Label/quencher-free detection of single-nucleotide changes in DNA using isothermal amplification and G-quadruplexes

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C6AN01600F, Communication

Il Joon Lee, Nam-In Goo, Dong-Eun Kim
We report a analytical method that exploits the interaction between G-quadruplexes and thioflavin T (ThT), for detecting mutant DNA species containing single-base changes. This system is a label/quencher-free fluorescent enhancement...
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IJMS, Vol. 17, Pages 1806: Different Susceptibilities between Apoe- and Ldlr-Deficient Mice to Inflammation-Associated Colorectal Carcinogenesis

Hypercholesterolemia resulting in atherosclerosis is associated with an increased risk of ischemic heart disease and colorectal cancer (CRC). However, the roles of apoliprotein (Apo) E (Apoe) and low-density lipoprotein (Ldl) receptor (Ldlr) in colorectal carcinogenesis have not yet been investigated. In this study, we examined the susceptibility of Apoe-deficient and Ldlr-deficient mice, which are genetic animal models of atherosclerosis to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colorectal carcinogenesis. In Experiment 1, male Apoe-deficient (n = 20) and wild type (WT) mice (C57BL/6J, n = 21) were treated with a single intraperitoneal (i.p.) injection of AOM (10 mg/kg body weight) and then given 1.5% DSS in drinking water for seven days. They were maintained up to week 20 and sacrificed for the histopathological examination of colorectal tumors. The mRNA expression of cyclooxygenase (Cox)-2, inducible nitric oxide synthase (Nos2), tumor necrosis factor (Tnf)-α interleukin (Il)-1β, and Il-6 was assayed in the colorectal mucosa. In Experiment 2, male Ldlr-deficient (n = 14) and WT mice (C57BL/6J, n = 10) were given a single i.p. injection of AOM (10 mg/kg body weight) and then given 2% DSS in drinking water for seven days. They were sacrificed at week 20 to evaluate their colorectum histopathologically. In Experiment 1, the multiplicity of CRCs was significantly higher in the Apoe-deficient mice (2.75 ± 1.48) than in the WT mice (0.62 ± 0.67). The serum lipoprotein levels in the Apoe-deficient mice were also significantly higher than in the WT mice. In Experiment 2, the incidence (29%) and multiplicity (0.50 ± 0.94) of CRCs in the Ldlr mice were significantly lower than in the WT mice (80% incidence and 3.10 ± 2.38 multiplicity). The mRNA expression of two inducible enzymes and certain pro-inflammatory cytokines in the colorectum of each genotype was greater than in the respective WT mice. The values in the Apoe-deficient mice were much greater than in the Ldlr mice. These findings suggest that Apoe-deficient mice showed increased susceptibility to inflammation-associated colorectal carcinogenesis due to their high reactivity to inflammatory stimuli.

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IJMS, Vol. 17, Pages 1805: Peculiarities of the Super-Folder GFP Folding in a Crowded Milieu

The natural cellular milieu is crowded by large quantities of various biological macromolecules. This complex environment is characterized by a limited amount of unoccupied space, limited amounts of free water, and changed solvent properties. Obviously, such a tightly packed cellular environment is poorly mimicked by traditional physiological conditions, where low concentrations of a protein of interest are analyzed in slightly salted aqueous solutions. An alternative is given by the use of a model crowded milieu, where a protein of interest is immersed in a solution containing high concentrations of various polymers that serve as model crowding agents. An expected outcome of the presence of such macromolecular crowding agents is their ability to increase conformational stability of a globular protein due to the excluded volume effects. In line with this hypothesis, the behavior of a query protein should be affected by the hydrodynamic size and concentration of an inert crowder (i.e., an agent that does not interact with the protein), whereas the chemical nature of a macromolecular crowder should not play a role in its ability to modulate conformational properties. In this study, the effects of different crowding agents (polyethylene glycols (PEGs) of various molecular masses (PEG-600, PEG-8000, and PEG-12000), Dextran-70, and Ficoll-70) on the spectral properties and unfolding–refolding processes of the super-folder green fluorescent protein (sfGFP) were investigated. sfGFP is differently affected by different crowders, suggesting that, in addition to the expected excluded volume effects, there are some changes in the solvent properties.

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IJMS, Vol. 17, Pages 1804: AQP2 Plasma Membrane Diffusion Is Altered by the Degree of AQP2-S256 Phosphorylation

Fine tuning of urine concentration occurs in the renal collecting duct in response to circulating levels of arginine vasopressin (AVP). AVP stimulates intracellular cAMP production, which mediates exocytosis of sub-apical vesicles containing the water channel aquaporin-2 (AQP2). Protein Kinase A (PKA) phosphorylates AQP2 on serine-256 (S256), which triggers plasma membrane accumulation of AQP2. This mediates insertion of AQP2 into the apical plasma membrane, increasing water permeability of the collecting duct. AQP2 is a homo-tetramer. When S256 on all four monomers is changed to the phosphomimic aspartic acid (S256D), AQP2-S256D localizes to the plasma membrane and internalization is decreased. In contrast, when S256 is mutated to alanine (S256A) to mimic non-phosphorylated AQP2, AQP2-S256A localizes to intracellular vesicles as well as the plasma membrane, with increased internalization from the plasma membrane. S256 phosphorylation is not necessary for exocytosis and dephosphorylation is not necessary for endocytosis, however, the degree of S256 phosphorylation is hypothesized to regulate the kinetics of AQP2 endocytosis and thus, retention time in the plasma membrane. Using k-space Image Correlation Spectroscopy (kICS), we determined how the number of phosphorylated to non-phosphorylated S256 monomers in the AQP2 tetramer affects diffusion speed of AQP2 in the plasma membrane. When all four monomers mimicked constitutive phosphorylation (AQP2-S256D), diffusion was faster than when all four were non-phosphorylated (AQP2-S256A). AQP2-WT diffused at a speed similar to that of AQP2-S256D. When an average of two or three monomers in the tetramer were constitutively phosphorylated, the average diffusion coefficients were not significantly different to that of AQP2-S256D. However, when only one monomer was phosphorylated, diffusion was slower and similar to AQP2-S256A. Thus, AQP2 with two to four phosphorylated monomers has faster plasma membrane kinetics, than the tetramer which contains just one or no phosphorylated monomers. This difference in diffusion rate may reflect behavior of AQP2 tetramers destined for either plasma membrane retention or endocytosis.

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IJMS, Vol. 17, Pages 1808: PPIC, EMP3 and CHI3L1 Are Novel Prognostic Markers for High Grade Glioma

Current treatment methods for patients diagnosed with gliomas have shown limited success. This is partly due to the lack of prognostic genes available to accurately predict disease outcomes. The aim of this study was to investigate novel prognostic genes based on the molecular profile of tumor samples and their correlation with clinical parameters. In the current study, microarray data (GSE4412 and GSE7696) downloaded from Gene Expression Omnibus were used to identify differentially expressed prognostic genes (DEPGs) by significant analysis of microarray (SAM) between long-term survivors (>2 years) and short-term survivors (≤2 years). DEPGs generated from these two datasets were intersected to obtain a list of common DEPGs. The expression of a subset of common DEPGs was then independently validated by real-time reverse transcription quantitative PCR (qPCR). Survival value of the common DEPGs was validated using known survival data from the GSE4412 and TCGA dataset. After intersecting DEPGs generated from the above two datasets, three genes were identified which may potentially be used to determine glioma patient prognosis. Independent validation with glioma patients tissue (n = 70) and normal brain tissue (n = 19) found PPIC, EMP3 and CHI3L1 were up-regulated in glioma tissue. Survival value validation showed that the three genes correlated with patient survival by Kaplan-Meir analysis, including grades, age and therapy.

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Simple and Specific Grafting of Antibacterial Peptides on Silicone Catheters

To fight against nosocomial infection initiated by colonization of medical devices, a strategy enabling the direct and fast functionalization of silicone surfaces is proposed. This strategy proceeds in a site-specific way using original hybrid silylated antibacterial peptides. This safe and up-scalable method guarantees a covalent and robust immobilization with the correct orientation of the bioactive moiety. Importantly it also avoids multi-step chemical modifications of the surface or multi-layer polymer coatings. As proof of concept, antibacterial silicone catheter has been prepared whose immediate and long term efficiency is superior by comparison to similar silver-embedded materials.

A strategy enabling the direct and fast functionalization of silicone surfaces with antibacterial peptides is developed. Thanks to hybrid silylated bioactive molecules, no multi step surface modifications or polymer coating are required. Antibacterial silicone catheters are obtained and proved to be more efficient than commercially available silver-embedded devices.

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Morphology of the canine omentum, part 1: arterial landmarks that define the omentum

Although the omentum remains an enigmatic organ, research during the last decades has revealed its fascinating functions including fat storage, fluid drainage, immune activity, angiogenesis and adhesion. While clinicians both in human and veterinary medicine are continuously exploring new potential omental applications, detailed anatomical data on the canine omentum are currently lacking, and information is often retrieved from human medicine. In this study, the topographic anatomy of the canine greater and lesser omentum is explored in depth. Current nomenclature is challenged, and a more detailed terminology is proposed. Consistent arteries that are contained within folds of the superficial omental wall are documented, described and named, as they can provide the anatomical landmarks that are necessary for unambiguous scientific communication on the canine omentum. In an included dissection video, the conclusions and in situ findings described in this study are demonstrated.

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Morphology of the canine omentum, part 2: the omental bursa and its compartments materialized and explored by a novel technique

The canine omental bursa is a virtual cavity enclosed by the greater and lesser omentum. While previous representations of this bursa were always purely schematic, a novel casting technique was developed to depict the three-dimensional organization of the omental bursa more consistently. A self-expanding polyurethane-based foam was injected into the omental bursa through the omental foramen in six dogs. After curing and the subsequent maceration of the surrounded tissues, the obtained three-dimensional casts could clearly and in a reproducible way reveal the omental vestibule, its caudal recess and the three compartments of the splenic recess. The cast proved to be an invaluable study tool to identify the landmarks that define the enveloping omentum. In addition, the polyurethane material can easily be discerned on computed tomographic images. When the casting technique is preceded by vascular injections, the blood vessels that supply the omentum can be outlined as well.

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Cell type-specific differences in β-glucan recognition and signalling in porcine innate immune cells

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Assessing disability weights based on the responses of 30,660 people from four European countries

Background: In calculations of burden of disease using disability-adjusted life years, disability weights are needed to quantify health losses relating to non-fatal outcomes, expressed as years lived with disability. In 2012 a new set of global disability weights was published for the Global Burden of Disease 2010 (GBD 2010) study. That study suggested that comparative assessments of different health outcomes are broadly similar across settings, but the significance of this conclusion has been debated. The aim of the present study was to estimate disability weights for Europe for a set of 255 health states, including 43 new health states, by replicating the GBD 2010 Disability Weights Measurement study among representative population samples from four European countries. Methods: For the assessment of disability weights for Europe we applied the GBD 2010 disability weights measurement approach in web-based sample surveys in Hungary, Italy, Netherlands, and Sweden. The survey included paired comparisons (PC) and population health equivalence questions (PHE) formulated as discrete choices. Probit regression analysis was used to estimate cardinal values from PC responses. To locate results onto the 0-to-1 disability weight scale, we assessed the feasibility of using the GBD 2010 scaling approach based on PHE questions, as well as an alternative approach using non-parametric regression. Results: In total, 30,660 respondents participated in the survey. Comparison of the probit regression results from the PC responses for each country indicated high linear correlations between countries. The PHE data had high levels of measurement error in these general population samples, which compromises the ability to infer ratio-scaled values from discrete choice responses. Using the non-parametric regression approach as an alternative rescaling procedure, the set of disability weights were bounded by distance vision mild impairment and anemia with the lowest weight (0.004) and severe multiple sclerosis with the highest weight (0.677). Conclusions: PC assessments of health outcomes in this study resulted in estimates that were highly correlated across four European countries. Assessment of the feasibility of rescaling based on a discrete choice formulation of the PHE question indicated that this approach may not be suitable for use in a web-based survey of the general population.

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The low global burden of trichinellosis: evidence and implications

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Data-driven methods for imputing national-level incidence in global burden of disease studies

Objective: To develop transparent and reproducible methods for imputing missing data on disease incidence at national-level for the year 2005. Methods: We compared several models for imputing missing country-level incidence rates for two foodborne diseases – congenital toxoplasmosis and aflatoxin-related hepatocellular carcinoma. Missing values were assumed to be missing at random. Predictor variables were selected using least absolute shrinkage and selection operator regression. We compared the predictive performance of naive extrapolation approaches and Bayesian random and mixed-effects regression models. Leave-one-out cross-validation was used to evaluate model accuracy. Findings: The predictive accuracy of the Bayesian mixed-effects models was significantly better than that of the naive extrapolation method for one of the two disease models. However, Bayesian mixed-effects models produced wider prediction intervals for both data sets. Conclusion: Several approaches are available for imputing missing data at national level. Strengths of a hierarchical regression approach for this type of task are the ability to derive estimates from other similar countries, transparency, computational efficiency and ease of interpretation. The inclusion of informative covariates may improve model performance, but results should be appraised carefully.

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Isolation and seroprevalence of Aeromonas spp. among common food animals slaughtered in Nagpur, Central India

Aeromonads are ubiquitous foodborne pathogens with a global distribution. Animal-origin foods and contaminated animals are the main sources of Aeromonas infection to humans. So far little is known about the occurrence of Aeromonas spp. in food-producing animals in India. The present study was conducted to determine the prevalence and seroprevalence of Aeromonas species from 50 each of meat, blood, and sera samples collected from cattle, buffaloes, goats, and pigs slaughtered in and around Nagpur, Central India. Alkaline peptone water and ampicillin dextrin agar were used to isolate Aeromonas spp. An indirect enzyme-linked immunosorbent assay (ELISA) was standardized by use of whole-cell antigen (WC) and outer membrane protein (OMP) of Aeromonas hydrophila (MTCC 646). Aeromonads were isolated from 44 (22%) of the meat samples, and 1 (0.5%) from the blood samples. Seroprevalence by indirect ELISA-based WC antigen was estimated as 68% in cattle, 44% in buffaloes, 60% in goats, and 30% in pigs. OMP-based ELISA yielded a seroprevalence of 56%, 48%, 52%, and 22% in cattle, buffaloes, goats, and pigs, respectively. The results revealed that OMP-based ELISA and WC-based ELISA were in agreement with one another. Isolation along with high seropositivity demonstrates the presence of foodborne Aeromonas spp. in the Nagpur city of Central India.

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Identification of a human intestinal myeloid cell subset that regulates gut homeostasis

Inappropriate activation of T helper (Th) cells, such as Th1 and Th17 cells, is implicated in the pathogenesis of chronic inflammatory disorders including ulcerative colitis (UC). CX₃CR1^high macrophages contribute to intestinal homeostasis through various mechanisms in mice. However, whether mononuclear phagocytes with regulatory functions are present in the human colon is not clearly defined. We investigated whether innate myeloid cells that suppress activation of effector T cells exist in the human intestinal mucosa. Among intestinal lamina propria cells, Lin^– HLA-DR^high CD14⁺ CD163^high cells were subdivided into CD160^low and CD160^high cells. Both subsets produced high levels of IL-10. CD163^high CD160^high cells suppressed effector T cell proliferation, whereas CD163^high CD160^low cells induced Th17 differentiation. Patients with UC exhibited increased numbers of CD163^high CD160^low cells, while showing profoundly decreased numbers of CD163^high CD160^high cells. In this context, CD163^high CD160^high cells had higher CD80/CD86 expression and lower IL10RB expression, and these cells did not suppress effector T cell proliferation. The CD163^high CD160^high subset in normal intestinal mucosa inhibits inappropriate Th1/Th17 responses through suppression of their proliferation, and its number and suppressive activity are impaired in patients with UC. These findings indicate how human innate immune cells might prevent UC development.

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Antibody-secreting cells in respiratory tract tissues in the absence of eosinophils as supportive partners

Antibody-secreting cells (ASCs) in respiratory tract tissues provide a first line of defense against invading pathogens. These cells often secrete IgA that is efficiently transcytosed across epithelial barriers into the airway lumen where pathogens can be blocked at their point of entry. Previous literature has reported that in the bone marrow, eosinophils are required for the maintenance of ASCs, and that eosinophils co-localize with ASCs as nearest neighbors. To determine if these rules similarly apply to the maintenance of ASCs in respiratory tract tissues, we evaluated virus-specific responses 1 month and 4 months following an intranasal virus infection of eosinophil-null (dblGATA-1) mice. Results showed that ASCs were fractionally reduced, but were nonetheless observed in respiratory tract tissues in the absence of eosinophils. Virus-specific antibodies were similarly observed in the airways of eosinophil-deficient mice. Respiratory tract ASCs were also present in mice lacking neutrophils (Mcl1^M). The staining of tissue sections from the upper respiratory tract of wild-type mice following viral infections demonstrated that virus-specific ASCs were most frequently situated adjacent to epithelial cells rather than eosinophils or neutrophils. Taken together, these data emphasize that rules for cell maintenance are not absolute and that ASCs can survive in the respiratory tract without eosinophils or neutrophils as their nearest neighbors.

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Table of Contents

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Phenotype, proliferation and apoptosis of B lymphocytes in hemodialysis patients treated with recombinant human erythropoietin

One of the major causes of disorders of the immune response in patients undergoing hemodialysis (HD) is weaker activity of their helper T lymphocytes (T_h cells), mainly reduced proliferative capacity associated with decreased expression of key surface antigens. Since cooperation between T_h and B lymphocytes is essential for B cell function, changes in T_h cell phenotype and ability to proliferate or produce cytokines could directly translate into an impaired humoral response. Therefore, we investigated the T cell-dependent activity of B cells in HD patients focusing mainly on their proliferative kinetics, susceptibility to apoptosis and the ability to produce antibodies. Since our previous studies have shown the beneficial effects of recombinant human erythropoietin (rhEPO) on T lymphocytes, we also investigated the in vivo and in vitro influence of rhEPO on B cells. Our results show that B lymphocytes of HD patients, especially of those who are not treated with rhEPO, have reduced proliferative capacity in vitro, reflected in low number of cell divisions, decreased percentage of proliferating cells and an increased susceptibility to apoptosis. They are also characterized by impaired ability to produce immunoglobulins. We have found no significant changes in the expression of key antigens of B lymphocytes with the exception of IL-10R. Furthermore, we demonstrated a time- and health status-dependent impact of rhEPO on patient's B cells. Our results show possible mechanisms responsible for the deficiency of humoral responses in HD patients which, at least partially, can be modulated through the supplementation with rhEPO.

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In This Issue

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Cell cycle arrest caused by MEK/ERK signaling is a mechanism for suppressing growth of antigen-hyperstimulated effector T cells

Suppression of T-cell growth is an important mechanism for establishment of self-tolerance and prevention of unwanted prolonged immune responses that may cause tissue damage. Although negative selection of potentially self-reactive T cells in the thymus as well as in peripheral tissues has been extensively investigated and well documented, regulatory mechanisms to dampen proliferation of antigen-specific effector T cells in response to antigen stimulation remain largely unknown. Thus, in this work, we focus on the identification of growth suppression mechanisms of antigen-specific effector T cells. In order to address this issue, we investigated the cellular and molecular events in growth suppression of an ovalbumin (OVA)-specific T-cell clone after stimulation with a wide range of OVA-peptide concentrations. We observed that while an optimal dose of peptide leads to cell cycle progression and proliferation, higher doses of peptide reduced cell growth, a phenomenon that was previously termed high-dose suppression. Our analysis of this phenomenon indicated that high-dose suppression is a consequence of cell cycle arrest, but not Fas–Fas ligand-dependent apoptosis or T-cell anergy, and that this growth arrest occurs in S phase, accompanied by reduced expression of CDK2 and cyclin A. Importantly, inhibition of MEK/ERK activation eliminated this growth suppression and cell cycle arrest, while it reduced the proliferative response to optimal antigenic stimulation. These results suggest that cell cycle arrest is the major mechanism regulating antigen-specific effector T-cell expansion, and that the MEK/ERK signaling pathway has both positive and negative effects, depending on the strength of antigenic stimulation.

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Important Announcement

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STAT4 is required for the generation of Th1 and Th2, but not Th17 immune responses during monophosphoryl lipid A adjuvant activity

STAT4 is critical for the production of IFN- during the generation of T_h1 immune responses. We investigated the role of STAT4 in mediating T_h1-inducing activity of a vaccine adjuvant monophosphoryl lipid A (MPL-A) using the standard antigen ovalbumin (OVA) in STAT4KO mice. Our results show that splenocytes from STAT4KO mice displayed lower OVA-specific T-cell proliferation and IL-2 production compared with wild-type (WT) mice. Further, IFN- production was diminished in STAT4KO-derived splenocytes but the levels of IL-12 and TNF-α were similar compared with WT mice. Interestingly, STAT4 deficiency also led to a decrease in IL-10 and T_h2 cytokines such as IL-4 and IL-13 upon MPL-A immunization, although IL-17 production was similar between WT- and STAT4KO-derived splenocytes. Our observations for defective T_h1 and T_h2 responses in STAT4KO mice were further supported by the low levels of T_h1-associated IgG2a and T_h2-associated IgG1 in the sera of these mice. Taken together, our results show that STAT4 plays a critical role in mediating both T_h1 and T_h2 responses upon immunization with MPL-A. Our study provides a better understanding of how MPL-A mediates T-cell activation which will be critical for future vaccine development.

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Left retrocaval ureter around the ipsilateral limb of a double caudal vena cava in a cat

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Plasma serotonin in horses undergoing surgery for small intestinal colic

This study compared serotonin concentrations in platelet poor plasma (PPP) from healthy horses and horses with surgical small intestinal (SI) colic, and evaluated their association with postoperative ileus, strangulation and non-survival. Plasma samples (with EDTA) from 33 horses with surgical SI colic were collected at several pre- and post-operative time points. Serotonin concentrations were determined using liquid-chromatography tandem mass spectrometry. Results were compared with those for 24 healthy control animals. The serotonin concentrations in PPP were sighificantly lower (P < 0.01) in pre- and post-operative samples from surgical SI colic horses compared to controls. However, no association with postoperative ileus or non-survival could be demonstrated at any time point. In this clinical study, plasma serotonin was not a suitable prognostic factor in horses with SI surgical colic.

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Development of the human infrahepatic inferior caval and azygos venous systems

Differences in opinion regarding the development of the infrahepatic inferior caval and azygos venous systems in mammals centre on the contributions of 'caudal cardinal', 'subcardinal', 'supracardinal', 'medial and lateral sympathetic line' and 'sacrocardinal' veins. The disagreements appear to arise from the use of topographical position rather than developmental origin as criterion to define separate venous systems. We reinvestigated the issue in a closely spaced series of human embryos between 4 and 10 weeks of development. Structures were visualized with the Amira reconstruction and Cinema4D remodelling software. The vertebral level and neighbouring structures were used as topographic landmarks. The main results were that the caudal cardinal veins extended caudally from the common cardinal vein between CS11 and CS15, followed by the development of the subcardinal veins as a plexus sprouting ventrally from the caudal cardinal veins. The caudal cardinal veins adapted their course from lateral to medial relative to the laterally expanding lungs, adrenal glands, definitive kidneys, sympathetic trunk and umbilical arteries between CS15 and CS18, and then became interrupted in the part overlaying the regressing mesonephroi (Th12-L3). The caudal part of the left caudal cardinal vein then also regressed. The infrarenal part of the inferior caval vein originated from the right caudal cardinal vein, while the renal part originated from subcardinal veins. The azygos veins developed from the remaining cranial part of the caudal cardinal veins. Our data show that all parts of the inferior caval and azygos venous systems developed directly from the caudal cardinal veins or from a plexus sprouting from these veins.

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Enantioselective pharmacokinetics of ketoprofen in calves after intramuscular administration of a racemic mixture

The pharmacokinetic properties of ketoprofen were determined in 4-week-old calves after intramuscular (IM) injection of a racemic mixture at a dose of 3 mg/kg body weight. Due to possible enantioselective disposition kinetics and chiral inversion, the plasma concentrations of the R(‒) and S(+) enantiomer were quantified separately, using a stereospecific HPLC-UV assay. A distinct predominance of the S(+) enantiomer was observed, as well as significantly different pharmacokinetic parameters between R(‒) and S(+) ketoprofen. More in specific, a greater value for the mean area under the plasma concentration-time curve (AUC0→∞) (46.92 ± 7.75 and 11.13 ± 2.18 µg.h/mL for the S(+) and R(‒) enantiomer, respectively), a lower apparent clearance (Cl/F) (32.8 ± 5.7 and 139.0 ± 25.1 mL/h.kg for the S(+) and R(‒) enantiomer, respectively) and a lower apparent volume of distribution (Vd/F) (139 ± 14.7 and 496 ± 139.4 mL/kg for the S(+) and R(‒) enantiomer, respectively) were calculated for the S(+) enantiomer, indicating enantioselective pharmacokinetics for ketoprofen in calves following IM administration.

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Embryonale Bauchtumoren im Kindes- und Jugendalter

Zusammenfassung

Hintergrund

Insbesondere im Kleinkindesalter stellen die embryonalen Tumoren Neuroblastom, Nephroblastom und Hepatoblastom eine wichtige Differenzialdiagnose bei Raumforderungen im Bauchraum dar. Aufgrund einer oft nur diskreten und unspezifischen Symptomatik ist der Anteil an Zufallsdiagnosen relativ hoch.

Diagnostik, Therapie und Prognose

Die Diagnostik umfasst die Bestimmung spezifischer Tumormarker, definierte Staginguntersuchungen mit bildgebender Diagnostik sowie histologische und molekulare Analysen des Tumorgewebes. Diagnostik und Therapie erfolgen ausschließlich in spezialisierten kinderonkologischen Zentren mit multidisziplinärer Expertise im Rahmen definierter Therapieoptimierungsstudien. Während die Prognose bei Nephroblastomen und Hepatoblastomen auch im metastasierten Stadium noch sehr gut ist, liegt die Überlebensrate metastasierter Neuroblastome bei <40 %.

Schlussfolgerung

Die Anwendung moderner Sequenziertechnologien erlaubt eine zunehmend präzisere Tumorklassifikation und Prognosevorhersage durch charakteristische molekulare Muster und die rationale Auswahl experimenteller Therapien in der Rezidivsituation.

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Maxillofacial Infections of Odontogenic Origin: Epidemiological, Microbiological and Therapeutic Factors in an Indian Population

Abstract

Odontogenic fascial space infections are commonly encountered by the oral and maxillofacial surgeon. A retrospective study of the epidemiological characteristics, microbiological analysis and treatment response to odontogenic infections treated in the oral and maxillofacial unit of a Dental school is presented. A retrospective analysis of case records of all odontogenic infections that reported to the oral and maxillofacial surgery unit in a Dental school over a period of 2 years was performed. Epidemiological data, microbiological profile and treatment responses were analysed. All data were subjected to statistical analysis using SPSS statistical package. Mann–Whitney U test, Kruskal–Wallis test and nonparametric tests were carried out. A total of 2,140 patients were included in this study. Mandibular third molars were the offending tooth in nearly 40 % of cases with 107 patients becoming symptomatic following a dental extraction procedure. All patients were treated with surgical incision and drainage, antibiotics and local wound care. More than 95 % cases needed intraoral incisions. Penicillin was the drug in most of the cases. The pterygomandibular space was the most commonly involved with 15 % reporting with multiple fascial space involvement. Microbiological analysis showed a predominance of aerobic gram positive organisms with Streptococcus sanguis most commonly isolated. Peptostreptococci and Propionibacterium were the common anaerobes isolated. More than 80 % of the strains isolated were sensitive to penicillin. The average length of stay was 6.3 days. Inadequate documentation with regards to referral patterns, antibiotic history was commonly observed in case records. Penicillin continues to remain the drug of choice for a vast majority of maxillofacial infections of odontogenic origin. A delay in reporting can lead to worsening of symptoms with consequent increase in surgical morbidity and costs of treatment. Preventive dental care remains the best option available to mitigate the consequences of poor oral hygiene. Poor awareness among patient population for regular dental reviews and oral hygiene maintenance emphasises the need for sensitisation and education programs.

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A Clinico-Pathological Study of Cervical Lymph Nodes

Abstract

Cervical lymphadenopathy is one of the commonest presenting complaint of patient in ENT OPD Fine Needle Aspiration Cytology (FNAC) is one of the most reliable, less expensive, and basic diagnostic procedure for the definitive and conclusive diagnosis for the immune system which reciprocates in the form of enlarged lymph nodes. A study was conducted in ENT Department of Santosh Medical College, Ghazibad from August 2015 to May 2016 on 64 patients with enlarged cervical lymph nodes. FNAC was done to make the diagnosis. Out of 64 patients (51.5 %) was reactive non-specific, 28 % tubercular, 3.1 % lymphoma and 17 % were malignant. FNAC is one of the most dependable diagnostic tools in case of cervical lymphadenopathy for early diagnosis and detection for the better management.

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Hemodynamic Effects of Topical Adrenaline During Septoplasty

Abstract

Vasoconstrictors agents is used in septal surgery, in attempt to improve haemostasis and thereby improve the surgical field. We aimed to compare the effect of lignocaine with adrenaline injection and alone lignocaine injection with topical adrenalin on perioperative hemodynamic effect, hemorrhage and postoperative pain. Patients undergoing surgery were randomised into two groups: group I in whom infiltration was performed with lignocaine (2 %) with adrenaline (1:100,000), group II in whom infiltration was performed with lignocaine (2 %) injection with topical adrenalin application (1:10,000). The two groups were matched by age, sex, body weight, pre-anesthesia blood pressure, heart rate, oxygen pressure and hemorrhage. The hemostatic effects postoperative pain in each group were analyzed. No statistically significant differences in operation time, hemodynamic effect, and intraoperative blood loss were reached between the two groups of patients (p > 0.05). But also group I had significantly better pain scores versus control group in the 2nd, 4th, 6th postoperative hours (p < 0.05). We suggest that the use of adrenaline infiltration during septal surgery is unnecessary and may subject the patient to the risk of cardiogenic side-effects of systemic absorption.

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Timing for Removal of Asymptomatic Long-Term Ventilation Tube in Children

Abstract

Otitis media with effusion (OME) is the most frequent illness in children. Surgical treatment options include ventilation tube insertion, adenoidectomy or both. Opinions regarding the risks, benefits and intubation period of ventilation tube insertion vary greatly. To determine the appropriate time for when to remove asymptomatic longterm ventilation T-tubes in children. In this prospective study, we analyzed the results of 120 pediatric patients (6–12 years) (240 ears) with persistent OME; we employed the Goode T-silicone tubes. We intentionally planned to remove the tubes at different time points of the study and divided our patients randomly into four subgroups with 30 patents (60 ears in each) according to the intubation period; group I: intubation for 6 months, group II: intubation for 12 months, group III: intubation for 18 months and group IV: intubation for 24 months. The relationship between intubation period and OME recurrence, the rate of persistent tympanic membrane (TM) perforation, granulation tissue or discharge near the tympanostomy tubes, normalization of Eustachian tube function and change of hearing level was analyzed in each patient group. The χ² analysis showed that the rate of normalization of ET function was significantly higher when tubes were removed after 12-months of intubation (P = 0.002), the rate of OME recurrence was significantly higher when tubes were removed before 12-months of intubation (P = 0.004), The rate of otorrhea significantly increased after 12-months of intubation, development of granulation around tubes was significantly higher after 18-months of tube insertion. The rate of appearance of permanent TM perforation significantly increased after 18-months from tube insertion (P = 0.008). Adenoidectomy did not significantly influence the recurrence rate of OME or the rate of persistent TM peroration after tube removal. Our present results suggest that the appropriate intubation period for healing OME in children would be at 12–18 months. Also, we can conclude that longterm ventilation tubes are recommended to avoid repeated intubation and to obtain sufficient results, although their performance is not always satisfactory; mainly because of accompanying complications.

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Otological Manifestations of Nonseptic Lateral Sinus Thrombosis: A Review

Abstract

Nonseptic lateral sinus thrombosis differs from septic lateral sinus thrombosis in that it is not associated with ear or sinus infection. Etiologies of these conditions are different and management of these conditions are different. Nonseptic lateral sinus thrombosis requires medical line of management and anticoagulant therapy where as septic lateral sinus thrombosis treatment involves surgical exploration of the mastoid cavity, sinus decompression, and long-term antibiotic therapy. Mastoid changes are frequently detected on computed tomography or magnetic resonance imaging in cases of nonseptic lateral sinus thrombosis. An otolaryngologic evaluation is usually required to exclude coexisting mastoiditis. An otologist should be familiar with the septic lateral sinus thrombosis and existence of nonseptic variant lateral sinus thrombosis for early recognition and initiation of appropriate treatment.

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Development of a capillary electrophoretic method for determination of plasma clearance of iohexol in dogs and cats

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The quintessence of medical science and practice

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Extensive myelitis after oral polio vaccination: MRI features

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Personalized medicine in oncology, the potential role of nuclear medicine imaging

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Aneurysmal bone cyst of the proximal phalanx

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Mobitz type II second-degree atrioventricular block during dobutamine stress echocardiography: true or false?

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Central blood pressure and its amplification: a final breakthrough or do we need more?

Blood pressure is one of the cardinal risk factors for atherosclerosis and cardiovascular diseases. Systolic and diastolic blood pressures are measured at the level of the brachial artery, positioned at a midthoracic level with an adequately sized cuff and bladder. Treatment of arterial hypertension with lifestyle and drugs has become one of the cornerstones of contemporary cardiology. Subjects and patients should all have office blood pressures ,140/90 mmHg. Office blood pressure measurements have to be complemented by out-of-office measurements in order to rely on frequent rather than punctual measurements.1 These non-invasive cuff brachial pressures underestimate invasively measured blood pressures,2 but nevertheless are the firm ground of evidence-based medicine, while invasive pressures are not. During the last decades,we have witnessed important research on properties of the arterial tree and on distortion of the pressurewaveform from the central aorta to the brachial and radial artery. This distortion was attributed to wave travel and wave reflection.3 This explains why the radial pressure wave is much more peaked than the central aortic or carotid pressure wave, and has a higher systolic pressure. Overall, the minimum (diastolic) and mean blood pressure values change little from one location to the other. On this physiological basis, researchers compute central-to-peripheral pressure amplification and central systolic pressure.

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Interprofessional education for collaborative practice: views from a global forum workshop

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Developping an early warning system for bovine respiratory disease

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R. Webster and M. Lark, Field sampling for environmental science and management

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Thirty years of transgenic research in plants

In 1983, the first transgenic tissues and plants were generated by means of disarmed Agrobacterium tumefaciens strains, in which the oncogenes had been replaced by antibiotic resistance markers. Hence, this Special Issue of The International Journal of Developmental Biology celebrates 30 years of transgenic research in plants! Eminent scientists working in the field of plant transformation or plant biotechnology have contributed to this publication and reviewed the state of the art of their particular subdomain or summarized the importance of transgenic research in the discovery of new mechanisms and the establishment of an entirely new field, such as epigenetics.

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Moving plates and melting icecaps: processes and forcing factors in geology, 4th international Geologica Belgica meeting, September 11-14, 2012

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A Novel Examination of Successful Aging Trajectories at the End of Life

Cosco, TD; Stephan, BC; Muniz, G; Brayne, C; CC75C Study Collaboration, .; (2016) A Novel Examination of Successful Aging Trajectories at the End of Life. Canadian Journal on Aging / La Revue canadienne du vieillissement 10.1017/S0714980816000519 . (In press).

http://ift.tt/2eU3QIr

A joint theoretical-experimental approach to investigate the effects of low oxygen environments upon therapeutic cell viability and VEGF production

Coy, R; Kennedy, G; Kayal, C; O'Rourke, C; Kingham, P; Phillips, J; Shipley, RJ; (2016) A joint theoretical-experimental approach to investigate the effects of low oxygen environments upon therapeutic cell viability and VEGF production. In: European Cells and Materials - Volume No 31 - Supplement 1. (pp. p. 174). European Cells & Materials Ltd: Uppsala, Sweden. Green open access

http://ift.tt/2eCIdOh

A mathematical model with the capacity to direct and accelerate the design of cellular peripheral nerve repair conduits

Shipley, RJ; (2016) A mathematical model with the capacity to direct and accelerate the design of cellular peripheral nerve repair conduits. In: European Cells and Materials - Volume No 31 - Supplement 1. (pp. p. 159). European Cells & Materials Ltd: Uppsala, Sweden. Green open access

http://ift.tt/2eU8hmD

In vitro experiments to inform cell seeding strategies and parameterize a mathematical model for peripheral nerve repair

Kennedy, G; Coy, R; Kayal, C; O'Rourke, C; Kingham, P; Shipley, RJ; Phillips, J; (2016) In vitro experiments to inform cell seeding strategies and parameterize a mathematical model for peripheral nerve repair. In: European Cells and Materials - Volume No 32 - Supplement 4. (pp. p. 21). European Cells & Materials Ltd Green open access

http://ift.tt/2eCIC3a

Effect of collagen gel concentration gradients on neurite elongation

Kayal, C; Shipley, RJ; Phillips, J; (2016) Effect of collagen gel concentration gradients on neurite elongation. In: European Cells and Materials - Volume No 32 - Supplement 4. (pp. p. 83). European Cells & Materials Ltd Green open access

http://ift.tt/2eU3OAj