Stroke after internal jugular venous cannulation typically leads to acute carotid or vertebral arteries injury and cerebral ischemia. We report the first case of delayed posterior cerebral infarction following loss of guide wire after left internal jugular venous cannulation in a 46-year-old woman with a history of inflammatory bowel disease. Our observation highlights that loss of an intravascular guide wire can be a cause of ischemic stroke in patients undergoing central venous catheterization. Inadequate placement of a jugular venous catheter is a well-known complication, with serious and immediate secondary complications including stroke. Acute complications are usually associated with injury to contiguous structures , leading0) to segment V3 with no signs of arterial dissection (A 46-year-old woman with a history of inflammatory bowel disease was admitted for recurrence of severe active colitis and treated by intravenous corticosteroids. Left internal jugular venous cannulation was performed for total parenteral nutrition using the Seldinger technique. During catheterization, the patient suddenly experienced transient dizziness and blurred vision. No further problems were observed after withdrawing the catheter. The anaesthetist did not report any inattention during the procedure. Five days after hospital discharge, the patient presented sudden onset of difficult swallowing. Neurological examination revealed left hemiataxia with hypermetria, left Horner's sign, right deviation of the uvula indicating left palatal palsy, and hypoesthesia of the left hemiface. General examination revealed left cervical subcutaneous hematoma with no hemodynamic impairment . Brain mssection . A lost ssection . Cervicassection , and totssection . The guiCases of acute stroke caused by vertebral intimal damage with thrombosis leading to posterior cerebral infarction during internal jugular venous cannulation have been previously reported –9, althoIn conclusion, our observation highlights that stroke after catheter placement is scarce but constitutes a major and potentially fatal complication of a benign condition.


Three techniques for the treatment of intractable pancreatic fistula: percutaneous transfistulous pancreatic duct drainage (PTPD), percutaneous transfistulous pancreatojejunostomy (PTPJ), and percutaneous transfistulous pancreatic duct embolization (PTPE) are presented as treatment options for intractable pancreatic fistula. PTPD is effective for most cases of intractable fistula that communicate with the main pancreatic duct. However, PTPD itself is not enough in some specific cases. PTPJ and PTPE are applicable in such cases. Pancreatic fistula (PF) remains a significant problem in the management of pancreatectomy. Despite decreased morbidity and mortality rates after pancreatic resection, PF remains a common and potentially lethal complication after pancreatectomy. Its reported incidence varies from 6 to 38% –7. If PFPF also sometimes becomes a significant problem in severe acute pancreatitis. Pseudocysts and postnecrotic collections of the pancreas are treated by percutaneous drainage if they are large and likely to aggravate the patients' condition. Approximately 65–90% of patients recover from this disease by percutaneous drainage alone . HoweverTechniques of percutaneous transfistulous drainage of the main pancreatic duct (percutaneous transfistulous pancreatic duct drainage: PTPD) for intractable PF cases are presented. Furthermore, percutaneous transfistulous pancreatojejunostomy (PTPJ) and percutaneous transfistulous pancreatic duct embolization (PTPE) are also presented as advanced techniques of PTPD.This technique is useful for major PF in which the main pancreatic duct is visualized in fistulography , 14. AnyWhen intractable PF is developed after pancreatoduodenectomy, abscess around the pancreatojejunostomy is drained percutaneously at first. Then, drainage catheters are inserted into the pancreatic duct (PTPD procedure) and jejunum, respectively. A guidewire is inserted into the jejunum via percutaneous transfistulous route through the drainage tube. The guidewire, grasped by a basket catheter inserted from the percutaneous transhepatic biliary drainage (PTBD) route under fluoroscopy, is led externally via the PTBD outlet Figures . FinallyLarge postnecrotic collection can be formed owing to disruption of the main pancreatic duct in some severe necrotizing acute pancreatitis Figures . In suchPF represents clinically relevant complications with life-threatening consequences  after pancreatic resection and in acute necrotizing pancreatitis. PTPD, PTPJ, and PTPE are presented as treatment options for intractable PF. Visualization of the main pancreatic duct during fistulography indicates that the PF is intractable.The conventional treatment strategy for PF consists of establishing adequate external drainage, treating infection, providing nutritional support, and reducing pancreatic juice secretion by parenteral nutrition or octreotide. With effective drainage, most of the PF can be cured by conservative treatment. However, the management of intractable PF cases has not been standardized and remains challenging. The management of intractable PF is individualized. Several procedures have been reported, including endoscopic drainage, percutaneous intervention , and surTranspapillary stents can bypass the high resistance of the sphincter of Oddi, ductal strictures, and calculi, thereby reducing the intraductal pressure that is the driving force behind the fistula. Endoscopic pancreatic sphincterotomy is also recommended for the treatment of PF after DP . HoweverIn necrotizing pancreatitis, disruption of main pancreatic duct appears to be associated with the most severe form of necrosis , 20. Uom


Pancreatic cancer shows a characteristic tissue structure called desmoplasia, which consists of dense fibrotic stroma surrounding cancer cells. Interactions between pancreatic cancer cells and stromal cells promote invasive growth of cancer cells and establish a specific microenvironment such as hypoxia which further aggravates the malignant behavior of cancer cells. Pancreatic stellate cells (PSCs) play a pivotal role in the development of fibrosis within the pancreatic cancer tissue, and also affect cancer cell function. PSCs induce epithelial-mesenchymal transition and cancer stem cell (CSC)-related phenotypes in pancreatic cancer cells by activating multiple signaling pathways. In addition, pancreatic cancer cells and PSCs recruit myeloid-derived suppressor cells which attenuate the immune reaction against pancreatic cancer cells. As a result, pancreatic cancer cells become refractory against conventional therapies. The formation of the CSC-niche by stromal cells facilitates postoperative recurrence, re-growth of therapy-resistant tumors and distant metastasis. Conventional therapies targeting cancer cells alone have failed to conquer pancreatic cancer, but targeting the stromal cells and immune cells in animal experiments has provided evidence of improved therapeutic responses. A combination of novel strategies altering stromal cell functions could contribute to improving the pancreatic cancer prognosis. The prognosis of pancreatic cancer remains poor despite diagnostic and therapeutic improvements. A sensitive early detection screening method has not yet become available, and clinical symptoms such as obstructive jaundice or back pain are signs of advanced disease. Most patients are not eligible for curative surgery, due to the local invasion and distant metastasis Hidalgo, . ChemothKras, inactivating mutations of tumor suppressor p16, p53, and Smad4  reside within pancreatic parenchyma and remain in a quiescent state in normal pancreas. Quiescent PSCs contain vitamin A droplets in the cytoplasm  than CD10− PSCs, whose siRNA-based knockdown attenuated the invasive capacity of the pancreatic cancer cells . EMT is characterized by the loss of epithelial phenotypes and gain of mesenchymal phenotypes, increased cellular migration and invasion, which is an indispensable process for the initiation of metastasis  are the counterpart of the normal stem cells  was correlated with the presence of a fibrotic focus in pancreatic cancer tissue, suggesting desmoplasia provides a hypoxic condition within the tumor  or granulocytic MDSC (CD11b+CD15+)] have been reported  and mutant p53 (inactivating mutation R172H) in the pancreas, recapitulating human pancreatic cancer including prominent desmoplasia  in pancreas (Chang et al., PSCs interact with another type of immune cells, which also promote the growth of pancreatic cancer. Mast cells trigger type I hypersensitivity in various diseases such as bronchial asthma and urticaria (Beunk et al., As summarized in this review, tumor-stromal interaction has pivotal role in pancreatic cancer progression. Interventions directed to the desmoplasia-inducing signaling pathways revealed favorable effects, such as the inhibition of Shh pathway or CTGF pathway in mouse model (Olive et al., Targeting immune cells could be an alternative approach to modify the tumor microenvironment. Restoring the immune reaction could be performed by several agents, such as ATRA or IL-12 in mouse model, which exhibited therapeutic effects (Kerkar et al., Pancreatic cancer is a deadly disease and its establishment proceeds silently. Stromal reaction and escape from immune surveillance are perpetuating systemic changes. The involvement of stromal cell activation and immunosuppression enable cancer cells to remain in a favorable niche, leading to distant metastasis and therapy resistance. A schematic view of the cancer cell-stromal cell interaction is shown in Figure 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.


TP63, TERT-CLPTMIL and 8q24.21, to be highly associated with disease risk. Whole transcriptome sequencing (RNA-Seq) is a revolutionary tool for generating a large amount of qualitative and quantitative information, thus helping to explore known and novel transcripts, splicing forms and fusion genes.Bladder cancer is the 9th most common cancer worldwide and the 13th most common cancer-related cause of death. Bladder cancer frequently recurs after the removal of primary carcinomas. This recurrence leads to repeated surgeries and long-term treatment and surveillance, making it the most expensive type of cancer to treat. Genetic factors and environmental factors such as cigarette smoking and occupational exposure to aromatic amines are linked to bladder cancer risk. Genome-wide association studies (GWAS) for bladder cancer have identified multiple genetic variants within genes and regions, including To understand the genetic and genomic landscape of the GWAS susceptibility regions, we investigated and characterized the entire transcriptome of normal and tumor bladder tissue samples by using powerful massively parallel RNA sequencing. We used an Illumina HiSeq 2000 instrument to sequence six paired samples of normal and tumor bladder tissues. For each of the samples, we generated 50 Gb of 100-bp reads to represent the whole transcriptome.Using the Bowtie/TopHat and Samtools packages, we successfully aligned approximately 80% of the total sequence reads against the human genome reference sequence (build 19). Our analysis sought to identify alternative splicing forms, novel exons, non-coding transcripts and chimeric fusion events. Total levels of mRNA in normal and tumor samples were evaluated by Cufflinks analysis based on the Ensembl transcripts database. Multiple splicing isoforms were identified for some of the GWAS susceptibility genes, and some of these isoforms were differentially expressed between the tumor and normal samples. We found that novel transcripts and non-coding RNAs corresponding to gene desert regions such as 8q24 were abundantly expressed. Our next step will focus on validation of these differentially expressed genes and novel transcripts by using quantitative RT-PCR on independent samples.Using RNA-Seq, we explored transcripts corresponding to candidate regions identified by bladder cancer GWAS. Some of these transcripts demonstrated splicing variability and differential levels of expression between normal and tumor tissue samples, which might be of importance for bladder cancer.


Pseudomonas, type III secretion systems (T3SS) and T3 effectors do not appear central to pathogenesis of pectobacteria. Indeed, recent genomic analysis of several Pectobacterium species including the emerging pathogen Pectobacterium wasabiae has shown that many strains lack the entire T3SS as well as the T3 effectors. Instead, this analysis has indicated the presence of novel virulence determinants. Resistance to broad host range pectobacteria is complex and does not appear to involve single resistance genes. Instead, activation of plant innate immunity systems including both SA  and JA (jasmonic acid)/ET (ethylene)-mediated defenses appears to play a central role in attenuation of Pectobacterium virulence. These defenses are triggered by detection of pathogen-associated molecular patterns (PAMPs) or recognition of modified-self such as damage-associated molecular patterns (DAMPs) and result in enhancement of basal immunity . In particular plant cell wall fragments released by the action of the degradative enzymes secreted by pectobacteria are major players in enhanced immunity toward these pathogens. Most notably bacterial pectin-degrading enzymes release oligogalacturonide (OG) fragments recognized as DAMPs activating innate immune responses. Recent progress in understanding OG recognition and signaling allows novel genetic screens for OG-insensitive mutants and will provide new insights into plant defense strategies against necrotrophs such as pectobacteria.Soft rot pectobacteria are broad host range enterobacterial pathogens that cause disease on a variety of plant species including the major crop potato. Pectobacteria are aggressive necrotrophs that harbor a large arsenal of plant cell wall-degrading enzymes as their primary virulence determinants. These enzymes together with additional virulence factors are employed to macerate the host tissue and promote host cell death to provide nutrients for the pathogens. In contrast to (hemi)biotrophs such as  Pseudomonas syringae and Xanthomonas spp. that rely on living plant cells for nutrient acquisition at least until later stages of infection. Their lifestyle is largely dependent on their ability to avoid and suppress plant defense responses most notably by secretion of effector proteins enabling them to obtain nutrients and multiply within living plant tissue , conserved structures such as the bacterial flagellin essential for the microbial lifestyle . The resPectobacterium and Dickeya are classical and well-studied examples of necrotrophic plant pathogenic bacteria. Their taxonomical classification has been revised several times in recent years. They were first characterized in the early 20th century , i.e., wasabi , P. wasabiae WPP163 (accession: CP001790.1), P. wasabiae SCC3193  and a polyketide phytotoxin  to virulence of the bacterium. T4SS machineries translocate DNA and/or proteins across the bacterial cell wall into bacterial or eukaryotic cells  but absent from genomes of other Pectobacterium species. These islands contain uncharacterized genes but also genes encoding for example a second type VI secretion (T6SS) machinery and a bacterial microcompartment of unknown function. T6SS is a common protein secretion system in Gram-negative bacteria and it has been reported to function in interactions with animals, plants and other bacteria  and EF-Tu receptor (EFR), that recognizes one of the most abundant and conserved proteins of bacteria, Ef-Tu (Pseudomonas and necrotrophic Pectobacterium trigger PTI responses through the recognition of flagellin (Inducible plant innate immunity responses are comprised of two separate lines of defense that are distinguished by the type of pathogen-derived molecules (elicitors) recognized. The first has an equivalent in animals and is triggered after the perception of a group of conserved, or general, pathogen-derived molecules, called PAMPs/MAMPs that can be present in both pathogenic and non-pathogenic microorganisms . Well-cha, Ef-Tu . Recognilagellin . Furtherlagellin .Pseudomonas syringae usually express 15–30 effectors depending on the strain , that controls several ABA- and JA-regulated genes resulted in decreased tolerance to necrotrophic pathogens but also to water deficit and salt stress  overlapping at least partly with those induced by PAMPs including oxidative burst, cell wall strengthening, production of phytoalexins and proteinase inhibitors as well as hormone biosynthesis  are involved in OG sensing. WAK1 and WAK2 have been shown to bind to pectin in vitro  and WAK1in vitro . The in x dimers . The eggx dimers . Even shWAK1 is up-regulated by OGs  OGs and also compared the expression changes between OG-PTI and Flg22-PTI . Furthermore, NO was found to contribute to OG-induced immunity against B. cinerea. Whether this applies to Pectobacterium remains to be demonstrated.Interestingly, recent studies indicate participation of NO in OG-PTI . It was Figure 1, PTI appears central to plant defense against broad host range bacterial necrotrophs like Pectobacterium. ETI, which is highly efficient against (hemi)biotrophs such as Pseudomonas is not an effective strategy to combat necrotroph infection, as ETI relies on localized cell death to trigger the downstream defense responses. Necrotrophs like Pectobacterium employ induction of cell death as part of their virulence strategy, thus ETI would rather enhance than prevent the infection. Indeed Pectobacterium species have a very limited arsenal of T3 effectors and those few that have been studied  appear to promote infection by causing cell death. Consequently, plant immune responses are triggered by recognition of conserved pathogen-associated molecular patterns (PAMPs) such as flagella or damage-associated molecular patterns (DAMPs) such as OGs released by the action of PCWDEs by respective pattern recognition receptors. While the PTI induced by PAMP recognition is a common response to both biotrophs and necrotrophs, DAMPs are more typical to necrotrophic interactions. Consequently, Pectobacterium strives to attenuate PTI particularly in the early phase of infection by tight control of PCWDE production minimizing DAMP generation. PAMP and DAMP recognition events trigger partly overlapping defense responses including induction of defense gene expression and synthesis of various defensive compounds such as phytoalexins, defensins, and PR-proteins – resulting in PTI. Indeed prior induction of either response will enhance plant resistance to Pectobacterium. Elucidating the molecular details of these two partially redundant signal networks is essential for our understanding of the plant-necrotroph interactions and can take advantage of the rapidly developing genomic techniques including transcriptional profiling and RNA sequencing combined with the powerful genetic screens available in Arabidopsis for mutants altered in their PTI responses. In particular elucidation of the less well-characterized OG-induced PTI deserves further studies including correlation of the chain length of the OG elicitor to a particular response at specific stages of infection and defining the downstream components that are most significant for bacterial resistance. Such studies would be crucial for providing new insights into plant defense strategies against necrotrophs. Further genome level analysis would also help to elucidate the interactions of Pectobacterium with other plant associated microbes, as well as their insect vectors.In summary, see 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.


Inhibiting transport of virions within the female reproductive tract is an attractive mechanism for transmission prevention. The mucosal environment varies with menstrual cycle and concurrent bacterial vaginosis (BV). Previous studies of transport within mucosal samples have focused on cervico-vaginal samples in exclusion. Severe BV corresponds to increased incidence of female-to-male HIV-1 transmission although the mechanism remains unclear.We have established a cohort of HIV +ve and –ve women to be longitudinally studied for correlates of inhibited transport phenotypes. Cervical and cervico-vaginal mucus samples  are collected, along with mucosal antibodies, vaginal smears, hormone levels, viral load, T cell monitoring panels as well as medical and behavioral history. Viral transport assays employ a diverse panel of viral isolates, testing clade specific effects. As of this interim analysis, over 60 study subjects have been recruited and repeat sampling is beginning.The hormone profile demarcating menstrual cycle phase correlates strongly with particle movement. In CVM, the nature of viral interactions with their environment changes; lowest progesterone to estradiol ratio corresponds with hindered diffusion. Non-reactive similarly sized PEGylated beads have freely diffusive behavior throughout the menstrual cycle. Cycle classification into follicular, mid-cycle and luteal periods demonstrates that CVM in the luteal phase is, unexpectedly, most permissive to viral transport. Severe BV has modest effects on pH of CVM and no effect on CM. This is reflected in viral transport characteristics whereby the magnitude and nature of movement is invariant during severe BV relative to healthy flora.It is unlikely that the mechanisms of increased transmission with BV are related to virus diffusing more freely within mucus. Correlates of hindered diffusion are not restricted to adaptive immune responses. This study begins to reveal the significance of immune correlates and hormone profiles on HIV-1 transmission mechanisms and transport in the female reproductive tract.


Ovis aries) to construct a linkage map for bighorn sheep, Ovis canadensis. We then assessed variability in genomic structure and recombination rates between bighorn sheep populations and sheep species.The construction of genetic linkage maps in free-living populations is a promising tool for the study of evolution. However, such maps are rare because it is difficult to develop both wild pedigrees and corresponding sets of molecular markers that are sufficiently large. We took advantage of two long-term field studies of pedigreed individuals and genomic resources originally developed for domestic sheep , resulting in an autosomal female map of 3166 cM and an autosomal male map of 2831 cM. Despite differing genome-wide patterns of heterochiasmy between the sheep species, sexual dimorphism in recombination rates was correlated between orthologous intervals.Ovis species. However, domestication may have played a role in altering patterns of heterochiasmy. Finally, we found that interval-specific patterns of sexual dimorphism were preserved among closely related Ovis species, possibly due to the conserved position of these intervals relative to the centromeres and telomeres. This study exemplifies how transferring genomic resources from domesticated species to close wild relative can benefit evolutionary ecologists while providing insights into the evolution of genomic structure and recombination rates of domesticated species.We have developed a first-generation bighorn sheep linkage map that will facilitate future studies of the genetic architecture of trait variation in this species. While domestication has been hypothesized to be responsible for the elevated mean recombination rate observed in domestic sheep, our results suggest that it is a characteristic of  The construction of genetic linkage maps in model organisms and domesticated species enables studies of the genetic architecture of trait variation and genome evolution. However, such resources for free-living populations of non-model species are still rare because it is difficult to acquire large enough pedigrees and associated sets of molecular markers ,2. The uOvis canadensis), a mountain ungulate inhabiting western North America )We constructed a first-generation bighorn sheep linkage map using DNA from two wild pedigreed population and genomic resources originally developed for domestic sheep. Since bighorn sheep and domestic sheep genomes are very similar, future efforts to increase marker density in specific chromosomal regions should be relatively straightforward. This could be achieved using bighorn sheep single nucleotide polymorphism (SNP) markers recently discovered using the OvineSNP50 Beadchip , additioThe main reason for developing genomic resources in bighorn sheep is to allow studies of complex trait genetic architecture and evolution under natural settings. In the NBR population, genomic resources will enable investigations into the genetic basis of fitness, inbreeding depression and genetic rescue . In RM, Ovis species while the unusual male-biased heterochiasmy might have been a consequence of domestication. Finally, we have demonstrated that interval-specific patterns of sexual dimorphism could be conserved among closely related species, possibly due to the position of these intervals relative to centromeres and telomeres.While resources developed for domestic sheep are obviously highly useful to bighorn sheep research, genomic research in bighorn sheep can also yield valuable information through comparisons with domestic sheep in return. For example, we have demonstrated how linkage mapping in bighorn sheep can be used to infer ancestral marker order in domestic sheep. Also, by comparing the domestic sheep map with the map of a close wild relative, we were able to determine that the elevated recombination rates observed in domestic sheep were likely a characteristic of The NBR population was established by transplanting four rams and eight potentially pregnant ewes from Banff National Park  in 1922 . The popThe RM population is native to a small isolated mountain range located about 50 km east of the Canadian Rockies in Alberta, Canada . ImmigraIn both populations, parentage was originally determined with ~30 microsatellite loci using the 95% confidence threshold in Cervus . For theIn addition to markers used for the initial pedigree reconstruction, microsatellites putatively distributed throughout the genome of our focal species were identified using the domestic sheep IMF map version 4.7 ,51. MarkWe constructed population-specific linkage maps as well as an integrated map where populations were treated as independent families using CRI-MAP . The sam10 likelihoods. The relative sex-averaged length of different maps was compared by summing the length of intervals that were present in both maps  of Lovich and Gibbons . This inSince the length of an interval partly depends on the subset of markers included in a linkage analysis, we assessed the validity of comparing intervals between maps constructed using different number of markers (the domestic sheep IMF map 4.7 contains about 1400 markers). To accomplish this, we repeated cross-species analyses using information derived from additional linkage maps based solely on markers mapped in both species. Results and conclusions were essentially the same as for previous analyses and are therefore not presented. These maps are available in Additional file All research protocols were approved by the University of Alberta Animal Use and Care Committee, affiliated with the Canadian Council for Animal Care (Certificate 610901).JP designed the study, conducted laboratory work, performed data analysis and wrote the manuscript. JTH designed and supervised fieldwork at NBR and performed paternity analyses. CSD implemented laboratory methods and performed laboratory work. JMM participated in laboratory work and data analysis. JFM provided marker information and constructed a domestic sheep linkage map composed solely of markers mapped in bighorn sheep. DWC planned and supervised the study. All co-authors read and commented on draft versions of the manuscript. All authors read and approved the final manuscript.List of markers, map position and variability. Excel document displaying List of markers, map position and variability.Click here for fileComparison of bighorn sheep population-specific maps. PDF displaying comparison of bighorn sheep population-specific maps.Click here for fileComparison of intervals present in both population-specific bighorn sheep maps. XLS file displaying comparison of intervals present in both population-specific bighorn sheep maps.Click here for fileComparison of intervals present in bighorn sheep and domestic sheep maps. XLS file displaying comparison of intervals present in bighorn sheep and domestic sheep maps.Click here for fileBighorn sheep mapping pedigrees. PDF file displaying bighorn sheep mapping pedigreesClick here for fileBighorn sheep and domestic sheep linkage maps based on shared markers only. XLS bighorn sheep and domestic sheep linkage maps based on shared markers onlyClick here for file


Implantation of pacemakers can be challenging in the context of dilated cardiac chambers and valvular regurgitation. We report a difficult case of single chamber pacemaker implantation in a patient with restrictrive cardiomyopathy resulting in grossly enlarged atria and severe tricuspid regurgitation. In this situation, use of a slittable guiding sheath, more typically used for coronary sinus lead implantation, greatly facilitated rapid and stable deployment of the right ventricular lead. An initial attempt at single chamber pacing using a screw-in right ventricular lead was difficult due to lead instability and took 3 hours   , Panel AGuiding sheaths are commonly used to facilitate coronary sinus lead implants  and paciOther strategies that could be considered in difficult pacing cases are alternative lead placement strategies by using either pre-shaped stylets  or self-shaped stylets. If apical positioning is difficult, then placement of the lead into the right ventricular outflow tract septum can be facilitated by shaping a stylet with a generous distal curve with a swan neck deformity (angulated posteriorly). The whole lead, with the stylet either fully inserted, or pulled back from the tip, is then inserted into the pulmonary artery initially, before being pulled down into a stable right ventricular outflow tract septal position .  The usOther strategies that might be considered include left ventricular lead placement through the coronary sinus , or use During acute implantation, the presence of a stable R wave suggests a good pacing site. Recent studies have shown that the current of injury is better than R wave, slew rate and impedance measurements at predicting acute stability during active fixation lead implants ,8. In chAlternative lead placement strategies, including the use of appropriately-selected tools may greatly facilitate difficult cases, even when these tools are not part of conventional equipment typically used for single chamber pacemaker implantation.


While increased pulmonary arterial expression of sGC has been reported in this mouse model of pulmonary hypertension, chronic hypoxia had minimal effects on relaxation to an NO donor. Catalase markedly restored contraction to phenylephrine and the aortic relaxation to hypoxia. Chronic treatment of mice with cobalt protoporphyrin IX, which induces heme oxygenase and ecSOD, attenuated the development of pulmonary hypertension without restoring relaxation to ACh. In addition, chronic treatment of mice with delta-aminolevulinic acid, a precursor to the sGC activator protoporphyrin IX and heme needed for sGC activation and heme oxygenase activity, also attenuated pulmonary hypertension development without restoring responses to ACh. Thus, redox mechanisms regulating PKG seem to be important contributors to vascular oxygen sensing mechanisms. In addition, increased ecSOD expression and PKG-mediated vasodilation to endogenously generated peroxide and other sGC activators may function as a protective mechanism against the development of hypoxia-induced pulmonary hypertension.There is much controversy in mechanisms controlling the pulmonary arterial response to acute and chronic hypoxia. Our previous work suggests bovine pulmonary arteries (BPA) contract to hypoxia via removal of a relaxation mediated by hydrogen peroxide derived from superoxide generated by Nox4 . In cont


Abiotic stress conditions adversely affect plant growth, resulting in significant decline in crop productivity. To mitigate and recover from the damaging effects of such adverse environmental conditions, plants have evolved various adaptive strategies at cellular and metabolic levels. Most of these strategies involve dynamic changes in protein abundance that can be best explored through proteomics. This review summarizes comparative proteomic studies conducted with roots of various plant species subjected to different abiotic stresses especially drought, salinity, flood, and cold. The main purpose of this article is to highlight and classify the protein level changes in abiotic stress response pathways specifically in plant roots. Shared as well as stressor-specific proteome signatures and adaptive mechanism(s) are simultaneously described. Such a comprehensive account will facilitate the design of genetic engineering strategies that enable the development of broad-spectrum abiotic stress-tolerant crops. Abiotic stresses such as drought, salinity, flood, and cold vastly affect plant growth and metabolism that ultimately disturbs plant life —acetone precipitation and phenol extraction method helped to overcome the above challenges to certain extent  . Firstly, breakthroughs in soft ionization methods such as matrix assisted laser desorption ionization (MALDI)  are also involved in the response of roots to drought stress.Evidence from several proteomic studies showed that roots respond to drought stress using mechanisms similar to those occurring in damaging cells. For instance, enhanced levels of proteosomal factors were detected in drought-tolerant varieties of rapeseed seedlings  in soil. Root is the primary organ of exposure and hence responds rapidly. Several proteomic-based investigations have provided new insight into root responses and adaptation against high salinity.++ signaling protein or Ca++ binding protein, (4) phosphoproteins involving activation of kinase cascade, and (5) ethylene receptors. Receptor protein kinases (RPKs) in rice roots  and calreticulin (CRT)  alteration in carbohydrate and energy metabolism, (2) changes in ion homeostasis and membrane trafficking, (3) ROS scavenging, and (4) dynamic reorganization of cytoskeleton and redistribution of cell wall components.Alteration in carbohydrates and energy metabolism under salinity can be addressed by the high abundance of enzymes involved in glycolysis, TCA cycle, electron transport chain (ETC), and ATP synthesis  was produced , amino acids (aspartate aminotransferase), and lipids (lipoxygenase) were induced as early flood responsive proteins  or freezing (<0°C) temperatures can induce ice formation in plant tissues, leading to cellular dehydration  were found to be higher in abundance as a chilling stress response in roots of rice (Cui et al., Several other proteome signatures provided insights on plants' preparation for recovery once the stress is being released. For example proteins involved in cellulose synthesis, such as UDP-glucose pyrophosphorylase were highly abundant in rice roots upon 48 h chilling stress (Amor et al., Proteomic analyses on plant roots under various abiotic stress conditions revealed important information on proteins involved in the abiotic stress response. This leads to the identification of molecular and cellular mechanisms that are specific to certain abiotic stress or shared between two or more abiotic stress conditions Figure . For insde novo protein synthesis, growth-related signaling, and secondary metabolism were enhanced during recovery from flood stress as a replenishment of the stress-induced effects. Together, these changes suggested a compensatory mechanism by which the stress-induced effects could significantly be recovered.At the recovery phase, increased lignin biosynthesis was found following cold and drought stress. This molecular mechanism results in enhanced mechanical strength of roots by hardening cell wall at the root tip. Changes in abundance for cytoskeleton associated proteins were also observed, that can be looked upon as compensation against reduced cell size as well as repairing injuries caused by drought, salinity, and flood stress. Moreover, the levels of proteins related to As mentioned in this review, majority of literature reported proteomic analyses of the root response at least after 24 h of exposure to cold, drought, high salinity, or flooding stress. Therefore, early proteomic changes associated with individual abiotic stress remain to be elucidated, which will allow the identification of distinct sets of effectors for stress signaling. The function of these early effectors may be masked by secondary processes at a later stage. Technically, most of these proteomic studies have utilized the gel based separation approaches Table  that resThe 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.


Strix occidentalis, the northern goshawk, Accipiter gentilis, and the Pacific fisher, Martes pennanti. Whether protection of these upper-trophic level species confers adequate conservation of avian forest diversity is unknown.As a result of past practices, many of the dry coniferous forests of the western United States contain dense, even-aged stands with uncharacteristically high levels of litter and downed woody debris. These changes to the forest have received considerable attention as they elevate concerns regarding the outcome of wildland fire. However, attempts to reduce biomass through fuel reduction  are often opposed by public interest groups whose objectives include maintaining habitat for species of concern such as the spotted owl, 2 area in the Sierra Nevada. Our approach, which accounts for variations in detectability of species, estimates occurrence probabilities of all species in a community by linking species occurrence models into one hierarchical community model, thus improving inferences on all species, especially those that are rare or observed infrequently. We address how the avian community is influenced by covariates related to canopy cover, tree size and shrub cover while accounting for the impacts of abiotic variables known to affect species distributions.We use a multi-species occurrence model to estimate the habitat associations of 47 avian species detected at 742 sampling locations within an 880-kmEnvironmental parameters estimated through our approach emphasize the importance of within and between stand-level heterogeneity in meeting biodiversity objectives and suggests that many avian species would increase under more open canopy habitat conditions than those favored by umbrella species of high conservation concern. Our results suggest that a more integrated approach that emphasizes maintaining a diversity of habitats across environmental gradients and minimizing urbanization may have a greater benefit to ecosystem functioning then a single-species management focus. Biodiversity is integral to ecosystem functioning Forested ecosystems support over 80% of terrestrial biodiversity worldwide and have high species diversity for many taxonomic groups, including birds Strix occidentalisMartes pennantiAccipiter gentilisStrix occidentalis occidentalis, and Pacific fisher are typically associated with denser, closed-canopy, multi-storied stands. Modification of these habitats to reduce the threat of fire is perceived to decrease habitat suitability for these old-growth forest associated species and fuel treatments in the Sierra Nevada are required to make special considerations for them. For instance, stands within spotted owl protected activity centers around known nests are required to be managed to maintain a minimum of 70 percent tree canopy cover and to retain dominant and co-dominant trees that are at least an average of 61 cm in diameter at breast height (DBH) Fuel reduction treatments are increasingly being applied in an attempt to reduce the risk of high-severity fire and increase forest resiliency Conservation of upper-trophic level species, such as the spotted owl, is thought to provide an umbrella of protection to other species that have similar habitat associations but have smaller area requirements 2 conservation area, the Lake Tahoe Basin, located in the central Sierra Nevada Mountains , white fir (Abies concolor), red fir (A. magnifica), incense-cedar , lodgepole pine (P. contorta), and sugar pine (P. lambertiana).The Lake Tahoe Basin is located on the eastern crest of the Sierra Nevada straddling the states of California and Nevada . ElevatiAvian point counts were conducted at 742 locations in the upland forested areas of the Lake Tahoe Basin Management Unit during the course of the breeding season (mid-May to early July) of 2002 to 2005 Sample locations were selected using a combination of systematic/grid sampling and stratified random sampling. Four points were randomly selected from within a hexagonal grid laid across the Lake Tahoe Basin using spacing parameters of the Forest Inventory and Analysis program (N = 98). An additional 74 locations were randomly selected across a range of urban development classes. At each of these primary sampling locations, a cluster of additional sampling points was conducted 200 m from each primary point count station. Sampling locations for each year of the study were selected randomly. Combined, these sampling designs ensured that data points were distributed across the basin and adequately addressed the influence of urbanization. There was a minimum distance of 200 m between all sampling points.We characterized habitat using several explanatory variables with Geographic Information Systems (GIS) for the area within a 150-m radius of the survey locations. Although birds were recorded only when detected within 100 m of a sample point, we selected a 150-m radius to define our habitat variables as birds on the edge of the sampling radius are likely responding to surrounding forest conditions. Habitat parameters were derived from a GIS vegetation layer (30-m×30-m raster cell) based on IKONOS satellite imagery collected in 2002 i, iz, is a Bernoulli process where the probability that species i is present at location j : We analyzed the data using a hierarchical multi-species modeling approach developed in Dorazio and Royle i at location j during sampling occasion k, denoted i at location j during sampling occasion k given that the species was present. We similarly modeled species detection probabilities using the logit link function:i species  implemented in the programs R and WinBUGS with flat priors for each of the community-level parameters. We ran three chains of the model for 15000 iterations after a burn-in of 10000 iterations and saved every fifth estimate . We assessed that the model had convergence using the R-hat statistic Calypte anna, blue-gray gnatcatcher Polioptila caerulea, bushtit Psaltriparus minimus, lazuli bunting Passerina amoena, and orange-crowned warbler Oreothlypis celata) and were considered vagrants or non-breeding periodics . The house finch Carpodacus mexicanus and mourning dove Zenaida macroura were also excluded from our analyses as their presence in forests is dependent upon urban development (i.e. they are not expected in forests lacking urbanization). These species were excluded from the model because they would not be representative of the community. Seven additional species considered very rare, Calliope hummingbird Stellula calliope, Hammond’s flycatcher Empidonax hammondii, lesser goldfinch Spinus psaltria, Pacific-slope flycatcher Empidonax difficilis, purple finch Carpodacus purpureus, ruby-crowned kinglet Regulus calendula, and yellow warbler Dendroica petechia), were observed fewer than 20 times, and they were included in our hierarchical model but not in our presentation of covariate estimates for individual species because their covariate estimates could be misleading. The mean and standard deviation of the occurrence and detection probabilities for all species included in the model are presented in We recorded 61 species of birds during 2021 visits to 742 point count stations. Of these 61 species detected, we excluded five species from our models as they typically breed at lower elevations  is likely to decrease the occurrence probabilities for old-forest associates. Further, our results also underscore the consistently negative impact of urban development on many avian species in the Lake Tahoe Basin and suggest that actively managing the extent and placement of urban development to minimize biodiversity impacts is as important as considerations of forest structure.Forest thinning projects have frequently been opposed by those concerned with maintaining suitable habitat for old-forest associated species of concern, such as the spotted owl, which require old forest conditions, namely high canopy cover and large trees Spizella passerina, that specialize on forest edge habitats and require both highly forested areas and shrub fields to meet their life history requirements. The results of our model indicate that past practices and management approaches that lead to increased homogenization of the forest will have negative impacts on avian diversity. Management approaches, such as fuel reduction treatments, or the use of prescribed or managed wildland fire, may be designed to restore at least some of the variability within and among stands that existed during an active fire regime, thereby enhancing habitat conditions for conserving avian biodiversity.Parameters estimated through our multi-species model emphasize the importance of within and between stand-level heterogeneity in meeting biodiversity objectives. At the stand level, some species responded positively to higher variance in tree size and canopy cover; thus, increasing forest heterogeneity in forest stands would improve habitat suitability for these species see . SpeciesThe link between habitat heterogeneity and biodiversity has been well-established (reviewed in Appendix S1Upland forest bird frequency status (ranging from very common to very rare) and mean detection and occupancy probabilities with one standard deviation.(DOCX)Click here for additional data file.Appendix S2Mean parameter estimates for upland bird species included in our analysis. Values indicate the change in occurrence predicted for each change in one standard deviation in the response variable. Bold indicates that the posterior interval did not overlap zero. The following seven species were excluded from this table  because they were observed fewer than 20 times: Calliope hummingbird Stellula calliope, Hammond’s flycatcher Empidonax hammondii, lesser goldfinch Spinus psaltria, Pacific-slope flycatcher Empidonax difficilis, purple finch Carpodacus purpureus, ruby-crowned kinglet Regulus calendula, and yellow warbler Dendroica petechia).(DOCX)Click here for additional data file.


Personalized medicine in the days of genetic research is seen as molecular biologic specification in individuals, not as individualized care oriented to patients needs in the sense of person-centered medicine. Yet the question can be raised whether this focus can ameliorate health care needs in view of the invested resources. Studies suggest that patients often miss authentically patient-centred care and individual physician-patient interaction and therefore decide to choose complementary and alternative medicine (CAM). By means of a meta-ethnography this project explored patients’ views about individualized medicine and described the patients’ perspectives of integrative and person-centred services.The procedure included first an electronic databases search for ‘qualitative research’ AND ‘CAM’ AND ‘patient expectations’ subject headings, supplemented with citation searches and hand searching. Second, studies were assessed using an inclusion/exclusion checklist and a quality score according to an adjusted checklist of Behrens and Langer. The third step was meta-ethnography according to Noblit and Hare's method to synthesize and interpret key concepts of individualized medicine using a line of argument synthesis.A set of 67 electronic databases including CAM, nursing, nutrition, psychological, social, medical databases, the Cochrane Library and DIMDI were searched. Nine thousand five hundred seventy-eight citations were screened, 63 full text publications reviewed, 38 appraised and 30 articles were included. The third-order constructs emerging through the synthesis and interpretation conducted by the multidisciplinary research team were: "Personal development", "holism", "alliance", "room for connecting different models", "self activation", "dimensions of well-being".The perspective of patients choosing alternative and complementary medicine regarding individualized care clearly differs from the current idea of personalized genetic medicine. Individualized medicine has therefore concurrently to bear in mind the humanistic approach of holistic, transformative, integrative and self-activation needs of patients. The allocation of resources should consider patients needs to enhance a high-quality biomedical or scientific health care system.


Reaxys is an authoritative web-based workflow solution designed for chemistry researchers in drug discovery, chemicals and academic research . Reaxys With historical coverage dating right back to 1771 and continuing through todays cutting-edge research, Reaxys covers the most important chemistry-related literature and patent sources and provides unparalleled depth of information on reactions, substances and related property data.To make the most effective use of this information Reaxys offers two new entry points into the data:• Chemical space analysis, analogue sourcing, fuelling hit-to-lead programs and IP prior-art searching are possible through the Reaxys Structure Flat File.• Programmatic interaction with the database by custom clients, downloading bulk data from Reaxys using scripts, executing batch queries and integrating Reaxys into server-based data-intensive pipelining or workflow applications are possible through the Reaxys APIs.The Reaxys Structure Flat File and the Reaxys APIs will facilitate chemoinformaticians and information managers to integrate Reaxys into chemical information processing environments. In our poster, we present common use cases and possible applications. In addition, we describe successful implementations, illustrating how additional insights and efficiency can be gained.


Astatotilapia latifasciata (Figure Haplochromis obliquidens. This species was described as Haplochromis latifasciatus [Astatotilapia [Haplochromis "zebra obliquidens" in the aquarium trade. Astatotilapia latifasciata has been reported to occur in Lake Nawampasa a small satellite lake of the much larger Lake Kyoga, and in Lake Kyoga located north of Lake Victoria in Uganda [After the publication of our work , we detea Figure , was errasciatus  and lateotilapia . Our misn Uganda .


The 2011 EMBO Conference Series on the Assembly and Function of Neuronal Circuits was held from 25 to 30 September 2011 at Monte Verità in Ascona, Switzerland. Approximately 100 participants explored current challenges and approaches to studying neural circuit function and organization. The 2011 EMBO Conference Series on the Assembly and Function of Neuronal Circuits was held from 25 to 30 September 2011 at Monte Verità in Ascona, Switzerland. Approximately 100 participants explored current challenges and approaches to studying neural circuit function and organization. The conference was organized into two sessions of oral presentations per day followed by an evening lecture and a nightly poster session at the Centro Stefano Franscini. The generously timed meals and coffee breaks offered additional opportunities for more informal and intimate discussions throughout the meeting.Caenorhabditis elegans, Drosophila, zebrafish, songbirds, rodents and macaques to electric fish, turtles and Egyptian fruit bats. In addition to experimental approaches, a few computational studies were presented that provide models to describe circuit dynamics, such as the influence of cortical inhibition.The topics spanned themes such as the importance of inhibition and its interplay with excitation in shaping circuit activity, the effects of neuromodulators on neurons and behavior, the genetic underpinnings of behavior and how specific neuron types wire and communicate. There was a notable trend toward the use of combinations of genetic, optical, electrophysiological and behavioral methods. We noticed a surge in the use of optogenetics for fine manipulation of genetically defined neurons, as well as many studies in awake, behaving animals, with the use of imaging or electrophysiology. A wide range of model organisms was used, from the traditionally popular Herein we sample a few highlights from the meeting that showcase the breadth of current research in neuronal circuits. Owing to space limitation, we apologize that we cannot comment on all of the presentations.Massimo Scanziani presented work on the mouse primary visual cortex (V1) and lateral geniculate nucleus (LGN). He expressed light-activated opsins, Channelrhodopsin-2 (ChR2) and archaerhodopsin (Arch) in layer VI (L6) pyramidal neurons and found that L6 excitation decreases firing rates in more superficial layers (presumably via interneurons) and in LGN . Sonja Hofer, who received a prize for the best short oral presentation, used a combination of two-photon microscopy and patch-clamp recordings to study the connectivity and tuning preferences of different cell types in mouse V1. She found that whereas excitatory pyramidal neurons receive sparse input from neurons with similar tuning preferences, parvalbumin (PV)-positive GABAergic interneurons receive input with high probability from neurons with diverse stimulus preferences. Yang Dan expressed ChR2 in subsets of interneurons and Arch in pyramidal neurons in mouse V1. Exciting PV neurons sharpened orientation tuning and enhanced direction selectivity . Exciting somatostatin neurons enhanced direction selectivity but did not change orientation tuning. Kevin Franks examined how recurrent connectivity in the piriform cortex (PCx) gates sensory information from the olfactory bulb. He found that a distributed and excitatory recurrent network in PCx activates strong feedback inhibition such that, if recurrent activity precedes sensory input, feedback inhibition will arise to suppress bulb-evoked spiking.Drosophila brain learn to select for sexually receptive females. He found that courtship learning depends on the activation of a specific class of dopaminergic neurons in the protocerebrum which project to neurons with a subtype of dopamine receptors in the mushroom body. David Anderson presented new techniques for the study of the role of dopaminergic neurons involved in hunger in Drosophila.Barry Dickson presented his work on how neural circuits in the male C. elegans to decide whether to exploit a food patch or to abandon it and explore other options. She found that this decision depends on the expression of the catecholamine receptor tyra-3, a homolog of the vertebrate adrenergic receptor. Alex Shier described the importance of hypocretin in sleep regulation in larval zebrafish and showed a promising technique for identifying drug targets using high-throughput behavioral screening.Cori Bargmann probed the genetic mechanisms that allow N-methyl-D-aspartate receptors at cortical dendrites. Bartlett Mel described theoretical approaches to understanding excitatory and inhibitory synaptic input to dendrites and stressed that dendrites must be considered processing units in their own right. Michael Haüsser showed in vivo patch recordings from orientation-tuned mouse V1 dendrites. Erin Schuman showed the existence of many mRNAs at dendrites, suggesting a place to look for a molecular basis for dendritic computation.Dendritic computation was featured in several studies. Jackie Schiller demonstrated supralinear summation between thalamocortical and corticocortical synapses via Drosophila olfactory system wires, and Oscar Marín showed how Cajal-Retzius cells in layer I in cortex are distributed across the future cortical surface. Tania Rinaldi Barkat showed that the auditory critical period for thalamocortical modification depends on telencephalin, a membrane adhesion protein, and that its loss induces precocious spine maturation on pyramidal cells in layer IV of the primary auditory cortex.A few talks addressed how neurons find their targets during development. Andrew Huberman described work addressing the problem of how retinal ganglion cells find their targets in the brain. Liqun Luo showed how the Nirao Shah showed that a sexually dimorphic gene with higher expression in the male mouse bed nucleus of the stria terminalis and medial amygdala may play a role in sexual behavior. Allison Doupe and Bence Ölveczky presented recordings from nuclei in songbirds to demonstrate the role of variability in producing learned motor patterns. Peer Wulff presented a study on how the selective ablation of PV neurons in the medial prefrontal cortex of mice impairs spatial working memory and cognitive flexibility. Daniel Salzman showed that neurons in the monkey basolateral amygdala (BLA) may contribute to selective attention via their projections to extrastriate cortex. Single BLA neurons showed sustained excitation or inhibition from stimuli that indicate high- or low value rewards. Adi Mizrahi showed that, by patching neurons in primary auditory cortex, pup odors modulate responses to ultrasonic pup vocalizations in lactating mothers, but not in naïve virgins. Alla Karpova observed abrupt and synchronous firing of neuronal ensembles in medial prefrontal cortex during transitions in behavioral strategies of rats performing two-alternative choice tasks. Nachum Ulanovsky demonstrated a large-scale cognitive map in bats and presented recordings from place cells in the hippocampus. He showed three-dimensional representations of space in the hippocampus as bats flew in the laboratory.Jeff Lichtman showed how axons at the neuromuscular junction connect to the muscle and showed preliminary efforts to image the mouse cortical connectome via large-scale serial electron microscopic reconstruction. Hongkui Zheng, from the Allen Institute for Brain Science, presented new initiatives to provide a whole-brain, three-dimensional map of axonal projections using cell-type specific creatinine (Cre) lines and Cre-dependent viral tracers.Amid talks about the remarkable wiring specificity of particular circuits, Haim Sompolinsky gave a thought-provoking lecture on how random connectivity may be an efficient strategy for encoding of sensory stimuli. He reviewed new developments in the field of compressed sensing and offered a glimpse of its potential use in neuroscience.The diversity of topics covered at this year's conference reflects the wide range of approaches neuroscientists currently use to study neuronal circuits. From examining the molecules and genes of specific cell-types to developing models of how networks of randomly connected neurons behave, the study of neuronal circuits is rapidly expanding, and we predict that it will continue to grow in the future.Arch: archaerhodopsin; BLA: basolateral amygdala; ChR2: channelrhodopsin-2; LGN: lateral geniculate nucleus; PCx: piriform cortex; PV: parvalbumin; V1: primary visual cortex.The authors declare that they have no competing interests.AYW and JYC wrote the meeting report, and both authors approved the final manuscript.


In eukaryotic organisms, DNA is packaged into chromatin structure, where most of DNA is wrapped into nucleosomes. DNA compaction and nucleosome positioning have clear functional implications, since they modulate the accessibility of genomic regions to regulatory proteins. Despite the intensive research effort focused in this area, the rules defining nucleosome positioning and the location of DNA regulatory regions still remain elusive.Ab initio physical descriptors derived from molecular dynamics were used to develop a computational method that accurately predicts nucleosome enriched and depleted regions.Naked (histone-free) and nucleosomal DNA from yeast were digested by microccocal nuclease (MNase) and sequenced genome-wide. MNase cutting preferences were determined for both naked and nucleosomal DNAs. Integration of their sequencing profiles with DNA conformational descriptors derived from atomistic molecular dynamic simulations enabled us to extract the physical properties of DNA on a genomic scale and to correlate them with chromatin structure and gene regulation. The local structure of DNA around regulatory regions was found to be unusually flexible and to display a unique pattern of nucleosome positioning. Our experimental and computational analyses jointly demonstrate a clear correlation between sequence-dependent physical properties of naked DNA and regulatory signals in the chromatin structure. These results demonstrate that nucleosome positioning around TSS (Transcription Start Site) and TTS (Transcription Termination Site) (at least in yeast) is strongly dependent on DNA physical properties, which can define a basal regulatory mechanism of gene expression. Further4 -9.in vivo is really dictated by the DNA sequence is still an issue of strong discussion [DNA underlying sequence has long been considered to be an important contributor to nucleosome assembly -13. Crysscussion -27.ab initio physical descriptors derived from molecular dynamics (MD) simulations of short DNA oligonucleotides [Our group and others have provided indirect evidence highlighting the connection between DNA physical properties and chromatin organization -30. In pleotides -35. Thisleotides ,37. VeryYeast DNA fragments were prepared and sequenced following the experimental approach described in Figure -8), while the same tetramer was rarely present at primary cutting sites  unveiled that LRs  are located in regions with large variations in flexibility, where an extremely flexible site is surrounded by stiff motifs ,The MNase tetramer preferences Tables  and 2 arAs previously suggested by other groups ,11,43-50-503. WheThe analysis of MD-derived descriptors of naked DNA showed that key genomic regions, such as at TSSs and TTSs, were marked by unusual flexibility properties  intrinsic physical properties of naked DNA determine major nucleosome location signals in yeast, especially those at TSS and TTS. This hypothesis is indirectly supported by very recent studies , where nEssential regions for gene regulation like TSSs and TTSs are characterized by unusual physical properties that disfavor positioning of nucleosomes and therefore expose DNA to interaction with regulatory proteins. This property of regulatory regions is quite general across the genome. The genes with well-defined CLRs at regulatory regions did not differ from those with more diffuse signals in terms of Gene Ontology analysis , promoteDrosophila melongaster genome with the high-resolution genomic nucleosome map available [All conclusions drawn here have been derived from the analysis of yeast genome and thus concerns exist whether they can be validated for higher eukaryotes with a different sequence composition at regulatory regions. Therefore, we compared the sequence-dependent physical properties of the vailable . The comvailable . Extensivailable . All theSaccharomyces cerevisiae BY4741 strain,  DNA were isolated from Cleaved DNA samples were sequenced on the Illumina/Solexa Genome Analyzer (GA) IIx to generate reads of 54 bp length. Data were processed with standard GA base calling pipeline to convert initial raw images into sequences. All sequencing experiments were done in duplicates. Pooled data highly converged, as the reproducibility of individual experiments was very large in all cases . Correction of nucleosomal digestion profiles was done by using the degradation profiles obtained for naked DNA as background  account for regions were MNase degradation has been especially extensive. Low coverage regions (LRs) were detected in both nucleosomal and naked DNA as genomic segments with non-zero coverage below certain thresholds , considering the equilibrium conformation as the origin of energies following the approach suggested by Lankas and others [tilt, kroll, kshift, ktilt, krise and kslide) are taken from the diagonal of the matrix. Ktotal is obtained as the product of the six pure stiffness constants and gives a rough global estimate of the flexibility of each base pair step  in solvent water by using a newly developed force-field . Base pad others ,32,42,41T Θ X; where Θ is the stiffness matrix derived from MD simulations; X (or XT) is the deformation vector (or its transposed), given by translating a relaxed DNA fiber into the coiled nucleosome core DNA conformation as described for averaging and smoothing of X-ray structures  declare that they have no competing interestsThe authors have made the following declarations about their contributions: MO had the idea and make the general planning of the study. Conceived and designed the experiments: OD MS MO. Performed the experiments: OD. Analyzed the data: OF FB AP MO. All authors contributed to the writing of the manuscript. All authors read and approved the final manuscript.Additional Methods, Additional Figures and Additional Tables. PDF document with detailed methods and additional results.Click here for file


Understanding population-level responses to human-induced changes to habitats can elucidate the evolutionary consequences of rapid habitat alteration. Reservoirs constructed on streams expose stream fishes to novel selective pressures in these habitats. Assessing the drivers of trait divergence facilitated by these habitats will help identify evolutionary and ecological consequences of reservoir habitats. We tested for morphological divergence in a stream fish that occupies both stream and reservoir habitats. To assess contributions of genetic-level differences and phenotypic plasticity induced by flow variation, we spawned and reared individuals from both habitats types in flow and no flow conditions. Body shape significantly and consistently diverged in reservoir habitats compared with streams; individuals from reservoirs were shallower bodied with smaller heads compared with individuals from streams. Significant population-level differences in morphology persisted in offspring but morphological variation compared with field-collected individuals was limited to the head region. Populations demonstrated dissimilar flow-induced phenotypic plasticity when reared under flow, but phenotypic plasticity in response to flow variation was an unlikely explanation for observed phenotypic divergence in the field. Our results, together with previous investigations, suggest the environmental conditions currently thought to drive morphological change in reservoirs  may not be the sole drivers of phenotypic change. Understanding how populations respond to widespread and rapid environmental change will be a first step in elucidating the evolutionary consequences of disturbed habitats. Habitats altered by humans may destine populations to extirpation . We also predicted C. venusta offspring reared in flowing water would have more fusiform body shapes compared with fish reared in lentic conditions and would parallel shape variation observed in reservoir and stream habitats.Here, we tested for phenotypic divergence of ats Fig. . Althougats Fig.  had prevC. venusta from three reservoirs in the Hilly Gulf Coastal Plains in northwest Mississippi, USA  were combined  from each population were split evenly  and stocked into one of four experimental stream units  located at the Lake Thoreau Environmental Center near Hattiesburg, MS  that transferred water from the outflow end of units to the upstream riffle  of groundwater. Thus, we had a 2 × 2 factorial design with population crossed with flow and nonflow treatments. Adult C. venusta were allowed to spawn and then removed once juvenile fish were observed. All adults were removed by 3 July 2012. Experimental stream units were then monitored, and juveniles were culled to keep densities approximately equal among the four units. Spawned C. venusta were removed on 10 September 2012 and then 1 December 2012, euthanized by overdose of MS-222 and preserved in 10% formalin. We only used individuals that had reached adult size in analyses.We assessed potential genotypic differences and flow-induced phenotypic plasticity in morphology between reservoir and stream populations by spawning http://life.bio.sunysb.edu/morph/) and R (R Development Core Team n = 18) but because some shape variables often do not explain an appreciable amount of variation . All mancova models assume multivariate normality, homogeneity of covariance matrices, independence of observations, linear relationships between covariates and dependent variables, and homogeneity of slopes among groups (Rencher mancova model included 8 shape variables (explaining 89.9% of the variation in shape) as dependent variables, standard length (SL) as a covariate , habitat type (to test for effects of stream or reservoir habitats), basin (to test for basin-level effects) as fixed factors. Heterogeneity of slopes was tested among basins, and between habitat types by including SL in the respective interaction terms. All nonsignificant interaction terms were removed from the final model, and F-values were approximated using Wilk's lambda. Because of the statistical power associated with mancova of shape data, we focused our interpretation of model results on effect strengths by use of partial eta squared  by the shape variables matrix to yield habitat divergence vector scores for each individual. This divergence vector summarizes the shape variation that was elicited in fish from reservoir and stream habitats. The nature of this shape change was visualized using thin-plate spline transformation grids.To assess the nature of morphological divergence in reservoir habitats, we calculated a morphological divergence vector as defined by Langerhans  between mancova to test for population-level differences and flow-induced phenotypic plasticity on body shape variation within mesocosm-reared C. venusta. The mancova model included 8 shape variables as dependent variables (explaining 89.0% of the variation in shape), Population (stream or reservoir) and treatment (flow or no flow) were included as fixed factors, and SL as a covariate. Heterogeneity of slopes was tested between populations and treatment by inclusion of SL in each respective interaction term. Nonsignificant interaction terms were omitted from the final model. To quantify the nature of population-level and flow-induced plasticity of body shape variation of mesocosm-reared individuals, divergence vectors for population and treatment were calculated from the final model (similar to above). We visualized shape deformations along each population and treatment divergence vector using thin-plate spline transformation grids. All analyses were conducted in R unless otherwise stated . We predict these species-specific responses are more likely due to underlying genetic variation and ecologies between the species that are interacting with similar environmental conditions in reservoirs.Repeated morphological divergence in replicate reservoirs suggests these habitats are facilitating phenotypic changes in populations of Franssen  demonstrC. venusta and C. lutrensis may explain their disparate responses to reservoir habitats, although data on their ecologies are limited. A better understanding the ecologies of these species or differences in their underlying genetic architecture may help elucidate mechanisms behind their disparate morphological changes in reservoir habitats.Morphological diversification in fishes has been linked to dissolved oxygen concentrations and light availability . This reversal of caudal regions of the two populations in mesocosms compared with field-collected fish likely indicates fish in the field are exposed to plasticity-inducing factors that were absent in mesocosms. In fishes, there is a general propensity for species inhabiting moving water to be more streamlined than fishes in lentic habitats . While continued exposure to environmental cues that elicit plasticity of traits can result in canalization . Nonetheless, the mancova of body shape variation of field-collected individuals indicated Basin and the Basin × Habitat interaction had significant effects on body shape variation, indicating fish body shape varied among basins and had dissimilar responses to reservoir habitats among basins. However, both of these effects explained less variation than the habitat term, suggesting variation between habitat types had a stronger influence on body shape variation than variation due to genetic variation among basins. While the lack of basin-level replication in the mesocosm experiment was not ideal, we think it is unlikely and have no evidence that would suggest nonadaptive evolutionary processes shaped the genetic structure of C. venusta in the Grenada basin.Lack of basin-level replication in the mesocosm experiment may limit our ability to extrapolate our results and interpretations to other reservoir systems. This would be especially true if drift, mutation, or recombination had stronger effects than selection on the genetic structure of C. venusta in reservoir habitats (compared with C. lutrensis) indicates selective pressures may vary among reservoirs or that different species respond to similar selective pressures in different fashions. Together, investigations of morphological changes of fishes in reservoir habitats may suggest that the reduction in factors that can contribute to morphological variation to one or two variables  may be an over-simplification when comparing phenotypic variation in different habitats. Indeed, a multitude of environmental conditions likely covary between these different habitats. A better understanding of the spatial and temporal variation in other potential environmental selective pressures and how these conditions interact with genetic variation to produce phenotypic variation will be needed to understand how reservoirs can alter the evolutionary trajectories of resident populations.The inability to elicit similar phenotypic variation in individuals reared in flow variation (this paper) and in the presence of predators Franssen  to morphMost organisms live in environments that have been altered at least to some extent by humans Palumbi . It will


Patients with Turner's syndrome have increased cardiovascular (CV) morbidity and mortality, potentially over and above that explained by the higher rate of both congenital heart disease and associated endocrine disorders and hypertension. GH administration to maximise adult height is a well-established treatment form but may affect cardiovascular status, ventricular mechanics and myocardial function. Furthermore, given the adverse CV effects of supra-physiological GH levels associated with acromegaly and in the field of sports doping, concern has been voiced about potential risks associated with this form of treatment.CMR based strain derivatives offer advanced analysis of myocardial deformation and function. Such technologies are thought to increase sensitivity and may allow detection of "pre-clinical" disease not apparent by assessment of conventional parameters such as ventricular volumes and ejection fraction (EF).52 patients with Turner syndrome underwent a comprehensive CV CMR study. Patients with structural heart disease such as aortic coarctation, haemodynamically important valve disease, previous myocardial infarction or cardiac surgery were excluded. Of the remaining 35 adult patients 14 had a history of previous exposure to GH (GH +ve), 21 had no history of GH treatment (GH -ve).Assessment of ventricular mass, volumes and derived EF was performed by means of signal intensity thresholding based detailed endocardial contouring using commercial software . LV/RV longitudinal and LV circumferential strain was analysed using an endocardial feature tracking software package .The demographic and haemodynamic data of both groups is summarised in Table Childhood GH exposure appears to have no detectable detrimental late effects on LV/RV ventricular performance. This study therefore provides further reassurance regarding the long term safety of childhood GH administration in patients with Turner's syndrome.None.


To assess our preoperative pickup of malignant axillary lymph nodes by ultrasound and FNA compared with one-stop nucleic acid amplification (OSNA) and final histology.At our unit all patients with invasive breast cancer undergo axillary ultrasound, and those with suspicious or equivocal findings undergo axillary FNA. If FNA is positive we proceed to axillary node clearance (ANC). If axillary assessment is normal we perform sentinel node biopsy (SNB) with intraoperative OSNA, unless planned for neoadjuvant chemotherapy or primary medical therapy. In patients with positive OSNA, further surgery is performed as per hospital protocol. Retrospective correlation of preoperative axillary ultrasound and FNA findings with intraoperative OSNA in the SNB group and final histology in the ANC group was performed, with patients diagnosed with invasive breast carcinoma between September 2010 and September 2011.n = 27: 22 imaging normal, three equivocal, two abnormal).See Figure This is the first study correlating preoperative imaging with OSNA. Our high rate of preoperative diagnosis is encouraging, but suggestions for improvement are discussed.


In clinical practice, the risk of cerebrovascular events originating from carotid atherosclerotic plaques is correlated to the degree of luminal narrowing, commonly designated the degree of stenosis. Though the degree of stenosis is a proven marker of plaque vulnerability, it is widely recognized that better risk markers for cerebrovascular events are needed. Known morphological features of plaque vulnerability are large lipid-rich necrotic cores (LR-NC) with thin fibrous caps that generate localized elevated mechanical stresses within the fibrous cap separating arterial lumen from LR-NC. Thus, determination of local biomechanics using computational simulations may have clinical implications.Biomechanical stress levels could be indicative of plaque rupture risk. Thus, we wished to determine whether different plaque morphologies in a longitudinal section affects the level of local mechanical forces.Two patients scheduled for carotid endarterectomy were scanned using MRI and idealized anatomical 2D models of individual carotid bifurcations were created figure . KeepingSignificant differences were apparent comparing the two different patient morphologies using surface plots of degree of stenosis, peak principal mechanical stresses, and fibrous cap thickness figure . In partIdentical plaque morphologies may yield significantly different mechanical stress levels depending on vessel geometry. Further studies are needed to determine if the varying stress levels are indicative of differing risks of plaque rupture.


The ability to accurately identify bird species is crucial for wildlife law enforcement and bird-strike investigations. However, such identifications may be challenging when only partial or damaged feathers are available for analysis.Meleagris gallopavo), Canada goose (Branta canadensis), blue heron (Ardea herodias) and pygmy owl . The mtDNA was successfully obtained from 'fresh' feathers, historic museum specimens and archaeological samples, demonstrating the sensitivity and versatility of this technique.By applying vigorous contamination controls and sensitive PCR amplification protocols, we found that it was feasible to obtain accurate mitochondrial (mt)DNA-based species identification with as few as two feather barbs. This minimally destructive DNA approach was successfully used and tested on a variety of bird species, including North American wild turkey (By applying appropriate contamination controls, sufficient quantities of mtDNA can be reliably recovered and analyzed from feather barbs. This previously overlooked substrate provides new opportunities for accurate DNA species identification when minimal feather samples are available for forensic analysis. Accurate identification of bird species is crucial for wildlife law enforcement and other aspects of wildlife forensics. Currently, many birds and bird products (such as feathers) are protected under the US Migratory Bird Treaty (MBTA), the US Endangered Species Act (ESA) and the Convention on International Trade in Endangered Species (CITES). Identification of these protected species by law enforcement personnel may be challenging when only partial or damaged feathers are available for examination. Additionally, other criminal investigations, such as bird larceny, may also be contingent upon accurate species identification of bird feathers . Althouget al. [GenBank: BLAST: Basic Local Alignment Search Tool; EDTA: ethylene diamine tetraacetic acid; PCR: polymerase chain reaction; MSSC: modified silica-spin column; QDIK: Qiagen's DNA Investigator Kit; SFU: Simon Fraser University.The authors declare that they have no competing interests.CFS participated in the design of the study, performed DNA extractions and PCR amplifications, conducted sequence alignments and species identifications, and drafted the manuscript. GPN conceived of the study, participated in its design and helped to draft the manuscript. DYY participated in the design and coordination of the study, performed DNA extractions and amplifications, and helped to draft the manuscript. All authors read and approved the final manuscript.


International policy is placing increasing emphasis on adaptation to climate change, including the allocation of new funds to assist adaptation efforts. Climate change adaptation funding may be most effective where it meets integrated goals, but global geographic priorities based on multiple development and ecological criteria are not well characterized. Here we show that human and natural adaptation needs related to maintaining agricultural productivity and ecosystem integrity intersect in ten major areas globally, providing a coherent set of international priorities for adaptation funding. An additional seven regional areas are identified as worthy of additional study. The priority areas are locations where changes in crop suitability affecting impoverished farmers intersect with changes in ranges of restricted-range species. Agreement among multiple climate models and emissions scenarios suggests that these priorities are robust. Adaptation funding directed to these areas could simultaneously address multiple international policy goals, including poverty reduction, protecting agricultural production and safeguarding ecosystem services. The need for adaptation to climate change is an emerging focus of international policy . The impEcosystem-based Adaptation is the use of ecosystem services to help people adapt to climate change. Intact ecosystems provide clean water, shoreline protection, and other services in the face of climate change, providing adaptation options that are often cheaper and more enduring than technical or engineering solutions . MaintaiPriorities linking ecosystems and food production are particularly important because human and natural responses to climate change are interwoven –8. ImpovAdaptation action in these areas could simultaneously enhance food security and maintain ecosystem function. This has policy relevance on multiple levels, as food security and ecosystem integrity are two of the three major benchmarks for climate change response established in the United Nations Framework Convention on Climate Change (UNFCCC), and make substantial contribution towards sustainable development, thus helping meet all three UNFCCC criteria . However2) which are indicative of highly complex and biodiverse ecosystems  pre pre43] pUncertainty associated with species and agricultural modeling is more difficult to constrain. In the tropics, species ranges may not sample all climatic conditions that are physiologically tolerable, resulting in over-estimation of range loss. Adaptation priorities for non-avian restricted-range species may not match those for birds, due to different taxonomic climatic tolerances. SDM are fitted to empirical data using current climatic conditions and may not simulate future range changes well when future climatic conditions are outside the range of current climate. Adaptation in agriculture may moderate crop losses, resulting in over-estimation of crop impacts. For instance, consumption may switch to crops which may be grown in a region but are not culturally favored, once suitability for preferred crops declines. For these reasons, regional analyses incorporating social factors, taxa other than birds, and analyses of adaptation capacity are essential complements to this global analysis.The priorities identified here reinforce and expand on the findings of other research into agricultural and biodiversity responses to climate change. Areas of agricultural vulnerability identified in this study overlap with those defined in other global assessments of agricultural impacts of climate change –46. For Possible adaptation responses in these priority areas might include actions that integrate adaptation for agriculture and ecosystems. For instance, agroforestry can help reduce soil temperatures and maintain soil moisture as air temperatures increase, and, with the appropriate choice of tree species, can help provide habitat for restricted-range birds and other wildlife. Protecting upland forests that provide fog interception or provide watershed protection for dams may be critical for agriculture in areas of declining precipitation, at the same time providing habitats that will permit range migrations in forest birds responding to climate change. Many of these solutions require planning on scales broader than individual farms or protected areas, which is why we have aggregated our results at spatial scales roughly coincident with scales of ecosystem and regional planning (one degree).It is likely that finer-grained analyses will confirm some or all of the regional priority areas identified  will be required. Both approaches can be effective , so wiseAdaptation practice is currently being pioneered in first-generation projects around the world. These efforts are addressing the adaptation needs of communities and ecosystems, increasingly recognizing deep interdependencies between the two. Meeting short-term development needs while establishing long-term sustainability of ecosystem services is a fundamental challenge. Among the best places to build experience in melding human and ecosystem responses will be regions experiencing substantial change in both. Innovative solutions and lessons from these areas can inform second-generation adaptation responses worldwide. Investment in the priority regions identified here is therefore a first step in developing a lasting, multi-sector approach to adaptation.Table S1Species and parameters used for EcoCrop modeling.Some crop species contained different species and varieties, so the model adapted the widest range of environmental requirement among species/varieties. The list of species used in the model appears below the table. Minimum and maximum temperature/precipitation requirements represent the environmental range where crop growth is possible and optimal minimum and maximum temperature/precipitation requirements are the environmental range of optimal growth.(DOCX)Click here for additional data file.Figure S1Performance of each SDM tested by overall accuracy, Kappa, TSS, MCC, specificity and sensitivity.Maxent scored highest performance except sensitivity that RF scored the highest performance.(TIF)Click here for additional data file.Figure S2Global map of crop suitability and suitability for range restricted birds change in 2050 under A2 emission scenario.Areas in which overall decreases are anticipated in crop suitability are shown in green, with increasing color intensity indicating multiple GCM agreement. Areas of declining climatic suitability for restricted range birds are shown in blue, with increasing color intensity indicating multiple GCM agreement. Overlap of declining crop suitability and declining restricted range bird climatic suitability is shown in shades of yellow (lowest GCM agreement) to red (highest GCM agreement).(TIF)Click here for additional data file.Figure S3Global map of crop suitability and suitability for range restricted birds change in 2050/2090 under B1 emission scenario.Areas in which overall decreases are anticipated in crop suitability are shown in green, with increasing color intensity indicating multiple GCM agreement. Areas of declining climatic suitability for restricted range birds are shown in blue, with increasing color intensity indicating multiple GCM agreement. Overlap of declining crop suitability and declining restricted range bird climatic suitability is shown in shades of yellow (lowest GCM agreement) to red (highest GCM agreement).(TIF)Click here for additional data file.Figure S4Global map of crop suitability and suitability for range restricted birds change in 2050/2090 under A2 emission scenario using the ensemble mean of 5 GCMs.Areas in which overall decreases are anticipated in crop suitability are shown in green. Areas of declining climatic suitability for restricted range birds are shown in blue. Overlap of declining crop suitability and declining restricted range bird climatic suitability is shown in red.(TIF)Click here for additional data file.Figure S5Global map of crop suitability and suitability for range restricted birds change in 2050/2090 under B1 emission scenario using mean of 5 GCMs.Areas in which overall decreases are anticipated in crop suitability are shown in green. Areas of declining climatic suitability for restricted range birds are shown in blue. Overlap of declining crop suitability and declining restricted range bird climatic suitability is shown in red.(TIF)Click here for additional data file.Figure S6Global map of crop suitability and suitability for range restricted birds change in 2090 under A2 emission scenario using 6 Species Distribution Model results.Areas in which overall decreases are anticipated in crop suitability are shown in green, with increasing color intensity indicating multiple GCM agreement. Areas of declining climatic suitability for restricted range birds are shown in blue, with increasing color intensity indicating multiple GCM agreement. Overlap of declining crop suitability and declining restricted range bird climatic suitability is shown in shades of yellow (lowest GCM agreement) to red (highest GCM agreement).(TIF)Click here for additional data file.


Stress myocardial perfusion MRI allows for accurate detection of flow-limiting stenosis in the coronary artery. However, reduced diagnostic accuracy of stress myocardial perfusion MRI was reported in patients with coronary artery bypass grafts (CABG). Flow measurement in CABG is another MR approach that permits functional assessment of graft stenosis. The purpose of this study was to evaluate the value of MR study that combines MR flow measurement of CABG and stress myocardial perfusion MRI in detecting graft stenosis.Thirty-two consecutive patients  with previous CABG surgery who had recurrent chest pain were studied. All patients gave informed consent and underwent both coronary angiography and cardiac MRI. After obtaining cine MRI, stress-rest myocardial perfusion MRI and late gadolinium enhanced (LGE) MRI, blood flow volume in the resting state was quantified in 61 graft conduits by using phase contrast cine MRI. The presence or absence of myocardial ischemia was visually determined by identifying stress-induced hypoenhancement in the absence of LGE or hypoenhancement larger than LGE. Stenoses ≥70% in grafts or grafted native vessels were considered significant on coronary angiography.Coronary angiography revealed significant stenoses in the grafts or grafted native vessels in 19 (31%) of the 61 CABG conduits. Stress-rest perfusion CMR alone yielded the sensitivity and specificity of 73% and 81%, respectively. Receiver operating characteristic analysis demonstrated that the optimal cutoff values of MR blood flow volume was 28mL/min for predicting significant stenosis on angiography . By combining MR blood flow measurement and stress-rest perfusion MRI, the sensitivity and specificity of MR study were improved to 95% and 81%.MR flow measurement of CABG combined with stress-rest perfusion MRI can provide excellent diagnostic accuracy for predicting significant stenoses in the grafts or grafted native vessels in patients with previous CABG.Departmental reseach funding.


Previously proposed panels of liver fibrosis usually include 2 to 7 blood markers. The majority of publications were concerned with liver fibrosis among patients with chronic hepatitis C (CHC). However, few studies have assessed drug-mediated liver fibrogenesis, non-alcoholic fatty liver disease (NAFLD), Schistosoma mansoni-induced liver fibrosis, and hepatitis B virus-related liver fibrosis. In the work entitled "Noninvasive assessment of liver fibrosis with the aspartate transaminase to platelet ratio index (APRI): Usefulness in patients with chronic liver disease," authors The authors came to the conclusion that APRI was significantly associated with fibrosis score in patients with CHC and NAFLD, but not in patients with CHB. However, some reports showed a significant correlation between fibrosis scores and APRI in Chinese  and KoreConsequently, studies that investigate populations with etiologically different liver fibrosis may require the use of indices that involve direct fibrogenesis and/or oxidative stress markers, in addition to liver specific markers. The limited number of variables in APRI may minimize its potential in monitoring the basic events in scar formation, which is the common scenario in etiologically different fibrosis. However, the contradictory outcomes of different studies in the last few years may raise the question: Do we need a common liver fibrosis index or etiology-related indices?


This study is to evaluate the early results treatment of patients with total occlusion of the left main coronary artery. Total occlusion of the left main coronary artery is a very rare finding in patients with acute coronary syndrome. In these cases, patients present various clinical symptoms, however the symptoms and the survival of these patients depend on the development of collaterals and adequate medical intervention.Between January 2002 till May 2013, four patients with acute coronary syndrome caused by total occlusion of the left main coronary artery underwent emergent coronary artery bypass grafting(CABG). All patients presented chest pain, signs of cardiogenic shock with CK-MB level above100 ng/ml on admission. IABP was inserted and emergent PCI and consecutive surgery within 24 hrs were performed. One patient out of the four underwent on-pump beating heart CABG, the rest of the patients underwent classical CABG with induced cardiac arrest using blood cardioplegia with maintained normothermia. Early postoperativeevaluation was performed in terms of: ejection fraction, bleedings, CK-MB level and deaths.Three patients, who underwent classical CABG with induced cardiac arrest using blood cardioplegia with maintained normothermia, survived, whereas patient who underwent on-pump beating heart CABG died in the post-operative period due to hemodynamic failure with an ineffective response to reanimation.It is very difficult to treat such patients with acute coronary syndrome complicated with cardiogenic shock caused by total occlusion of left main coronary artery. Such patients could develop massive myocardial infarction and should be treated immediately with emergent PCI, IABP and emergent CABG within 24 hours.On-pump beating heart CABG is possible in these patients, however we recommend treating such highly risky patients by CABG with induced cardiac arrest using blood cardioplegia with maintained normothermia.


Lupus nephritis belongs to the most serious organ involvements in juvenile systemic lupus erythematosus (SLE) and its adequate treatment is crucial for the prognosis of the disease. The intensity of the treatment should be determined by the kidney biopsy findings scored by the WHO or ISN/RPS classifications. Considering the benefits and risks of the kidney biopsy, some authors have suggested indications for its performance in lupus nephritis based on clinical manifestations comprising significant proteinuria, haematuria with proteinuria, presence of cellular casts and elevated serum creatinine. However, many studies have revealed notable discrepancies between the clinical signs and biopsy findings. Thus, performing kidney biopsy especially in a juvenile SLE patient with no clinical signs of renal disease remains controversial.To emphasize the role of renal biopsy in patients with juvenile SLE with normal clinical kidney manifestations.A case report of a patient diagnosed and treated in a pediatric rheumatology centre in multidisciplinary collaboration.A thirteen-year-old boy presented with arthritis and pleural effusion. His laboratory tests showed elevated ESR, anemia, leukopenia, decreased C3 and C4, positive ANA and anti-dsDNA. Despite normal urine sediment, creatinine clearence and no proteinuria, kidney biopsy was performed and revealed diffuse proliferative lupus glomerulonephritis class IV-S(A) according to the ISN/RPS 2003 classification. In the next course Libman-Sacks endocarditis occurred. With diagnose of juvenile SLE with severe kidney involvement the patient was treated with corticosteroids and intravenous cyclophosphamide followed by azathioprine, which was later switched to cyclosporine A, subsequently in combination with mycophenolate mofetil. Despite the serious course of the disease urine analysis and creatinine clearence remained normal for the whole period.Based on our experience with a patient with juvenile SLE with severe lupus nephritis despite their normal urine analysis and creatinine level, in accordance with some other authors, we recommend performing kidney biopsy in newly diagnosed juvenile SLE patients unless the risk to benefit ratio of the procedure is very high.