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Παρασκευή 3 Μαρτίου 2017

Effects of combined prokinetic administration on gastric emptying in critically ill patients

Publication date: Available online 3 March 2017
Source:Arab Journal of Gastroenterology
Author(s): Afshin Gholipour Baradari, Mohammad Reza Khajavi, Abolfazl Firouzian, Abbas Alipour, Hojatallah Daneshpour, Yunes Panahi, Amirhossein Sahebkar
Background and study aimsCombination of prokinetic drugs with different mechanisms of action is frequently used when feeding intolerance is not improved with a single agent. In this study, we evaluated the effect of combined infusion of neostigmine and metoclopramide on gastric passage in critically ill patients in the intensive care unit (ICU).Patients and methodsThis study is a randomized double-blind controlled trial in 90 patients between 20 and 60years of age who were under mechanical ventilation and had gastric residual volumes (GRVs) >120mL 3h after the last lavage. Patients were randomly assigned to one of the following three groups: intravenous neostigmine 2.5mg, intravenous metoclopramide 20mg, and combination of both agents at the mentioned doses. Gastric volume aspiration was first performed before starting the study and then at 3, 6, 9, and 12h after the infusion of study drugs was finished. Increase in gastric lavage was defined as an aspiration volume of >120mL.ResultsIn total, 86 cases in the three groups completed the treatment (all 90 patients included in the study were analysed according to an intention-to-treat approach). There was no significant difference detected at baseline in age, intubation duration, albumin, haemoglobin, haematocrit, total leucocytic count (WBC), Na, K, Mg, and sequential organ failure assessment score between the study groups. In the combination group, 96.7% of patients showed GRV improvement (GRV<120cc), whereas in the metoclopramide and neostigmine groups, 50% and 43.3% of the patients, respectively, showed improvement (p<0.001). The frequency of overall adverse effects in the metoclopramide, neostigmine, and combination groups were 3.3%, 16.7%, and 10%, respectively (p=0.28).ConclusionsThe present results suggested that combination therapy with metoclopramide and neostigmine decreases GRV in critically ill patients with a higher efficacy than monotherapies.



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Lichen scrofulosorum: importance of early recognition

Summary

Lichen scrofulosorum (LS), a tuberculid affecting children and young adults, usually presents with asymptomatic skin-coloured to erythematous follicular and perifollicular papules over the trunk and extremities. An underlying focus of tuberculosis can be detected, but occasionally other mycobacterial infections may be responsible. The eruption is associated with a positive tuberculin test or positive interferon-gamma release assay. Perifollicular granulomas and absence of bacilli are the histopathological characteristics. LS can go unsuspected because of its waxing and waning course and close resemblance to other dermatoses. This article reviews the different clinical presentations and various associations of LS. We reiterate that the focus of internal infection may be subtle and go undetected, emphasizing the need for correct diagnosis and early treatment.



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Visual acuity, oncologic, and toxicity outcomes with 103Pd vs. 125I plaque treatment for choroidal melanoma

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Publication date: Available online 3 March 2017
Source:Brachytherapy
Author(s): Kirtesh R. Patel, Roshan S. Prabhu, Jeffrey M. Switchenko, Mudit Chowdhary, Caroline Craven, Pia Mendoza, Hasan Danish, Hans E. Grossniklaus, Thomas M. Aaberg, Thomas Aaberg, Sahitya Reddy, Elizabeth Butker, Chris Bergstrom, Ian R. Crocker
PurposeTo evaluate outcomes of choroidal melanoma patients treated with 125I or 103Pd plaque brachytherapy.Methods and MaterialsFrom 1993 to 2012, our institution treated 160 patients with 103Pd (56.1%) and 125 patients with 125I (43.9%) plaque brachytherapy. Tumor outcomes, visual acuity (VA), and toxicity were compared. Multivariate analyses (MVAs) and propensity score analysis were used to help address differences in baseline characteristics.ResultsMedian followup was longer for 125I patients, 52.7 vs. 43.5 months (p < 0.01). At baseline, 103Pd patients had lower rates of VA worse than 20/200 (4.4% vs. 16%, p = 0.002), T3–T4 tumors (17.5% vs. 32.8%, p = 0.03), and transpupillary thermotherapy use (3.1% vs. 9.6%, p = 0.001). Both 103Pd and 125I provided >90% 3-year overall survival and >93% 5-year secondary enucleation-free survival. On MVA, radionuclide was not predictive for tumor outcomes. A higher percentage maintained vision better than 20/40 with 103Pd (63% vs. 35%, p = 0.007) at 3 years. MVA demonstrated 103Pd radionuclide (odds ratio [OR]: 2.12, p = 0.028) and tumor height ≤5 mm (OR: 2.78, p = 0.017) were associated with VA better than 20/40. Propensity score analysis matched 23 125I with 107 103Pd patients. 103Pd continued to predict better VA at 3 years (OR: 8.10, p = 0.014). On MVA for the development of VA worse than 20/200 or degree of vision loss, radionuclide was not significant. Lower rates of radiation retinopathy were seen with 103Pd than 125I (3 years: 47.3% vs. 63.9%, p = 0.016), with radionuclide significant in MVA.ConclusionsBoth 125I and 103Pd achieve excellent tumor control. An increased probability of long-term VA better than 20/40 and reduced risk of radiation retinopathy is associated with 103Pd.



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Lung Mass as the Complement to Lung Air Content in Quantitative CT of the COPD Lung

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Publication date: April 2017
Source:Academic Radiology, Volume 24, Issue 4
Author(s): Eric A. Hoffman, John D. Newell




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Comparative Effectiveness of Imaging Modalities for the Diagnosis and Treatment of Intussusception

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Publication date: Available online 3 March 2017
Source:Academic Radiology
Author(s): Anne G. Carroll, Richard G. Kavanagh, Caoilfhionn Ni Leidhin, Noelle M. Cullinan, Lisa P. Lavelle, Dermot E. Malone
Rationale and ObjectivesThe purpose of this study was to critically appraise and compare the diagnostic performance of imaging modalities that are used for the diagnosis of intussusception and methods used in the treatment of ileocolic intussusception.MethodsA focused clinical question was constructed and the literature was searched using the patient, intervention, comparison, outcome (PICO) method comparing radiography, ultrasound, and computed tomography in the detection of intussusception. The same methods were used to compare pneumatic (gas) reduction and hydrostatic (liquid) reduction using saline, water-soluble contrast, and barium. Retrieved articles were appraised and assigned a level of evidence based on the Oxford University Centre for Evidence-Based Medicine hierarchy of validity for diagnostic studies.ResultsThe retrieved sensitivity for the diagnosis of intussusception using plain radiography is 48% (95% confidence interval [CI], 44%–52%), with a specificity of 21% (95% CI, 18%–24%). The retrieved sensitivity for the diagnosis of intussusception using ultrasound is 97.9% (95% CI, 95%–100%), with a specificity of 97.8% (95% CI, 97%–99%). Based on a good quality meta-analysis, the combined success rate of gas enema reduction was shown to be 82.7% (95% CI, 79.9%–85.6%) compared to a combined success rate of 69.6% (95% CI, 65.0%–74.1%) for liquid enema reduction.ConclusionsThe best available evidence recommends ultrasound as the diagnostic modality of choice for the diagnosis of ileocolic intussusception in children. In stable children without signs of peritonism, nonoperative reduction is the treatment of choice. Pneumatic (gas) reduction enema has been shown to be superior to hydrostatic (liquid) enema reduction.



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Psychophysiological Measurement of Backward Response Activation in the Prioritized Processing Paradigm.

Author: Miller, Jeff
DOI: 10.1037/xhp0000356
Publication Date: POST AUTHOR CORRECTIONS, 2 March 2017


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Temporal Binding and Internal Clocks: No Evidence for General Pacemaker Slowing.

Author: Fereday, Richard; Buehner, Marc J.
DOI: 10.1037/xhp0000370
Publication Date: POST AUTHOR CORRECTIONS, 2 March 2017


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The Necessity of Visual Attention to Scene Categorization: Dissociating "Task-Relevant" and "Task-Irrelevant" Scene Distractors.

Author: Gronau, Nurit; Izoutcheev, Anna
DOI: 10.1037/xhp0000365
Publication Date: POST AUTHOR CORRECTIONS, 2 March 2017


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Time and temperature mediated evolution of CDHA from ACP nanoparticles in deep eutectic solvents: Kinetic and thermodynamic considerations

Publication date: 15 May 2017
Source:Materials & Design, Volume 122
Author(s): Mohammad Karimi, Saeed Hesaraki, Masoud Alizadeh, Asghar Kazemzadeh
Calcium phosphate (CP) nanoparticles were synthesized in choline chloride-urea deep eutectic solvent (DES). The effect of synthesis time and temperature on crystallinity, particulate properties, and elemental/chemical purity of the CP nanoparticles were investigated by X-ray diffraction, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, and Fourier transform infra-red spectroscopy. The results confirmed the formation of amorphous calcium phosphate (ACP) nanoparticles (at 25°C for 10min) with spherical morphology, mean diameter of 29nm, and high elemental-structural purity. The increase of synthesis time from 10min to 48h at 25°C had no significant influence on the phase transformation of ACP nanoparticle so that the nanoparticles showed high degree of amorphization after 48h. The crystallization of particles rapidly rose upon increase of the synthesis temperature so that the nanoparticles of calcium-deficient hydroxyapatite (CDHA) with percent crystallinity of ~97% were obtained in choline chloride-urea DES at 150°C after 24h. Kinetic and thermodynamic studies revealed that upon increase of temperature from 25 to 150°C, the rate constant and Gibbs free energy for growth of CP crystals in the DES rises from 8.70×10−4 to 1.37×10−3min−1 and 3.22×10+2 to 4.57×10+2KJ·mol−1, respectively.

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Nucleation and growth mechanisms of nano-scaled Si precipitates in Al-7Si supersaturated solid solution

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Maowen Liu, Hui Fu, Lixi Tian, Wenlong Xiao, Qiuming Peng, Chaoli Ma
A dense uniform distribution of nano-scaled Si precipitates has been achieved in Al-7Si alloy by high pressure solution treatment (HPST) and aging treatment. Precipitation behavior of Si phase was investigated using transmission electron microscopy (TEM). The results reveal that Si clusters initially precipitate from the Al(Si) solid solution, providing preferable nucleation sites for the equilibrium Si phase. The Si crystals exhibit spherical shape at first, and then grow rapidly parallel to {111}Si planes. The shortage of growth ledges on {111} interfaces leads to the inhibition of growth perpendicular to these planes, which results in Si triangles and platelets with high aspect ratio. An equation about the relationship between the relative free energy and the equilibrium ledge densities on Al-Si interfaces was proposed.

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Cyclopropenone-masked dibenzocyclooctyne end-functionalized polymers from reversible addition-fragmentation chain transfer polymerization

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Lin Qu, Ying Wu, Peng Sun, Ke Zhang, Zhengping Liu
Functional reversible addition-fragmentation chain transfer polymerization (RAFT) agent was developed to have a cyclopropenone-masked dibenzocyclooctyne end group. RAFT polymerization was then explored on three typical types of vinyl monomers in free radical polymerization such as styrene, methyl methacrylate, and tert-butyl acrylate. The living polymerization behaviors were demonstrated for all three cases, which guaranteed the production of well-defined polystyrene, poly (methyl methacrylate), and poly (tert-butyl acrylate) end-functionalized with cyclopropenone-masked dibenzocyclooctyne groups from the convenient RAFT polymerization technique. Under UV irradiation, the cyclopropenone-masked dibenzocyclooctyne end group could be quantitatively changed to dibenzocyclooctyne clickable group, which was widely used in the metal-free strain-promoted azide-alkyne cycloaddition (SPAAC) click reaction. Subsequently, using the dibenzocyclooctyne end-functionalized polymers as building blocks, a practical and efficient metal-free method was developed for the formation of topological polymers including block and bottlebrush polymers based on the SPAAC click reaction.

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Sharp and strong “Brill transition” of poly(hexamethylene dithiocarbonate)

Publication date: 24 March 2017
Source:Polymer, Volume 113
Author(s): Ti-Peng Zhao, Annamaria Celli, Xiang-Kui Ren, Jia-Ru Xu, Shuang Yang, Chen-Yang Liu, Er-Qiang Chen
In this paper, the reversible crystal-crystal transition of poly(hexamethylene dithiocarbonate) (PHMDC) has been systematically studied. According to various experimental results, we confirm that the transition shares the common features with Brill transition that is widely observed in nylons. This transition is clearly associated with the reversible trans-gauche conformational transformation of the methylene sequences in the crystal lattice. Therefore, in addition to its analogue poly(octamethylene carbonate) POMC (ACS Macro Lett. 2015, 4, 317–321), PHMDC can be considered as a new example of the polymers exhibiting Brill transition outside the nylon family. Careful examination of the experimental data reveals that for PHMDC the enthalpy ratio of the Brill transition to the melting is a constant of ∼2/3, independent of the crystallization condition applied. Furthermore, the difference between the Brill transition temperatures determined from heating and cooling is also a constant, which is of ∼4 °C. These new observations are obtained because the Brill transition of PHMDC is sharp and possesses a large transition enthalpy. Such a transition is associated with that the methylene segments in PHMDC can change their conformation between trans and gauche rapidly and completely in a narrow temperature interval.

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Near-infrared luminescent erbium complexes with 8-hydroxyquinoline-terminated hyperbranched polyester

Publication date: 24 March 2017
Source:Polymer, Volume 113
Author(s): Dan Liu, Chengjian Li, Yaling Xu, Dapeng Zhou, Hongmei Wang, Ping Sun, Huasheng Jiang
Novel 8-hydroxyquinoline-terminated hyperbranched polyesters (1-HBPQ and 2-HBPQ) were synthesized and characterized by 1H-NMR and UV-Vis analyses. Then, two erbium complexes (1-HBPQ-Er3+-HQ and 2-HBPQ-Er3+-HQ) were prepared by using 1-HBPQ or 2-HBPQ as the macromolecular ligand and 8-hydroxyquinoline (HQ) as a second ligand. The FTIR spectra and UV-Vis absorption spectra confirmed that both the macromolecular ligand and the second ligand were successfully coordinated with Er3+ ions. The erbium complexes emitted intense near-infrared luminescence at about 1530 nm, which corresponds to the 4I13/2-4I15/2 transition of Er3+ ions. Moreover, their full width at half maximum (FWHM) values were greater than 80 nm. The erbium complexes exhibited good solubility in conventional solvents and excellent near-infrared luminescence properties, indicating their promising potential as gain medium materials in optical amplification devices.

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Ignoring Memory Hints: The Stubborn Influence of Environmental Cues on Recognition Memory.

Author: Selmeczy, Diana; Dobbins, Ian G.
DOI: 10.1037/xlm0000383
Publication Date: POST AUTHOR CORRECTIONS, 2 March 2017


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Accessibility Limits Recall From Visual Working Memory.

Author: Rajsic, Jason; Swan, Garrett; Wilson, Daryl E.; Pratt, Jay
DOI: 10.1037/xlm0000387
Publication Date: POST AUTHOR CORRECTIONS, 2 March 2017


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Reading Time Allocation Strategies and Working Memory Using Rapid Serial Visual Presentation.

Author: Busler, Jessica N.; Lazarte, Alejandro A.
DOI: 10.1037/xlm0000392
Publication Date: POST AUTHOR CORRECTIONS, 2 March 2017


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A Two-Phase Model of Resource Allocation in Visual Working Memory.

Author: Ye, Chaoxiong; Hu, Zhonghua; Li, Hong; Ristaniemi, Tapani; Liu, Qiang; Liu, Taosheng
DOI: 10.1037/xlm0000376
Publication Date: POST AUTHOR CORRECTIONS, 2 March 2017


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Predicting and Priming Thematic Roles: Flexible Use of Verbal and Nonverbal Cues During Relative Clause Comprehension.

Author: Kowalski, Alix; Huang, Yi Ting
DOI: 10.1037/xlm0000389
Publication Date: POST AUTHOR CORRECTIONS, 2 March 2017


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The Case of the Missing Visual Details: Occlusion and Long-Term Visual Memory.

Author: Williams, Carrick C.; Burkle, Kyle A.
DOI: 10.1037/xlm0000393
Publication Date: POST AUTHOR CORRECTIONS, 2 March 2017


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Combined venomics, antivenomics and venom gland transcriptome analysis of the monocoled cobra (Naja kaouthia) from China

Publication date: Available online 3 March 2017
Source:Journal of Proteomics
Author(s): Ning Xu, Hong-Yan Zhao, Yin Yin, Shan-Shan Shen, Lin-Lin Shan, Chuan-Xi Chen, Yan-Xia Zhang, Jian-Fang Gao, Xiang Ji
We conducted an omics-analysis of the venom of Naja kaouthia from China. Proteomics analysis revealed six protein families [three-finger toxins (3-FTx), phospholipase A2 (PLA2), nerve growth factor, snake venom metalloproteinase (SVMP), cysteine-rich secretory protein and ohanin], and venom-gland transcriptomics analysis revealed 28 protein families from 79 unigenes. 3-FTx (56.5% in proteome/82.0% in transcriptome) and PLA2 (26.9%/13.6%) were identified as the most abundant families in venom proteome and venom-gland transcriptome. Furthermore, N. kaouthia venom expressed strong lethality (i.p. LD50: 0.79μg/g) and myotoxicity (CK: 5939U/l) in mice, and showed notable activity in PLA2 but weak activity in SVMP, l-amino acid oxidase or 5′ nucleotidase. Antivenomic assessment revealed that several venom components (nearly 17.5% of total venom) from N. kaouthia could not be thoroughly immunocaptured by commercial Naja atra antivenom. ELISA analysis revealed that there was no difference in the cross-reaction between N. kaouthia and N. atra venoms against the N. atra antivenom. The use of commercial N. atra antivenom in treatment of snakebites caused by N. kaouthia is reasonable, but design of novel antivenom with the attention on enhancing the immune response of non-immunocaptured components should be encouraged.Biological significanceThe venomics, antivenomics and venom-gland transcriptome of the monocoled cobra (Naja kaouthia) from China have been elucidated. Quantitative and qualitative differences are evident when venom proteomic and venom-gland transcriptomic profiles are compared. Two protein families (3-FTx and PLA2) are found to be the predominated components in N. kaouthia venom, and considered as the major players in functional role of venom. Other protein families with relatively low abundance appear to be minor in the functional significance. Antivenomics and ELISA evaluation reveal that the N. kaouthia venom can be effectively immunorecognized by commercial N. atra antivenom, but still a small number of venom components could not be thoroughly immunocaptured. The findings indicate that exploring the precise composition of snake venom should be executed by an integrated omics-approach, and elucidating the venom composition is helpful in understanding composition-function relationships and will facilitate the clinical application of antivenoms.

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Proteomic analysis of chondromodulin-I-induced differentiation of mesenchymal stem cells into chondrocytes

Publication date: Available online 2 March 2017
Source:Journal of Proteomics
Author(s): Shuang-chun Xing, Lian-xin Du, Wei Zhou, Yu-qiang Hu, Ya Feng, Hong-feng Liang, Lin Sang, Min Qi, Li-jie Zhai, Zhi-qiang Wang
To identify novel proteins that might help clarify the molecular mechanisms underlying chondromodulin-I (ChM-I) induction of mesenchymal stem cells (MSCs) differentiate into chondrocytes. MSCs are triggered to differentiate into chondrocytes, which are recognized as important factors in cartilage tissue engineering. ChM-I is a glycoprotein that stimulates the growth of chondrocytes and inhibits angiogenesis in vitro. In this study, the proteomic approach was used to evaluate protein changes between undifferentiated MSCs and ChM-I-transfected MSCs. The expression of the protein spots was analyzed using two-dimensional gel electrophoresis. Then, 14 protein spots were identified between MSCs and ChM-I-transfected MSCs. 309 proteins were identified using mass spectrometry (MS). The differentially regulated proteins were categorized and annotated using Protein Analysis Through Evolutionary Relationships (PANTHER) analysis with the aid of the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. These proteins are included in a variety of metabolic pathways and signal transduction pathways, such as focal adhesion, glycolysis, actin cytoskeleton regulation, and ribosome. These results demonstrate novel information about the molecular mechanism by which ChM-I induce MSCs to differentiate into chondrocytes. These results also provide a solid foundation for the development of tissue-engineered cartilage.

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Klinefelter syndrome: cardiovascular abnormalities and metabolic disorders

Abstract

Klinefelter syndrome (KS) is one of the most common genetic causes of male infertility. This condition is associated with much comorbidity and with a lower life expectancy. The aim of this review is to explore more in depth cardiovascular and metabolic disorders associated to KS. KS patients have an increased risk of cerebrovascular disease (standardized mortality ratio, SMR, 2.2; 95% confidence interval, CI, 1.6–3.0), but it is not clear whether the cause of the death is of thrombotic or hemorrhagic nature. Cardiovascular congenital anomalies (SMR, 7.3; 95% CI, 2.4–17.1) and the development of thrombosis or leg ulcers (SMR, 7.9; 95% CI, 2.9–17.2) are also more frequent in these subjects. Moreover, cardiovascular abnormalities may be at least partially reversed by testosterone replacement therapy (TRT). KS patients have also an increased probability of endocrine and/or metabolic disease, especially obesity, metabolic syndrome and type 2 diabetes mellitus. The effects of TRT on these abnormalities are not entirely clear.



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Early inflammatory changes in radiation-induced oral mucositis

Abstract

Purpose

Early inflammation is a major factor of mucosal reactions to radiotherapy. Pentoxifylline administration resulted in a significant amelioration of radiation-induced oral mucositis in the mouse tongue model. The underlying mechanisms may be related to the immunomodulatory properties of the drug. The present study hence focuses on the manifestation of early inflammatory changes in mouse tongue during daily fractionated irradiation and their potential modulation by pentoxifylline.

Materials and methods

Daily fractionated irradiation with 5 fractions of 3 Gy/week (days 0–4, 7–11) was given to the snouts of mice. Groups of 3 animals per day were euthanized every second day between day 0 and 14. Pentoxifylline (15 mg/kg, s. c.) was administered daily from day 5 to the day before sacrifice. The expression of the inflammatory proteins TNFα, NF-κB, and IL-1β were analysed.

Results

Fractionated irradiation increased the expression of all inflammatory markers. Pentoxifylline significantly reduced the expression of TNFα and IL-1β, but not NF-κB.

Conclusion

Early inflammation, as indicated by the expression of the inflammatory markers TNFα, NF-κB, and IL-1β, is an essential component of early radiogenic oral mucositis. Pentoxifylline differentially modulated the expression of different inflammatory markers. The mucoprotective effect of pentoxifylline does not appear to be based on modulation of NF-κB-associated inflammation.



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Examining predictors of chemical toxicity in freshwater fish using the random forest technique

Abstract

Chemical pollution is one of the main issues globally threatening the enormous biodiversity of freshwater ecosystems. The toxicity of substances depends on many factors such as the chemical itself, the species affected, environmental conditions, exposure duration, and concentration. We used the random forest technique to examine the factors that mediate toxicity in a set of widespread fishes and analyses of covariance to further assess the importance of differential sensitivity among fish species. Among 13 variables, the 5 most important predictors of toxicity with random forests were, by order of importance, the chemical substance itself (i.e., Chemical Abstracts Service number considered as a categorical factor), octanol-water partition coefficient (log P), pollutant prioritization, ecological structure-activity relationship (ECOSAR) classification, and fish species for 50% lethal concentrations (LC50) and the chemical substance, fish species, log P, ECOSAR classification, and water temperature for no observed effect concentrations (NOECs). Fish species was a very important predictor for both endpoints and with the two contrasting statistical techniques used. Different fish species displayed very different relationships with log P, often with different slopes and with as much importance as the partition coefficient. Therefore, caution should be exercised when extrapolating toxicological results or relationships among species. In addition, further research is needed to determine species-specific sensitivities and unravel the mechanisms behind them.



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Lactational exposure to abamectin induced mortality and adverse biochemical and histopathological effects in suckling pups

Abstract

Information about the adverse effects of lactation transfer of abamectin (ABA) is important for human health, especially in the third-world countries where breastfeeding is the only source of nutrition for infants. So, the present study was undertaken to evaluate the adverse effects of breastfeeding exposure to ABA on oxidative damage and liver and kidney dysfunction in suckling rats. Dams were orally administered ABA at a doses 22.10, 11.05, and 2.21 mg a.i./kg b.wt from postnatal day 1 (PND1) until day 20 (PND20). The signs of toxicity and high mortality were recorded in suckling male (67.5%) and female (55.0%) pups whose mother exposed to the ABA at dose 22.1 mg a.i./kg b.wt. ABA induced significantly decrease in body weights of mothers and their male and female pups and significant increase in relative liver weights. It caused oxidative stress in the liver and kidney of mothers and their pups by increasing the level of malondialdehyde (MDA) and decreased activities of superoxide dismutase (SOD) and glutathione-transferase (GST). ABA altered the level of serum liver and kidney dysfunction biomarkers either in the mothers or their male and female pups in a dose-dependent manner. It caused histopathological alterations in the liver and kidney tissues. It can be decided that ABA was accumulated in mother's milk, transferred through breast feeding, and induced mortality in their suckling pups. It caused oxidative stress, lipid peroxidation, and biochemical and histopathological alterations in the liver and kidney of mothers and their suckling pups. The results in the present study add some information about the adverse effect of lactation transfer of ABA, which is important for human health in the third-world countries where breastfeeding may be the only source of nutrition for infants in the first and most critical weeks of life.



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Trimethylamine removal by plant capsule of Sansevieria kirkii in combination with Bacillus cereus EN1

Abstract

Trimethylamine (TMA) contamination produces a strong "fishy" odor and can cause pathological changes in humans. By screening native microorganisms from Sansevieria kirkii exposed to 100 ppm TMA, it was shown that endophytic bacteria number 1 (EN1) and number 2 (EN2) have a higher TMA tolerance and removal capacity than other bacteria species in a closed system. In addition, EN1 and EN2 demonstrated the ability to produce high quantities of indole-3-acetic acid (IAA) and use 1-aminocyclopropane-1-carboxylic acid (ACC), which is found normally in plant growth-promoting bacteria (PGPB). Moreover, 16S ribosomal DNA (rDNA) sequences of EN1 and EN2 identification showed that EN1 and EN2 was the same bacteria species, Bacillus cereus. B. cereus EN1 was chosen to apply with S. kirkii to remove TMA in a plant capsule, which was compared to control conditions. It was found that 500 g of soil with S. kirkii inoculated with B. cereus EN1 had a higher TMA removal efficiency than other conditions. Moreover, the flow rate of TMA-contaminated gas was varied (0.03–1 L min−1) to calculate the loading rate and elimination capacity. The maximum loading rate of 500 g soil with B. cereus EN1-inoculated S. kirkii was 2500 mg m−3 h−1, while other conditions showed only around 250–750 mg m−3 h−1. Therefore, a plant capsule with B. cereus EN1-inoculated S. kirkii had the potential to be applied in TMA-contaminated air.



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Reclamation of Cr-contaminated or Cu-contaminated agricultural soils using sunflower and chelants

Abstract

Chromium (Cr) and copper (Cu) are pollutants with a strong environmental impact. "Green biotechnology" as phytoremediation represents a sustainability opportunity for soil reclamation. In this study, we evaluated the possibility to reclaim agricultural soils located in the Solofrana valley, contaminated by Cr or Cu. Chromium contamination derives by repeated flooding events of Solofrana rivers containing Cr because of leather tanning plants, while Cu soil pollution was due to the use of Cu-rich pesticides in agriculture. Both metals showed a very low bioavailability. In order to perform an assisted phytoremediation of polluted fields, we carried out a preliminary ex situ experimentation testing for the first time sunflowers (cv. Pretor) and chelants (ethylenediaminetetraacetic acid (EDTA) and/or ethylene diamine disuccinate (EDDS)), useful when metal bioavailability is low. No symptoms of toxicity were observed in sunflowers grown on both soils, while biomass was improved when EDDS was added. Cr and Cu bioavailability was only slightly enhanced by chelants at the end of the treatments. Both Cr and Cu were mainly accumulated in the roots; moreover, Cu was also translocated to the aboveground organs in the presence of EDTA. The ex situ experimentation demonstrated that assisted phytoremediation is a very slow process not useful in the case of persistent pollution.



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Degradation of chloramphenicol by potassium ferrate (VI) oxidation: kinetics and products

Abstract

The oxidation of chloramphenicol (CAP) by potassium ferrate (VI) in test solution was studied in this paper. A series of jar tests were performed at bench scale with pH of 5–9 and molar ratio [VI/CAP] of 16.3:1–81.6:1. Results showed that raising VI dose could improve the treatment performance and the influence of solution pH was significant. VI is more reactive in neutral conditions, presenting the highest removal efficiency of CAP. The rate law for the oxidation of CAP by VI was first order with respect to each reactant, yielding an overall second-order reaction. Furthermore, five oxidation products were observed during CAP oxidation by VI. Results revealed that VI attacked the amide group of CAP, leading to the cleavage of the group, while benzene ring remained intact.



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Interactions micro-organismes et voies aériennes distales : spécificités pédiatriques

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Publication date: Available online 3 March 2017
Source:Revue des Maladies Respiratoires
Author(s): J. de Blic, J. Brouard, A. Vabret, A. Deschildre
Le spectre des virus à tropisme respiratoire s'élargit et des maladies émergentes sont régulièrement décrites depuis une quinzaine d'années. L'origine de ces virus respiratoires émergents peut être zoonotique (par franchissement de barrière d'espèce, après mutations pour les virus à ARN tels que les virus aviaires influenza de type A ou les coronavirus), ou liée aux nouvelles techniques d'identification (métapneumovirus, bocavirus). Les relations entre bronchiolite et asthme sont désormais mieux appréhendées grâce au suivi prospectif de cohortes de nouveau-nés. Le rôle des rhinovirus devient prépondérant par rapport au virus respiratoire syncytial. L'identification de facteurs de prédispositions immunologiques, fonctionnelles, atopiques et génétiques, pour la survenue de l'asthme après une infection à rhinovirus suggère que l'infection virale révèle un terrain prédisposé plutôt qu'elle est à l'origine de l'asthme. Le rôle des bactéries dans l'histoire naturelle de l'asthme commence également à être mieux cerné. Les résultats de la cohorte danoise COPSAC ont montré la fréquence des identifications bactériennes au cours des épisodes sifflants avant 3 ans, ainsi que l'impact de la colonisation bactérienne à l'âge de un mois sur la survenue de l'asthme à l'âge de 5 ans. Le rôle des infections bactériennes dans l'asthme sévère du jeune enfant est également discuté.The spectrum of respiratory viruses is expanding and emerging diseases have been described regularly over the last fifteen years. The origin of these emerging respiratory viruses may be zoonotic (by crossing species barrier, after changes to RNA viruses such as avian influenza virus type A or coronaviruses), or related to the use of new identification techniques (metapneumovirus, bocavirus). The relationship between bronchiolitis and asthma is now better understood thanks to prospective follow up of birth cohorts. The role of rhinovirus has become predominant with respect to respiratory syncytial virus. The identification of predisposing factors immunological, functional, atopic and genetic, for the onset of asthma after rhinovirus infection suggests that viral infection reveals a predisposition rather than itself being a cause of asthma. The role of bacteria in the natural history of asthma is also beginning to be better understood. The results of the COPSAC Danish cohort have shown the frequency of bacterial identification during wheezy episodes before 3 years, and the impact of bacterial colonization at the age of one month on the onset of asthma by age 5 years. The role of bacterial infections in severe asthma in young children is also discussed.



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Numéro 2/2017. Réponses

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Publication date: Available online 3 March 2017
Source:Revue des Maladies Respiratoires





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Regulating Damage from Sterile Inflammation: A Tale of Two Tolerances

Publication date: Available online 3 March 2017
Source:Trends in Immunology
Author(s): Shin-Rong Wu, Pavan Reddy
The severity of immunopathology from non-infectious inflammation is mainly understood and is managed by targeting immune cells. However, the role of target tissues in determining damage severity has been largely overlooked. Here, we discuss the concept of 'tissue tolerance' for tissue-intrinsic programs that ameliorate organ damage in the setting of sterile immunopathology.



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Neurogenic bladder dysfunction does not correlate with astrocyte and microglia activation produced by graded force in a contusion-induced spinal cord injury

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Publication date: Available online 3 March 2017
Source:Brain Research Bulletin
Author(s): Alvaro Munoz
Rodent models for the study of neurogenic bladder dysfunction after spinal cord injury (SCI) are difficult to standardize, particularly when evaluating the specific contribution of the SCI to end-organ function. The purpose of this study was to evaluate the degree of bladder dysfunction associated with a highly reproducible, contusion-induced SCI in female rats. An infinite horizon impactor was used to create a contusion SCI with a magnitude of either 100 or 150 kDyne at the T8/T9 thoracic region of female Sprague-Dawley rats. Locomotor function, and the presence of astrocytes (positive regions for Glial Fibrillary Acidic Protein) and microglia (positive cells for the integrin CD11b) at the SCI site were determined at four weeks after SCI. Similarly, cystometric properties were characterized in urethane anesthetized rats at four weeks post-SCI. The significant increases in astrocyte and microglia in the T8/T9 region in all of the SCI animals did not correlate with locomotor impairment or bladder dysfunction. After performing the cystometric studies substantial differences were found in both SCI groups when compared to intact animals, specifically a high frequency of non-voiding contractions, different durations for intraluminal pressure-high frequency oscillations, intercontractile intervals, impaired micturition volumes, and estimated voiding efficiency. These results suggest that a contusion SCI can increase microglia and astrocyte activation without a strong association with bladder dysfunction. The present study will be important for precise considerations about correlating the intensity of a SCI with impairment outcomes at both locomotor or organ function levels.



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Commentary on “The Impact of Patient Demographics, Anatomy, Comorbidities and Peri-operative Planning on the Primary Functional Maturation of Autogenous Radiocephalic Arteriovenous Fistula”

Publication date: Available online 3 March 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): S.K. Kakkos, I.A. Tsolakis




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Current Status of Targeted Radioprotection and Radiation Injury Mitigation and Treatment Agents: A Critical Review of the Literature

Publication date: Available online 2 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Noah S. Kalman, Sherry S. Zhao, Mitchell S. Anscher, Alfredo I. Urdaneta
As more cancer patients survive their disease, concerns about radiotherapy-induced side effects have increased. The concept of radioprotection and radiation injury mitigation and treatment offers the possibility to enhance the therapeutic ratio of radiotherapy by limiting radiotherapy-induced normal tissue injury without compromising its anti-tumor effect. Advances in the understanding of the underlying mechanisms of radiation toxicity have stimulated radiation oncologists to target these pathways across different organ systems. These generalized radiation injury mechanisms include production of free radicals such as superoxides, activation of inflammatory pathways, and vascular endothelial dysfunction leading to tissue hypoxia. There is a significant body of literature evaluating the effectiveness of various treatments in preventing, mitigating or treating radiation induced normal tissue injury. While some reviews have focused on a specific disease site or agent, this critical review focuses on a mechanistic classification of activity and assesses multiple agents across different disease sites. The classification of agents used herein further offers a useful framework to organize the multitude of treatments that have been studied. Many commonly available treatments have demonstrated benefit in prevention, mitigation, and/or treatment of radiation toxicity and warrant further investigation. These drug-based approaches to radioprotection and radiation injury mitigation and treatment represent an important method of making radiotherapy safer.



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Effectiveness Between Early and Late Closure of Rectal Cancer Patients with Temporary Ileostomy: A Prospective Study

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Publication date: Available online 2 March 2017
Source:Current Problems in Cancer
Author(s): Li Zhen, Yanan Wang, Ze Zhang, Tongwei Wu, Ruoyan Liu, Tingting Li, Liying Zhao, Haijun Deng, Xiaolong Qi, Guoxin Li
Background & aimsA temporary stoma is often used in rectal cancer surgery to protect a distal anastomosis, which remains a major concern after rectal cancer surgery, particularly after low anterior resection. The temporary stoma is scheduled for closure. However, the optimal time of closure of the protecting stoma remains unclear due to sparse studies and data. We aimed to detect the efficacy of between early and late temporary ileostomy closure in patients with rectal cancer during or after neoadjuvant chemotherapy (NACRT).MethodWe conducted a prospective, two-group design between early and late ileostomy closure group in patients after rectal cancer surgery with temporary stoma. Participants were recruited in a teaching hospital in Guangzhou, China. 161 patients confirmed diagnosis of rectal cancer underwent curative surgery and temporary ileostomy. Paticipants with temporary ileostomy received closure surgery after one (early) or six (late) months were assessed by clinical parameters and quality of life (QOL).ResultsPatients in late closure (LC) group received more adjuvant chemotherapy cycles but with comparable incidence of stoma closure-related complications and length of hospital stay compared to early closure (EC) group.ConclusionParticipants in LC group with standardized postoperative chemotherapy might have a better prognosis compared with those in EC group. An increased emphasis should be given to choose the optimal closure time of rectal cancer patients with temporary ileostomy. Colorectal nurses could provide support to physician for observation of prognosis of different closure time.



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Hemi-facial reconstruction following extensive crush avulsion injury of the face

Abstract

Post-traumatic facial defects need to be treated sensitively, as the emotional repercussions and possible deformity can have lasting effects on the patient's psychological well-being. Thus, the management of posttraumatic facial injuries requires meticulous planning and adherence to both aesthetic and reconstructive principles. We describe the case of a 29-year-old male who underwent multistage reconstruction following extensive facial injuries. The clinical challenges presented by this rare case and steps of the reconstruction procedure are presented. Sequential flaps that were placed during the restoration survived, and the patient had no lasting donor site morbidity. Post-surgery, the patient's self-confidence was dramatically improved, as were his interactions with his family and friends. Careful planning and staged microvascular procedures were important in the management of this patient with severe injuries. The patient was rehabilitated and able to live a near-normal life, without the need for synthetic implants or lifelong immune suppression.

Level of Evidence: Level V, therapeutic study.



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Ecotoxicological characterization of polyoxyethylene glycerol ester non-ionic surfactants and their mixtures with anionic and non-ionic surfactants

Abstract

This paper reports on a study that investigated the aquatic toxicity of new non-ionic surfactants derived from renewable raw materials, polyoxyethylene glycerol ester (PGE), and their binary mixtures with anionic and non-ionic surfactants. Toxicity of pure PGEs was determined using representative organisms from different trophic levels: luminescent bacteria (Vibrio fischeri), microalgae (Pseudokirchneriella subcapitata), and freshwater crustaceans (Daphnia magna). Relationships between toxicity and the structural parameters such as unit of ethylene oxide (EO) and hydrophilic-lipophilic balance (HLB) were evaluated. Critical micellar concentration (CMC) in the conditions of the toxicity test was also determined. It was found that the toxicity of the aqueous solutions of PGE decreased when the number of EO units in the molecule, HLB, and CMC increased. PGEs showed lower CMC in marine medium, and the toxicity to V. ficheri is lower when the CMC was higher. Given their non-polar nature, narcosis was expected to be the primary mode of toxic action of PGEs. For the mixture of surfactants, we observed that the mixtures with PGE that had the higher numbers of EO units were more toxic than the aqueous solutions of pure surfactants. Moreover, we found that concentration addition was the type of action more likely to occur for mixtures of PGE with lower numbers of EO units with non-ionic surfactants (alkylpolyglucoside and fatty alcohol ethoxylate), whereas for the mixture of PGE with lower EO units and anionic surfactant (ether carboxylic derivative), the most common response type was response addition. In case of mixtures involving amphoteric surfactants and PGEs with the higher numbers of EO units, no clear pattern with regard to the mixture toxicity response type could be observed.



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Environmental behavior of sulfadiazine, sulfamethazine, and their metabolites

Abstract

Sulfonamides are one of the most frequently used antibiotics worldwide. Therefore, processes that determine their fate in the environment are of great interest. In the present work, biodegradation as biotic process and hydrolysis and photolysis as abiotic processes were investigated. In biodegradation experiments, it was found out that sulfonamides (sulfadiazine and sulfamethazine) and their N 4-acetylated metabolites were not readily biodegradable. The results showed that decrease of concentrations were in the range from 4% for sulfadiazine to 22% for N 4-acetylsulfamethazine. Hydrolytic experiments examined at pH values normally found in the environment also showed their resistance. However, photolysis proved to be significant process for decreasing concentrations of sulfonamides and their metabolites in three various aqueous matrices (Milli-Q water, river water, and synthetic wastewater). In addition, influence of ubiquitous water constituents (Cl, NO3, SO42−, PO43−, and humic acids) was also investigated, showing their different impact on photolysis of investigated pharmaceuticals. The results showed that photolysis followed first-order kinetics in all cases. The obtained results are very important for assesing the environmental fate of sulfonamides and their metabolites in the aquatic environment.



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How interacting fungal species and mineral nitrogen inputs affect transfer of nitrogen from litter via arbuscular mycorrhizal mycelium

Abstract

In the karst landscape, widespread in the world including southern China, soil nutrient supply is strongly constrained. In such environments, arbuscular mycorrhizal (AM) fungi may facilitate plant nutrient uptake. However, the possible role of different AM fungal species, and their interactions, especially in transferring nitrogen (N) from litter to plant, is poorly understood. We conducted two microcosm experiments to investigate the role that two karst soil AM fungi, Glomus etunicatum and Glomus mosseae, play in the transfer of N from decomposing litter to the host plant and to determine how N availability influences these processes. In experiment 1, Cinnamomum camphora tree seedlings were grown in compartments inoculated with G. etunicatum. Lolium perenne leaf litter labeled with δ15N was added to the soil in unplanted compartments. Compartments containing the δ15N labeled litter were either accessible to hyphae but not to seedling roots or were not accessible to hyphae or roots. The addition of mineral N to one of the host compartments at the start of the experiment significantly increased the biomass of the C. camphora seedlings, N content and N:P ratio, AM mycelium length, and soil microbial biomass carbon and N. However, significantly, more δ15N was acquired, from the leaf litter by the AM hyphae and transferred to the host when mineral N was not added to the soil. In experiment 2, in which C. camphora seedlings were inoculated with both G. etunicatum and G. mosseae rather than with G. mosseae alone, there was a significant increase in mycelial growth (50.21%), in soil microbial biomass carbon (417.73%) in the rhizosphere, and in the amount of δ15N that was transferred to the host. These findings suggest that maintaining AM fungal diversity in karst soils could be important for mediating N transfer from organic material to host plants in N-poor soils.



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The Role of Minimally Invasive Surgery in Treatment of Cholangiocarcinoma

Publication date: Available online 3 March 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Giovanni Battista Levi Sandri, Gabriele Spoletini, Gianluca Mascianà, Marco Colasanti, Pasquale Lepiane, Giovanni Vennarecci, Vito D'Andrea, Giuseppe Maria Ettorre
Cholangiocarcinoma (CC) is the second most common type of primary liver cancer after hepatocellular carcinoma. Surgical resection is considered the only curative treatment for CC. In general, laparoscopic liver surgery (LLS) is associated with improved short-term outcomes without compromising the long-term oncological outcome. However, the role of LLS in the treatment of CC is not yet well established. In addition, CC may arise in any tract of the biliary tree, thus requiring different types of treatment, including pancreatectomies and extrahepatic bile duct resections.This review presents and discusses the state of the art in the laparoscopic and robotic surgical treatment of all types of CC.An electronic search was performed to identify all studies dealing with laparoscopic or robotic surgery and cholangiocarcinoma.Laparoscopic resection in patients with intrahepatic CC (ICC) is feasible and safe. Regarding oncologic adequacy, as R0 resections, depth of margins, and long-term overall and disease-free survival, laparoscopy is comparable to open procedures for ICC. An adequate patient selection is required to obtain optimal results.Use of laparoscopy in perihilar CC (PHC) has not gained popularity. Further studies are still needed to confirm the benefit of this approach over conventional surgery for PHC.Laparoscopic pancreaticoduodenectomy for distal CC (DCC) represents one of the most advanced abdominal operations owing to the necessity of a complex dissection and reconstruction and has also had small widespread so far.Minimally invasive surgery seems feasible and safe especially for ICC. Laparoscopy for PHC is technically challenging notably for the caudate lobectomy. Not least as for the LLR, the robotic approach for DCC appears technically achievable in selected patients.



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Vaccinations in early life are not associated with development of islet autoimmunity in type 1 diabetes high-risk children: Results from prospective cohort data

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Publication date: Available online 3 March 2017
Source:Vaccine
Author(s): Andreas Beyerlein, Andreas N. Strobl, Christiane Winkler, Michaela Carpus, Annette Knopff, Ewan Donnachie, Donna P. Ankerst, Anette-G. Ziegler
Aims/hypothesisVaccinations in early childhood potentially stimulate the immune system and may thus be relevant for the pathogenesis of autoimmune diseases such as type 1 diabetes (T1D). We determined the association of vaccination burden with T1D-associated islet autoimmunity in children with high familial risk followed prospectively from birth.MethodsA total of 20,570 certified vaccination records from 1918 children were correlated with time to onset of T1D-associated islet autoimmunity using Cox regression, considering multiple time periods up until age two years and vaccination types, and adjusting for HLA genotype, sex, delivery mode, season of birth, preterm delivery and maternal T1D status. Additionally, prospective claims data of 295,420 subjects were used to validate associations for the tick-borne encephalitis (TBE) vaccination.ResultsMost vaccinations were not associated with a significantly increased hazard ratio (HR) for islet autoimmunity (e.g. HR [95% confidence interval]: 1.08 [0.96–1.21] per additional vaccination against measles, mumps and rubella at age 0–24months). TBE vaccinations within the first two years of life were nominally associated with a significantly increased autoimmunity risk (HR: 1.44 [1.06–1.96] per additional vaccination at age 0–24months), but this could not be confirmed with respect to outcome T1D in the validation cohort (HR: 1.02 [0.90–1.16]).ConclusionsWe found no evidence that early vaccinations increase the risk of T1D-associated islet autoimmunity development. The potential association with early TBE vaccinations could not be confirmed in an independent cohort and appears to be a false positive finding.



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VaxArray assessment of influenza split vaccine potency and stability

Publication date: Available online 3 March 2017
Source:Vaccine
Author(s): Laura R. Kuck, Stephen Saye, Sam Loob, Sylke Roth-Eichhorn, Rose Byrne-Nash, Kathy L. Rowlen
Vaccine manufacturers require more rapid and accurate tools to characterize the potency and stability of their products. Currently, the gold standard for influenza vaccine potency is the single radial immunodiffusion (SRD) assay, which has inherent disadvantages. The primary objective of this study was to investigate the ability of the VaxArray Influenza (VXI) seasonal hemagglutinin (sHA) potency assay to accurately quantify potency and stability in finished vaccines as well as to quantify hemagglutinin protein (HA) within crude in-process samples. Monobulk intermediates and mono- and multivalent vaccines were tested using VXI. Quantification of HA in crude samples was evaluated by spiking known concentrations of HA into allantoic fluid. VXI generated SRD equivalent potency measurements with high accuracy (within ±10%) and precision (CV 10±4%) for antigen components of monobulk intermediates and multivalent split vaccines. For these vaccines and vaccine intermediates, the VXI linear dynamic range was ∼0.01–0.6μg/mL, which is 12× greater than the linear range of SRD. The measured sample limit of detection (LOD) for VXI varied from 0.005 to 0.01μg/mL for the different subtypes, which in general is ≥600× lower than the LOD for SRD. VXI was able to quantify HA in crude samples where HA only accounts for 0.02% of the total protein content. Stability indication was investigated by tracking measured potency as a function of time at elevated temperature by both SRD and VXI. After 20 h at 56°C, the ratio of VXI to SRD measured potency in a quadrivalent vaccine was 76%, 125%, 60%, and 98% for H1/California, H3/Switzerland, B/Phuket and B/Brisbane, respectively. Based on the study results, it is concluded that VXI is a rapid, multiplexed immunoassay that can be used to accurately determine flu vaccine potency and stability in finished product and in crude samples from upstream processes.



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Adverse events following quadrivalent meningococcal CRM-conjugate vaccine (Menveo®) reported to the Vaccine Adverse Event Reporting system (VAERS), 2010–2015

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Publication date: Available online 3 March 2017
Source:Vaccine
Author(s): Tanya R. Myers, Michael M. McNeil, Carmen S. Ng, Rongxia Li, Paige W. Lewis, Maria V. Cano
BackgroundLimited data are available describing the post-licensure safety of meningococcal vaccines, including Menveo®. We reviewed reports of adverse events (AEs) to the Vaccine Adverse Event Reporting System (VAERS) to assess safety in all age groups.MethodsVAERS is a national spontaneous vaccine safety surveillance system co-administered by the Centers for Disease Control and Prevention and the US Food and Drug Administration. We searched the VAERS database for US reports of adverse events in persons who received Menveo from 1 January 2010 through 31 December 2015. We clinically reviewed reports and available medical records for serious AEs, selected pre-specified outcomes, and vaccination during pregnancy. We used empirical Bayesian data mining to identify AEs that were disproportionately reported after receipt of Menveo.ResultsDuring the study period, VAERS received 2614 US reports after receipt of Menveo. Of these, 67 were classified as serious, including 1 report of death. Adolescents (aged 11–18years) accounted for 74% of reports. Most of the reported AEs were non-serious and described AEs consistent with data from pre-licensure studies. Anaphylaxis and syncope were the two most common events in the serious reports. We did not identify any new safety concerns after review of AEs that exceeded the data mining threshold, although we did observe disproportionate reporting for terms that were not associated with an adverse event (e.g., "incorrect drug dosage form administered", "wrong technique in drug usage process"). Although reports were limited, we did not find any evidence for concern regarding the use of Menveo during pregnancy.ConclusionsIn our review of VAERS reports, findings of AEs were consistent with the data from pre-licensure studies. Vaccine providers should continue to emphasize and adhere to proper administration of the vaccine.



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Safety and immunogenicity of inactivated varicella-zoster virus vaccine in adults with hematologic malignancies receiving treatment with anti-CD20 monoclonal antibodies

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Publication date: Available online 3 March 2017
Source:Vaccine
Author(s): Janie Parrino, Shelly A. McNeil, Steven J. Lawrence, Eva Kimby, Marco F. Pagnoni, Jon E. Stek, Yanli Zhao, Ivan S.F. Chan, Susan S. Kaplan
BackgroundImmunocompromised patients can experience significant morbidity and occasional mortality from complications associated with herpes zoster (HZ), but live attenuated HZ vaccine is contraindicated for these patients. Inactivated zoster vaccine (ZVIN) is in development for prevention of HZ in immunocompromised patients. However, there are limited data in the literature regarding the effect of anti-CD20 monoclonal antibodies on vaccine-related cell-mediated immune response. This study evaluated safety and immunogenicity of ZVIN in patients with hematologic malignancies (HM) receiving anti-CD20 monoclonal antibodies (alone or in combination chemotherapy regimens) and not likely to undergo hematopoietic cell transplant (HCT) (n=80).MethodsThis was an open-label, single-arm, multicenter Phase I study (NCT01460719) of a 4-dose ZVIN regimen (∼30days between doses) in patients ⩾18years old. Blood samples were collected prior to dose 1 and 28days Postdose 4 to measure varicella zoster virus (VZV)-specific T-cell responses using interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT). The primary hypothesis was that ZVIN would elicit significant VZV-specific immune responses at ∼28days Postdose 4, with a geometric fold rise (GMFR) >1.0. All vaccinated patients were evaluated for adverse events (AE) through 28days Postdose 4.ResultsZVIN elicited a statistically significant VZV-specific immune response measured by IFN-γ ELISPOT at 28days Postdose 4 (GMFR=4.34 [90% CI:3.01, 6.24], p-value<0.001), meeting the pre-specified success criterion.Overall, 85% (68/80) of patients reported ⩾1 AE, 44% (35/80) reported ⩾1 injection-site AE, and 74% (59/80) reported ⩾1 systemic AE. The majority of systemic AEs were non-serious and considered unrelated to vaccination by the investigator. Frequencies of AEs did not increase with subsequent doses of vaccine. No recipient of ZVIN had rash polymerase chain reaction (PCR) positive for VZV vaccine strain.ConclusionsIn adults with HM receiving anti-CD20 monoclonal antibodies, ZVIN was well-tolerated and elicited statistically significant VZV-specific T-cell responses ∼28days Postdose 4.CLINICALTRIALS.GOV identifier: NCT01460719.



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Long-term mortality after IPD and bacteremic versus non-bacteremic pneumococcal pneumonia

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Publication date: Available online 3 March 2017
Source:Vaccine
Author(s): Gertjan H.J. Wagenvoort, Elisabeth A.M. Sanders, Hester E. de Melker, Arie van der Ende, Bart J. Vlaminckx, Mirjam J. Knol
BackgroundShort-term mortality after invasive pneumococcal disease (IPD) and pneumococcal pneumonia is high but data on long-term mortality (including the comparison between bacteremic and non-invasive/non-bacteremic pneumococcal pneumonia) within the first years after diagnosis are scarce.MethodsAdult patients with 'non-pneumonia' IPD and 'invasive pneumonia' (from 2004 to 2012) and with 'bacteremic' vs 'non-invasive/non-bacteremic (NI/NB)' pneumococcal pneumonia (from 2008 to 2012) diagnosed by negative blood culture but a positive urinary antigen test (UAT) were identified in a Dutch hospital. Mortality of patients up to 10years after diagnosis was compared with age- and sex-matched life-expectancy data of the general population. Multivariable Cox regression analysis was used to study predictors for mortality in invasive pneumonia patients and to adjust for confounders comparing mortality between bacteremic and NI/NB/UAT-positive pneumonia patients.ResultsOf 228 invasive pneumonia patients 17% died within 30days and in 30-day survivors cumulative long-term mortality at 1 and 5years were 16% and 39% as compared with 3% and 15% in age- and sex-matched persons. High mortality was largely dependent on pre-existent comorbidities. In invasive pneumonia patients who survived the first 30days, age, male gender, chronic cardiovascular disease, malignancy and PCV7 serotype disease were independent predictors for higher long-term mortality. For bacteremic pneumonia patients (n=128) 30-day mortality was 16% and almost similar to 14% in NI/NB/UAT-positive pneumococcal pneumonia patients (n=170). In 30-day survivors of bacteremic pneumonia (n=108, median age 66years), cumulative mortality at 1 and 3years were 13% and 29% as compared with 18% and 40% in NI/NB/UAT-positive pneumococcal pneumonia patients (n=146, median age 67years) without a significant difference in mortality.ConclusionsApproximately 40% of all patients, who survived the first 30days after presentation with non-pneumonia IPD and pneumococcal pneumonia died within the following 5years. High long-term mortality was largely dependent on pre-existent comorbidity.



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Developing and financing neglected disease vaccines in our new era of “blue marble health” and the anthropocene epoch

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Publication date: Available online 3 March 2017
Source:Vaccine
Author(s): Peter J. Hotez
New findings of widespread neglected diseases among the poor living in wealthy group of 20 (G20) economies and the concept of "blue marble health" offer innovative mechanisms for financing urgently new vaccines, especially for vector-borne neglected tropical diseases (NTDs). This approach could complement or parallel a recently suggested global vaccine development fund for pandemic threats.



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Report from the World Health Organization’s third Product Development for Vaccines Advisory Committee (PDVAC) meeting, Geneva, 8–10th June 2016

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Publication date: Available online 3 March 2017
Source:Vaccine
Author(s): Birgitte K. Giersing, Johan Vekemans, Samantha Nava, David C. Kaslow, Vasee Moorthy
The third meeting of WHO's Product Development for Vaccines Advisory Committee (PDVAC) was held in June 2016, with a remit to revisit the pathogen areas for which significant progress has occurred since recommendations from the 2015 meeting, as well as to consider new advances in the development of vaccines against other pathogens. Since the previous meeting, significant progress has been made with regulatory approvals of the first malaria and dengue vaccines, and the first phase III trials of a respiratory syncytial virus (RSV) vaccine candidate has started in the elderly and pregnant women. In addition, PDVAC has also supported vaccine development efforts against important emerging pathogens, including Middle Eastern Coronavirus (MERS CoV) and Zika virus. Trials of HIV and tuberculosis vaccine candidates are steadily progressing towards pivotal data points, and the leading norovirus vaccine candidate has entered a phase IIb efficacy study. WHO's Immunization, Vaccine and Biologicals (IVB) department is actively working in several pathogen areas on the recommendation of PDVAC, as well as continuing horizon scanning for advances in the development of vaccines that may benefit low and middle income countries (LMICs), such as the recent licensure of the enterovirus 71 (EV71) vaccine in China. Following on from discussions with WHO's Strategic Advisory Group of Experts (SAGE) on Immunization, PDVAC will also look beyond licensure and consider data needs for vaccine recommendation and implementation to reduce the delay between vaccine approval and vaccine impact.



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A randomized study of fever prophylaxis and the immunogenicity of routine pediatric vaccinations

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Publication date: Available online 3 March 2017
Source:Vaccine
Author(s): Jacek Wysocki, Kimberly J. Center, Jerzy Brzostek, Ewa Majda-Stanislawska, Henryk Szymanski, Leszek Szenborn, Hanna Czajka, Barbara Hasiec, Jerzy Dziduch, Teresa Jackowska, Anita Witor, Elżbieta Kopińska, Ryszard Konior, Peter C. Giardina, Vani Sundaraiyer, Scott Patterson, William C. Gruber, Daniel A. Scott, Alejandra Gurtman
ObjectiveProphylactic antipyretic use during pediatric vaccination is common. This study assessed whether paracetamol or ibuprofen prophylaxis interfere with immune responses to the 13-valent pneumococcal conjugate vaccine (PCV13) given concomitantly with the combined DTaP/HBV/IPV/Hib vaccine.MethodsSubjects received prophylactic paracetamol or ibuprofen at 0, 6–8, and 12–16 h after vaccination, or 6–8 and 12–16 h after vaccination at 2, 3, 4, and 12months of age. At 5 and 13months, immune responses were evaluated versus responses in controls who received no prophylaxis.ResultsAfter the infant series, paracetamol recipients had lower levels of circulating serotype-specific pneumococcal anticapsular immunoglobulin G than controls, reaching significance (P<0.0125) for 5 serotypes (serotypes 3, 4, 5, 6B, and 23F) when paracetamol was started at vaccination. Opsonophagocytic activity assay (OPA) results were similar between groups. Ibuprofen did not affect pneumococcal responses, but significantly (P<0.0125) reduced antibody responses to pertussis filamentous hemagglutinin and tetanus antigens after the infant series when started at vaccination. No differences were observed for any group after the toddler dose.ConclusionsProphylactic antipyretics affect immune responses to vaccines; these effects vary depending on the vaccine, antipyretic agent, and time of administration. In infants, paracetamol may interfere with immune responses to pneumococcal antigens, and ibuprofen may reduce responses to pertussis and tetanus antigens. The use of antipyretics for fever prophylaxis during infant vaccination merits careful consideration.ClinicalTrials.gov identifier: NCT01392378https://clinicaltrials.gov/ct2/show/NCT01392378?term=NCT01392378&rank=1



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World Health Organization (WHO), Eastern Mediterranean Regional Office (EMRO) Regional Technical Advisory Group (RTAG) on immunization: Request for nominations

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Publication date: Available online 3 March 2017
Source:Vaccine





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Seguimiento de pacientes pediátricos con histiocitosis de Langerhans mediante PET/TC con 18F-FDG

Publication date: Available online 3 March 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): J.R. Garcia, E. Riera, P. Bassa, S. Mourelo, M. Soler
ObjetivoEvaluar el impacto de la 18F-FDG PET/TC en la identificación de focos de enfermedad activa y el seguimiento terapéutico en un grupo de pacientes pediátricos con histiocitosis de células de Langerhans (HCL).MétodoEntre 2007-2013 se efectuaron 13 estudios 18F-FDG PET/TC de seguimiento en 7 pacientes diagnosticados de HCL (4 niñas, 3 varones; 1-12 años). Se analizaron los hallazgos PET y se correlacionaron con los de la TC y la RM, así como el seguimiento evolutivo con estas técnicas.ResultadosLa PET fue negativa en 4 pacientes (todos diagnosticados de lesiones óseas y afectación hipofisaria en un caso). La TC mostró persistencia de lesiones, de carácter residual, en todos los pacientes, y la RM de hipófisis mostró su normalización. La PET permaneció negativa a los 10, 14, 25 y 28 meses, sin detectar nuevas lesiones mediante TC ni RM. La PET fue positiva en 3 pacientes (uno con adenopatías cervicales y 2 con lesiones óseas y afectación hipofisaria en uno de ellos, no identificada por la PET). Los hallazgos de la TC fueron adenopatía cervical patológica (n=1) y lesiones óseas (n=2), y de la RM, lesión hipofisaria (n=1). En el paciente con adenopatía cervical la anatomía patológica mostró afectación por HCL. En los otros 2 pacientes, la PET permaneció positiva, con aumento de la captación ósea de 18F-FDG a los 17 y 19 meses.ConclusiónEn este estudio preliminar, la 18F-FDG PET constituye una técnica de imagen útil, junto con otras pruebas diagnósticas, para identificar lesiones activas y monitorizar la respuesta terapéutica en pacientes pediátricos con HCL.PurposeWe evaluated the impact of 18F-FDG PET/CT in identifying sites of active disease and to assess therapeutic follow up in a group of pediatric patients with Langerhans cell histiocytosis (LCH).MethodDuring 2007-2013, 13 18F-FDG PET/CT studies were performed for follow-up in 7 patients with a diagnosis of LCH (4 female, 3 male; 1-12 years-old). PET findings were analyzed and correlated with the CT and MRI. Findings were also follow-up by these techniques.ResultsPET was negative in 4 patients (all diagnosed with bone lesions and one with pituitary involvement also). CT findings showed residual morphological bone lesions in all patients, and hypophysis MRI study showed no abnormal signal. PET remained negative at 10, 14, 25 and 28 months, and no new lesions on CT and MRI were detected. PET was positive in 3 patients (one with cervical lymphadenopathy and 2 with bone lesions, one also with pituitary involvement not identified by PET). CT findings showed pathological cervical lymphadenopathy (n=1), bone lesions (n=2) and also a pituitary MRI lesion (n=1). In a patient with cervical lymphadenopathy histology demonstrated LCH involvement. In the other 2 patients, PET remained positive with an increase of 18F-FDG bone uptake at 17 and 19 months.ConclusionIn our preliminar study, 18F-FDG PET is a useful imaging procedure, along with other diagnostic tools, for identification of active lesions.



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Incidental meningioma detected by using 99mTc-MIBI SPECT/CT

Publication date: Available online 3 March 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): D. Albano, L. Camoni, G. Bosio, F. Bertagna




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Hydrothorax secondary to peritoneal dialysis detected by peritoneal scintigraphy

Publication date: Available online 3 March 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): D. Balaguer, P. Abreu, T. Mut, M.D. Reyes, M.C. Plancha, E. Caballero




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Assessment of cardiovascular impairment in obese patients: Limitations and troubleshooting of available imaging tools

Publication date: Available online 3 March 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): V. Gaudieri, C. Nappi, W. Acampa, R. Assante, E. Zampella, M. Magliulo, M. Petretta, A. Cuocolo
The prevalence and severity of obesity have increased over recent decades, reaching worldwide epidemics. Obesity is associated to coronary artery disease and other risk factors, including hypertension, heart failure and atrial fibrillation, which are all increased in the setting of obesity. Several noninvasive cardiac imaging modalities, such as echocardiography, cardiac computed tomography, magnetic resonance and cardiac gated single-photon emission computed tomography, are available in assessing coronary artery disease and myocardial dysfunction. Yet, in patients with excess adiposity the diagnostic accuracy of these techniques may be limited due to some issues. In this review, we analyze challenges and possibilities to find the optimal cardiac imaging approach to obese population.



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Lésions cutanées de médecine traditionnelle soudanaise

Publication date: Available online 3 March 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): P. Charlier, F. Bou Abdallah, Y. Mostefai, L. Brun, C. Hervé




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Editorial Board

Publication date: February 2017
Source:Acta Oecologica, Volume 79





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Synthesis and Molecular Docking Studies of New Furochromone Derivatives As p38 α MAPK Inhibitors Targeting Human Breast Cancer MCF-7cells

Publication date: Available online 3 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Kamelia M. Amin, Yasmin M. Syam, Manal M. Anwar, Hamed I. Ali, Tamer M. Abdel-Ghani, Aya M. Serry
Based on the reported high expression of p38α MAP kinase in invasive breast cancers and the activity of different functionalized chromone derivatives as p38α inhibitors, a new set of 4,9-dimethoxy/4-methoxy-7-methyl-5-oxo-5H-furo[3,2-g]chromone derivatives were efficiently synthesized aiming to introduce new p38α MAP kinase suppressors as new anti-breast cancer tools. Using GOLD program, molecular docking study of the target compounds into p38 α MAP kinase binding pocket was performed to highlight their scores, mode of binding and the important interactions to the amino acid residues of the enzyme. MTT assay investigated that fifteen target compounds produced marked cytotoxic potency higher than that obtained by Doxorubicin against MCF-7 cancer cells of IC50 values ranging from 0.007 to 0.17 uM vs IC50; 0.62 uM of doxorubicin. Eleven selected compounds were evaluated for their inhibitory potency against p38 α MAPK kinase. The derivatives IVa, Va,b, VIa, IXb and XIIIa represented significant activity (IC50; 0.19-0.67 uM) comparing to the reference drug SB203580 (IC50; 0.50 uM). In virtue of its promising cytotoxic and p38α MAP kinase inhibition potency, the furochromone derivative IXb was selected as a representative example to investigate its mechanistic effects on cell cycle progression and induction of apoptosis in MCF-7 cell lines. The results showed that the compound IXb induced cell cycle cessation at G2/M phase preventing its mitotic cycle, alongside its noteworthy activation of caspases-9 and -3 which might mediate the apoptosis of MCF-7 cells.

Graphical abstract

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The assessment and appraisal of regenerative medicines and cell therapy products: an exploration of methods for review, economic evaluation and appraisal.

Determining the long-term effectiveness and costs of regenerative medicines will be associated with considerable uncertainty and potential bias, but existing methods are sufficient to incorporate this uncertainty for decision-making.

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The Fourth Industrial Revolution: Proceedings of a Workshop—in Brief.

In October 2016, the National Academies of Sciences, Engineering, and Medicine held a meeting to consider the Fourth Industrial Revolution and its implications for manufacturing, as well as its likely social and economic effects. The meeting also explored the cross-sector collaboration between government, universities, and industry needed to accommodate emerging developments in the key technologies of the Fourth Industrial Revolution, namely artificial intelligence, virtual and augmented reality, and the Internet of Things. This publication briefly summarizes the presentations and discussions from the meeting.

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Unveiling the Role of Senescence-Induced Cellular Plasticity

Publication date: 2 March 2017
Source:Cell Stem Cell, Volume 20, Issue 3
Author(s): Jumpei Taguchi, Yasuhiro Yamada
Mice expressing Yamanaka factors develop teratomas containing iPSCs, suggesting that somatic cells are reprogrammable in vivo. Recent studies in Cell, Science, and this issue of Cell Stem Cell (Ocampo et al., 2016; Mosteiro et al., 2016; Chiche et al., 2017, respectively) report crosstalk between reprogramming and senescence, providing insights on cellular plasticity in multicellular organisms.

Teaser

Mice expressing Yamanaka factors develop teratomas containing iPSCs, suggesting that somatic cells are reprogrammable in vivo. Recent studies in Cell, Science, and this issue of Cell Stem Cell (Ocampo et al., 2016; Mosteiro et al., 2016; Chiche et al., 2016, respectively) report crosstalk between reprogramming and senescence, providing insights on cellular plasticity in multicellular organisms.


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A Back Door to Cortical Development

Publication date: 2 March 2017
Source:Cell Stem Cell, Volume 20, Issue 3
Author(s): Gerd Kempermann
The mammalian cortex develops in an "inside-out" manner, as neural stem and progenitor cells lining the ventricles build the brain from within. Bifari et al. (2017), in this issue of Cell Stem Cell, find a small set of cortical neurons that appear to originate from radial glia-like progenitors in the meninges, suggesting an outside-in contribution to corticogenesis.

Teaser

The mammalian cortex develops in an "inside-out" manner, as neural stem and progenitor cells lining the ventricles build the brain from within. Bifari et al. (2017), in this issue of Cell Stem Cell, find a small set of cortical neurons that appear to originate from radial glia-like progenitors in the meninges, suggesting an outside-in contribution to corticogenesis.


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Pericytes or Mesenchymal Stem Cells: Is That the Question?

Publication date: 2 March 2017
Source:Cell Stem Cell, Volume 20, Issue 3
Author(s): Elena Cano, Véronique Gebala, Holger Gerhardt
For almost a decade, mesenchymal stem cells (MSCs) were believed to reside as perivascular cells in vivo. In this issue of Cell Stem Cell, Guimarães-Camboa et al. (2017) challenge this idea and use lineage tracing to demonstrate that perivascular cells do not behave as tissue-specific progenitors in various organs, despite showing MSC potential in vitro.

Teaser

For almost a decade, mesenchymal stem cells (MSCs) were believed to reside as perivascular cells in vivo. In this issue of Cell Stem Cell, Guimarães-Camboa et al. (2017) challenge this idea and use lineage tracing to demonstrate that perivascular cells do not behave as tissue-specific progenitors in various organs, despite showing MSC potential in vitro.


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Bridging the Gaps: iPSC-Based Models from CHIP to MDS to AML

Publication date: 2 March 2017
Source:Cell Stem Cell, Volume 20, Issue 3
Author(s): Kathrin M. Bernt
Myeloid malignancies exist on a spectrum from asymptomatic clonal hematopoiesis to overt leukemia and exhibit substantial clonal heterogeneity. Both aspects are challenging to capture in experimental models. In two landmark studies in this issue of Cell Stem Cell, Kotini et al. (2017) and Chao et al. (2017) establish iPSC-based experimental platforms that recapitulate disease stages and clonal architecture.

Teaser

Myeloid malignancies exist on a spectrum from asymptomatic clonal hematopoiesis to overt leukemia and exhibit substantial clonal heterogeneity. Both aspects are challenging to capture in experimental models. In two landmark studies in this issue of Cell Stem Cell, Kotini et al. (2017) and Chao et al. (2017) establish iPSC-based experimental platforms that recapitulate disease stages and clonal architecture.


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Bringing a Leukemic Stem Cell Gene Signature into Clinics: Are We There Yet?

Publication date: 2 March 2017
Source:Cell Stem Cell, Volume 20, Issue 3
Author(s): Guillaume Richard-Carpentier, Guy Sauvageau
Prognostic markers that capture leukemia stem cell (LSC) activity can be useful for the risk stratification of acute myeloid leukemia (AML) patients. In a recent issue of Nature, Ng et al. (2016) develop a prognostic score based on a 17-gene expression signature of LSCs to predict outcome in AML patients.

Teaser

Prognostic markers that capture leukemia stem cell (LSC) activity can be useful for the risk stratification of acute myeloid leukemia (AML) patients. In a recent issue of Nature, Ng et al. (2016) develop a prognostic score based on a 17-gene expression signature of LSCs to predict outcome in AML patients.


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Unsaturated Fatty Acids Maintain Cancer Cell Stemness

Publication date: 2 March 2017
Source:Cell Stem Cell, Volume 20, Issue 3
Author(s): Abir Mukherjee, Hilary A. Kenny, Ernst Lengyel
Investigation of the metabolic regulation of cancer stem cells is an emerging field that offers promising approaches for identifying and targeting recalcitrant stem cell populations. In this issue of Cell Stem Cell, Li et al. (2017) indicate that increased lipid desaturation is essential to stem-like characteristics in ovarian cancer cells.

Teaser

Investigation of the metabolic regulation of cancer stem cells is an emerging field that offers promising approaches for identifying and targeting recalcitrant stem cell populations. In this issue of Cell Stem Cell, Li et al. (2017) indicate that increased lipid desaturation is essential to stem-like characteristics in ovarian cancer cells.


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DNA Damage-Induced HSPC Malfunction Depends on ROS Accumulation Downstream of IFN-1 Signaling and Bid Mobilization

Publication date: 2 March 2017
Source:Cell Stem Cell, Volume 20, Issue 3
Author(s): Alpaslan Tasdogan, Suresh Kumar, Gabriele Allies, Julia Bausinger, Franziska Beckel, Helmut Hofemeister, Medhanie Mulaw, Vikas Madan, Karin Scharffetter-Kochanek, Michaela Feuring-Buske, Konstanze Doehner, Günter Speit, A. Francis Stewart, Hans Joerg Fehling




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IMRT Plus Cisplatin Versus IMRT in Patients With Stage 2 Nasopharyngeal Carcinoma

Condition:   Nasopharyngeal Carcinoma
Interventions:   Radiation: Intensity modulated radiotherapy;   Drug: Cisplatin
Sponsor:   Nanfang Hospital of Southern Medical University
Not yet recruiting - verified September 2016

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Stereotactic Radiotherapy Combined With Chemotherapy or Not for Treatment of Oligometastases in HNSCC

Condition:   Head and Neck Squamous Cell Carcinoma
Interventions:   Drug: Chemotherapy;   Radiation: Stereotactic radiotherapy
Sponsor:   Groupe Oncologie Radiotherapie Tete et Cou
Recruiting - verified February 2017

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Fever and Malaise in an Infant

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Publication date: Available online 2 March 2017
Source:The Journal of Emergency Medicine
Author(s): David S. Young, Emily S. Miller, Kriti Bhatia




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Fever and Back Pain in a Preschool Teacher

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Publication date: Available online 2 March 2017
Source:The Journal of Emergency Medicine
Author(s): Kimberly A. Stanford, Emily S. Miller, Kriti Bhatia




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Pediatric Sepsis Secondary to an Occult Dental Abscess: A Case Report

Publication date: Available online 3 March 2017
Source:The Journal of Emergency Medicine
Author(s): Peter Holmberg, Thomas Hellmich, James Homme
BackgroundIn general, hematogenous spread of bacteria in children is uncommon. Bacteremia, however, is a known complication of dental procedures and severe caries, but is infrequently associated with primary, asymptomatic, non-procedural-related, dentoalveolar infection.Case ReportThe patient is a 7-year-old previously healthy boy who presented to the Emergency Department (ED) with "fever, mottling, and shaking chills." In the ED, he appeared systemically ill with fever, mottling, delayed capillary refill, and rigors. Physical examination by three different physicians failed to reveal any focus of infection. Laboratory evaluation, including blood cultures, was obtained. The patient later developed unilateral facial swelling and pain, and a dentoalveolar abscess was found. He was started on antibiotics, underwent pulpectomy and eventually, extraction, prior to improvement in symptoms. Blood cultures grew two separate anaerobic bacteria (Veillonella and Lactobacillus). This is, to our knowledge, one of the first reported cases of pediatric sepsis with two different anaerobic organisms secondary to occult dentoalveolar abscess in a pediatric patient.Why Should an Emergency Physician Be Aware of This?It is imperative for emergency physicians to recognize the possibility of pediatric sepsis in the setting of acute maxillary or mandibular pain, as well as in patients for whom no clear focus of infection can be found. This is particularly important for those who appear ill at presentation or meet systemic inflammatory response syndrome criteria and would benefit from further laboratory evaluation, including blood cultures, and possibly antibiotic therapy.



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Valence and arousal of emotional stimuli impact cognitive-motor performance in an oddball task

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Publication date: Available online 2 March 2017
Source:Biological Psychology
Author(s): Yingzhi Lu, Kyle J. Jaquess, Bradley D. Hatfield, Chenglin Zhou, Hong Li
It is widely recognized that emotions impact an individual's ability to perform in a given task. However, little is known about how emotion impacts the various aspects of cognitive -motor performance. We recorded event-related potentials (ERPs) and chronometric responses from twenty-six participants while they performed a cognitive-motor oddball task in regard to four categories of emotional stimuli (high-arousing positive-valence, low-arousing positive-valence, high-arousing negative-valence, and low-arousing negative-valence) as "deviant" stimuli. Six chronometric responses (reaction time, press time, return time, choice time, movement time, and total time) and three ERP components (P2, N2 and late positive potential) were measured. Results indicated that reaction time was significantly affected by the presentation of emotional stimuli. Also observed was a negative relationship between N2 amplitude and elements of performance featuring reaction time in the low-arousing positive-valence condition. This study provides further evidence that emotional stimuli influence cognitive-motor performance in a specific manner.



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The effects of strengthening exercises for wrist flexors and extensors on muscle strength and counter-stroke performance in amateur table tennis players

Publication date: Available online 3 March 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Raoyrin Chanavirut, Nontawit Udompanich, Phraophimon Udom, Ponlapat Yonglitthipagon, Wanida Donpunha, Saowanee Nakmareong, Juinichiro Yamauchi
This study aims to evaluate the effects of strengthening exercises on wrist flexor and extensor strength, hand grip strength, and counter-stroke performance. Thirty amateur table tennis players were recruited and randomly allocated into two groups: the control and the training group (n=15/group). Pre- and post-data were collected. The training group performed home exercises for six weeks using a bucket filled with water, while the controls were asked to keep their lifestyle as usual. The general characteristics were no significant differences. The training group showed significantly higher levels of wrist flexor and extensor strength than the control group (p<0.05). However, the difference in hand grip strength was not statistically significant. Both groups showed significant improvement in counter-stroke performance (p<0.05), however, there was no difference between the groups. In conclusion, specific strengthening exercises increase wrist flexor and extensor strength, but they have no effect on either hand grip strength or counter-stroke performance.



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Anti-PD-L1 atezolimumab-Induced Autoimmune Diabetes: a Case Report and Review of the Literature

Abstract

Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors trigger an immune-mediated anti-tumour response by promoting the activation of cytotoxic T lymphocytes. Although proven to be highly effective in the treatment of several malignancies they can induce significant immune-related adverse events (irAEs) including endocrinopathies, most commonly hypophysitis and thyroid dysfunction, and rarely autoimmune diabetes. Here we present the first case report of a patient with a primary diagnosis of urothelial cancer developing PD-L1 inhibitor-induced autoimmune diabetes. A euglycemic 57 year old male presented to clinic with dehydration after the fifth cycle of treatment with the novel PD-L1 inhibitor atezolizumab. Blood tests demonstrated rapid onset hyperglycaemia (BM 24 mmol/L), ketosis and a low C-peptide level (0.65 ng/mL) confirming the diagnosis of type 1 diabetes. He responded well to insulin therapy and was discharged with stable blood glucose levels. Due to the widening use of PD-1/PD-L1 inhibitors in cancer treatment clinicians need to be aware of this rare yet treatable irAE. Given the morbidity and mortality associated with undiagnosed autoimmune diabetes we recommend routine HbA1c and plasma glucose testing in all patients prior to and during treatment with PD-1/PD-L1 inhibitors until more evidence has accumulated on identifying those patients with a pre-treatment risk of such irAEs.



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Outcome in advanced non-small cell lung cancer patients with successful rechallenge after recovery from epidermal growth factor receptor tyrosine kinase inhibitor-induced interstitial lung disease

Abstract

Purpose

Several non-small cell lung cancer (NSCLC) cases of successful rechallenge with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) after recovery from gefitinib or erlotinib-induced interstitial lung disease (ILD) have been reported, but it is not clear whether the rechallenge affects the outcome.

Methods

We retrospectively evaluated the difference in the outcome between advanced NCLC patients with active EGFR mutations who received EGFR-TKI rechallenge after recovery from EGFR-TKI-induced ILD and those who did not.

Results

EGFR-TKI-induced ILD occurred in 11 (10%) of 110 patients receiving gefitinib, five (7%) of 73 patients receiving erlotinib and one (8%) of 13 patients receiving afatinib. Diffuse alveolar damage pattern ILD was observed in six cases, four of which had chemotherapy-related death. Five of 13 patients who had recovered from ILD received EGFR-TKI rechallenge with concurrent oral administration of prednisolone 0.5 mg/kg after the strict informed consent of the risk for the recurrence of severe ILD. All of the five patients achieved a partial response. The median overall survival from the occurrence of EGFR-TKI-induced ILD was longer in patients with EGFR-TKI rechallenge than that in patients without (15.5 vs. 3.5 months, p = 0.029). The adverse events of EGFR-TKI rechallenge were tolerable, but one case receiving EGFR-TKI rechallenge with the suspected drug exhibited the recurrence of grade 3 ILD after the discontinuation of prednisolone.

Conclusions

EGFR-TKI rechallenge with concurrent prednisolone therapy might be salvage therapy in advanced NSCLC patients with active EGFR mutations after recovery from EGFR-TKI-induced ILD.



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Retina tissue engineering by conjunctiva mesenchymal stem cells encapsulated in fibrin gel: Hypotheses on novel approach to retinal diseases treatment

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Publication date: Available online 2 March 2017
Source:Medical Hypotheses
Author(s): Mostafa Soleimannejad, Somayeh Ebrahimi-Barough, Samad Nadri, Mohammad Riazi-Esfahani, Masoud Soleimani, Seyed Mohammad Tavangar, Jafar Ai
BackgroundRetinitis pigmentosa (RP) and Age related macular degeneration (AMD) are two retinal diseases that progress by photoreceptor cells death. In retinal transplantation studies, stem and progenitor cells inject into the sub retinal space or vitreous and then these cells can be migrate to the site of retinal degeneration and locate in the host retina and restitute vision.Presentation of the hypothesisOur hypothesis suggests that using human conjunctiva stem cells (as the source for increasing the number of human stem cells progenitor cells in retina dysfunction diseases) with fibrin gel and also assessing its relating in vitro (cellular and molecular processes) and in vivo (vision tests and pathology) could be a promising strategy for treatment of AMD and RP disorders.Testing the hypothesisIn this idea, we describe a novel approach for retina tissue engineering with differentiation of conjunctiva mesenchymal stem cells (CJMSCs) into photoreceptor-like cells in fibrin gel with induction medium contain taurine. For assessment of differentiation, immunocytochemistry and real time PCR are used for the expression of Rhodopsin, RPE65, Nestin as differentiated photoreceptor cell markers in 2D and 3D culture. The results show that fibrin gel will offer a proper 3D scaffold for CJMSCs derived photoreceptor cell-like cells.Implications of the hypothesisApplication of immune-privileged, readily available sources of adult stem cells like human conjunctiva stem cells with fibrin gel would be a promising strategy to increase the number of photoreceptor progenitor cells and promote involuntary angiogenesis needed in retina layer repair and regeneration.



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Social death, melancholia, and zombies: same patterns?

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Publication date: Available online 2 March 2017
Source:Medical Hypotheses
Author(s): P. Charlier, S. Deo, J. Hassin, C. Hervé




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Long-term non-invasive ventilation therapies in children: a scoping review

Long-term non-invasive ventilation (NIV) is a common modality of breathing support used for a range of sleep and respiratory disorders. The aim of this scoping review was to provide a summary of the literature relevant to long-term NIV use in children. We used systematic methodology to identify 11581 studies with final inclusion of 289. We identified 76 terms referring to NIV; the most common term was NIV (22%). Study design characteristics were most often single center (84%), observational (63%), and retrospective (54%).

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Adrenocortical Carcinoma Arising in an Adrenal Rest: a Case Report and Review of the Literature

Abstract

Carcinomas arising from embryonic adrenal rests are rare with only a handful of reported cases. We report a case of an adrenocortical carcinoma arising from an adrenal rest located between the bladder and prostate in a 51 year-old man. The patient presented following a year of rectal pain and constipation. Computed tomography (CT) scan revealed a 9 cm pelvic mass that appeared to arise from the soft tissue between the bladder and prostate, with displacement of the organs and narrowing of the rectal lumen, suspected to be a sarcoma. The surgically resected specimen showed a well-circumscribed, partially encapsulated tumor measuring 10.0 cm in greatest dimension. Both adrenal glands were identified intraoperatively. Grossly, the lesion was heterogeneous tan-brown to yellow, hemorrhagic and necrotic. Histology revealed sheets and nests of high-grade pleomorphic tumor cells with abundant clear to vacuolated cytoplasm with areas of necrosis, a high mitotic index (>10 mitoses/10 HPF) and foci suspicious for lymphovascular invasion. Adjacent adrenal cortical-type tissue was identified. Immunohistochemical stains revealed the tumor cells were weakly and focally positive for MiTF, Melan-A, inhibin and synaptophysin, and negative for CKAE1/AE3, HMB-45, calretinin, EMA, SMA, chromogranin, PAX8, MDM2 and CDK4. Based upon the morphologic and immunohistochemical profile, this was diagnosed as an adrenocortical carcinoma, arising in an adrenal rest. To our knowledge, no such tumor has been previously described in this location.



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Identification and quantification of 12 pharmaceuticals in water collected from milking parlors: Food safety implications

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Publication date: Available online 2 March 2017
Source:Journal of Dairy Science
Author(s): María Veiga-Gómez, Carolina Nebot, Carlos Manuel Franco, Jose Manuel Miranda, Beatriz Vázquez, Alberto Cepeda
The introduction of drug residues into the food chain and their presence in drinking water has been recently investigated. The aim of this work was to monitor the presence of 19 active drugs in water samples collected from milking parlors of dairy farms located in Galicia (northwest Spain), one of the main Spanish milking areas. Overall, 65% of the samples tested positive for at least one of the compounds analyzed. A total of 12 drugs were measured, with concentrations ranging between 17 and 3,941 ng/L. Considering that a mixture of compounds may contribute to the overall effect of each compound and might increase or reduce its toxicity, it should be noted that 29% of the samples tested contained more than one pharmaceutical. To date, the effects of the continuous consumption of these mixtures of drugs in water or milk are unknown; however, antimicrobials may affect the human gut microbiota or have toxic effects in sensitive individuals.



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Short communication: Glucose kinetics in dairy heifers limit-fed a low- or high-forage ration at 4 levels of nitrogen intake

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Publication date: Available online 2 March 2017
Source:Journal of Dairy Science
Author(s): G.I. Zanton, A.J. Heinrichs
The objective of this research was to evaluate the effect of level of forage and N intake on glucose kinetics in growing dairy heifers. Eight Holstein heifers (beginning at 362 ± 7 kg of body weight and 12.3 ± 0.4 mo of age) were fed 8 rations according to a split-plot, 4 × 4 Latin square design with rations containing either high (75% forage dry matter) or low (25% forage dry matter) levels of forage and 4 levels of N intake (0.94, 1.62, 2.30, 2.96 g of N/kg of metabolic BW per day). Diets were limit-fed to maintain equal predicted metabolizable energy intake over the four 28-d periods; dietary N was increased through the substitution of high-N ingredients for corn. Blood samples were collected from all heifers at times throughout d 18 to 19 to characterize glucose concentration over the course of a day, and glucose tolerance tests were conducted over the last 8 d of each period (1 heifer/d) at 4 h before feeding. Glucose concentration transiently declined after feeding for all dietary groups, but we found no evidence of a differential response over time that could be attributed to diet. When averaged over a day, glucose concentration was affected by an interaction between level of forage and N intake; however, this response appeared related more to the level of starch in the diet than to the effects of either forage or N intake per se. Early-phase kinetic response of glucose disposal after an intravenous glucose bolus was not affected by dietary treatment, which is consistent with no difference in area under the curve through 30 min. Area under the curve through 120 min tended to linearly decrease with decreasing dietary N intake. This response corresponded to the kinetic analysis, in which heifers consuming higher N intake had an attenuated return to baseline glucose levels. Additionally, heifers consuming lower N intake maintained a period of glucose concentration below baseline before returning to baseline. We concluded that the response to an intravenous glucose bolus differs in dairy heifers fed diets differing in N intake, whereas forage level did not affect this response. This should be considered when formulating rations for low N intake by replacing high-N for high-starch feedstuffs when limit-feeding dairy heifers.



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Genetic and functional analysis of the bovine uterine microbiota. Part I: Metritis versus healthy cows

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Publication date: Available online 2 March 2017
Source:Journal of Dairy Science
Author(s): M.L.S. Bicalho, V.S. Machado, C.H. Higgins, F.S. Lima, R.C. Bicalho
Metritis is a uterine disease that affects 10 to 30% of all lactating dairy cows and has detrimental effects on reproductive performance, milk production, and survival. Data regarding the identity and abundance of bacterial genes governing traits such as virulence, antibiotic resistance, and stress responses could enable identification of previously unknown agents that play a role in metritis pathogenesis. Moreover, such knowledge could lead to the development of improved treatments or preventive methods. Therefore, the objectives of this study were to characterize the uterine microbial population and to differentiate, for the first time, the microbial functional diversity in cows with metritis versus healthy cows. In addition, we aimed to identify relationships between microbial genes and postpartum uterine health. Uterine swabs were collected from 24 cows within 3 to 12 d in milk; 12 cows were diagnosed with metritis and the other 12 were healthy. Metritis was defined as a watery, reddish or brownish uterine discharge having a fetid smell, and rectal temperature greater than 39.5°C. Cows with a clear and viscous uterine discharge, not fetid or mucopurulent, were classified as healthy. Microbial metagenomic DNA from uterine swab samples was subjected to whole-genome shotgun sequencing on the Illumina MiSeq platform (Illumina Inc., San Diego, CA). The MG-RAST server (metagenomic rapid annotations using subsystems technology; http://ift.tt/1qOVzJC) and STAMP software (http://ift.tt/UtpTJL) were used to detect statistically significant differences in the abundance of taxonomic and functional features between the uterine microbial metagenomes of metritic and healthy cows. Our results showed an increased abundance of Fusobacteria and Bacteroidetes in metritic cows, confirming the potential role of those 2 taxa in the pathogenesis of metritis. The MG-RAST analysis revealed a significantly higher abundance of genes for protein transport across the cytoplasmic membrane and type VI bacterial secretion systems in the metritic microbiota. Additionally, genes coding for resistance to acid stress were exclusive to the metritis microbiota, suggesting that microbial resistance to acid stress is important for microbial survival in the infected uterus. On the other hand, genes coding for adhesion molecules, bacteriocins, and antibacterial peptides were significantly associated with the uterine microbiota of healthy cows, as was tolerance to colicin E2.



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