Hydrogen peroxide test for intraoperative bile leak detection

Publication date: Available online 6 March 2017
Source:Medical Journal Armed Forces India
Author(s): V. Trehan, Pankaj P. Rao, C.S. Naidu, Anuj K. Sharma, A.K. Singh, Sanjay Sharma, Amit Gaur, S.V. Kulkarni, N. Pathak
BackgroundBile leakage (BL) is a common complication following liver surgery, ranging from 3 to 27% in different series. To reduce the incidence of post-operative BL various BL tests have been applied since ages, but no method is foolproof and every method has their own limitations. In this study we used a relatively simpler technique to detect the BL intra-operatively. Topical application of 1.5% diluted hydrogen peroxide (H2O2) was used to detect the BL from cut surface of liver and we compared this with conventional saline method to know the efficacy.MethodsA total of 31 patients included all patients who underwent liver resection and donor hepatectomies as part of Living Donor Liver Transplantation. After complete liver resection, the conventional saline test followed by topical diluted 1.5% H2O2 test was performed on all.ResultsA BL was demonstrated in 11 patients (35.48%) by the conventional saline method and in 19 patients (61.29%) by H2O2 method. Statistically compared by Wilcoxon signed-rank test showed significant difference (P=0.014) for minor liver resections group and (P=0.002) for major liver resections group.ConclusionThe topical application of H2O2 is a simple and effective method of detection of BL from cut surface of liver. It is an easy, non-invasive, cheap, less time consuming, reproducible, and sensitive technique with no obvious disadvantages.



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Cover_spine

Publication date: February 2017
Source:Cancer Genetics, Volume 211





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Editorial Board

Publication date: February 2017
Source:Cancer Genetics, Volume 211





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Table of Contents

Publication date: February 2017
Source:Cancer Genetics, Volume 211





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Efficacy of aflibercept (EYLEA®) on inhibition of human VEGF in vitro

Publication date: Available online 7 March 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): M. Schicht, K. Hesse, H. Schröder, E. Naschberger, W. Lamprecht, F. Garreis, F.P. Paulsen, L. Bräuer
IntroductionPathological formation of blood vessels plays a key role in the growth and metastasis of tumors and also in several serious ophthalmological diseases such as wet age-related macular degeneration (AMD) or diabetic retinopathy. In AMD treatment, aflibercept (tradename EYLEA^®) is used to deactivate the underlying pathological neovascularisation. Aflibercept is a recombinant fusion protein which binds to vascular endothelial growth factor (VEGF) receptors, thereby inhibiting VEGF pathway activation. VEGF is one of the most important angiogenesis factors.ObjectiveThis analysis investigates lasting efficacy of aflibercept in vitro for later application as therapeutic agent against macular degeneration (AMD).Material and MethodsVEGF-ELISA assays were performed to investigate binding affinities at different aflibercept concentrations. The impact of VEGF on the proliferation of human umbilical vein endothelial cells (HUVEC) was investigated using proliferation assays. Moreover, time-dependent kinetic studies were performed to analyze different aflibercept storage durations with regard to its inhibitory capabilities on human VEGF.Results and ConclusionOur results reveal that aflibercept significantly lowers the amount of unbound VEGF as well as the proliferation rate of HUVEC. Moreover, in contrast to specifications given by the manufacturer, aflibercept retains its full inhibitory effect up to at least 120hours after transference from the original vial into the injection syringe.



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What do we know about the structure of human Thymic Hassall’s corpuscles? A histochemical, immunohistochemical, and electron microscopic study

Publication date: Available online 6 March 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Renáta Mikušová, Veronika Mešťanová, Štefan Polák, Ivan Varga
Hassall's corpuscles are the most prominent structures in the human thymus. However, relatively few analyses have been performed to determine their function and cellular origins during development. In this study, we evaluated the cellular microenvironment of human thymic Hassall's corpuscles using histochemistry, immunohistochemistry, and transmission electron microscopy. We examined 95 human thymic tissue samples, which were perioperatively obtained from children undergoing cardiac surgery. To characterize the complex cellular microenvironment of human thymic corpuscles, we used a panel of 14 different antibodies to identify discrete cell types. We also utilized various histochemical methods (PAS reaction, alcian blue staining, alkaline phosphatase and acid phosphatase activity staining, von Kossa staining of calcified particles) and transmission electron microscopy to visualize these structures. Considerable variation in the sizes, shapes, and numbers of Hassall's corpuscles was observed, even amongst children of the same age. Inside the largest Hassall's corpuscles, cystic dilatation with an accumulation of cellular debris was found. These morphological observations might be associated with disruptions in the formation, migration, or differentiation of cardiac neural crest cells, which are essential for heart and thymus development. Immunohistochemical staining and electron microscopy revealed that Hassall's corpuscles resemble other types of stratified squamous epithelia. Most Hassall's corpuscles are heterocellular, consisting of thymic epithelial cells, macrophages, interdigitating dendritic cells, myoid cells, and, occasionally, mast cells and lymphocytes. To explore the potential functions of Hassall's corpuscles, we found that the concentrations of B − lymphocytes and BCL2-positive lymphocytes suggested a role in regulation of lymphopoiesis. We also found that these structures do not originate from the perivascular epithelium as previously proposed, nor could we identify blood or lymph endothelial cells in close proximity. This leaves the origins of Hassall's corpuscles an open question.



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Precuneus proportions and cortical folding: a morphometric evaluation on a racially diverse human sample

Publication date: Available online 6 March 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Emiliano Bruner, Ana Sofia Pereira-Pedro, Xu Chen, James K. Rilling
Recent analyses have suggested that the size and proportions of the precuneus are remarkably variable among adult humans, representing a major source of geometrical difference in midsagittal brain morphology. The same area also represents the main midsagittal brain difference between humans and chimpanzees, being more expanded in our species. Enlargement of the upper parietal surface is a specific feature of Homo sapiens, when compared with other fossil hominids, suggesting the involvement of these cortical areas in recent modern human evolution. Here, we provide a survey on midsagittal brain morphology by investigating whether precuneus size represents the largest component of variance within a larger and racially diverse sample of 265 adult humans. Additionally, we investigate the relationship between precuneus shape variation and folding patterns. Precuneus proportions are confirmed to be a major source of human brain variation even when racial variability is considered. Larger precuneus size is associated with additional precuneal gyri, generally in its anterior district. Spatial variation is most pronounced in the dorsal areas, with no apparent differences between hemispheres, between sexes, or among different racial groups. These dorsal areas integrate somatic and visual information together with the lateral elements of the parietal cortex, representing a crucial node for self-centered mental imagery. The histological basis and functional significance of this intra-specific variation in the upper precuneus remains to be evaluated.



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Paying respect to human cadavers: we owe this to the first teacher in anatomy

Publication date: Available online 6 March 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Sanjib Kumar Ghosh
Every human cadaver which undergoes anatomical dissection enriches medical science and deserves to be treated with utmost respect. The aim of the present study is to identify the practices followed by medical schools across the globe to ensure that the human cadaver is treated with respect and dignity while it is utilized within the domain of medical education. The article undertakes a review of the literature and takes note of the practice of students taking an oath prior to dissecting cadavers whereby they reflect on their conduct and habits in the dissection room. It emphasizes the guidelines adopted by medical schools to ensure respectful handling of human cadavers during dissection and highlights traditional ways to honor them followed in some parts of the world. The article attempts to focus on the noble endeavour of funeral ceremonies to pay homage to the departed soul who enlightened the students with the knowledge of human anatomy. Finally it converges on the memorial services incorporated into anatomy programs to instill in students an appreciation of the humanity of those who went under the knife as a service to mankind. Based on the observations made in the present study some recommendations are also proposed regarding good practices in human cadaveric dissection. In order to bind science and humanity it is critical to realize our responsibility to reciprocate the anatomical gift of a human body with respect, compassion, care and dignity.



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Chemosynthesis pathway and bioactivities comparison of saponins in radix and flower of Panax notoginseng (Burk.) F.H. Chen

Publication date: 6 April 2017
Source:Journal of Ethnopharmacology, Volume 201
Author(s): Xin Zhou, Lin-Lin Chen, Rui Fang Xie, Wing Lam, Zi-Jia Zhang, Zao-Li Jiang, Yung-Chi Cheng
Ethnopharmacological relevancePanax notoginseng (Burk.) F.H. Chen is a well known medicinal plant. Its radix is used in the history while its flower is recently used for health care. In this study we compared chemical ingredients and bioactivities in cell culture for radix and flower of Panax notoginseng (Burk.) F.H. Chen.Materials and methodsThe liquid chromatography-mass spectrometry system was applied to determine the contents of saponins in flower and radix of Panax notoginseng (Burk.) F.H. Chen. Transcription specific luciferase reporter assay and qPCR method for selected RNA were carried out to assess the impacts of flower and radix extract on the transcription signal pathways.ResultsThe results of chemical analysis showed that the contents of saponins in flower and radix are very different: the contents of Rg1, Rb1, Re, R1, Rg3-20R, Rh1 and Rf in radix are abundant; in contrast, the contents of Rb3, Fc, Ft1, Rb2 and Rh2-20s in flowers are plentiful. There are substantial variations of those saponin contents from one batch vs another. Based on relative content of saponins, the chemosynthesis pathway of ingredients in radix and flower are proposed: for radix, both PPT (Protopanaxatriol) and PPD (Protopanaxadiol) type triterpenoids are involved, the main pathway is PPT→Rb1→Rg1→R1 or PPD→Rh2 20s→Rg3(20s)→Rd→Rb1; for flowers, only PPD is main passage with PPD→Rh2 (20s)→Rg3(20s)→Rd→Rb2→Fc.The results of signal transcription assays demonstrated that herb water extract of radix and flower had no significant influences on most of transcription activities. However, total saponins of radix and flower which have highly content of saponins were able to inhibit the inflammatory related transcriptional activities and their related mRNA expression of IFNα, TNFα, il-6 and TGFβ as well as induce anti-oxygen NrF2 activities.In summary, although chemical ingredients and chemosynthesis pathway of flower and radix for Panax notoginseng (Burk.) F.H. Chen were different, these differences might not result in their differences of pharmacological activities.

Graphical abstract

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Kai Xin San aqueous extract improves Aβ1-40-induced cognitive deficits on adaptive behavior learning by enhancing memory-related molecules expression in the hippocampus

Publication date: 6 April 2017
Source:Journal of Ethnopharmacology, Volume 201
Author(s): Cong Lu, Zhe Shi, Xiuping Sun, Ruile Pan, Shanguang Chen, Yinghui Li, Lina Qu, Lihua Sun, Haixia Dang, Lanlan Bu, Lingling Chen, Xinmin Liu
Ethnopharmacological relevanceKai Xin San (KXS), a traditional formula of Chinese medicine, has been used to treat dementia.Aim of the studyThe present study aimed to investigate its ameliorating effects on Aβ1-40-induced cognitive impairment in rats using a series of novel reward-directed instrumental learning tasks, and to determine its possible mechanism of action.Materials and methodsRats were pretreated with KXS aqueous extract (0.72 and 1.44g/kg, p.o.) for 10 days, and were trained to gain reward reinforcement by lever pressing at the meantime. Thereafter, rats received a bilateral microinjection of Aβ1-40 in CA1 regions of the hippocampus. Cognitive performance was evaluated with the goal directed (higher response ratio) and habit (visual signal discrimination and extinction) learning tasks, as well as on the levels of memory-related biochemical parameters and molecules.ResultsOur findings first demonstrated that KXS can improve Aβ1-40-induced amnesia in RDIL via enhancing the comprehension of action-outcome association and the utilization of cue information to guide behavior. Then, its ameliorating effects should be attributed to the modulation of memory-related molecules in the hippocampus.ConclusionIn conclusion, KXS has the potential to prevent and/or delay the deterioration of cognitive impairment in AD.

Graphical abstract

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Effects of dichloromethane and butanol fractions of Gochnatia polymorpha floccosa in maternal reproductive outcome, embryo-fetal development and DNA integrity in mice

Publication date: 22 March 2017
Source:Journal of Ethnopharmacology, Volume 200
Author(s): Lucas Roberto Pessatto, Sarah Alves Auharek, Caroline Amélia Gonçalves, Natan de David, Antônio Carlos Duenhas Monreal, Cândida Aparecida Leite Kassuya, Andréia Conceição Milan Brochado Antoniolli-Silva, Maria Élida Alves Stefanello, Rodrigo Juliano Oliveira
Ethnopharmacological relevanceGochnatia polymorpha ssp. floccosa (Asteraceae) also known as ''Cambará'' is used as medicinal plant in Brazil to treat infections and inflammation. Previous studies showed that its ethanolic extract could be bioprospecting of a new anti-inflammatory phytotherapy for use during pregnancy. This work aimed to evaluate dichloromethane (DCM) and butanolic (BT) fractions from G. polymorpha on embryo-fetal development and DNA integrity in mice.Materials and methodsFemale mice were treated with 50 and 20mg/kg of the DCM and BT fractions, respectively, during organogenesis and gestational period.Results and conclusionThe present study shows that DCM and BT fractions from G. polymorpha possess mutagenic activity but are not teratogenic. Based on the fact that the reproductive indices are similar in control and treated animals, we may infer that the mutagenic effect was in somatic cell, at least in part, because the reabsorption number and reabsorption rates did not change in DCM and BT exposed groups.

Graphical abstract

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Nuclear Factor Y in Development and Disease

Publication date: Available online 7 March 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Roberto Mantovani




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Expression of Rac1 alternative 3′ UTRs is a cell specific mechanism with a function in dendrite outgrowth in cortical neurons

Publication date: Available online 6 March 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Sandra Oliveira Braz, Andrea Cruza, Andrea Lobo, Joana Bravo, Joana Moreira-Ribeiro, Isabel Pereira-Castro, Jaime Freitas, Joao B. Relvas, Teresa Summavielle, Alexandra Moreira
The differential expression of mRNAs containing tandem alternative 3′ UTRs, achieved by mechanisms of alternative polyadenylation and post-transcriptional regulation, has been correlated with a variety of cellular states. In differentiated cells and brain tissues there is a general use of distal polyadenylation signals, originating mRNAs with longer 3′ UTRs, in contrast with proliferating cells and other tissues such as testis, where most mRNAs contain shorter 3′ UTRs. Although cell type and state are relevant in many biological processes, how these mechanisms occur in specific brain cell types is still poorly understood. Rac1 is a member of the Rho family of small GTPases with essential roles in multiple cellular processes, including cell differentiation and axonal growth. Here we used different brain cell types and tissues, including oligodendrocytes, microglia, astrocytes, cortical and hippocampal neurons, and optical nerve, to show that classical express mRNAs with alternative 3′ UTRs differently, by gene- and cell- specific mechanisms. In particular, we show that Rac1 originate mRNA isoforms with longer 3′ UTRs specifically during neurite growth of cortical, but not hippocampal neurons. Furthermore, we demonstrate that the longest Rac1 3′ UTR is necessary for driving the mRNA to the neurites, and also for neurite outgrowth in cortical neurons. Our results indicate that the expression of Rac1 longer 3′ UTR is a gene and cell-type specific mechanism in the brain, with a new physiological function in cortical neuron differentiation.



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Utility of repetitive nerve stimulation test for ALS diagnosis

Publication date: Available online 6 March 2017
Source:Clinical Neurophysiology
Author(s): Yuki Hatanaka, Mana Higashihara, Takashi Chiba, Yosuke Miyaji, Yasuomi Kawamura, Masahiro Sonoo
ObjectiveDecremental responses in the repetitive nerve stimulation (RNS) test in amyotrophic lateral sclerosis (ALS) patients have been reported, although their possible diagnostic role has received little investigation. We investigated their diagnostic role in differentiation between ALS and cervical spondylotic amyotrophy (CSA), an important ALS mimic especially in Japan.MethodsPatients were prospectively enrolled and the diagnosis was confirmed by follow-up. RNS was performed on the abductor pollicis brevis (APB), upper trapezius (trapezius) and deltoid muscles.ResultsEnrolled subjects consisted of 53 ALS and 37 CSA patients. Abnormal decremental responses (> 5%) were observed in 32%, 51% and 75% of ALS patients and 3%, 0% and 20% of CSA patients for the APB, trapezius and deltoid muscles, respectively. The sensitivity for 23 ALS patients with upper-limb onset was 78% for the trapezius and 100% for the deltoid muscles.ConclusionsAn abnormal decremental response in the trapezius muscle was 100% specific to ALS in comparison with CSA: abnormal decrement in this muscle would strongly suggest ALS. No decrement in the deltoid muscle might exclude ALS in patients having symptoms with upper-limb onset.SignificanceRNS is useful in differentiation between ALS and CSA.



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Vibration-induced nystagmus in patients with vestibular schwannoma: characteristics and clinical implications

Publication date: Available online 6 March 2017
Source:Clinical Neurophysiology
Author(s): Jeon Mi Lee, Mi Joo Kim, Jin Won Kim, Dae Bo Shim, Jinna Kim, Sung Huhn Kim
ObjectiveTo investigate the clinical significance of vibration-induced nystagmus (VIN) in unilateral vestibular asymmetry and vestibular schwannoma.MethodsThirteen patients with vestibular schwannoma underwent the VIN test, in which stimulation was applied to the mastoid processes and sternocleidomastoid (SCM) muscles on the ipsilateral and contralateral sides of lesions. Preoperative VIN was measured, and changes in VIN were followed up for 6 months after tumor removal. Significance of VIN was determined by evaluation of its sensitivity, correlation with vestibular function tests and tumor volume, and postoperative changes.ResultsThe overall pre and postoperative sensitivities of VIN were 92.3% and 100%, respectively, considering stimulation at all four sites. Maximum slow-phase velocity (MSPV) of VIN was linearly correlated with caloric weakness and tumor volume, especially when stimulation was applied to the SCM muscle. Postoperative MSPV of VIN exhibited stronger linear correlation with postoperative changes in canal paresis value and inverse correlation with tumor size upon stimulation of the ipsilateral SCM muscle than upon stimulation of other sites. During the 6-month follow-up period, persistence of VIN without changes in MSPV was observed even after vestibular compensation.ConclusionsEvoking VIN by stimulation of the mastoid processes and SCM muscles is effective for detecting vestibular asymmetry. It could also help determine the degree of vestibular asymmetry and volume of vestibular schwannoma if stimulation is applied to the SCM muscle.SignificanceThe results of this study could provide clues for the basic application of VIN in patients with vestibular loss and vestibular schwannoma.



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Can epileptiform abnormalities predict delayed cerebral ischemia in subarachnoid hemorrhage?

Publication date: Available online 6 March 2017
Source:Clinical Neurophysiology
Author(s): Andrew Martin, Jan Claassen




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Bilateral sequential motor cortex stimulation and skilled task performance with non-dominant hand

Publication date: Available online 6 March 2017
Source:Clinical Neurophysiology
Author(s): Milan B. Jelić, Saša R. Filipović, Sladjan D. Milanović, Vuk B. Stevanović, Ljubica Konstantinović
ObjectiveTo check whether bilateral sequential stimulation (BSS) of M1 with theta burst stimulation (TBS), using facilitatory protocol over non-dominant M1 followed by inhibitory one over dominant M1, can improve skilled task performance with non-dominant hand more than either of the unilateral stimulations do. Both, direct motor cortex (M1) facilitatory non-invasive brain stimulation (NIBS) and contralateral M1 inhibitory NIBS were shown to improve motor learning.MethodsForty right-handed healthy subjects were divided into 4 matched groups which received either ipsilateral facilitatory (intermittent TBS [iTBS] over non-dominant M1), contralateral inhibitory (continuous TBS [cTBS] over dominant M1), bilateral sequential (contralateral cTBS followed by ipsilateral iTBS), or placebo stimulation. Performance was evaluated by Purdue peg-board test (PPT), before (T0), immediately after (T1), and 30 min after (T2) an intervention.ResultsIn all groups and for both hands, the PPT scores increased at T1 and T2 in comparison to T0, showing clear learning effect. However, for the target non-dominant hand only, immediately after BSS (at T1) the PPT scores improved significantly more than after either of unilateral interventions or placebo.ConclusionM1 BSS TBS is an effective intervention for improving motor performance.SignificanceM1 BSS TBS seems as a promising tool for motor learning improvement with potential uses in neurorehabilitation.



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Functional connectivity and network analysis during hypoactive delirium and recovery from anesthesia

Publication date: Available online 6 March 2017
Source:Clinical Neurophysiology
Author(s): Tianne Numan, Arjen J.C. Slooter, Arendina W. van der Kooi, Annemieke M.L. Hoekman, Willem J.L. Suyker, Cornelis J. Stam, Edwin van Dellen
ObjectiveTo gain insight in the underlying mechanism of reduced level of consciousness due to hypoactive delirium versus recovery from anesthesia, we studied functional connectivity and network topology using electroencephalography (EEG).MethodsEEG recordings were performed in age and sex-matched patients with hypoactive delirium (n=18), patients recovering from anesthesia (n=20), and non-delirious control patients (n=20), all after cardiac surgery. Functional and directed connectivity were studied with phase lag index and directed phase transfer entropy. Network topology was characterized using the minimum spanning tree (MST). A random forest classifier was calculated based on all measures to obtain discriminative ability between the three groups.ResultsNon-delirious control subjects showed a back-to-front information flow, which was lost during hypoactive delirium (p=0.01) and recovery from anesthesia (p<0.01). The recovery from anesthesia group had more integrated network in the delta band compared to non-delirious controls. In contrast, hypoactive delirium showed a less integrated network alpha band. High accuracy for discrimination between hypoactive delirious patients and controls (86%) and recovery from anesthesia and controls (95%) were found. Accuracy for discrimination between hypoactive delirium and recovery from anesthesia was 73%.ConclusionLoss of functional and directed connectivity were observed in both hypoactive delirium and recovery from anesthesia, which might be related to the reduced level of consciousness in both states. These states could be distinguished in topology, which was a less integrated network during hypoactive delirium.SignificanceFunctional and directed connectivity are similarly disturbed during reduced level of consciousness due to hypoactive delirium and sedatives, however topology was differently affected.



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Transcription factors SF1 and cJUN cooperate to activate the Fdx1 promoter in MA-10 Leydig cells

Publication date: Available online 6 March 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Pauline Roumaud, Arlette Rwigemera, Luc J. Martin
The Ferredoxin 1 (FDX1) protein supports steroid biosynthesis in steroidogenic cells through electron transfer to the rate-limiting steroidogenic enzyme, CYP11A1. The latter catalyzes the conversion of cholesterol to pregnenolone through side chain cleavage inside the mitochondria. Thus far, only several transcription factors have been implicated in the regulation of mouse Fdx1 promoter activity in Leydig cells. These include the nuclear receptor SF1 and SP1. Since two conserved regulatory elements for AP1 transcription factors have been located at −764 and −617bp of the Fdx1 promoter, we hypothesized that cJUN may cooperate with other partners to regulate Fdx1 in Leydig cells. Indeed, we report that SF1 and cJUN interact and cooperate to activate the Fdx1 promoter in MA-10 and TM3 Leydig cells. Furthermore, we found that such activation requires different regulatory elements located between −124 and −306bp of the Fdx1 promoter and involves recruitment of SF1 to this region. Using RNA interference, the importance of SF1 in transcriptional regulation of Fdx1 was confirmed, whereas cJUN was dispensable even though it cooperated with SF1 to upregulate Fdx1 expression in MA-10 cells. Thus, our data provides new insights in the molecular mechanisms that control mouse Fdx1 transcription, possibly leading to regulation of CYP11A1 enzyme activation, in Leydig cells.



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Digoxin Plus Trametinib Therapy Achieves Disease Control in BRAF Wild-Type Metastatic Melanoma Patients

Publication date: April 2017
Source:Neoplasia, Volume 19, Issue 4
Author(s): Arthur E. Frankel, Ugur Eskiocak, Jennifer G. Gill, Stacy Yuan, Vijayashree Ramesh, Thomas W. Froehlich, Chul Ahn, Sean J. Morrison
This is the first prospective study of a combination therapy involving a cardenolide and a MEK inhibitor for metastatic melanoma. Whereas BRAF mutant melanomas can exhibit profound responses to treatment with BRAF and MEK inhibitors, there are fewer options for BRAF wild-type melanomas. In preclinical studies, we discovered that cardenolides synergize with MEK inhibitor to promote the regression of patient-derived xenografts irrespective of BRAF mutation status. We therefore conducted a phase 1B study of digoxin 0.25 mg and trametinib 2 mg given orally once daily in 20 patients with advanced, refractory, BRAF wild-type melanomas. The most common adverse events were rash, diarrhea, nausea, and fatigue. The response rate was 4/20 or 20% with response durations of 2, 4, 6, and 8 months. The disease control rate (including partial responses and stable disease) was 13/20 or 65% of patients, including 5/6 or 83% of patients with NRAS mutant melanomas and 8/14 or 57% of NRAS wild-type melanomas. Patients with stable disease had disease control for 2, 2, 2, 4, 5, 6, 7, 10, and 10 months. Xenografts from four patients recapitulated the treatment responses observed in patients. Based on these pilot results, an expansion arm of digoxin plus MEK inhibitor is warranted for NRAS mutant metastatic melanoma patients who are refractory or intolerant of immunotherapy.Key pointsDigoxin plus trametinib is well tolerated and achieves a high rate of disease control in BRAF wild-type metastatic melanoma patients.



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IL-33/ST2 immune responses to respiratory bacteria in pediatric asthma.

IL-33/ST2 immune responses to respiratory bacteria in pediatric asthma.

Sci Rep. 2017 Mar 06;7:43426

Authors: Hentschke I, Graser A, Melichar VO, Kiefer A, Zimmermann T, Kroß B, Haag P, Xepapadaki P, Papadopoulos NG, Bogdan C, Finotto S

Abstract
Here we investigated the relationship between local bacterial colonization and anti-bacterial immune responses in pre-school asthmatic and control children within the EU-wide study PreDicta. In this cohort of pre-school asthmatic children, nasopharyngeal colonization with Gram-negative bacteria such as Haemophilus influenzae and Moraxella catarrhalis was found to be associated with the highest interferon beta (IFNβ) and IL-33 levels in the nasal pharyngeal fluids (NPF). IL33R-ST2 was found induced in the blood of asthmatic children with additional Gram + bacteria in the nasopharynx (Gr+/-). Furthermore, asthmatic children had more episodes of infection that required antibiotic therapy than the control group. Treatment with antibiotics associated with reduced ST2 in blood cells of both asthmatic and control children and reduced IL-33 levels in the airways of asthmatic children. In the absence of Staphylococcus (S.) aureus in NPF, antibiotic therapy associated with decreased IL-33 levels in the NPF and lower ST2 values in the blood of control children but not of asthmatic children. These data suggest that, in asthmatic children, Gram- bacteria, which persist after antibiotic therapy, contributes to IL-33 locally and associated with Gr + bacteria colonization in the airways, inhibited IFN-β and in the absence of Staphylococcus (S.) aureus, induced ST2 bearing cells in their blood.

PMID: 28262704 [PubMed - in process]

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Nasopharyngeal and Oropharyngeal Colonization by Staphylococcus aureus and Streptococcus pneumoniae and Prognostic Markers in Children with Sickle Cell Disease from the Northeast of Brazil.

Related Articles

Nasopharyngeal and Oropharyngeal Colonization by Staphylococcus aureus and Streptococcus pneumoniae and Prognostic Markers in Children with Sickle Cell Disease from the Northeast of Brazil.

Front Microbiol. 2017;8:217

Authors: Rocha LC, Carvalho MO, Nascimento VM, Dos Santos MS, Barros TF, Adorno EV, Reis JN, da Guarda CC, Santiago RP, Gonçalves MS

Abstract
We investigated the nasopharynx and oropharynx microbiota in sickle cell disease (SCD) to identify the microorganisms, antibiotic sensitivity, prevalent serotypes, and association of with laboratorial markers. Oropharynx/nasopharynx secretions were investigated in 143 SCD children aging 6 months to 17 years. Pathogens were isolated using standard procedures, and laboratorial markers were performed by automated methods. Staphylococcus aureus (S. aureus) was isolated from nasopharynx and oropharynx of 64 and of 17 SCD children respectively. Streptococcus pneumoniae (S. pneumoniae) was isolated from the nasopharynx and oropharynx of eight SCD patients. Serotypes of S. pneumoniae were 19F, 23F, and 14. All isolates were susceptible to penicillin, and patients whose nasopharynx and oropharynx were colonized by S. pneumoniae had high concentrations of aspartate transaminase, alanine transaminase, and ferritin. S. pneumoniae isolated were not penicillin-resistant serotypes suggesting that the use of penicillin for prophylaxis and/or treatment of infections is safe. Our finding of colonization and laboratory evaluation in SCD patients suggests that microorganisms are involved in the modulation of chronic inflammatory. The association of colonized microorganisms and laboratorial markers suggest a new approach to these patients follow-up, and additional studies of microorganism colonization and their association with SCD patients' clinical outcome will improve control and prevention strategies.

PMID: 28261176 [PubMed - in process]

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Microbiome in atopic dermatitis.

Related Articles

Microbiome in atopic dermatitis.

Clin Cosmet Investig Dermatol. 2017;10:51-56

Authors: Wollina U

Abstract
Atopic dermatitis (AD) is a common chronic inflammatory skin disease affecting ~10-20% of the general population. AD is characterized by disturbances in epidermal barrier function and hyperactive immune response. Recently, changes in the skin and intestinal microbiome have been analyzed in more detail. The available data suggest a link between disturbed skin microbiome and course of the disease. Flares of the disease are associated with an expansion of Staphylococcus aureus on lesional skin and a substantial loss of biodiversity in skin microbiome. Staphylococci exoproteins and superantigens evoke inflammatory reactions in the host. Skin microbiome includes superficial stratum corneum that is affected by environmental factors such as exposure to germs and cleansing. Available evidence argues for a link between epidermal barrier impairment and disturbances in skin microbiome in AD. In contrast to skin microbiome, intestinal microbiome seems to become stabilized after infancy. There is also a significant heritable component for intestinal microbiome. The microbial taxa, relative percentages and quantities vary remarkably between the different parts of the intestinal tract. Early intestinal microbial colonization may be a critical step for prevention of further development of AD. Skin barrier-aimed topical treatments help to develop a neo-microbiome from deeper compartments. Probiotics, prebiotics and synbiotics have been investigated for the treatment of AD, but further investigations are needed. Targeted treatment options to normalize skin and intestinal microbiome in AD are under investigation.

PMID: 28260936 [PubMed - in process]

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Single chamber microbial fuel cell (SCMFC) with a cathodic microalgal biofilm: A preliminary assessment of the generation of bioelectricity and biodegradation of real dye textile wastewater

Publication date: June 2017
Source:Chemosphere, Volume 176
Author(s): Washington Logroño, Mario Pérez, Gladys Urquizo, Abudukeremu Kadier, Magdy Echeverría, Celso Recalde, Gábor Rákhely
An air exposed single-chamber microbial fuel cell (SCMFC) using microalgal biocathodes was designed. The reactors were tested for the simultaneous biodegradation of real dye textile wastewater (RTW) and the generation of bioelectricity. The results of digital image processing revealed a maximum coverage area on the biocathodes by microalgal cells of 42%. The atmospheric and diffused CO2 could enable good algal growth and its immobilized operation on the cathode electrode. The biocathode-SCMFCs outperformed an open circuit voltage (OCV), which was 18%–43% higher than the control. Furthermore, the maximum volumetric power density achieved was 123.2 ± 27.5 mW m⁻³. The system was suitable for the treatment of RTW and the removal/decrease of COD, colour and heavy metals. High removal efficiencies were observed in the SCMFCs for Zn (98%) and COD (92–98%), but the removal efficiencies were considerably lower for Cr (54–80%). We observed that this single chamber MFC simplifies a double chamber system. The bioelectrochemical performance was relatively low, but the treatment capacity of the system seems encouraging in contrast to previous studies. A proof-of-concept experiment demonstrated that the microalgal biocathode could operate in air exposed conditions, seems to be a promising alternative to a Pt cathode and is an efficient and cost-effective approach to improve the performance of single chamber MFCs.

Graphical abstract

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Enzymatically synthesized glycogen inhibits colitis through decreasing oxidative stress

Publication date: May 2017
Source:Free Radical Biology and Medicine, Volume 106
Author(s): Takakazu Mitani, Yasukiyo Yoshioka, Takashi Furuyashiki, Yoko Yamashita, Yasuhito Shirai, Hitoshi Ashida
Inflammatory bowel diseases are a group of chronic inflammation conditions of the gastrointestinal tract. Disruption of the mucosal immune response causes accumulation of oxidative stress, resulting in the induction of inflammatory bowel disease. In this study, we investigated the effect of enzymatically synthesized glycogen (ESG), which is produced from starch, on dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in C57BL/6 mice. Oral administration of ESG suppressed DSS- and TNBS-induced shortening of large intestine in female mice and significant decreased DSS-induced oxidative stress and TNBS-induced pro-inflammatory cytokine expression in the large intestine. ESG increase in the expression levels of heme oxygenase-1 (HO-1) and NF-E2-related factor-2 (Nrf2), a transcription factor for HO-1 expressed in the large intestine. Furthermore, ESG-induced HO-1 and Nrf2 were expressed mainly in intestinal macrophages. ESG is considered to be metabolized to resistant glycogen (RG) during digestion with α-amylase in vivo. In mouse macrophage RAW264.7 cells, RG, but not ESG decreased 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced reactive oxygen species (ROS). Knockdown of Nrf2 inhibited RG-induced HO-1 expression and negated the decrease in AAPH-induced ROS brought about by RG. RG up-regulated the protein stability of Nrf2 to decrease the formation of Nrf2-Keap1 complexes. RG-induced phosphorylation of Nrf2 at Ser40 was suppressed by ERK1/2 and JNK inhibitors. Our data indicate that ESG, digested with α-amylase to RG, suppresses DSS- and TNBS-induced colitis by increasing the expression of HO-1 in the large intestine of mice. Furthermore, we demonstrate that RG induces HO-1 expression by promoting phosphorylation of Nrf2 at Ser40 through activation of the ERK1/2 and JNK cascade in macrophages.

Graphical abstract

http://ift.tt/2mA8iC1

Melatonin and nitric oxide regulate sunflower seedling growth under salt stress accompanying differential expression of Cu/Zn SOD and Mn SOD

Publication date: May 2017
Source:Free Radical Biology and Medicine, Volume 106
Author(s): Dhara Arora, Satish C. Bhatla
Salinity results in significant reduction in sunflower (Helianthus annuus L.) seedling growth and excessive generation of reactive oxygen species (ROS). Present work highlights the possible role of melatonin as an antioxidant through its interaction with nitric oxide (NO), and as an early and long distance NaCl-stress sensing signaling molecule in seedling cotyledons. Exogenous melatonin (15µM)±NaCl (120mM) inhibit seedling growth, which is also correlated with NO availability, accumulation of potential superoxide anion (O2^•-) and peroxynitrite anion (ONOO^-), extent of tyrosine-nitration of proteins, spatial localization and activity of superoxide dismutase (SOD) isoforms. NO acts as a positive modulator of melatonin accumulation in seedling cotyledons as a long-distance signaling response. Modulation of superoxide anion and peroxynitrite anion content by melatonin highlights its crucial role in combating deleterious effects of ROS and reactive nitrogen species (RNS). Present findings provide evidence for an interaction between melatonin and NO in their effect on seedling growth under salt stress accompanying differential modulation of two SOD isoforms, i.e. Cu/Zn SOD and Mn SOD.



http://ift.tt/2mAjVci

The carboxyl terminus of heat shock protein 70-interacting protein (CHIP) participates in high glucose-induced cardiac injury

Publication date: May 2017
Source:Free Radical Biology and Medicine, Volume 106
Author(s): Wenjun Xiong, Shiwen Liu, Wenyao Cai, Jinhua Wen, Yongnan Fu, Jingtian Peng, Zeqi Zheng
The carboxyl terminus of heat shock protein 70-interacting protein (CHIP) is confirmed to have a protective effect on the myocardium, but its effect on diabetic cardiomyopathy is unclear. Small interfering RNA (siRNA) was used for knockdown experiments in neonatal rat cardiomyocytes to examine the function of CHIP in high glucose-induced injury. High glucose stimulated the production of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate oxidase (NOX), interleukin-1β (IL-1β), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) production. However, cardiomyocytes lacking CHIP suffered from increased oxidative stress and inflammatory responses. High glucose increased the expression of Bax and caspase-3 mRNAs, decreased the expression of Bcl-2 mRNA, and up-regulated the expression of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) proteins. However, upon CHIP knockdown, the expression of Bax and caspase-3 mRNAs increased even further, and the expression of Bcl-2 mRNA was further suppressed. The expression of the phosphorylated p65 and p38 proteins (p-p65 and p-p38) was also further enhanced. Thus, CHIP is a potent cardioprotective molecule.



http://ift.tt/2n0OcOL

Microvascular NADPH Oxidase in Health and Disease

Publication date: Available online 6 March 2017
Source:Free Radical Biology and Medicine
Author(s): Yao Li, Patrick J. Pagano
The systemic and cerebral microcirculation contribute critically to regulation of local and global blood flow and perfusion pressure. Microvascular dysfunction, commonly seen in numerous cardiovascular pathologies, is associated with alterations in the oxidative environment including potentiated production of reactive oxygen species (ROS) and subsequent activation of redox signaling pathways. NADPH oxidases (Nox) are a primary source of ROS in the vascular system and play a central role in cardiovascular health and disease. In this review, we focus on the roles of Noxs in ROS generation in resistance arterioles and capillaries, and summarize their contributions to microvascular physiology and pathophysiology in both systemic and cerebral microcirculation. In light of the accumulating evidence that Noxs are pivotal players in vascular dysfunction of resistance arterioles, selectively targeting Nox isozymes could emerge as a novel and effective therapeutic strategy for preventing and treating microvascular diseases.

Graphical abstract

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Systematic in vitro assessment of responses of roGFP2-based probes to physiologically relevant oxidant species

Publication date: May 2017
Source:Free Radical Biology and Medicine, Volume 106
Author(s): Alexandra Müller, Jannis F. Schneider, Adriana Degrossoli, Nataliya Lupilova, Tobias P. Dick, Lars I. Leichert
The genetically encoded probes roGFP2-Orp1 and Grx1-roGFP2 have been designed to be selectively oxidized by hydrogen peroxide (H2O2) and glutathione disulfide (GSSG), respectively. Both probes have demonstrated such selectivity in a broad variety of systems and conditions. In this study, we systematically compared the in vitro response of roGFP2, roGFP2-Orp1 and Grx1-roGFP2 to increasing amounts of various oxidant species that may also occur in biological settings. We conclude that the previously established oxidant selectivity is highly robust and likely to be maintained under most physiological conditions. Yet, we also find that hypochlorous acid, known to be produced in the phagocyte respiratory burst, can lead to non-selective oxidation of roGFP2-based probes at concentrations ≥2µM, in vitro. Further, we confirm that polysulfides trigger direct roGFP2 responses. A side-by-side comparison of all three probes can be used to reveal micromolar amounts of hypochlorous acid or polysulfides.



http://ift.tt/2n0B9ga

Preface

Publication date: Available online 6 March 2017
Source:Free Radical Biology and Medicine
Author(s): Tomas Lindahl




http://ift.tt/2mA9FAP

Predictive value of biochemical and tissue modifications for wound healing in post-bariatric patients

Abstract

Background

Bariatric surgery, despite its beneficial effects, is responsible for highly frequent wound healing complications, as it has already been demonstrated in post-biliopancreatic diversion (BPD) patients.

The aim of this study was to analyze results and wound healing process in a population submitted to Roux-en-Y gastric bypass (RYGB), a procedure involving both a malabsorptive and restrictive approach.

Methods

Thirteen non-smokers and non-diabetic patients submitted to laparoscopic RYGB underwent abdominoplasty. Biochemical parameters before and after bariatric surgery were evaluated. The content of total protein and hydroxyproline (revealing collagen amount) was assessed in multiple biopsies before and after RYGB. Skin samples were subjected to macroscopic and histological evaluation, where elastic fibers content was put into evidence by a specific stain (Wigert–Van Gieson).

Results

Most of the biochemical parameters analyzed showed a mild reduction after weight loss surgery. Neither tissue proteins nor hydroxyproline were significantly reduced after RYGB. Macroscopically, equal thickness of the two adipose tissue layers (areolar and lamellar) was observed in addition to normal consistency and compactness. Histological evaluation revealed fibroblast augmentation, hypertrophic adipocytes, and augmented dimension. Results were then compared with those previously obtained in post-BPD population.

Conclusion

Despite that further elaborations are needed, RYGB, compared to BPD, seems to be associated with minor modifications of tissues and biochemical and tissue parameter values, possibly leading to a lower wound complication rate.

Level of Evidence: Level IV, prognostic study

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Microsurgical reconstruction in mandible osteoradionecrosis: a clinical experience from Portugal

Abstract

Background

Osteoradionecrosis (ORN) is one of the most feared complications of head and neck cancer radiotherapy. The most common location for facial ORN is the mandible. Optimal clinical management is still under debate, insofar as a clear definition of its pathological process is yet to be obtained. Osseous surgical debridement is mandatory in advanced stages, but the reconstructive technique has to be specifically tailored to ORN characteristics.

Methods

Data from patients with ORN treated in our institution from 2000 to 2014 was reviewed. Twenty-one patients were included. We retrospectively analyzed risk factors, severity of bone lesions, extension of bone resection, reconstructive option, and complications. A control group without ORN was used for comparison.

Results

In this study, radical excision and reconstruction with free flaps was the treatment of choice for moderate and severe ORN. We found a statistically significant higher rate of salvage procedures in ORN patients when compared with the control non-ORN cohort (p < 0.05). Sixty percent of the patients with ORN achieved stable coverage; 83.3% of the patients had evidence of bone union in imaging exams, and 75% recovered oral feeding capability. There was a tendency towards healing problems in ORN patients, but it did not reach statistical significance.

Conclusion

Although there was a higher rate of surgical complications in ORN patients when compared to the control group, microsurgical approach leads to good morphofunctional results in moderate to severe ORN.

Level of Evidence: Level IV, therapeutic study.

http://ift.tt/2n0PYzt

Genotoxicity of the herbicide imazethapyr in mammalian cells by oxidative DNA damage evaluation using the Endo III and FPG alkaline comet assays

Abstract

We evaluated the role of oxidative stress in the genotoxic damage induced by imazethapyr (IMZT) and its formulation Pivot® in mammalian CHO-K1 cell line. Using the alkaline comet assay, we observed that a concentration of 0.1 μg/mL of IMZT or Pivot® was able to induce DNA damage by increasing the frequency of damaged nucleoids. To test whether the DNA lesions were caused by oxidative stress, the DNA repair enzymes endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase (Fpg), which convert base damage to strand breaks, were used. Our results demonstrate that after treatment of CHO-K1 cells with the pure active ingredient as well as the commercial formulation Pivot®, an increase in DNA strand breaks was observed after incubation of both Endo III and Fpg enzymes, indicating that both compounds induce DNA damage involving both pyrimidine and purine-based oxidations, at least in CHO-K1 cells. Our findings confirm the genotoxic potential of IMZT and suggest that this herbicide formulation must be employed with great caution, especially not only for exposed occupational workers but also for other living species.

http://ift.tt/2mRqWWG

Distribution and residue profile of organochlorine pesticides and polychlorinated biphenyls in sediment and fish of Lake Manzala, Egypt

Abstract

Sediment and fish (Oreochromis niloticus) samples collected from Lake Manzala were analyzed to assess the spatial distribution of OCPs and 96 PCBs. Relatively higher concentrations of chlorpyrifos, ∑DDT, and HCB were found, particularly at the Bahr Al-Baqar drain station, which has uncontrolled inputs of untreated domestic, agricultural, and industrial wastes. The concentrations of ∑PCBs ranged from 19 to 69 ng/g dw and from 7.4 to 29 ng/g dw for sediment and fish samples, respectively. Ratios of DDT to its metabolites suggest that the source of ∑DDT is from past usage of technical DDT in the regions surrounding the lake. Sediment quality guidelines were exceeded in 88, 75, and 42% of sediments for the Effects Range Low (ERL) for ∑PCBs, ∑DDT, and 4,4′-DDE, respectively. Sediment from the Bahr Al-Baqar drain exceeded the Probable Effects Level (PEL) for DDT isomers 2,4′ and 4,4′. All fish samples from Lake Manzala were well below action and tolerance levels set by US EPA for ∑DDT, chlordane, dieldrin, heptachlor, mirex, and PCBs.

Highlights

• Distributions of OCPs and PCBs in sediment and tilapia from Lake Manzala were investigated.

• Chlorpyrifos, ∑DDT, and HCB sediment concentrations were spatially variable and relatively elevated.

• ∑96PCBs, ∑DDT, and 4,4′-DDE exceeded the Effects Range Low in 88, 75, and 42% of the sediments, respectively.

• The major input from Cairo, the Bahr Al-Baqar drain, exceeded the Probable Effects Level for DDT isomers in sediments.

• OCP and PCB concentrations in tilapia were below action and tolerance levels set by the US-EPA.

http://ift.tt/2na0zaw

Soil moisture could enhance electrokinetic remediation of arsenic-contaminated soil

Abstract

Electrokinetic remediation (EKR) is the most efficient technique for remediation of fine-grained soil. The primary removal mechanisms of heavy metal in EKR are the electromigration and electroosmosis flow under appropriate electric gradients. Most EKR studies have researched the variation according to the electrolyte and electric voltage. Also, EKR could be influenced by the migration velocity of ions, while few studies have investigated the effect of moisture content. In this study, soil moisture was controlled by using tap water and NaOH as electrolytes to enhance electromigration and electroosmosis flow. In both electrolytes, the higher moisture content led to the more As removal efficiency, but there were no differences between tap water and NaOH. Therefore, tap water was the most cost-effective electrolyte to remove As from fine-grained soil.

http://ift.tt/2mRnhrQ

Pinus sylvestris as a bio-indicator of territory pollution from aluminum smelter emissions

Abstract

The study demonstrates the efficiency of using Pinus sylvestris L. as a bio-indicator of polluting substances that enter the environment with the emission of a large aluminum smelter. Recent research has demonstrated that pollution from aluminum smelter emissions covers a vast territory. The highest content of polluting elements is registered at a distance of 3 km from the smelter, with maximum concentrations found in the industrial zone (0.5 km from the smelter). The farther from the aluminum smelter, the lower the amount of polluting elements in the needles, although the F level still exceeds the background values at a distance of about 60 km from the source, the levels of Zn, Pb, and Cd up to 50 km, S up to 40 km, and Fe and Cu up to 35 km mostly in north-eastern and south-eastern directions correlating with prevailing atmospheric transfer of the emissions. Pollution with polycyclic aromatic hydrocarbons (PAHs) is also most expressed at a distance of 3 km from the smelter, then it gradually decreases to coincide with background concentrations at a distance of more than 60 km. This is confirmed by changes in overall PAH content and in qualitative and quantitative compositions of individual PAHs. The greatest number of components (17 substances) has been found in samples from the territory of the plant area: phenanthrene, fluoranthene, pyrene, chrysene, acenaphthylene, acenaphthene, anthracene, fluorene, benz[а]anthracene, benz[b]fluoranthene, benz[k]fluoranthene, benz[а]pyrene, benz[е]pyrene, perylene, indeno[1,2,3-c,d]pyrene, benz[g,h,i]perylene, and dibenz[a,h]anthracene. The farther away from the plant, the lower the number of components detected in PAH fraction, mainly due to the fact that the concentrations of most toxic PAHs with five or six aromatic rings (benz[b]fluoranthene, benz[k]fluoranthene, benz[а]pyrene, benz[е]pyrene, perylene, indeno[1,2,3-c,d]pyrene, benz[g,h,i]perylene, dibenz[a,h]anthracene) fall below the method detection limit. High concentrations of benz[а]pyrene and perylene in pine needles at the territories adjacent to the aluminum smelter confirm the technogenic character of forest pollution by PAHs.

http://ift.tt/2n9KPUO

Mitigating biochar phytotoxicity via lanthanum (La) participation in pyrolysis

Abstract

Biochar (BC) produced from oak sawdust by slow pyrolysis was investigated to check the potential inhibition to early growth of tomato for phytotoxicity assessment. An inverted-U-shaped dose-response relationship between BC dosage and seed germination/seedling growth can be observed. Half maximal effective concentration (EC₅₀), based on the inhibition rate of root and stem length, was 65.7 and 74.0 g kg⁻¹, respectively. At the highest BC dosage of 80.0 g kg⁻¹, germination rate, root, and shoot length were notably inhibited by 34.9, 62.3, and 62.2% compared with their corresponding controls (without BC). Fluorescence intensity, indicating reactive oxygen species (ROS) generation in leaf and root, was 177.7 and 344.5% higher than the control. Similar results on H₂O₂ content in leaf and root were observed as well. Besides, membrane leakage from the leaf and root cells was 2.1- and 1.3-fold higher than the corresponding controls. These results proved that BC exhibited significant phytotoxicity in the early growth stage of tomato. Unlike BC, the inhibitions on seed germination and seedling growth, the ROS accumulation, and the plasma membrane damage were not obvious with increasing La-BC dosage. These results indicated that BC phytotoxicity can be greatly mitigated by La involvement in pyrolysis, which was potentially associated with the reduced organic compounds and free radicals in La-BC. Besides, bio-available La in La-BC was partially involved in mitigating the phytotoxicity.

http://ift.tt/2mRDmxS

Economic impacts of calving season and parity on reproduction and production traits of buffaloes in the sub-tropics

Abstract

In order to enhance the profitability of dairy buffaloes, it is necessary to develop an understanding of the factors affecting their reproduction and milk production ability. Thus, the objective of this study was to elucidate the economic impacts of calving season and parity on reproduction and production indices of Egyptian dairy buffaloes (1180) reared under subtropical environmental conditions. Buffaloes calving in the autumn season had lesser days open, calving interval, and service per conception (108.25 days, 414.16 days, and 1.67, respectively), while spring calvers showed the greater calculations (210.27 days, 522.82 days, and 2.39, respectively). The buffaloes calving for the first time had the longest days open, calving interval, and number of services per conception among different parities (176.21 days, 490.05 days, and 2.18, respectively), then decreased thereafter. Furthermore, buffaloes calving in the winter season had the significantly highest total milk yield, milk revenue, total revenue, profit, and profit/cost ratio (1981.4 kg, 1769.1 $, 2019.5 $, 662.9 $, and 0.49, respectively) in comparison with other seasons. The total milk yield, lactation period, profit, and profit/cost ratio were increased to reach the peak values in the fourth parity (2051.5 kg, 252.44 days, 674.8 $, and 0.48, respectively), then decreased thereafter. In conclusion, buffaloes at the fourth parity and those calving in the winter season had the best milk yield, milk revenue, total revenue, and profit/cost ratio. Therefore, breeders must pay more attention to calving season and parity as they play an important role in the farm profitability and productivity and should counteract the adverse effects of periodical and seasonal changes. It is recommended to make estrus synchronization for more calvings in the winter season. Finally, choose the best lifetime for keeping the animal in production.

http://ift.tt/2n9NLkm

A new LDMI decomposition approach to explain emission development in the EU: individual and set contribution

Abstract

This study breaks down carbon emissions into six effects within the current 28 European Union (EU) countries group, thereafter, they are divided into two different groups (the first 15 countries (EU-15) and the last 13 entering the EU (EU13)). Country-specific highlights are also examined. It analyses the evolution of the effects using a data span that runs from 1990 to 2014, to determine which of them had more impact on the intensity of emissions, while also breaking down the complete period into two distinct periods (before the Kyoto protocol (1990–2004) and after Kyoto (2005–2014)). In order to add more knowledge to the current literature, both the additive and multiplicative decomposition techniques were used to examine carbon dioxide (CO₂) emissions and the selected six components: carbon intensity, fossil fuel consumption, energy intensity, oil imports intensity, oil dependence, and population effect. Results point to different adapting velocities for Kyoto targets and necessary compromises. The different velocities were translated into different positive and negative impacts in the change of behavior of CO₂ emissions throughout Europe. A stress in the fluctuations in CO₂ variations before and after Kyoto and between the two different groups of EU countries could be noticed. Moreover, energy intensity and per capita dependence of oil products were identified as the major responsible components for the total and negative changes of emissions in recent years. A decrease in total changes of emissions is observed due to the fossil fuel energy consumption effect and total petroleum products effects. It is possible to infer from here that increased renewable capacity is contributing in a positive way to eco-efficiency, and should therefore be accounted for in national policymakers' decisions in the strongest way possible. Results also seem to indicate that per capita dependence of oil products has decreased, despite oil imports intensity constancy and increased renewable capacity, however, with clear heterogeneous effects, worthy of consideration when defining policies.

http://ift.tt/2mRDk9e

Trends in the levels of urine and serum creatinine: data from NHANES 2001–2014

Abstract

Data from the National Health and Nutrition Examination Survey were used to study trends for urine and serum creatinine over 2001–2014 for those aged ≥20 years. In the absence of chronic kidney disease, levels of urine creatinine decreased for the total population, for those aged 20–29, 50–59, and ≥70 years, for males, and for Mexican Americans and other race/ethnicities. Levels of serum cotinine also exhibited a decreasing trend over 2001–2014 for the total population, for those aged 20–29 and 40–49 years, for females, and for non-Hispanic whites and Mexican Americans. In general, levels of serum creatinine and urine creatinine were positively correlated for chronic kidney disease stages 1–3 and negatively correlated for chronic kidney disease stages 4 and 5.

http://ift.tt/2n9Kv8M

Oxidative stress and related biomarkers in cupric and cuprous chloride-treated rainbow trout

Abstract

We examined the time-course stress responses in the liver of rainbow trout exposed to cuprous chloride (CuCl) and cupric chloride (CuCl₂). The treatment groups received a single intraperitoneal injection of CuCl or CuCl₂ (both at a dose of 0.01 and 0.05 mg/kg); the control group received only the physiologic solution vehicle. Liver tissue samples were analyzed for total copper, superoxide dismutase, catalase, glutathione peroxidases, glutathione reductase, glutathione S-transferase, glyoxalases, and lactate dehydrogenase at 3, 6, and 9 days post-injection. Total glutathione, metallothionein, and malondialdehyde levels were also measured. The time course of metal accumulation differed between the groups; no dose-response relationship for metal load was found. Both copper species elicited significant changes in oxidative stress markers and in metal trapping. Copper underwent adaptive shifts in glutathione and metallothionein concentrations. The defense strategy primarily versus CuCl₂ first involved glutathione, with a peak in metallothionein levels at day 6 for CuCl₂ (at both doses) and for CuCl (0.05 mg/kg). Early stimulation of lipid peroxidation was noted after treatment with the higher copper dose and at day 9 after treatment with the lower dose of both CuCl and CuCl₂. Antioxidant enzyme activity was impaired due to a more or a less severe oxidative stress condition in relation to the copper species and exposure time. Copper dynamics, in terms of metal accumulation and homeostatic regulation, is noticeably complex. The present findings may advance our understanding of the effects of both copper species on the antioxidant response of rainbow trout.

http://ift.tt/2mRCWYd

Distribution and mobility of lead (Pb), copper (Cu), zinc (Zn), and antimony (Sb) from ammunition residues on shooting ranges for small arms located on mires

Abstract

An environmental survey was performed on shooting ranges for small arms located on minerotrophic mires. The highest mean concentrations of Pb (13 g/kg), Cu (5.2 g/kg), Zn (1.1 g/kg), and Sb (0.83 g/kg) in the top soil were from a range located on a poor minerotrophic and acidic mire. This range had also the highest concentrations of Pb, Cu, Zn, and Sb in discharge water (0.18 mg/L Pb, 0.42 mg/L Cu, 0.63 mg/L Zn, and 65 μg/L Sb) and subsurface soil water (2.5 mg/L Pb, 0.9 mg/L Cu, 1.6 mg/L Zn, and 0.15 mg/L Sb). No clear differences in the discharge of ammunition residues between the mires were observed based on the characteristics of the mires. In surface water with high pH (pH ~7), there was a trend with high concentrations of Sb and lower relative concentrations of Cu and Pb. The relatively low concentrations of ammunition residues both in the soil and soil water, 20 cm below the top soil, indicates limited vertical migration in the soil. Channels in the mires, made by plant roots or soil layer of less decomposed materials, may increase the rate of transport of contaminated surface water into deeper soil layers and ground water. A large portion of both Cu and Sb were associated to the oxidizable components in the peat, which may imply that these elements form inner-sphere complexes with organic matter. The largest portion of Pb and Zn were associated with the exchangeable and pH-sensitive components in the peat, which may imply that these elements form outer-sphere complexes with the peat.

http://ift.tt/2n9KHoq

Assessment of pesticide contamination in Akkar groundwater, northern Lebanon

Abstract

According to its high production and value, Akkar is considered as the second agricultural region in Lebanon. Groundwater constitutes the principal source of water in Akkar including drinking water of local inhabitants in Akkar. As such, the contamination of groundwater by organic pollutants can impact directly the population health. In this study, we evaluated the contamination status of groundwater in this region. Three classes of pesticides including 19 organochlorine (OC) pesticides, 8 organophosphorus (OP) pesticides, and 6 organonitrogen (ON) pesticides were monitored in 15 groundwater samples collected from different villages on the Akkar plain. Samples were extracted by using solid phase extraction (SPE) and analyzed by gas chromatography coupled with mass spectrometry (GC-MS). The results showed high contamination of Akkar groundwater by OCs with levels that can reach 58.9 μg/L. They were detected in the majority of the sample and represent 95–100% of ∑pesticides. Our results showed the recent use of these molecules with an average level of 0.3 and 0.39 μg/L for ∑HCHs and DDTs, respectively. Their concentrations were higher than those observed in the same region in 2014 and other regions elsewhere. OPs were also detected at high levels and among them, methylparathion was the predominant OP detected (44.6 μg/L). For ONs, lower levels were measured in all samples with a mean value of 5.6 μg/L. As a conclusion of this work, groundwater on the plain of Akkar was remarkably contaminated by the studied pesticides; indefinitely, more efforts should be taken to manage the pesticide use in this region, assess, and reduce their effects on human health. In the future, the application of organic farming can be a great solution to the groundwater contamination problem.

http://ift.tt/2mREGR4

The study of mechanisms of biological activity of copper oxide nanoparticle CuO in the test for seedling roots of Triticum vulgare

Abstract

The rapid development of nanotechnology raises questions assessment of their impact on living objects. In the present study, we evaluated the impact of nanoparticle (NP) CuO at concentrations ranging from 0.8 to 63.5 g/l in the test on wheat seedlings Triticum vulgare during 1–72 h. In the viability test (WST-test), cells were isolated from the roots of seedlings T. vulgare, 12 h not observed increase reductase activity after 24 h decreased rate of not more than 19% compared with the control. The number of dead cells in seedlings of T. vulgaris after exposure with CuO nanoparticles to the test with Evans blue increased by 5–15% compared to control. We observed that a significant increase in copper revenues leaves 4.5–8.9 times more in relation to the control and the roots—in 5–9.7 times. During the determined amount of active oxygen species, a significant proportional increase in the total pool of reactive oxygen species (ROS) in roots increased to 27.6% after exposure to NP CuO compared with the control. It is shown that in the introduction in medium, the NP CuO in the doses ranging from 3.2 to 63.5 g/l leads to DNA fragmentation and increases the fragments less than 3000 bp on 51.4–62.8%. The totality of our results influences nanoforms of copper oxide on the amount of ROS, and the viability of the genomic component of the cells shows different mechanisms of damage in the activation of a metabolic reaction, to determine the concentration of nano-CuO.

http://ift.tt/2n9N36W

The effect of age at surgery and compensatory articulation on speech outcome in submucous cleft palate patients treated with double-opposing Z-plasty: A 10-year experience

Submucous cleft palate is a congenital deformity that may present as velopharyngeal insufficiency. The degree of anatomical abnormality varies widely among patients and does not predict severity of symptom. We present our 10-year experience treating submucous cleft palate patients with double opposing z-plasty and explore the effect of age at surgery and compensatory articulation on speech.

http://ift.tt/2lRN2U0

White matter alterations to cingulum and fornix following very preterm birth and their relationship with cognitive functions

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Chiara Caldinelli, Sean Froudist-Walsh, Vyacheslav Karolis, Chieh-En Tseng, Matthew P. Allin, Muriel Walshe, Marion Cuddy, Robin M. Murray, Chiara Nosarti
Very preterm birth (VPT; <32 weeks of gestation) has been associated with impairments in memory abilities and functional neuroanatomical brain alterations in medial temporal and fronto-parietal areas. Here we investigated the relationship between structural connectivity in memory-related tracts and various aspects of memory in VPT adults (mean age 19) who sustained differing degrees of perinatal brain injury (PBI), as assessed by neonatal cerebral ultrasound. We showed that the neurodevelopmental consequences of VPT birth persist into young adulthood and are associated with neonatal cranial ultrasound classification. At a cognitive level, VPT young adults showed impairments specific to effective organization of verbal information and visuospatial memory, whereas at an anatomical level they displayed reduced volume of memory-related tracts, the cingulum and the fornix, with greater alterations in those individuals who experienced high-grade PBI. When investigating the association between these tracts and memory scores, perseveration errors were associated with the volume of the fornix and dorsal cingulum (connecting medial frontal and parietal lobes). Visuospatial memory scores were associated with the volume of the ventral cingulum (connecting medial parietal and temporal lobes). These results suggest that structural connectivity alterations could underlie memory difficulties in preterm born individuals.



http://ift.tt/2mgWhAJ

Electrocorticographic delineation of human auditory cortical fields based on effects of propofol anesthesia

Publication date: 15 May 2017
Source:NeuroImage, Volume 152
Author(s): Kirill V. Nourski, Matthew I. Banks, Mitchell Steinschneider, Ariane E. Rhone, Hiroto Kawasaki, Rashmi N. Mueller, Michael M. Todd, Matthew A. Howard
The functional organization of human auditory cortex remains incompletely characterized. While the posteromedial two thirds of Heschl's gyrus (HG) is generally considered to be part of core auditory cortex, additional subdivisions of HG remain speculative. To further delineate the hierarchical organization of human auditory cortex, we investigated regional heterogeneity in the modulation of auditory cortical responses under varying depths of anesthesia induced by propofol. Non-invasive studies have shown that propofol differentially affects auditory cortical activity, with a greater impact on non-core areas. Subjects were neurosurgical patients undergoing removal of intracranial electrodes placed to identify epileptic foci. Stimuli were 50Hz click trains, presented continuously during an awake baseline period, and subsequently, while propofol infusion was incrementally titrated to induce general anesthesia. Electrocorticographic recordings were made with depth electrodes implanted in HG and subdural grid electrodes implanted over superior temporal gyrus (STG). Depth of anesthesia was monitored using spectral entropy. Averaged evoked potentials (AEPs), frequency-following responses (FFRs) and high gamma (70–150Hz) event-related band power were used to characterize auditory cortical activity. Based on the changes in AEPs and FFRs during the induction of anesthesia, posteromedial HG could be divided into two subdivisions. In the most posteromedial aspect of the gyrus, the earliest AEP deflections were preserved and FFRs increased during induction. In contrast, the remainder of the posteromedial HG exhibited attenuation of both the AEP and the FFR. The anterolateral HG exhibited weaker activation characterized by broad, low-voltage AEPs and the absence of FFRs. Lateral STG exhibited limited activation by click trains, and FFRs there diminished during induction. Sustained high gamma activity was attenuated in the most posteromedial portion of HG, and was absent in all other regions. These differential patterns of auditory cortical activity during the induction of anesthesia may serve as useful physiological markers for field delineation. In this study, the posteromedial HG could be parcellated into at least two subdivisions. Preservation of the earliest AEP deflections and FFRs in the posteromedial HG likely reflects the persistence of feedforward synaptic activity generated by inputs from subcortical auditory pathways, including the medial geniculate nucleus.



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Individual differences and time-varying features of modular brain architecture

Publication date: 15 May 2017
Source:NeuroImage, Volume 152
Author(s): Xuhong Liao, Miao Cao, Mingrui Xia, Yong He
Recent studies have suggested that human brain functional networks are topologically organized into functionally specialized but inter-connected modules to facilitate efficient information processing and highly flexible cognitive function. However, these studies have mainly focused on group-level network modularity analyses using "static" functional connectivity approaches. How these extraordinary modular brain structures vary across individuals and spontaneously reconfigure over time remain largely unknown. Here, we employed multiband resting-state functional MRI data (N=105) from the Human Connectome Project and a graph-based modularity analysis to systematically investigate individual variability and dynamic properties in modular brain networks. We showed that the modular structures of brain networks dramatically vary across individuals, with higher modular variability primarily in the association cortex (e.g., fronto-parietal and attention systems) and lower variability in the primary systems. Moreover, brain regions spontaneously changed their module affiliations on a temporal scale of seconds, which cannot be simply attributable to head motion and sampling error. Interestingly, the spatial pattern of intra-subject dynamic modular variability largely overlapped with that of inter-subject modular variability, both of which were highly reproducible across repeated scanning sessions. Finally, the regions with remarkable individual/temporal modular variability were closely associated with network connectors and the number of cognitive components, suggesting a potential contribution to information integration and flexible cognitive function. Collectively, our findings highlight individual modular variability and the notable dynamic characteristics in large-scale brain networks, which enhance our understanding of the neural substrates underlying individual differences in a variety of cognition and behaviors.



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Fully-integrated framework for the segmentation and registration of the spinal cord white and gray matter

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Sara M. Dupont, Benjamin De Leener, Manuel Taso, Arnaud Le Troter, Sylvie Nadeau, Nikola Stikov, Virginie Callot, Julien Cohen-Adad
The spinal cord white and gray matter can be affected by various pathologies such as multiple sclerosis, amyotrophic lateral sclerosis or trauma. Being able to precisely segment the white and gray matter could help with MR image analysis and hence be useful in further understanding these pathologies, and helping with diagnosis/prognosis and drug development. Up to date, white/gray matter segmentation has mostly been done manually, which is time consuming, induces a bias related to the rater and prevents large-scale multi-center studies. Recently, few methods have been proposed to automatically segment the spinal cord white and gray matter. However, no single method exists that combines the following criteria: (i) fully automatic, (ii) works on various MRI contrasts, (iii) robust towards pathology and (iv) freely available and open source. In this study we propose a multi-atlas based method for the segmentation of the spinal cord white and gray matter that addresses the previous limitations. Moreover, to study the spinal cord morphology, atlas-based approaches are increasingly used. These approaches rely on the registration of a spinal cord template to an MR image, however the registration usually doesn't take into account the spinal cord internal structure and thus lacks accuracy. In this study, we propose a new template registration framework that integrates the white and gray matter segmentation to account for the specific gray matter shape of each individual subject. Validation of segmentation was performed in 24 healthy subjects using T2*-weighted images, in 8 healthy subjects using diffusion weighted images (exhibiting inverted white-to-gray matter contrast compared to T2*-weighted), and in 5 patients with spinal cord injury. The template registration was validated in 24 subjects using T2*-weighted data. Results of automatic segmentation on T2*-weighted images was in close correspondence with the manual segmentation (Dice coefficient in the white/gray matter of 0.91/0.71 respectively). Similarly, good results were obtained in data with inverted contrast (diffusion-weighted image) and in patients. When compared to the classical template registration framework, the proposed framework that accounts for gray matter shape significantly improved the quality of the registration (comparing Dice coefficient in gray matter: p=9.5×10⁻⁶). While further validation is needed to show the benefits of the new registration framework in large cohorts and in a variety of patients, this study provides a fully-integrated tool for quantitative assessment of white/gray matter morphometry and template-based analysis. All the proposed methods are implemented in the Spinal Cord Toolbox (SCT), an open-source software for processing spinal cord multi-parametric MRI data.

Graphical abstract

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Opioid suppression of conditioned anticipatory brain responses to breathlessness

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Anja Hayen, Vishvarani Wanigasekera, Olivia K. Faull, Stewart F. Campbell, Payashi S. Garry, Simon J.M. Raby, Josephine Robertson, Ruth Webster, Richard G. Wise, Mari Herigstad, Kyle T.S. Pattinson
Opioid painkillers are a promising treatment for chronic breathlessness, but are associated with potentially fatal side effects. In the treatment of breathlessness, their mechanisms of action are unclear. A better understanding might help to identify safer alternatives. Learned associations between previously neutral stimuli (e.g. stairs) and repeated breathlessness induce an anticipatory threat response that may worsen breathlessness, contributing to the downward spiral of decline seen in clinical populations. As opioids are known to influence associative learning, we hypothesized that they may interfere with the brain processes underlying a conditioned anticipatory response to breathlessness in relevant brain areas, including the amygdala and the hippocampus.Healthy volunteers viewed visual cues (neutral stimuli) immediately before induction of experimental breathlessness with inspiratory resistive loading. Thus, an association was formed between the cue and breathlessness. Subsequently, this paradigm was repeated in two identical neuroimaging sessions with intravenous infusions of either low-dose remifentanil (0.7ng/ml target-controlled infusion) or saline (randomised).During saline infusion, breathlessness anticipation activated the right anterior insula and the adjacent operculum. Breathlessness was associated with activity in a network including the insula, operculum, dorsolateral prefrontal cortex, anterior cingulate cortex and the primary sensory and motor cortices.Remifentanil reduced breathlessness unpleasantness but not breathlessness intensity. Remifentanil depressed anticipatory activity in the amygdala and the hippocampus that correlated with reductions in breathlessness unpleasantness. During breathlessness, remifentanil decreased activity in the anterior insula, anterior cingulate cortex and sensory motor cortices. Remifentanil-induced reduction in breathlessness unpleasantness was associated with increased activity in the rostral anterior cingulate cortex and nucleus accumbens, components of the endogenous opioid system known to decrease the perception of aversive stimuli.These findings suggest that in addition to effects on brainstem respiratory control, opioids palliate breathlessness through an interplay of altered associative learning mechanisms. These mechanisms provide potential targets for novel ways to develop and assess treatments for chronic breathlessness.



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Selective expansion of human regulatory T cells in nasal polyps, and not adjacent tissue microenvironments, in individual patients exposed to steroids

Publication date: Available online 6 March 2017
Source:Clinical Immunology
Author(s): Justin A Edward, Mrinmoy Sanyal, Wei Le, Ethan Soudry, Vijay R Ramakrishnan, Dawn T Bravo, Alan L Nguyen, David Zarabanda, Todd T Kingdom, Peter H Hwang, C Garrison Fathman, Jayakar V Nayak
Severe forms of chronic rhinosinusitis (CRS), a common upper airway inflammatory disorder, are associated with nasal polyps (NPs). NP disease is ameliorated by glucocorticoid (GC) treatment, whose cellular effects are poorly understood. We therefore assessed the influence of GC therapy on NPs in CRS patients, focusing on regulatory T (Treg) cells. Treg cell populations were analyzed by flow cytometry in NPs and control tissues from GC-treated CRS patients and controls. After GC exposure, selective expansion of Treg cells was seen within NPs, and not blood or adjacent ethmoid tissues. To confirm direct GC effects, NPs from the same patients were biopsied prior to, and following, 1week of oral GC exposure. Direct expansion of Tregs into the same NP bed was detected in 4/4 CRS patients following GC exposure. Treg cell spikes into NPs were secondary to cellular recruitment given limited Ki67 expression within these regulatory cells. Chemokine gene expression profiling identified several chemokines, notably CCL4, induced within NPs upon GC treatment. Neutralization of chemokine receptor/ligand interactions using CCR4 small molecule antagonists reduced Treg migration towards GC-treated NPs in an ex vivo migration assay. Our findings suggest that the common use of GCs in the treatment of NP disease leads to recruitment of Treg cells from peripheral sites into NP tissues, which may be critical to the anti-inflammatory effect of GCs. Mechanistically Treg expansion appears to be conferred, in part, by chemokine receptor/ligand interactions induced following corticosteroid therapy.



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The anti-sepsis activity of the components of Huanglian Jiedu Decoction with high lipid A-binding affinity

Publication date: May 2017
Source:International Immunopharmacology, Volume 46
Author(s): Guirong Chen, Yubin Xu, Jing Jing, Brianna Mackie, Xinchuan Zheng, Xu Zhang, Jing Wang, Xuetao Li
Huanglian Jiedu Decoction (HJD), one of the classic recipes for relieving toxicity and fever, is a common method for treating sepsis in China. However, the effective components of HJD have not yet been identified. This experiment was carried out to elucidate the effective components of HJD against sepsis. Thus, seven fractions from HJD were tested using a biosensor to test their affinity for lipid A. The components obtained that had high lipid A-binding fractions were further separated, and their affinities to lipid A were assessed with the aid of a biosensor. The levels of LPS in the blood were measured, and pathology experiments were conducted. The LPS levels and mRNA expression analysis of TNF-α and IL-6 of the cell supernatant and animal tissue were evaluated to investigate the molecular mechanisms. Palmatine showed the highest affinity to lipid A and was evaluated by in vitro and in vivo experiments. The results of the in vitro and in vivo experiments indicated that the levels of LPS, TNF-α and IL-6 of the palmatine group were significantly lower than those of the sepsis model group (p<0.01). The group treated with palmatine showed strong neutralizing LPS activity in vivo. The palmatine group exhibited stronger protective activity on vital organs compared to the LPS-induced animal model. This verifies that HJD is a viable treatment option for sepsis given that there are multiple components in HJD that neutralize LPS, decrease the release of IL-6 and TNF-α induced by LPS, and protect vital organs.

Graphical abstract

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Cutaneous dermal non-neural granular cell tumor is a granular cell dermal root sheath fibroma

Abstract

Dermal non-neural granular cell tumor (NNGCT) was first described in 1991 as an S100-negative polypoid non-melanocytic tumor. Although originally introduced in the literature as a primary cutaneous tumor, it was later emphasized that such qualification could not be held until the line of differentiation was clarified. It was also demonstrated that not all cases were polypoid. In the current study we try to further characterize this entity by presenting five cases of NNGCT. As expected, not all of them were polypoid. The ages of the patients varied from 10 to 43 (mean age 22). They all were composed of S100-negative granular cells with variable atypia and mitotic figures. None of them recurred in follow up of up to 12 years (mean 8.2 years). We found evidence of folliculocentricity in four cases (in one case, this feature could not be investigated because the biopsy was a small shave specimen), that is, tumors were always surrounding, embedding, or following a hair follicle. In some occasions, such features were better demonstrated by immunohistochemistry against the arrector pili muscle. Our cases showed intense immunoexpression of CD10 and CD68. We conclude that NNGCT is morphologically related to the hair follicle and we believe that it is a granular cell dermal root sheath fibroma.

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Patterns of Lymph Node Positivity on 11C–acetate PET Imaging in Correlation to the RTOG Pelvic Radiation Field for Prostate Cancer

Publication date: Available online 6 March 2017
Source:Practical Radiation Oncology
Author(s): Chris McClinton, Maryam Niroumand, Sumit Sood, Veer Shah, Jacqueline Hill, Reginald W Dusing, Xinglei Shen
Purpose¹¹C–acetate PET imaging allows for detection of occult metastatic disease that may otherwise go undetected with standard imaging for prostate cancer (PCa). The aim of this study was to evaluate lymph node coverage of the standard RTOG whole pelvic radiotherapy (WPRT) field in patients found to have node-positive PCa determined by ¹¹C–acetate PET imaging.Materials and MethodsA retrospective analysis was conducted on 125 PCa patients who underwent ¹¹C–acetate PET scans at our institution between 2007 and 2014. Patients were included if they had evidence of nodal disease without distant metastatic cancer. Individual lymph nodes were characterized by location, size, and relationship to the RTOG WPRT field.ResultsA total of 55 ¹¹C–acetate PET scans (from 54 men) met criteria for inclusion in the study. Median age at diagnosis was 61 years. Median PSA values at diagnosis and at the time of the scan were 9.2 ng/mL and 8.1 ng/mL, respectively. A total of 159 positive lymph nodes were identified – 78% of which were less than 1cm in size. The most frequently involved lymphatic regions were the external iliacs (38.4%), para-aortics (19.5%), and common iliacs (16.3%). Additionally, 10.1% of positive nodes were identified as nodes of Cloquet. Of the positive nodes, 51.6% were determined to reside outside of the radiation field and, of those, the most common sites were para-aortic (36.9%), proximal common iliac (17.8%), distal external iliac (17.8%), and nodes of Cloquet (17.8%).ConclusionsBased on ¹¹C–acetate PET imaging in patients with PCa, the standard RTOG WPRT field may miss more than half of all positive lymph nodes. Clinicians should be aware of the potential for insufficient nodal coverage when using the standard RTOG WPRT field in patients with node-positive PCa. ¹¹C–acetate PET imaging may be useful in defining target volumes for these patients.



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Daily CT Guidance Improves Target Coverage During Definitive Radiation Therapy for Gastric MALT Lymphoma

Publication date: Available online 6 March 2017
Source:Practical Radiation Oncology
Author(s): He Wang, Sarah A. Milgrom, Bouthaina S. Dabaja, Grace L. Smith, Mary Martel, Chelsea C. Pinnix
PurposeRadiation therapy (RT) for gastric mucosa-associated lymphoid tissue (MALT) lymphoma is challenging, due to variation in the stomach's position, size, and shape. We investigated the inter-fractional changes in stomach location, consequent dosimetric effects, and impact of daily computed tomography image guidance (CT-IGRT).Methods and MaterialsTwelve patients treated for gastric MALT lymphoma with intensity modulated radiation therapy (IMRT), using a breath-hold technique and restriction of oral intake, were studied retrospectively. The planning target volume (PTV) comprised a 0.5–1.0cm expansion of the stomach. The prescription dose was 30Gy in 15–20 fractions. CT-IGRT was performed daily using CT-on-rails. Dosimetry was calculated on 229 daily CT images after bony vs. CT-based soft tissue alignment, and doses delivered to the target and adjacent structures were compared to the treatment plan. Target coverage was expressed as the percent of the clinical target volume (CTV) and PTV receiving ≥95% of the prescribed dose (V95%).ResultsThe average change in stomach volume was −12.4% (range: −47.6 to 38.6%). The average shift required for target coverage was 1.0 cm (maximum: 2.2 cm). With CT-based alignment to the stomach, the average V95% was 98.5% for CTV and 94.9% for PTV; with bony alignment, these values were 94.5% and 90.4%, respectively (P<0.01 for CTV and PTV). With bony alignment, the PTV V95% was ≤90% in 4 patients (33%) over the course of treatment and was as low as 72.5% for one fraction. The kidney position varied with respect to the stomach and bony anatomy. Consequently, the dose to the left kidney was higher based on daily CT scans than planning scans. Dose to other OARs did not vary significantly.ConclusionsSubstantial inter-fractional variation in stomach volume was observed, despite treatment with breath-hold and restriction of oral intake. Daily CT-IGRT improved target coverage, enabling excellent coverage despite the use of small PTV margins.



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Masthead

Publication date: March–April 2017
Source:Practical Radiation Oncology, Volume 7, Issue 2





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Editorial Board

Publication date: March–April 2017
Source:Practical Radiation Oncology, Volume 7, Issue 2





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In response to narrative oncology piece by E.C. Halperin, Military metaphors and the consequences of the language of cancer

Publication date: Available online 6 March 2017
Source:Practical Radiation Oncology
Author(s): Giulio J. D'Angio




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Table of Contents

Publication date: March–April 2017
Source:Practical Radiation Oncology, Volume 7, Issue 2





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No catheter angiography is needed in patients with an obscure acute gastrointestinal bleed and negative CTA

Publication date: May–June 2017
Source:Clinical Imaging, Volume 43
Author(s): Pratik A. Shukla, Adam Zybulewski, Marcin K. Kolber, Erik Berkowitz, James Silberzweig, Morris Hayim
PurposeTo evaluate the negative predictive power of computed tomography angiography (CTA) for the identification of obscure acute gastrointestinal (GI) bleeding (GI bleeding not visualized/treated by endoscopy) on subsequent mesenteric angiography (MA) with the intention to treat.Materials and methodsA retrospective chart review of patients was performed who underwent mesenteric angiography for the evaluation/treatment of acute GI bleeding between November 2012 and July 2016. Patients with negative CTA examinations that proceeded to MA were identified. Negative predictive value (NPV) was calculated.Results20 patients (14 male, 6 female; average age: 73.1±12.8years) underwent 20 negative CTA examinations for the evaluation and treatment of GI bleeding followed by mesenteric angiography. Eighteen of 20 patients had negative subsequent MA (negative predictive value, NPV=90%). Both false negative cases were upper GI bleed (vs 0 lower GI bleed); this difference was significant (p<0.05).ConclusionsThe high NPV of CTA for the evaluation of GI bleeding suggests utility for excluding patients that are unlikely to benefit from MA and subsequent endovascular therapy. CTA may be considered for the first line diagnostic study for the evaluation of obscure GI bleeding.



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Fluorocholine PET/CT predicts skeletal progression, skeletal event and cancer specific survival in patients with biochemical relapse for prostate cancer

Publication date: May–June 2017
Source:Clinical Imaging, Volume 43
Author(s): Fabio Zattoni, Emanuela Agostini, Francesco Cattaneo, Marco Maruzzo, Umberto Basso, Filiberto Zattoni, Laura Evangelista
PurposeThe aim of our study is to evaluate the prognostic impact of ¹⁸F-Choline (FCh) positron emission tomography (PET)/computed tomography (CT), CT alone and methylene diphophonate bone scan (MDP-BS) in prostate cancer (PCa) patients with biochemical relapse.MethodsWe retrospectively selected 58 patients who underwent, between June 2010 and February 2013, both FCh-PET/CT and MDP-BS within a maximum time interval of 5months. All patients had a biochemical PCa recurrence after radical prostatectomy and/or radiation therapy. Two independent observers reviewed FCh-PET/CT and MDP-BS images. The bone window of CT portion from FCh-PET/CT was separately assessed. Time to progression (TTP), skeletal event free survival (SES) and cancer specific survival (CSS) were defined as the length of time between imaging and progression of disease, skeletal related events and cancer specific mortality, respectively. A patient based and a K agreement analysis was used to compare the findings of all three imaging modalities. Kaplan-Meier and log-rank analysis were computed for survival assessment. A multivariate Cox regression analysis was used to identify the independent predictors for TTP.ResultsBone metastases were detected in 22 (38%) patients at FCh-PET/CT, in 27 (47%) at MDP-BS and in 24 (41%) at CT. The agreement between FCh-PET/CT and MDP-BS, CT and MDP-BS, and FCh-PET/CT and CT were moderate/fair (respectively, k: 0.474, 0.267 and 0.424; all p<0.05). After 38months (IQR: 27–54months) of follow-up, 33 (57%) patients had a new recurrence of disease, 12 (21%) had skeletal related events and 19 (33%) died. Three subjects (5%) were lost during the observational period. At survival analyses, a worse TTP, SES and CSS were found in patients with a positive FCh-PET/CT at bone level than those with a negative scan (all p≤0.05). Conversely, any significant difference in TTP, SES and CSS was found for patients with both a positive MDP-BS and CT scan. At univariate analysis, a positive FCh-PET/CT at skeletal level was associated with all events (all p<0.05). However, only a positive FCh-PET/CT at any site was an independent prognostic variable of TTP (HR: 3.08; CI 95%: 1.85–9.05; p=0.04).ConclusionsPET/CT should be preferred to CT and BS in patients with prostate cancer with bone metastasis because it allows a better stratification of TTP, SES and CCS compared to CT and BS.



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Robust detection and segmentation of cell nuclei in biomedical images based on a computational topology framework

Publication date: Available online 6 March 2017
Source:Medical Image Analysis
Author(s): Rodrigo Rojas-Moraleda, Wei Xiong, Niels Halama, Katja Breitkopf-Heinlein, Steven Dooley, Luis Salinas, Dieter W. Heermann, Nektarios A. Valous
The segmentation of cell nuclei is an important step towards the automated analysis of histological images. The presence of a large number of nuclei in whole-slide images necessitates methods that are computationally tractable in addition to being effective. In this work, a method is developed for the robust segmentation of cell nuclei in histological images based on the principles of persistent homology. More specifically, an abstract simplicial homology approach for image segmentation is established. Essentially, the approach deals with the persistence of disconnected sets in the image, thus identifying salient regions that express patterns of persistence. By introducing an image representation based on topological features, the task of segmentation is less dependent on variations of color or texture. This results in a novel approach that generalizes well and provides stable performance. The method conceptualizes regions of interest (cell nuclei) pertinent to their topological features in a successful manner. The time cost of the proposed approach is lower-bounded by an almost linear behavior and upper-bounded by O(n2) in a worst-case scenario. Time complexity matches a quasilinear behavior which is O(n1+ɛ) for ε < 1. Images acquired from histological sections of liver tissue are used as a case study to demonstrate the effectiveness of the approach. The histological landscape consists of hepatocytes and non-parenchymal cells. The accuracy of the proposed methodology is verified against an automated workflow created by the output of a conventional filter bank (validated by experts) and the supervised training of a random forest classifier. The results are obtained on a per-object basis. The proposed workflow successfully detected both hepatocyte and non-parenchymal cell nuclei with an accuracy of 84.6%, and hepatocyte cell nuclei only with an accuracy of 86.2%. A public histological dataset with supplied ground-truth data is also used for evaluating the performance of the proposed approach (accuracy: 94.5%). Further validations are carried out with a publicly available dataset and ground-truth data from the Gland Segmentation in Colon Histology Images Challenge (GlaS) contest. The proposed method is useful for obtaining unsupervised robust initial segmentations that can be further integrated in image/data processing and management pipelines. The development of a fully automated system supporting a human expert provides tangible benefits in the context of clinical decision-making.

Graphical abstract

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Impact of osteopathic therapy on pro-prioceptive balance and quality of life in patients with dizziness

Publication date: Available online 6 March 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): L. Papa, A. Amodio, F. Biffi, A. Mandara
The aim of the study was to evaluate the efficacy of osteopathic manipulative treatment (OMT) in patients with Benign-Paroxysmal-Positional Vertigo (BPPV).Thirty-one patients with BPPV were randomly assigned into two groups: 19 patients received osteopathic treatments (TG) and 12 patients received sham therapy (SG), both in four weekly sessions. Before the first and the last treatment, those patients were evaluated using Dizziness Handicap Inventory (DHI) and stabilometric platform to assess lifestyle modification and balance functions.After the treatment session, TG compared to SG showed an improvement in DHI global (p=0.02), functional (p=0.03) and physical (p=0.03) components, as well as a reduction of swinging area (p=0.02). An association between swinging area and lifestyle measures (global [r=0.53; p=0.02]; functional [r=0.50; p=0.03]; physical [r=0.60; p= 0.01]) changes were found in TG.These findings suggest that OMT could be a useful approach to reduce imbalance symptoms and to improve the quality of life in patients suffering from dizziness.



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