phenotypic similarities between fibroblast-like synoviocytes and mesothelial cells stated above could lead to the suggestion that mesothelial cells may represent a putative cellular surrogate of fibroblast-like synoviocytes and suggest thus that mesothelial cells could be potentially useful for the regeneration of the synovial membrane lining.The vestibular duct  is a small cavity filled with perilymph inside the cochlea of the inner ear. The scala vestibuli is separated from the scala media by a very thin membrane termed vestibular membrane or Reissner’s membrane. The Reissner’s membrane facing the scala vestibuli is covered by a monolayer of mesothelial cells. The opposite side facing the cochlear duct a cavity filled by endolymph is covered by an epithelium. A thin basal lamina separates the mesothelium and epithelium layers : Structural molecules produced by cells and excreted to the extracellular space within the tissues and that provide cohesive structure to hold tissues together.Great omentum: A large fold of the peritoneum hanging down from the stomach and containing abundant vasculature and perivascular adipose tissue.Heterologous transplant: Cells, grafts, or tissues derived from an individual of a different species in which they are transplanted, being therefore antigenically dissimilar.Immunomodulation: The adjustment of the immune response to a desired level through immunopotentiation, immunosuppression, or induction of immunologic tolerance.Immunosuppression: Reduction of the immune response, generally through the use of drugs, active molecules, or cells to prevent grafts rejection or control autoimmune diseases.Lineage tracing study: Identification and follow-up of all progeny of a single cell using different experimental strategies available for lineage tracing such as live-cell imaging, fluorescent reporter constructs, inducible gene expression, and inducible recombinases.Matrix: The intercellular substance of a tissue or the tissue from which a structure develops.Mesoderm: One of the three primary germ layers developing in the early embryo.Mesothelial cells: A type of simple squamous epithelial cells lining the walls of celomic body cavities and visceral organs located inside.Mesothelioma: Tumor arising from malignant transformation of mesothelial cells.Myofibroblast: A fibroblastic cell with some contractile properties and that is usually considered an intermediate cell between fibroblasts and smooth muscle cells.Parietal mesothelial cells: The mesothelial cells lining the parietal surface of serous body cavities.Polymeric molecules: Molecules of high molecular weight generated through polymerization of smaller molecules (monomers). They are produced either by living organisms or chemically.Regulatory T cells: A subtype of T lymphocytes with immunosuppressive properties and capacities to abrogate autoimmune diseases.Serosal membranes: Membranes lining serous cavities and composed of a single layer of simple squamous epithelial resting on a basement membrane underneath.Simple squamous epithelium: A simple epithelium composed by a single layer of thin and flat polygonal epithelial cells with secretive properties.Transdifferentiation: The transformation of a differentiated somatic cell into another type without the need of reverting into an intermediate pluripotent state.Vascular endothelium: The monolayer of cells lining the lumen of blood vessels.Visceral mesothelial cells: Mesothelial cells covering visceral organs inside body cavities.Visceral organs: Organs located within internal body cavities, especially those located within the abdomen.Christian Claude Lachaud, Abdelkrim Hmadcha, and Bernat Soria are inventors of the Patent  filed by the Fundación Progreso y Salud, Vissum Corporation and NewBiotechnic SA. Berta Rodriguez-Campins is an employee of NBT SA.


ETCO2 is currently the only parameter proven to correlate with the likelihood of return of spontaneous circulation (ROSC), although the prediction of long-term outcome based on ETCO2 values has not been established [2 adequately, invasive airway management is necessary and measured values are influenced by different lung pathologies.The goal of cardiopulmonary resuscitation (CPR) is to preserve the pre-arrest neurological state by maintaining sufficient cerebral blood flow and oxygenation, but the predictors thereof remain largely unknown. Despite recent attempts to improve the quality of basic and advanced life support, no monitored link to the neurological and physiological response of these CPR efforts has been established. The difficult decision to end pre-hospital resuscitation efforts is currently based on the circumstances of cardiac arrest, length of resuscitation efforts (if available), knowledge of pre-morbid physiological reserves, and (if present) end-tidal carbon dioxide  measures the regional difference between oxygenated and deoxygenated hemoglobin, which expresses the difference in oxygen supply and demand. It determines cerebral tissue saturation non-invasively and independent of pulsatile flow. Müllner and colleagues  were theAlmost 20 years after the first published study on cerebral saturation monitoring during CPR, a revival of cerebral saturation measurement during CPR is taking place. Recent published research measures cerebral saturation in patients with ongoing CPR at arrival to the emergency department, but different cerebral saturation devices and different methods for analysis of NIRS data are used. The latest research on NIRS in the CPR setting focuses on two main questions.Firstly, can cerebral saturation values predict ROSC or neurological outcome? Ito and colleagues  observedThe second question recently addressed is whether cerebral saturation values can guide CPR efforts. Cerebral saturation measurements are probably more useful as a dynamic measurement instead of a static, single value. Hence, low cerebral saturation values could be interpreted as a need for interventions aimed at improving cerebral oxygenation during CPR. Sustained low cerebral saturation values, despite these interventions, could indicate futile CPR efforts. It has been noted that no patients with a mean cerebral saturation of less than 30% achieved ROSC . In contIn conclusion, preliminary data suggest that monitoring of cerebral saturation during CPR seems a likely predictor of both ROSC and neurological outcome and that it might have a role guiding CPR interventions. Although the current knowledge, obtained from small observational studies, is limited, both the further development of NIRS devices and the likely execution of well-designed large blinded observational trials, particularly in the difficult environment of out-of-hospital CPR, bode well for the future. A real-time monitoring tool providing vital information on the neurological and physiological response to CPR efforts and with predictive value for neurological outcome seems close at hand.


Stone tools provide some of the most abundant, continuous, and high resolution evidence of behavioral change over human evolution, but their implications for cognitive evolution have remained unclear. We investigated the neurophysiological demands of stone toolmaking by training modern subjects in known Paleolithic methods  and collecting structural and functional brain imaging data as they made technical judgments  about planned actions on partially completed tools. Results show that this task affected neural activity and functional connectivity in dorsal prefrontal cortex, that effect magnitude correlated with the frequency of correct strategic judgments, and that the frequency of correct strategic judgments was predictive of success in Acheulean, but not Oldowan, toolmaking. This corroborates hypothesized cognitive control demands of Acheulean toolmaking, specifically including information monitoring and manipulation functions attributed to the "central executive" of working memory. More broadly, it develops empirical methods for assessing the differential cognitive demands of Paleolithic technologies, and expands the scope of evolutionary hypotheses that can be tested using the available archaeological record. Enhancement of prefrontal executive control is seen as critical to the emergence of modern human cognition –4, but eExperimental replication of prehistoric behavior is a core research method in archaeology , 15 thatOur previous research examined brain responses to naturalistic stone toolmaking behavior execution , 21 and physical accuracy of predicted outcomes vs. their strategic appropriateness in achieving toolmaking goals. This manipulation approximates a conventional archaeological distinction between savoir-faire (know-how) and connaissance (knowledge about) in stone toolmaking . Although progress in archaeological and comparative research has fostered healthy skepticism regarding such naive appraisals , results5. Althou


Transfer cells are ubiquitous plant cells that play an important role in plant development as well as in responses to biotic and abiotic stresses. They are highly specialized and differentiated cells playing a central role in the acquisition, distribution and exchange of nutrients. Their unique structural traits are characterized by augmented ingrowths of invaginated secondary wall material, unsheathed by an amplified area of plasma membrane enriched in a suite of solute transporters. Similar morphological features can be perceived in vascular root feeding cells induced by sedentary plant-parasitic nematodes, such as root-knot and cyst nematodes, in a wide range of plant hosts. Despite their close phylogenetic relationship, these obligatory biotrophic plant pathogens engage different approaches when reprogramming root cells into giant cells or syncytia, respectively. Both nematode feeding-cells types will serve as the main source of nutrients until the end of the nematode life cycle. In both cases, these nematodes are able to remarkably maneuver and reprogram plant host cells. In this review we will discuss the structure, function and formation of these specialized multinucleate cells that act as nutrient transfer cells accumulating and synthesizing components needed for survival and successful offspring of plant-parasitic nematodes. Plant cells with transfer-like functions are also a renowned subject of interest involving still poorly understood molecular and cellular transport processes. Products secreted by nematodes through their stylet induce the differentiation of root cells into feeding structures and the content of this secretion remains largely unidentified  and RKN nematodes (family Meloidogynidae) are considered the major economically important plant parasitic species . FeedingFigures 2A,B; Root-knot nematodes induce galls composed of giant cells surrounded by neighboring cells (NCs), giving the root a shape of a knot  genes  genes ,b; polygenes PG;  and pect PG; PE; ,b. This  trans-differentiation of parenchyma vascular cells into giant or syncytial TCs.Apart from cell wall changes pathogens may also locally interfere with signaling pathways changing the concentration of sugars such as sucrose  or plantFigure 3; Figures 1A and 3; As mentioned above, RKN species induce root galls containing giant-feeding cells in a large variety of plant hosts. In giant cells induced by RKN, wall thickening is observed as patches expanding, merging, branching and often of uneven cell wall material deposition at early stages of giant cell development suggesting an existing mechanism responsible for depositing irregular cell wall material  of the Potato leaf roll polerovirus fused to GFP , although showing a strong reduction in wound callose and papillary callose formation after mechanical wounding and infection with Sphaerotheca fusca  family were verified to be upregulated in young nematode feeding sites  and three down-regulated  genes in syncytia were validated by quantitative RT-PCR. While STP4, STP7, and STP12 belong to the STP sugar transport protein family, MEX1 and GTP2 are plastidial transporter genes, and SFP1 is a senescence-related monosaccharide transporter. A T-DNA insertion line of the most up-regulated gene (STP12) showed that insufficient sugar in feeding sites resulted in increased male ratios since females need higher sugar concentration in order to grow and reproduce , and PSK (phytosulfokines) are also associated with the RKN or CN feeding cell formation  and the transport occurring within these solute transfer sites involving the feeding cell and numerous phloem and xylem elements along this sink. It remains ambiguous as to what switches ordinary plant cells into transfer-feeding cells that supply nematodes with solutes for their development and reproduction. These plant cellular morphological changes might be caused directly or indirectly by secreted products or feeding activity employed by the nematode during parasitism. What triggers and regulates the switch from apoplasmic to symplastic solute supply and the gating of PD is yet to be discovered. Further functional genetic approaches as well as microscopic studies will help to elucidate genes involved in this process in order to comprehend how nematode induced TCs operate.Nematode-induced syncytia or giant cells constitute a multinucleate model of TCs, and it is generally believed that wall protuberances arise as a result of nematode demand for nutrients. Although some information on solute supply has been mostly reported for syncytia induced by 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.