Τρίτη, 16 Μαΐου 2017

Hepatozoon caimani Carini, 1909 (Adeleina: Hepatozoidae) in wild population of Caiman yacare Daudin, 1801 (Crocodylia: Alligatoridae), Pantanal, Brazil

Abstract

Previous studies showed infections of Hepatozoon caimani in wild populations of caimans in wide regions from Brazil; some of those demonstrated that trophic chain are linked to natural infections through paratenic hosts or by the direct ingestion of vectors. These studies life cycle of H. caimani contributed inestimably to the knowledge of transmission routes, yet but lack enhancement tools for better detail of parasite. This study reports the forms in the blood and tissues, and also partial molecular characterization of the H. caimani following part of the 18S rRNA region. In the southern Pantanal, there were sampling 39 adult caimans (Caiman yacare), where 31 (79.5%) were parasitized by H. caimani. Free gametocytes had an average intensity of 19.6% and intraerythrocytic forms 7.42%, in the blood smears. In stained smears of the liver and lungs of naturally infected caimans which were examined, monozoic and dizoic cysts were found in these tissues, generally next to the vessels. In the histopathology, meronts were observed in the wall of vessels from liver and kidney ducts. Blood samples were forwarded to PCR process and produced amplicons with about 600 and 900 bp, respectively, for the primers HEPF300/HEP900 and HEMO1/HEMO2. This was the first report of molecular confirmation of Hepatozoon in populations of naturally infected caimans of morphological detail of the gametocytes in scanning electron microscopy and histology of merogony in livers and kidneys of C. yacare.



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Ant-mediated indirect negative effects of aphids on spider mites living on the same plant

Abstract

Some aphid species are known to have mutualistic relationships with tending ants; that is, the aphids supply the ants with honeydew and are protected by the ants. Although spider mites and honeydew-producing aphids often live on the same host plant, it has not previously been determined whether the ants tending these aphids affect spider mite survival. Using replicated microcosms, each containing an artificial ant nest, we compared experimentally the survival of two-spotted spider mites on kidney bean plants with and without cowpea aphids. Our results showed significantly fewer spider mites on plants with aphids, indicating that spider mites were preyed upon by ants tending aphids. On the other hand, there was no detectable plant-mediated indirect effect of aphids on mite performance in the microcosms. Therefore, we conclude that aphids indirectly reduced the survival of spider mites living on the same host plant via their tending ants. Nonetheless, spider mites did not avoid settling on plant leaves infested with aphids.



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CAGI4 SickKids clinical genomes challenge: A pipeline for identifying pathogenic variants

Abstract

Compared with earlier more restricted sequencing technologies, identification of rare disease variants using whole genome sequence has the possibility of finding all causative variants, but issues of data quality and an overwhelming level of background variants complicate the analysis. The CAGI4 SickKids clinical genome challenge provided an opportunity to assess the landscape of variants found in a difficult set of 25 unsolved rare disease cases. To address the challenge, we developed a three-stage pipeline, first carefully analyzing data quality, then classifying high quality gene specific variants into seven categories, and finally examining each candidate variant for compatibility with the often complex phenotypes of these patients for final prioritization. Variants consistent with the phenotypes were found in 24 out of the 25 cases, and in a number of these, there are prioritized variants in multiple genes. Data quality analysis suggests that some of the selected variants are likely incorrect calls, complicating interpretation. The data providers followed up on three suggested variants with Sanger sequencing, and in one case a prioritized variant was confirmed as likely causative by the referring physician, providing a diagnosis in a previously intractable case.

This article is protected by copyright. All rights reserved



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Reporting practices for unsolicited and secondary findings from next generation sequencing technologies: Perspectives of laboratory personnel

ABSTRACT

While next generation sequencing has enormous potential to identify genetic causes of disease, the nature of the technology means that it can also identify additional information about the individual receiving sequencing that is unrelated to the original rationale for testing. Reporting these unsolicited findings (UF) to clinicians, and subsequently to patients, could lead to potentially lifesaving interventions. Most international guidelines provide limited specific recommendations as to whether these UF should be reported. Little research has been conducted exploring which of these variants are reported in practice.

26 interviews were conducted with 27 laboratory personnel, representing 24 laboratories in Europe (12), Canada (5) and Australasia (7) to explore their reporting practices. There is considerable variation between laboratories in the reporting of UF. While some limit their reporting to findings that are relevant to the clinical question, others report UF to varying degrees. In addition, most laboratory personnel interviewed said that their laboratories do not actively search for secondary findings in disease-causing genes unrelated to the clinical question, such as those suggested by the ACMG. Our study highlights that laboratories are still grappling with decisions about which UF to report from NGS and are calling for more guidance.

This article is protected by copyright. All rights reserved



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CAGI4 Crohn's exome challenge: Marker SNP versus exome variant models for assigning risk of Crohn disease

ABSTRACT

Understanding the basis of complex trait disease is a fundamental problem in human genetics. The CAGI Crohn's Exome challenges are providing insight into the adequacy of current disease models by requiring participants to identify which of a set of individuals has been diagnosed with the disease, given exome data. For the CAGI4 round, we developed a method that used the genotypes from exome sequencing data only to impute the status of Genome Wide Association Studies (GWAS) marker single nucleotide polymorphisms (SNPs). We then used the imputed genotypes as input to several machine learning methods that had been trained to predict disease status from marker SNP information. We achieved the best performance using Naïve Bayes and with a consensus machine learning method, obtaining an area under the curve (AUC) of 0.72, larger than other methods used in CAGI4. We also developed a model that incorporated the contribution from rare missense variants in the exome data, but this performed less well. Future progress is expected to come from the use of whole genome data rather than exomes.

This article is protected by copyright. All rights reserved



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IJMS, Vol. 18, Pages 856: Natural Killer Cells Response to IL-2 Stimulation Is Distinct between Ascites with the Presence or Absence of Malignant Cells in Ovarian Cancer Patients

Peritoneal ascites are a distinguishable feature of patients with advanced epithelial ovarian cancer (EOC). The presence of different lymphocyte subsets has been reported in EOC-associated ascites, which also can or not contain malignant cells. The goal of this study was to analyze the functional characteristics of natural killer (NK) cells from EOC-associated ascites in terms of their expression of activating receptors and ascites’ contents of lymphocyte subtypes, cytokine profile and presence of EOC cells. NK cell function was evaluated by the expression of the degranulation marker CD107a in resting and interleukin (IL)-2 stimulated NK cells from ascites and blood. Degranulation of NK cells from EOC cell-free ascites was significantly (p < 0.05) higher than all the other groups, either in their resting state or after IL-2 stimulation, suggesting a previous local stimulation. In contrast, treatment with IL-2 had no effect on NK cells from ascites with EOC cells. The amount of regulatory T cells was significantly higher in ascites with EOC cells compared to EOC cell-free ascites. Ascites with EOC cells also had higher levels of tumor necrosis factor (TNF)-α, suggesting inflammation related to the malignancy. In conclusion, the functional performance of NK cells was distinct between EOC cell-free ascites and ascites with EOC cells. The impairment of NK cell response to IL-2 in ascites with EOC cells was consistent with an immunosuppressive tumor microenvironment.

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Title Page/Sections Editors

Publication date: May 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1860, Issue 5





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Test-Retest Reliability of the Dual-Microphone Voice Range Profile

The voice range profile (VRP) measures vocal intensity and fundamental frequency. Phonosurgical and logopedic treatment outcome studies using the VRP report voice improvements of 3–6 semitones (ST) in ST range and 4–7 decibels (dB) in sound pressure level range after treatment. These small improvements stress the importance of reliable measurements. The aim was to evaluate the test-retest reliability of the dual-microphone computerized VRP on participants with healthy voices.

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Hypoxic Pathobiology of Breast Cancer Metastasis

Publication date: Available online 16 May 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Luana Schito, Sergio Rey
Dissemination of breast cancer cells (BCCs) to distant sites (metastasis) is the ultimate cause of mortality in patient with breast cancer. Hypoxia (low O2) is a microenvironmental hallmark of most solid cancers arising as a mismatch between cellular O2 consumption and supply. Hypoxic selection of BCCs triggers molecular and cellular adaptations dependent upon hypoxia-inducible factors (HIFs), a family of evolutionarily conserved transcriptional activators that coordinate the expression of numerous genes controlling each step of the metastatic process. In this review, we summarize current advances in the understanding of HIF-driven molecular mechanisms that promote BCC metastatic dissemination and patient mortality. In addition, we discuss the clinical and therapeutic implications of HIF targeting in breast cancers.



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The INO80 Complex Removes H2A.Z to Promote Presynaptic Filament Formation during Homologous Recombination

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Claudio A. Lademann, Jörg Renkawitz, Boris Pfander, Stefan Jentsch
The INO80 complex (INO80-C) is an evolutionarily conserved nucleosome remodeler that acts in transcription, replication, and genome stability. It is required for resistance against genotoxic agents and is involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). However, the causes of the HR defect in INO80-C mutant cells are controversial. Here, we unite previous findings using a system to study HR with high spatial resolution in budding yeast. We find that INO80-C has at least two distinct functions during HR—DNA end resection and presynaptic filament formation. Importantly, the second function is linked to the histone variant H2A.Z. In the absence of H2A.Z, presynaptic filament formation and HR are restored in INO80-C-deficient mutants, suggesting that presynaptic filament formation is the crucial INO80-C function during HR.

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Teaser

The chromatin remodeler INO80-C is required for efficient DSB repair. Lademann et al. find that INO80-C has a dual role in homologous recombination, functioning during DNA end resection and Rad51 filament formation. Specifically, the second function is critical for DNA repair and is mechanistically promoted by a turnover of the histone variant H2A.Z.


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Modeling Genomic Instability and Selection Pressure in a Mouse Model of Melanoma

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Lawrence N. Kwong, Lihua Zou, Sharmeen Chagani, Chandra Sekhar Pedamallu, Mingguang Liu, Shan Jiang, Alexei Protopopov, Jianhua Zhang, Gad Getz, Lynda Chin
Tumor evolution is an iterative process of selection for pro-oncogenic aberrations. This process can be accelerated by genomic instability, but how it interacts with different selection bottlenecks to shape the evolving genomic landscape remains understudied. Here, we assessed tumor initiation and therapy resistance bottlenecks in mouse models of melanoma, with or without genomic instability. At the initiation bottleneck, whole-exome sequencing revealed that drug-naive tumors were genomically silent, and this was surprisingly unaffected when genomic instability was introduced via telomerase inactivation. We hypothesize that the strong engineered alleles created low selection pressure. At the therapy resistance bottleneck, strong selective pressure was applied using a BRAF inhibitor. In the absence of genomic instability, tumors acquired a non-genomic drug resistance mechanism. By contrast, telomerase-deficient, drug-resistant melanomas acquired highly recurrent copy number gains. These proof-of-principle experiments demonstrate how different selection pressures can interact with genomic instability to impact tumor evolution.

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Teaser

In this study, Kwong et al. use genetically engineered mouse models of melanoma, whole-exome sequencing, telomere dysfunction, and targeted therapy to study how genomic instability and selection pressures interact to shape tumor evolution. They find that genomic instability manifests itself differentially under conditions of low and high selective pressure.


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Thymidine Catabolism as a Metabolic Strategy for Cancer Survival

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Sho Tabata, Masatatsu Yamamoto, Hisatsugu Goto, Akiyoshi Hirayama, Maki Ohishi, Takuya Kuramoto, Atsushi Mitsuhashi, Ryuji Ikeda, Misako Haraguchi, Kohichi Kawahara, Yoshinari Shinsato, Kentaro Minami, Atsuro Saijo, Masaki Hanibuchi, Yasuhiko Nishioka, Saburo Sone, Hiroyasu Esumi, Masaru Tomita, Tomoyoshi Soga, Tatsuhiko Furukawa, Shin-ichi Akiyama
Thymidine phosphorylase (TP), a rate-limiting enzyme in thymidine catabolism, plays a pivotal role in tumor progression; however, the mechanisms underlying this role are not fully understood. Here, we found that TP-mediated thymidine catabolism could supply the carbon source in the glycolytic pathway and thus contribute to cell survival under conditions of nutrient deprivation. In TP-expressing cells, thymidine was converted to metabolites, including glucose 6-phosphate, lactate, 5-phospho-α-D-ribose 1-diphosphate, and serine, via the glycolytic pathway both in vitro and in vivo. These thymidine-derived metabolites were required for the survival of cells under low-glucose conditions. Furthermore, activation of thymidine catabolism was observed in human gastric cancer. These findings demonstrate that thymidine can serve as a glycolytic pathway substrate in human cancer cells.

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Teaser

Tabata et al. find that thymidine phosphorylase (TP)-mediated thymidine catabolism can supply carbon to the glycolytic pathway in mammalian cells. In TP-expressing cancer cells, thymidine contributes to cell survival under nutrient starvation.


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The Presence of Interleukin-13 at Pancreatic ADM/PanIN Lesions Alters Macrophage Populations and Mediates Pancreatic Tumorigenesis

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Geou-Yarh Liou, Ligia Bastea, Alicia Fleming, Heike Döppler, Brandy H. Edenfield, David W. Dawson, Lizhi Zhang, Nabeel Bardeesy, Peter Storz
The contributions of the innate immune system to the development of pancreatic cancer are still ill defined. Inflammatory macrophages can initiate metaplasia of pancreatic acinar cells to a duct-like phenotype (acinar-to-ductal metaplasia [ADM]), which then gives rise to pancreatic intraepithelial neoplasia (PanIN) when oncogenic KRas is present. However, it remains unclear when and how this inflammatory macrophage population is replaced by tumor-promoting macrophages. Here, we demonstrate the presence of interleukin-13 (IL-13), which can convert inflammatory into Ym1+ alternatively activated macrophages, at ADM/PanIN lesions. We further show that Ym1+ macrophages release factors, such as IL-1ra and CCL2, to drive pancreatic fibrogenesis and tumorigenesis. Treatment of mice expressing oncogenic KRas under an acinar cell-specific promoter with a neutralizing antibody for IL-13 significantly decreased the accumulation of alternatively activated macrophages at these lesions, resulting in decreased fibrosis and lesion growth.

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Teaser

Liou et al. show that PanIN and Tuft cells produce IL-13 and that the presence of IL-13 at early pancreatic lesions leads to the accumulation of alternatively activated macrophages. Alternatively activated macrophages release factors, such as IL-1ra and CCL2, to drive pancreatic fibrosis and lesion growth.


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Crystal Structure of Tetrameric Arabidopsis MYC2 Reveals the Mechanism of Enhanced Interaction with DNA

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Teng-fei Lian, Yong-ping Xu, Lan-fen Li, Xiao-Dong Su
Jasmonates (JAs) are essential plant hormones that play important roles in the regulation of plant growth and the response to environmental stress. In the JA signaling pathway, the core transcription factors are a class of basic helix-loop-helix (bHLH) proteins, including MYC2, MYC3, and MYC4, that have different regulatory capacities. Here, we report the 2.7 Å crystal structure of the MYC2 bHLH domain complexed with G-box DNA, showing a cis-tetrameric structure. Biochemical assays confirmed that full-length MYC2 forms a stable homo-tetramer both in solution and in DNA-bound states, whereas MYC3 forms only a homodimer. Isothermal titration calorimetry (ITC) assays demonstrated that tetramerization enhanced DNA binding affinity, and fluorescence resonance energy transfer (FRET) assay indicated DNA looping potential of tetrameric MYC2. Luciferase assay further confirmed the importance of tetramerization in transcriptional regulation. Our studies provide a mechanistic explanation for the regulatory differences of MYC transcription factors.

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Teaser

Lian et al. solved the crystal structure of the Arabidopsis transcription factor MYC2-DNA complex and showed that MYC2 and MYC3 exist as homotetramer and homodimer in solution, respectively, explaining the different regulatory capacities of these bHLH transcription factors.


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Widespread Mitotic Bookmarking by Histone Marks and Transcription Factors in Pluripotent Stem Cells

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Yiyuan Liu, Bobbie Pelham-Webb, Dafne Campigli Di Giammartino, Jiexi Li, Daleum Kim, Katsuhiro Kita, Nestor Saiz, Vidur Garg, Ashley Doane, Paraskevi Giannakakou, Anna-Katerina Hadjantonakis, Olivier Elemento, Effie Apostolou
During mitosis, transcription is halted and many chromatin features are lost, posing a challenge for the continuity of cell identity, particularly in fast cycling stem cells, which constantly balance self-renewal with differentiation. Here we show that, in pluripotent stem cells, certain histone marks and stem cell regulators remain associated with specific genomic regions of mitotic chromatin, a phenomenon known as mitotic bookmarking. Enhancers of stem cell-related genes are bookmarked by both H3K27ac and the master regulators OCT4, SOX2, and KLF4, while promoters of housekeeping genes retain high levels of mitotic H3K27ac in a cell-type invariant manner. Temporal degradation of OCT4 during mitotic exit compromises its ability both to maintain and induce pluripotency, suggesting that its regulatory function partly depends on its bookmarking activity. Together, our data document a widespread yet specific bookmarking by histone modifications and transcription factors promoting faithful and efficient propagation of stemness after cell division.

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Teaser

During mitosis, cell identity is temporarily challenged. Liu et al. reveal that maintenance and acquisition of stem cell identity rely on persistent binding of key histone modifications and transcription factors on specific sites of mitotic chromatin.


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Inhibitory Control of Feature Selectivity in an Object Motion Sensitive Circuit of the Retina

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Tahnbee Kim, Daniel Kerschensteiner
Object motion sensitive (OMS) W3-retinal ganglion cells (W3-RGCs) in mice respond to local movements in a visual scene but remain silent during self-generated global image motion. The excitatory inputs that drive responses of W3-RGCs to local motion were recently characterized, but which inhibitory neurons suppress W3-RGCs’ responses to global motion, how these neurons encode motion information, and how their connections are organized along the excitatory circuit axis remains unknown. Here, we find that a genetically identified amacrine cell (AC) type, TH2-AC, exhibits fast responses to global motion and slow responses to local motion. Optogenetic stimulation shows that TH2-ACs provide strong GABAA receptor-mediated input to W3-RGCs but only weak input to upstream excitatory neurons. Cell-type-specific silencing reveals that temporally coded inhibition from TH2-ACs cancels W3-RGC spike responses to global but not local motion stimuli and, thus, controls the feature selectivity of OMS signals sent to the brain.

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Teaser

Kim and Kerschensteiner report that a specific amacrine cell type (TH2-AC) distinguishes local and global motion in the kinetics of its responses. Optogenetic activation and cell-type-specific silencing show that TH2-ACs provide strong inhibitory input to object motion sensitive retinal ganglion cells (W3-RGCs) and that this input suppresses W3-RGC responses to global motion stimuli.


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Endogenous Replication Stress in Mother Cells Leads to Quiescence of Daughter Cells

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Mansi Arora, Justin Moser, Harsha Phadke, Ashik Akbar Basha, Sabrina L. Spencer
Mammalian cells have two fundamentally different states, proliferative and quiescent, but our understanding of how and why cells switch between these states is limited. We previously showed that actively proliferating populations contain a subpopulation that enters quiescence (G0) in an apparently stochastic manner. Using single-cell time-lapse imaging of CDK2 activity and DNA damage, we now show that unresolved endogenous replication stress in the previous (mother) cell cycle prompts p21-dependent entry of daughter cells into quiescence immediately after mitosis. Furthermore, the amount of time daughter cells spend in quiescence is correlated with the extent of inherited damage. Our study thus links replication errors in one cell cycle to the fate of daughter cells in the subsequent cell cycle. More broadly, this work reveals that entry into quiescence is not purely stochastic but has a strong deterministic component arising from a memory of events that occurred in the previous generation(s).

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Teaser

Arora et al. find that unresolved DNA replication errors in mother cells are passed on to daughter cells, prompting entry of daughter cells into a temporary quiescence whose duration is correlated with the extent of inherited damage. The authors thereby uncover a key source of heterogeneity in cell-cycle duration.


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Huntington’s Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Ryan G. Lim, Chris Quan, Andrea M. Reyes-Ortiz, Sarah E. Lutz, Amanda J. Kedaigle, Theresa A. Gipson, Jie Wu, Gad D. Vatine, Jennifer Stocksdale, Malcolm S. Casale, Clive N. Svendsen, Ernest Fraenkel, David E. Housman, Dritan Agalliu, Leslie M. Thompson
Brain microvascular endothelial cells (BMECs) are an essential component of the blood-brain barrier (BBB) that shields the brain against toxins and immune cells. While BBB dysfunction exists in neurological disorders, including Huntington’s disease (HD), it is not known if BMECs themselves are functionally compromised to promote BBB dysfunction. Further, the underlying mechanisms of BBB dysfunction remain elusive given limitations with mouse models and post-mortem tissue to identify primary deficits. We undertook a transcriptome and functional analysis of human induced pluripotent stem cell (iPSC)-derived BMECs (iBMEC) from HD patients or unaffected controls. We demonstrate that HD iBMECs have intrinsic abnormalities in angiogenesis and barrier properties, as well as in signaling pathways governing these processes. Thus, our findings provide an iPSC-derived BBB model for a neurodegenerative disease and demonstrate autonomous neurovascular deficits that may underlie HD pathology with implications for therapeutics and drug delivery.

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Lim et al. show that HD iPSCs-derived brain microvascular endothelial cells have impaired angiogenic and barrier properties. Transcriptomic analysis provides mechanistic insights into pathways that underlie dysfunction, and WNT inhibition prevents angiogenic deficits. This system also suggests strategies to reduce disease burden and assess BBB penetration of drugs for HD.


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CNS Macrophages Control Neurovascular Development via CD95L

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Si Chen, Nathalie Tisch, Marcel Kegel, Rosario Yerbes, Robert Hermann, Hannes Hudalla, Cecilia Zuliani, Gülce Sila Gülcüler, Klara Zwadlo, Jakob von Engelhardt, Carmen Ruiz de Almodóvar, Ana Martin-Villalba
The development of neurons and vessels shares striking anatomical and molecular features, and it is presumably orchestrated by an overlapping repertoire of extracellular signals. CNS macrophages have been implicated in various developmental functions, including the morphogenesis of neurons and vessels. However, whether CNS macrophages can coordinately influence neurovascular development and the identity of the signals involved therein is unclear. Here, we demonstrate that activity of the cell surface receptor CD95 regulates neuronal and vascular morphogenesis in the post-natal brain and retina. Furthermore, we identify CNS macrophages as the main source of CD95L, and macrophage-specific deletion thereof reduces both neurovascular complexity and synaptic activity in the brain. CD95L-induced neuronal and vascular growth is mediated through src-family kinase (SFK) and PI3K signaling. Together, our study highlights a coordinated neurovascular development instructed by CNS macrophage-derived CD95L, and it underlines the importance of macrophages for the establishment of the neurovascular network during CNS development.

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Chen et al. identify CNS macrophages as regulators of neurovascular remodeling. Using cell-specific knockout models, they demonstrate that CNS macrophage-derived CD95L binds to the CD95 receptor on neurons and endothelial cells to promote neurovascular development through SFK and PI3K signaling. Furthermore, neuronal function is impaired long term in the absence of CD95L.


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The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Hugo G. Hilton, Curtis P. McMurtrey, Alex S. Han, Zakia Djaoud, Lisbeth A. Guethlein, Jeroen H. Blokhuis, Jason L. Pugh, Ana Goyos, Amir Horowitz, Rico Buchli, Ken W. Jackson, Wilfred Bardet, David A. Bushnell, Philip J. Robinson, Juan L. Mendoza, Michael E. Birnbaum, Morten Nielsen, K. Christopher Garcia, William H. Hildebrand, Peter Parham
HLA-B46:01 was formed by an intergenic mini-conversion, between HLA-B15:01 and HLA-C01:02, in Southeast Asia during the last 50,000 years, and it has since become the most common HLA-B allele in the region. A functional effect of the mini-conversion was introduction of the C1 epitope into HLA-B46:01, making it an exceptional HLA-B allotype that is recognized by the C1-specific natural killer (NK) cell receptor KIR2DL3. High-resolution mass spectrometry showed that HLA-B46:01 has a low-diversity peptidome that is distinct from those of its parents. A minority (21%) of HLA-B46:01 peptides, with common C-terminal characteristics, form ligands for KIR2DL3. The HLA-B46:01 peptidome is predicted to be enriched for peptide antigens derived from Mycobacterium leprae. Overall, the results indicate that the distinctive peptidome and functions of HLA-B46:01 provide carriers with resistance to leprosy, which drove its rapid rise in frequency in Southeast Asia.

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Hilton et al. show how the recombination that formed HLA-B∗46:01 endowed it with a distinctive peptidome and unique functional properties. These properties likely protect carriers from severe infection with Mycobacterium leprae, the cause of leprosy, and they may account for the high frequency of HLA-B∗46:01 in Southeast Asia.


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Absence of Specific Chlamydia trachomatis Inclusion Membrane Proteins Triggers Premature Inclusion Membrane Lysis and Host Cell Death

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Mary M. Weber, Jennifer L. Lam, Cheryl A. Dooley, Nicholas F. Noriea, Bryan T. Hansen, Forrest H. Hoyt, Aaron B. Carmody, Gail L. Sturdevant, Ted Hackstadt
Chlamydia trachomatis is a human pathogen associated with significant morbidity worldwide. As obligate intracellular parasites, chlamydiae must survive within eukaryotic cells for sufficient time to complete their developmental cycle. To promote host cell survival, chlamydiae express poorly understood anti-apoptotic factors. Using recently developed genetic tools, we show that three inclusion membrane proteins (Incs) out of eleven examined are required for inclusion membrane stability and avoidance of host cell death pathways. In the absence of specific Incs, premature inclusion lysis results in recognition by autophagolysosomes, activation of intrinsic apoptosis, and premature termination of the chlamydial developmental cycle. Inhibition of autophagy or knockdown of STING prevented host cell death and activation of intrinsic apoptosis. Significantly, these findings emphasize the importance of Incs in the establishment of a replicative compartment that sequesters the pathogen from host surveillance systems.

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Weber el al use genetic means to disrupt Chlamydia trachomatis proteins essential for parasitophorous vacuole (inclusion) membrane stability. Premature inclusion lysis exposes chlamydiae to the cytosol to induce autophagic and apoptotic pathways. Understanding how normally anti-apoptotic chlamydiae induce apoptosis will help define mechanisms of chlamydial intracellular survival.


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Innate Recognition of Intracellular Bacterial Growth Is Driven by the TIFA-Dependent Cytosolic Surveillance Pathway

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Ryan G. Gaudet, Cynthia X. Guo, Raphael Molinaro, Haila Kottwitz, John R. Rohde, Anne-Sophie Dangeard, Cécile Arrieumerlou, Stephen E. Girardin, Scott D. Gray-Owen
Intestinal epithelial cells (IECs) act as sentinels for incoming pathogens. Cytosol-invasive bacteria, such as Shigella flexneri, trigger a robust pro-inflammatory nuclear factor κB (NF-κB) response from IECs that is believed to depend entirely on the peptidoglycan sensor NOD1. We found that, during Shigella infection, the TRAF-interacting forkhead-associated protein A (TIFA)-dependent cytosolic surveillance pathway, which senses the bacterial metabolite heptose-1,7-bisphosphate (HBP), functions after NOD1 to detect bacteria replicating free in the host cytosol. Whereas NOD1 mediated a transient burst of NF-κB activation during bacterial entry, TIFA sensed HBP released during bacterial replication, assembling into large signaling complexes to drive a dynamic inflammatory response that reflected the rate of intracellular bacterial proliferation. Strikingly, IECs lacking TIFA were unable to discriminate between proliferating and stagnant intracellular bacteria, despite the NOD1/2 pathways being intact. Our results define TIFA as a rheostat for intracellular bacterial replication, escalating the immune response to invasive Gram-negative bacteria that exploit the host cytosol for growth.

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Teaser

Gaudet et al. describe an innate immune pathway that confers the ability to detect replicating bacteria free in the host cytosol. This pathway, mediated by the protein TIFA, informs the host to the magnitude of intracellular bacterial proliferation, providing the contextual signal to dramatically amplify the inflammatory response to virulent pathogens.


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A Murine Intestinal Intraepithelial NKp46-Negative Innate Lymphoid Cell Population Characterized by Group 1 Properties

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Aline Van Acker, Konrad Gronke, Aindrila Biswas, Liesbet Martens, Yvan Saeys, Jessica Filtjens, Sylvie Taveirne, Els Van Ammel, Tessa Kerre, Patrick Matthys, Tom Taghon, Bart Vandekerckhove, Jean Plum, Ildiko Rita Dunay, Andreas Diefenbach, Georges Leclercq
The Ly49E receptor is preferentially expressed on murine innate-like lymphocytes, such as epidermal Vγ3 T cells, intestinal intraepithelial CD8αα+ T lymphocytes, and CD49a+ liver natural killer (NK) cells. As the latter have recently been shown to be distinct from conventional NK cells and have innate lymphoid cell type 1 (ILC1) properties, we investigated Ly49E expression on intestinal ILC populations. Here, we show that Ly49E expression is very low on known ILC populations, but it can be used to define a previously unrecognized intraepithelial innate lymphoid population. This Ly49E-positive population is negative for NKp46 and CD8αα, expresses CD49a and CD103, and requires T-bet expression and IL-15 signaling for differentiation and/or survival. Transcriptome analysis reveals a group 1 ILC gene profile, different from NK cells, iCD8α cells, and intraepithelial ILC1. Importantly, NKp46CD8ααLy49E+ cells produce interferon (IFN)-γ, suggesting that this previously unrecognized population may contribute to Th1-mediated immunity.

Graphical abstract

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Teaser

Van Acker et al. define an intestinal intraepithelial innate lymphoid cell population that is dependent on T-bet and IL-15 and displays a group 1 ILC gene profile uniquely different from NK cells, iCD8α cells, and previously described ILC1 cells. Upon stimulation, these cells produce the Th1-related cytokine IFN-γ.


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Fatty Acid Oxidation in Zebrafish Adipose Tissue Is Promoted by 1α,25(OH)2D3

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Xuyan Peng, Guohui Shang, Wenqing Wang, Xiaowen Chen, Qiyong Lou, Gang Zhai, Dongliang Li, Zhenyu Du, Yali Ye, Xia Jin, Jiangyan He, Yi Zhang, Zhan Yin
1α,25(OH)2D3 (vitamin D3) is crucial for mineral homeostasis in mammals, but the precise effects of 1α,25(OH)2D3 in adipose tissue remain to be clarified in vivo. The initial 25-hydroxylation is catalyzed by liver microsomal cytochrome P450 2R1 (CYP2R1), which is conserved in vertebrates. To probe the physiological function(s) of 1α,25(OH)2D3 in teleosts, we generated two independent cyp2r1-deficient zebrafish lines. These mutants exhibit retarded growth and increased obesity, especially in the visceral adipose tissue (VAT). These defects could be rescued with 25(OH)D3 treatments. ChIP-PCR analyses demonstrated that pgc1a is the target of the vitamin D receptor in the liver and VAT of zebrafish. Significantly decreased protein levels of Pgc1a, impaired mitochondrial biogenesis, and free fatty acid oxidation are also observed in the cyp2r1 mutant VAT. Our results demonstrate that regulation of 1α,25(OH)2D3 during lipid metabolism occurs through the regulation of Pgc1a for mitochondrial biogenesis and oxidative metabolism within zebrafish VAT.

Graphical abstract

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Teaser

Peng et al. find that Cyp2r1 depletion results in 1,25(OH)2D3 deficiency, retarded growth, and excessive visceral adipose tissue (VAT) in zebrafish. 1,25(OH)2D3 regulates lipid metabolism through the regulation of Pgc1a, controlling mitochondrial biogenesis and oxidative metabolism in zebrafish VAT.


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Lack of MTTP Activity in Pluripotent Stem Cell-Derived Hepatocytes and Cardiomyocytes Abolishes apoB Secretion and Increases Cell Stress

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Ying Liu, Donna M. Conlon, Xin Bi, Katherine J. Slovik, Jianting Shi, Hailey I. Edelstein, John S. Millar, Ali Javaheri, Marina Cuchel, Evanthia E. Pashos, Jahangir Iqbal, M. Mahmood Hussain, Robert A. Hegele, Wenli Yang, Stephen A. Duncan, Daniel J. Rader, Edward E. Morrisey
Abetalipoproteinemia (ABL) is an inherited disorder of lipoprotein metabolism resulting from mutations in microsomal triglyceride transfer protein (MTTP). In addition to expression in the liver and intestine, MTTP is expressed in cardiomyocytes, and cardiomyopathy has been reported in several ABL cases. Using induced pluripotent stem cells (iPSCs) generated from an ABL patient homozygous for a missense mutation (MTTPR46G), we show that human hepatocytes and cardiomyocytes exhibit defects associated with ABL disease, including loss of apolipoprotein B (apoB) secretion and intracellular accumulation of lipids. MTTPR46G iPSC-derived cardiomyocytes failed to secrete apoB, accumulated intracellular lipids, and displayed increased cell death, suggesting intrinsic defects in lipid metabolism due to loss of MTTP function. Importantly, these phenotypes were reversed after the correction of the MTTPR46G mutation by CRISPR/Cas9 gene editing. Together, these data reveal clear cellular defects in iPSC-derived hepatocytes and cardiomyocytes lacking MTTP activity, including a cardiomyocyte-specific regulated stress response to elevated lipids.

Graphical abstract

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Teaser

Liu et al. use patient-specific iPSCs and CRISPR/Cas9 genome editing to uncover the functional consequences of MTTP mutations in human hepatocytes and cardiomyocytes. They find that MTTP is required for apoB secretion and that its absence results in increased cell stress in cardiomyocytes.


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Systems Analysis Reveals High Genetic and Antigen-Driven Predetermination of Antibody Repertoires throughout B Cell Development

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Victor Greiff, Ulrike Menzel, Enkelejda Miho, Cédric Weber, René Riedel, Skylar Cook, Atijeh Valai, Telma Lopes, Andreas Radbruch, Thomas H. Winkler, Sai T. Reddy
Antibody repertoire diversity and plasticity is crucial for broad protective immunity. Repertoires change in size and diversity across multiple B cell developmental stages and in response to antigen exposure. However, we still lack fundamental quantitative understanding of the extent to which repertoire diversity is predetermined. Therefore, we implemented a systems immunology framework for quantifying repertoire predetermination on three distinct levels: (1) B cell development (pre-B cell, naive B cell, plasma cell), (2) antigen exposure (three structurally different proteins), and (3) four antibody repertoire components (V-gene usage, clonal expansion, clonal diversity, repertoire size) extracted from antibody repertoire sequencing data (400 million reads). Across all three levels, we detected a dynamic balance of high genetic (e.g., >90% for V-gene usage and clonal expansion in naive B cells) and antigen-driven (e.g., 40% for clonal diversity in plasma cells) predetermination and stochastic variation. Our study has implications for the prediction and manipulation of humoral immunity.

Graphical abstract

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Teaser

Greiff et al. develop an integrated systems immunology approach for quantifying the extent of antibody repertoire predetermination. They find a dynamic balance of both high genetic (maximum: 99%) and antigen-driven (maximum: 40%) repertoire predetermination. The authors also uncover stochastic variation across B cell development, antigen exposure, and repertoire components (germline gene usage, clonal expansion, clonal diversity, repertoire size), which has implications for the prediction and manipulation of humoral immunity.


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A Temporal Proteomic Map of Epstein-Barr Virus Lytic Replication in B Cells

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Ina Ersing, Luis Nobre, Liang Wei Wang, Lior Soday, Yijie Ma, Joao A. Paulo, Yohei Narita, Camille W. Ashbaugh, Chang Jiang, Nicholas E. Grayson, Elliott Kieff, Steven P. Gygi, Michael P. Weekes, Benjamin E. Gewurz
Epstein-Barr virus (EBV) replication contributes to multiple human diseases, including infectious mononucleosis, nasopharyngeal carcinoma, B cell lymphomas, and oral hairy leukoplakia. We performed systematic quantitative analyses of temporal changes in host and EBV proteins during lytic replication to gain insights into virus-host interactions, using conditional Burkitt lymphoma models of type I and II EBV infection. We quantified profiles of >8,000 cellular and 69 EBV proteins, including >500 plasma membrane proteins, providing temporal views of the lytic B cell proteome and EBV virome. Our approach revealed EBV-induced remodeling of cell cycle, innate and adaptive immune pathways, including upregulation of the complement cascade and proteasomal degradation of the B cell receptor complex, conserved between EBV types I and II. Cross-comparison with proteomic analyses of human cytomegalovirus infection and of a Kaposi-sarcoma-associated herpesvirus immunoevasin identified host factors targeted by multiple herpesviruses. Our results provide an important resource for studies of EBV replication.

Graphical abstract

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Teaser

Ersing et al. present a temporal proteomic map of EBV B cell lytic replication. Tandem-mass-tag-based proteomics uncover extensive remodeling of the human proteome by EBV, conserved across the two major EBV strains. Cell-cycle, innate, and adaptive immune pathways are modulated, complement is upregulated, and the B cell receptor is degraded by infection.


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A Design Principle for an Autonomous Post-translational Pattern Formation

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Shuhei S. Sugai, Koji L. Ode, Hiroki R. Ueda




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Ultrasound as point of care in management of polytrauma and its complication

Abstract

Purpose

Traumatic injuries constitute a major risk for patients in emergency units. Point-of-care ultrasound may be a determinant in reducing the deleterious impact of complications and in prognosis.

Methods

We describe the case of a 28-year-old female who reported cranial trauma, abdominal and thoracic trauma, and suspected bilateral fracture of the femur.

Results

Ultrasound was useful for evaluating and monitoring multiple organ failure.

Conclusion

Combining cost-effective advantages with bedside real-time imaging, ultrasound is a powerful adjunct to standard clinical assessment in the management of polytrauma when it is administered at the point of care.



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Characterization of an autotrophic bioreactor microbial consortium degrading thiocyanate

Abstract

Thiocyanate (SCN) forms as a by-product of cyanidation during gold ore processing and can be degraded by a variety of microorganisms utilizing it as an energy, nitrogen, sulphur and/or carbon source. In complex consortia inhabiting bioreactor systems, a range of metabolisms are sustained by SCN degradation; however, despite the addition or presence of labile carbon sources in most bioreactor designs to date, autotrophic bacteria have been found to dominate key metabolic functions. In this study, we cultured an autotrophic SCN-degrading consortium directly from gold mine tailings. In a batch-mode bioreactor experiment, this consortium degraded 22 mM SCN, accumulating ammonium (NH4+) and sulphate (SO42−) as the major end products. The consortium consisted of a diverse microbial community comprised of chemolithoautotrophic members, and despite the absence of an added organic carbon substrate, a significant population of heterotrophic bacteria. The role of eukaryotes in bioreactor systems is often poorly understood; however, we found their 18S rRNA genes to be most closely related to sequences from bacterivorous Amoebozoa. Through combined chemical and phylogenetic analyses, we were able to infer roles for key microbial consortium members during SCN biodegradation. This study provides a basis for understanding the behaviour of a SCN degrading bioreactor under autotrophic conditions, an anticipated approach to remediating SCN at contemporary gold mines.



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Structural modulation of gut microbiota in Bama minipigs in response to treatment with a “growth-promoting agent”, salbutamol

Abstract

Even though salbutamol (SAL) had remarkable effects on the enhancement of growth rate and carcass composition in different livestock species such as cattle, pigs, sheep and poultry, it was banned as a growth promoter because of its adverse effects on health. However, the specific mechanism by which salbutamol enhances growth efficiency remains unknown. In this study, Bama pigs were randomly allocated to receive salbutamol (5 mg/kg) for 30 or 60 days and were compared with untreated pigs. Pigs treated with salbutamol demonstrated enhanced growth rates and carcass composition; however, they showed deterioration in blood biochemical indices and organ development. We hypothesized that salbutamol exerts its effects by modulating the composition of the gut microbiota population. The faecal microbiome of pigs was characterized via pyrosequencing of the bacterial 16S rRNA gene. The gut microbiota population analysis showed that salbutamol caused shifts in the microbial composition of less abundant species. Redundancy analysis indicated an increase in abundance of the phylum Bacteroidetes, class Betaproteobacteria, family Christensenellaceae and genus Lactobacillus, and a decreased ratio of the phylum Firmicutes, class Clostridia and genera Ruminococcus, Blautia and Subdoligranulum. In conclusion, our study provided circumstantial evidence that the various effects of salbutamol are caused by gut microbiota modulation, and several potential candidates were identified for SAL detection via the gut microbiota. Our findings provided new insights into the roles of the gut microbiota during salbutamol treatment, and these findings will aid in the screening of alternative strategies for animal health improvement and production enhancement.



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Different fermentation processes produced variants of an anti-CD52 monoclonal antibody that have divergent in vitro and in vivo characteristics

Abstract

The anti-CD52 antibody has already been approved for the treatment of patients with resistant chronic lymphocytic leukemia, relapsing-remitting multiple sclerosis, and has demonstrable efficacy against stem cell transplantation rejection. A CHO cell line expressing a humanized anti-CD52 monoclonal antibody (mAb-TH) was cultivated in both fed-batch and perfusion modes, and then purified. The critical quality attributes of these mAb variants were characterized and the pharmacokinetics (PK) properties were investigated. Results showed that the perfusion culture achieved higher productivity, whereas the fed-batch culture produced more aggregates and acid components. Additionally, the perfusion culture produced similar fucose, more galactose and a higher proportion of sialic acid on the anti-CD52 mAb compared to the fed-batch culture. Furthermore, the perfusion process produced anti-CD52 mAb had higher complement-dependent cytotoxicity (CDC) efficacy than that produced by the fed-batch culture, a result probably linked to its higher galactose content. However, antibody produced by fed-batch and perfusion cultures showed similar PK profiles in vivo. In conclusion, perfusion is a more efficient method than fed-batch process in the production of functional anti-CD52 monoclonal antibody. Product quality variants of anti-CD52 mAb were found in different cell culture processes, which demonstrated different physiochemical and biological activities, but comparable PK properties. Whether these observations apply to all mAbs await further investigation.



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Selection and characterization of an anaerobic microbial consortium with high adaptation to crude glycerol for 1,3-propanediol production

Abstract

Crude glycerol is an ideal feedstock for bioproduction of 1,3-propanediol (1,3-PDO) while pure culture always shows low substrate tolerance and limited productivity. In this study, an anaerobic microbial consortium for conversion of crude glycerol was selected and its 1,3-PDO production capacity was evaluated. The consortium was obtained from anaerobic activated sludge by 19 serial transfers and mainly consisted of 94.64% Clostridiaceae and 4.47% Peptostreptococcaceae. The consortium adapted well with high glycerol concentration of 120 g/L as well as wide substrate concentration fluctuation from 15 to 80 g/L, producing 60.61 and 82.66 g/L 1,3-PDO in the batch and fed-batch fermentation, with the productivity of 3.79 and 3.06 g/(L∙h), respectively, which are among the best results published so far. Furthermore, mini consortia isolated by serial dilution exhibited similar microbial composition but gradually decreasing tolerance to crude glycerol. Four randomly selected Clostridium butyricum displayed different substrate tolerance and insufficient 1,3-PDO production capacity. This work demonstrated that the high adaptation to crude glycerol of the consortium was the collaborative effort of different individuals.



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Biomarkers of oxidative damage in bacteria for the assessment of sanitation efficacy in lettuce wash water

Abstract

In the fresh produce industry, validation of sanitation efficacy is critical to prevent cross-contamination of produce. The current validation approaches are either based on time-consuming plate counting assays or indirect measurements of chemical properties of wash water. In the study, the focus was to identify biomarkers that can provide direct assessment of oxidative damage in bacteria upon exposure to sanitizers in the presence of fresh produce and correlation of these oxidative biomarkers with logarithmic inactivation of bacteria. Two endogenous bacterial biomarkers, protein carbonylation and thiol oxidation, were evaluated for assessing oxidative damage in Escherichia coli O157:H7 and Listeria innocua during sanitation of pre-cut lettuce leaves with NaOCl or H2O2. Results show that NaOCl treatment was more effective than H2O2 for oxidation of both the intracellular thiols and protein carbonylation in the selected strains. Statistical analysis of the measurements illustrates that oxidation of the intracellular thiol induced by NaOCl or H2O2 was correlated with logarithmic reduction of E. coli O157:H7 and L. innocua. In contrast, changes in the protein carbonylation content were not correlated with reduction in bacterial cell viability. In summary, these results provide a novel approach to validate sanitation efficacy for the fresh produce industry.



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Evaluation of leg wrapping for the prevention of postspinal hypotension in cesarean section under spinal anesthesia

Aparna Abhijit Bagle, Adithya Vishnu, Anil Kumar, Amit Malik, Vinit Garg, Gayatri Khanvilkar

Anesthesia: Essays and Researches 2017 11(2):439-443

Background: Spinal blockade provides excellent anesthesia for patients undergoing cesarean section. However, hypotension after spinal anesthesia is a common adverse effect that is commonly experienced in patients undergoing cesarean section. The aim of our study was to analyze if a simple technique like leg wrapping with elastic crepe bandage would be effective in controlling postspinal hypotension. Materials and Methods: Sixty full-term pregnant patients who were posted for cesarean section belonging to American Society of Anesthesiologists I and II were divided into two groups. Patients in Group W had their legs wrapped with elastic crepe bandage and in the other Group N, leg wrapping was not done. All the patients were preloaded with Ringer lactate at 10 ml/kg before the spinal anesthesia. The hemodynamic parameters were monitored every 3 min until the delivery of the baby and every 5 min until the end of surgery. If hypotension occurred, then along with crystalloid loading a bolus dose of mephentermine 6 mg was given intravenously. Statistical Analysis: Statistical software “Numbers version 3.6.1 (2566)” was used for statistical calculations. Results: Frequency of hypotension in Group W (10%) was significantly less compared to Group N (60%). Vasopressor requirement was significantly less in Group W (P = 0.009), which was highly significant. Conclusion: Wrapping of lower extremities was a simple, easy, and an effective method of decreasing episodes of hypotension and vasopressor requirement after spinal anesthesia in cesarean patients and needs to be practiced routinely.

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Effect of single compared to repeated doses of intravenous S(+) ketamine on the release of pro-inflammatory cytokines in patients undergoing radical prostatectomy

Hassan Mohamed Ali, Ali M Mokhtar

Anesthesia: Essays and Researches 2017 11(2):282-286

Background: Radical prostatectomy is a major surgical procedure that is associated with marked inflammatory response and impairment of the immune system which may affect the postoperative outcome. The aim of this study was to evaluate the effect of preincision single or multiple doses of S(+) ketamine on the pro-inflammatory cytokines, namely tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Patients and Methods: This is a randomized controlled trial including 60 American Society of Anesthesiologists Physical Status I and II patients scheduled for radical prostatectomy under combined general-epidural anesthesia in Cairo university Teaching Hospital. Patients were randomly divided into three groups each of twenty patients: Group I received no S(+) ketamine (control group), Group II received S(+) ketamine as a single preincision dose, and Group III received preincision and repeated doses of S(+) ketamine. S(+) ketamine was injected as a single intravenous dose of 0.5 mg/kg in Group II and III, repeated as 0.2 mg/kg at 20 min interval until 30 min before the end of surgery. Results: The three groups were comparable in age, weight, and duration of the operation. The study also revealed that a single preincision dose of S(+) ketamine decreased TNF-α to reach 1027.04 ± 50.13 μ/ml and IL-6 to reach 506.89 ± 25.35 pg/ml whereas the repeated doses of S(+) ketamine decreased TNF-α to reach 905.64 ± 35065 μ/ml and IL-6 to reach 412.79 ± 16.5 pg/ml (P < 0.05). Conclusion: S(+) ketamine suppresses pro-inflammatory cytokine production, especially when given in repeated doses.

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Anesthetic management of a parturient with severe pulmonary restenosis posted for cesarean section

Rajkiran Babubhai Shah, Beena P Butala, Geeta P Parikh

Anesthesia: Essays and Researches 2017 11(2):517-519

Adults with congenital heart disease are increasing due to improvement in infant heart surgery and availability of better cardiac care. Pregnancy in these patients requires multidisciplinary team approach due to circulatory changes. We describe an anesthetic management of the parturient undergoing cesarean section having severe pulmonary restenosis.

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Comparison of usefulness of ketamine and magnesium sulfate nebulizations for attenuating postoperative sore throat, hoarseness of voice, and cough

Sunil Rajan, George Jacob Malayil, Rekha Varghese, Lakshmi Kumar

Anesthesia: Essays and Researches 2017 11(2):287-293

Context: Postoperative sore throat (POST) is a complication that is unresolved in patients undergoing endotracheal intubation. Aim: To compare the effects of ketamine and magnesium sulfate nebulizations in two strengths, on the incidence and severity of POST, hoarseness, and cough. Settings and Design: Sixty surgical patients undergoing elective abdominal and lower limb surgeries under combined epidural and general anesthesia were included in this prospective, randomized, double-blinded study. Subjects and Methods: Patients in each group were nebulized with the respective study drug 15 min prior to the surgery, i.e., ketamine in Group K, magnesium sulfate 250 mg, and 500 mg in Group M1 and Group M2, respectively, and normal saline as control in Group C. A standardized anesthesia protocol was followed for all patients. After extubation, the patients were asked to grade POST, hoarseness, and cough at 0, 2, 4, 12, and 24 h. Statistical Analysis Used: One-way analysis of variance, Chi-square test, Fisher's exact test, paired t-tests, and Wilcoxon's signed-rank test as applicable. Results: Ketamine and magnesium sulfate 500 mg demonstrated a statistically significant decrease in POST at 0, 2, and 4 h, and postoperative hoarseness at 0 h. There was decrease in the incidence and severity of sore throat, hoarseness, and cough at all periods in the study groups as compared with control. Conclusion: Nebulization with ketamine 50 mg and magnesium sulfate 500 mg, 15 min before induction of general anesthesia and intubation, reduce the incidence and severity of POST and hoarseness of voice.

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Prophylactic use of intravenous clonidine compared to tramadol in prevention of intraoperative shivering under regional anesthesia

Sarmila Guha (Banerjee), Pallab Kumar Nath, Rita Halder, Ujjwal Bandyopadhyay

Anesthesia: Essays and Researches 2017 11(2):477-482

Objectives: This study aimed to evaluate the relative efficacy of prophylactic intravenous (IV) clonidine and tramadol for control of intraoperative shivering following spinal anesthesia. Materials and Methods: After institutional ethical clearance, 142 patients were chosen from either gender, aged 20–60 years, physical status American Society of Anesthesiology Class I and II scheduled for elective infraumbilical surgery under spinal anesthesia. Patients were randomized into two groups: Group C (n = 71) received injection clonidine 50 μg) IV in 100 ml normal saline (NS) over 10 min and Group T (n = 71) received injection tramadol 50 mg IV. In 100 ml NS over 10 min after spinal anesthesia. Results: Incidence of shivering was not significant when compared between the two groups (P > 0.05). The axillary temperatures fell significantly in Group C from the baseline and remained at a significantly lower level up to 60 min after rescue drug was administered in patients who shivered. There was a similar fall in axillary temperature in Group T in patients having shivering, but the difference was not significant. When compared between the two groups among patients who shivered, the difference in fall of temperature was not significant. Side effects such as hypotension, bradycardia, and sedation were significantly more common in clonidine group, whereas nausea was significantly more common patients of tramadol group. Conclusion: Prophylactic administration of both tramadol and clonidine is effective for controlling shivering under spinal anesthesia. However, tramadol is better because of higher response rate, less sedation, and lesser hemodynamic alterations.

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Efficacy of dexmedetomidine infusion for procedural comfort and intraoperative sedation in patients undergoing surgeries with subarachnoid block: A randomized double-blind clinical trial

Dewan Roshan Singh, Kusha Nag, Amrutha Bindu Nagella, VR Hemanth Kumar, Antony John Charles

Anesthesia: Essays and Researches 2017 11(2):294-299

Introduction: There is increasing evidence to include sedation as an integral part of regional anesthesia to ensure patient comfort. This may compromise patient cooperation, an important component of regional anesthesia. We decided to determine the efficacy of dexmedetomidine (0.3 μg/kg/h and 0.5 μg/kg/h) for allaying procedural discomfort and ensuring their cooperation in patients undergoing surgery with subarachnoid block. Setting: Tertiary care center. Materials and Methods: Sixty patients with the American Society of Anesthesiologists physical status Class I and II posted for surgeries under subarachnoid block were randomized into two groups of 30 each to receive dexmedetomidine in a loading dose of 1 μg/kg in both groups followed by continuous infusion of 0.3 μg/kg/h in Group D 0.3 and 0.5 μg/kg/h in Group D 0.5. Observer assessment sedation score, ease of positioning score, response to spinal needle insertion, hemodynamic parameters, patient satisfaction (PS) score, and surgeon satisfaction (SS) score were evaluated. Results: Median observer Assessment Sedation Score ranged between four and three at all times during dexmedetomidine infusion in Group D 0.3. In Group D 0.5, median Observer assessment of alertness/sedation scale ranged between three and two. Ease of positioning (P = 1.000) and response to spinal needle insertion (P = 0.521) were comparable in both groups. PS was higher in Group D 0.5 as compared to Group D 0.3. SS score was comparable in both the groups. Conclusion: Intravenous dexmedetomidine infusion 0.3 μg/kg/h produces effective sedation in patients undergoing surgery with spinal anesthesia while ensuring patient cooperation for positioning and without any recall of the procedure in postoperative period.

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A simple novel technique to make any supraglottic airway device magnetic resonance imaging compatible: A fusion of the past with the present

Ashish Kannaujia, Saipriya Tewari, Alka Verma

Anesthesia: Essays and Researches 2017 11(2):535-536



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Lignocaine versus ropivacaine infiltration for postpartum perineal pain

Jyoti P Deshpande, Girish Y Saundattikar

Anesthesia: Essays and Researches 2017 11(2):300-303

Background: Millions of women worldwide undergo postpartum perineal repair under local infiltration. Inadequate postpartum pain management can negatively impact a mother's physical and psychological recovery. Aims: To study and compare the analgesic effect and maternal satisfaction with lignocaine versus ropivacaine infiltration for postpartum perineal pain relief. Materials and Methods: After clearance from the Institutional Ethics Committee, a double-blind prospective randomized study carried out on 100 parturients of aged 18–40 years who had spontaneous vaginal delivery, comparing 1% lignocaine and 0.75% ropivacaine infiltration for the repair of selective episiotomy or perineal injury. Time of the first analgesic (TFA) demand, maternal satisfaction at 24 h, and visual analog scale (VAS) pain score were studied. Statistical Analysis: Chi-square test and Student's t-test were used and P< 0.05 was considered as significant. Results: VAS pain score was significantly lower at 2 and 4 h in ropivacaine group versus lignocaine group (P < 0.0001). Significantly, longer TFA (10.2 ± 1.54 vs. 2.20 ± 0.44 h, P< 0.0001) and higher percentage of maternal satisfaction (86% vs. 44%) were observed in ropivacaine as compared to lignocaine group (P < 0.0001). Conclusions: Prolonged analgesia and higher rate of maternal satisfaction were found when ropivacaine infiltration was used for perineal repair as compared to lignocaine.

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The postdural puncture headache and back pain: The comparison of 26-gauge atraucan and 26-gauge quincke spinal needles in obstetric patients

Mehmet Salim Akdemir, Ayhan Kaydu, Yonca Yanlı, Mehtap Özdemir, Erhan Gökçek, Haktan Karaman

Anesthesia: Essays and Researches 2017 11(2):458-462

Background: The postdural puncture headache (PDPH) and postdural puncture backache (PDPB) are well-known complications of spinal anesthesia. There are some attempts to reduce the frequency of complication such as different design of the spinal needles. Aims: The primary outcome of this study is to compare the incidence of PDPH between 26-gauge Atraucan and 26-gauge Quincke spinal needles in elective cesarean operations. The severity of symptoms, the incidence of backache, technical issues, and comparison of cost of needles are secondary outcomes. Materials and Methods: After Investigational Review Board approval, a randomized, prospective, double-blinded study was designed in 682 American Society of Anesthesiologists I–II women having elective cesarean operations under spinal anesthesia. Patients were divided into two groups as 26-gauge Atraucan Group A (n = 323) and 26-gauge Quincke spinal needles Group Q (n = 342). All patients were questioned about backache 1 week later. Differences between categorical variables were evaluated with Chi-square test. Continuous variables were compared by Student's t-test for two independent groups. A two-sided P< 0.05 was considered statistically significant for all analyses. Results: There were no significant differences between groups in all demographic data. The one attempt success rate of the dural puncture in Group A (70,58%) and in Group Q (69.3%) was similar (P > 0.05). The incidence of PDPH was 6.5% in Group A and 4.9% in Group Q (P > 0.05). The epidural blood patch was performed to the three patients in Group A and five patients in Group Q who had severe headache (P > 0.05). The incidence of PDPB was 4.33% versus 2.04% in Group A and Group Q (P > 0.05). Conclusions: The incidence of complication rates and technical handling characteristics did not differ between two groups. Quincke needle is cheaper than Atracaun needle, so it can be a cost-effective choice in obstetric patients.

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Financial implications of intravenous anesthetic drug wastage in operation room

Suvarna Kaniyil, A Krishnadas, Arun Kumar Parathody, KT Ramadas

Anesthesia: Essays and Researches 2017 11(2):304-308

Background and Objectives: Anesthetic drugs and material wastage are common in operation rooms (ORs). In this era of escalating health-care expenditure, cost reduction strategies are highly relevant. The aim of this study was to assess the amount of daily intravenous anesthetic drug wastage from major ORs and to estimate its financial burden. Any preventive measures to minimize drug wastage are also looked for. Methods: It was a prospective study conducted at the major ORs of a tertiary care hospital after getting the Institutional Research Committee approval. The total amount of all drugs wasted at the end of a surgical day from each major OR was audited for five nonconsecutive weeks. Drug wasted includes the drugs leftover in the syringes unutilized and opened vials/ampoules. The total cost of the wasted drugs and average daily loss were estimated. Results: The drugs wasted in large quantities included propofol, thiopentone sodium, vecuronium, mephentermine, lignocaine, midazolam, atropine, succinylcholine, and atracurium in that order. The total cost of the wasted drugs during the study period was Rs. 59,631.49, and the average daily loss was Rs. 1987.67. The average daily cost of wasted drug was maximum for vecuronium (Rs. 699.93) followed by propofol (Rs. 662.26). Interpretation and Conclusions: Financial implications of anesthetic drug wastage can be significant. Propofol and vecuronium contributed maximum to the financial burden. Suggestions for preventive measures to minimize the wastage include education of staff and residents about the cost of drugs, emphasizing on the judicial use of costly drugs.

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The analgesic efficacy of dexamethasone added to ropivacaine in transversus abdominis plane block for transabdominal hysterectomy under subarachnoid block

Jyoti P Deshpande, Poonam S Ghodki, Shalini P Sardesai

Anesthesia: Essays and Researches 2017 11(2):499-502

Background and Aims: Ultrasound-guided transversus abdominis plane (TAP) block has been proven as a safe and effective analgesic technique for several lower abdominal surgeries. Various adjuvants have been used to intensify the quality and prolong the local anesthetic effect. We evaluated the analgesic efficacy of dexamethasone addition to ropivacaine in TAP block following open abdominal hysterectomy. Materials and Methods: After clearance from the Institutional Ethics Committee, a double-blind, prospective, randomized study was carried out on sixty patients aged 40–60 years posted for elective open abdominal hysterectomy comparing bilateral TAP block using 20 ml of 0.5% ropivacaine + 1 ml of 0.9% saline (control Group R) or 20 ml of 0.5% ropivacaine + 4 mg dexamethasone (Group RD). The aim of our study was to observe postoperative pain score (visual analog scale [VAS]), time for first analgesic (TFA) demand, total analgesic consumption, and incidence of nausea or vomiting. Statistical Analysis: Chi-square test and Student's t-test were used, and P< 0.05 was considered as statistically significant. Results: Postoperative VAS pain scores were significantly lower at 4, 6, and 12 h in Group RD as compared to Group R (P < 0.05). Significantly longer TFA (13.2 ± 7.6 vs. 7.1 ± 4.6 h, P< 0.001) with lesser tramadol requirement in first 24 h (50.2 ± 34 vs. 94 ± 35 mg, P< 0.001) were observed in Group RD as compared to Group R. Incidence of nausea or vomiting was statistically insignificant between the groups (P > 0.05). Conclusions: Addition of dexamethasone to ropivacaine TAP block prolonged the postoperative analgesia and reduced analgesic requirement following abdominal hysterectomy.

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Dexmedetomidine as an anesthetic adjuvant in intracranial surgery

Ankita Batra, Reetu Verma, VK Bhatia, Girish Chandra, Shashi Bhushan

Anesthesia: Essays and Researches 2017 11(2):309-313

Background: The basic principle of neuroanesthesia is to provide hemodynamic stability, provision of optimal operative conditions, maintenance of cerebral perfusion pressure, and cerebral oxygenation. Aim: This study was undertaken to see the effect of dexmedetomidine infusion on hemodynamics and its ability to act as an anesthetic adjuvant in patients undergoing supratentorial tumor surgery. Setting and Design: Prospective randomized control double blind study. Subjects and Methods: In this study, we compared two groups with 25 patients in each group. Group C patients received saline infusion during surgery and 4 μg/kg of fentanyl intravenously (i.v.) at the induction and at pin head application. Group D patients received dexmedetomidine infusion during surgery at the rate of 0.4 μg/kg/h and 2 μg/kg of fentanyl i.v. at the induction and at pin head application Statistical Analyses Used: Parametric data were analyzed using Student's t-test. The categorical data were studied using Chi-squared test or Fisher's test as appropriate. Results: The vitals remained within 20% of baseline in both groups during the study period except at the time of extubation where the rise in heart rate was more than 20% in control group. The requirement of thiopentone for induction was significantly less in dexmedetomidine group. In dexmedetomidine group, less number of patients required intraoperative fentanyl (P < 0.05), and the time to rescue analgesic was also more in Group D (P < 0.05). Conclusion: Dexmedetomidine infusion started before surgery maintains hemodynamic stability intraoperatively and is effective in attenuating the cardiovascular responses to intubation, skull pin application, and extubation. It decreases the requirement of other anesthetic agents as well.

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Continuous positive airway pressure prevents hypoxia in dental patient with obstructive sleep apnea syndrome under intravenous sedation

Anton A Kasatkin, Aleksei P Reshetnikov, Aleksandr L Urakov, Dmitrii Y Baimurzin

Anesthesia: Essays and Researches 2017 11(2):528-530

Use of sedation in patients with obstructive sleep apnea (OSA) in dentistry is limited. Hypoxia may develop during medication sleep in dental patients with OSA because of repetitive partial or complete obstruction of the upper airway. In this regard, anesthesiologists prefer not to give any sedative to surgical patients with OSA or support the use of general anesthesia due to good airway control. We report a case where we could successfully sedate a dental patient with OSA using intraoperative continuous positive airway pressure (CPAP) without hypoxia. Use of sedation and intraoperative CPAP in patients with OSA may be considered only if the effectiveness at home CPAP therapy is proven.

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Hemodynamic responses at intubation, change of position, and skin incision: A comparison of multimodal analgesia with conventional analgesic regime

Keelara Shivalingaiah Savitha, Radhika Dhanpal, MS Vikram

Anesthesia: Essays and Researches 2017 11(2):314-320

Background: Lumbar spine surgery is associated with hemodynamic variations at intubation, change of position, and skin incision. A balanced anesthesia with multimodal analgesia (MMA) is necessary to attenuate these changes. Aim: To assess the relative effectiveness of preemptive MMA compared with the conventional analgesic regime in suppressing the hemodynamic response to endotracheal intubation, prone positioning, and skin incision. Settings and Design: A randomized, prospective study involving 42 patients belonging to the American Society of Anesthesiologists Physical Status 1 and II scheduled to undergo elective lumbar spine surgery were allocated into two groups of 21 each. Materials and Methods: Forty-two patients were randomly allocated into Groups A and B. Group A (study group) received diclofenac, paracetamol, clonidine, and bupivacaine with adrenaline skin infiltration and Group B (control group) injection paracetamol and saline with adrenaline skin infiltration. Statistical Analysis Used: Hemodynamic parameters (heart rate [HR], systolic blood pressure [SBP], diastolic blood pressure [DBP], and mean arterial pressure [MAP]) between the groups following intubation, prone position, and skin incision were noted and compared using repeated measure analysis of variance. One sample t-test was used to compare the standard mean concentration with the means of the study and control groups. P< 5% being considered statistically significant. Results: In the study group, HR, SBP, DBP, and MAP were lower at intubation and change of position as compared to the control group and were statistically significant. Conclusion: Preemptive MMA with balanced anesthesia is effective in attenuating the hemodynamic responses to multiple noxious stimuli during lumbar spine surgery.

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An audit of comparison of perioperative outcomes with the introduction of standardized preoperative evaluation form at a tertiary care hospital in rural India

Shraddha Vidyadhar Naik, Bilal Mohammad, Vitthal K Dhulkhed

Anesthesia: Essays and Researches 2017 11(2):426-430

Introduction: Preoperative evaluation of a patient is the fundamental component of anaesthetic practice. Inadequate documentation and record keeping on the preoperative evaluation form (PEF) can be a major obstacle to attaining good practice and improving patient outcomes following operative procedures. Aim: The aim of the study was to conduct an audit to assess the quality of the preoperative anaesthetic information gathered and to observe the quality profile after the introduction of a standardized pre-operative evaluation form. Study Design: This was a retrospective study, using a sample of 3000 files of patients who underwent elective surgery in a tertiary care hospital of rural India. We devised 11 quality indicators, looking at factors in the pre-operative, peri-operative and post-operative period, and used them to audit 3000 patient records in our Hospital. Results: We found several areas where quality could be significantly improved;last minute postponement/change of plan of planned surgeries has reduced from 134 (8.9%) to 23 (1.53%) cases after implementation of standardised PEF. 784 (52.26%) patients were not formally handed over to the theatre recovery staff before implementation of standardised PEF compared to 147(9.8%) after implementation of standardised PEF. Conclusion: This audit found several areas of practice that fall below expected standards before the introduction of standardised PEF, but after the introduction of standardised PEF there is a significant improvement in quality of pre anaesthetic evaluation and overall outcome of the patient. We therefore advocate the use of such standardised PEFs for performing preoperative and perioperative assessment of surgical patients.

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To study the efficacy of intravenous dexamethasone in prolonging the duration of spinal anesthesia in elective cesarean section

Priyanka Sunil Shalu, Poonam Sachin Ghodki

Anesthesia: Essays and Researches 2017 11(2):321-325

Background and Aims: Various additives have been evaluated for the purpose of enhancing quality of analgesia and prolonging duration of spinal anesthesia. This randomized, double-blind study was conducted to evaluate the efficacy of intravenous dexamethasone in spinal anesthesia. Methods: A total of sixty patients scheduled for lower segment cesarean section under spinal anesthesia were randomly allocated into two groups, group SD and group SN, including thirty patients each. All the patients received injection bupivacaine 0.5% heavy 10 mg through spinal anesthesia. Group SD received injection dexamethasone 8 mg intravenously, and group SN received injection normal saline (NS) 2 cc immediately after spinal anesthesia. Duration of sensory block, motor block, postoperative analgesia, visual analog pain scale (VAS) score, time of rescue analgesia, total analgesic requirement in the first 24 h, intra- and post-operative hemodynamics, and side effects if any were recorded. Whenever demanded rescue analgesia was given in the form of injection tramadol 100 mg. Results: The mean duration of sensory block (min) in group SD and group SN was 162.50 and 106.17, respectively which was highly significant. Similarly, time to the requirement of first rescue analgesia was prolonged in group SD (8.67 h) as compared to group SN (4.40 h). Significant changes were also seen in VAS score in postoperative period after 1 h of surgery in group SD and group SN. Duration of motor block, intra- and post-operative hemodynamic parameters were comparable in both the groups. No side effects were recorded in both the groups. Conclusion: We concluded that administration of dexamethasone 8 mg intravenously prolongs the duration of postoperative analgesia and sensory block in patients undergoing lower segment cesarean section under spinal anesthesia.

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Anesthesiologist's role in relieving patient's anxiety

Brij Mohan, Rajan Kumar, Joginder Pal Attri, Veena Chatrath, Neeru Bala

Anesthesia: Essays and Researches 2017 11(2):449-452

Introduction: Anesthesia and surgery have proved to be highly anxiety provoking and with the rise of elective surgery, its aspect of patient's experience has become prominent in time. However, our fault as anesthesiologists is that we have not made people get versed with what we people as anesthesiologist do in the operating room. Hence, keeping in view all this, a study was carried out, in which video information/images regarding anesthesia and surgical procedure was shown to patients on PowerPoint Presentation. Different images showing previous patient's hospital journey were shown to educate patients. Methods: Two hundred patients scheduled to undergo elective surgery were taken and were divided into two groups of 100 each. Patients (study group or Group I) were shown video clippings/images of other previously operated patients and their hospital journey including surgery and anesthesia for which patient came in hospital. The study was carried out on the patient in each group while Group II was treated in normal way and not shown any type of images/videos. Hamilton Anxiety Rating Scale was used as a criterion to measure the level of anxiety in Group I and II at four different intervals that are before pre anesthetic check up (PAC), after showing videos and images in Group I, 1 h before surgery and 8 h after surgery. Statistical Analysis: The results of observation of both the groups at different intervals time were statistically compared and analyzed. These characteristics were analyzed using the “Chi-square tests” and “unpaired t-test.” Results: Video and images information if done preoperatively have been shown to reduce patient's anxiety, although little is known regarding the effects of the method. Conclusion: Showing videos/images of hospital journey for educating the patients before the operation is beneficial to patients undergoing elective surgery.

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Randomized controlled trial for evaluating the analgesic effect of nalbuphine as an adjuvant to bupivacaine in supraclavicular block under ultrasound guidance

Nazia Nazir, Shruti Jain

Anesthesia: Essays and Researches 2017 11(2):326-329

Introduction: Benefits of regional anesthesia can be prolonged by adding adjuvants to local anesthetics. This study was designed to test the efficacy of adding nalbuphine to bupivacaine in supraclavicular brachial plexus blockade using ultrasound (US) guidance. Methodology: This was a prospective, randomized, double-blind study involving sixty patients of either sex undergoing elective orthopedic procedures of upper limb. In control Group C (n = 30), 30 mL of 0.375% bupivacaine + 1 mL normal saline and in study Group N (n = 30), 30 mL of 0.375% bupivacaine + 1 mL (10 mg) nalbuphine were used for giving supraclavicular block under US guidance. Parameters assessed were onset and duration of sensory and motor block, duration of analgesia (DOA), and any adverse events. Data between the groups were analyzed using independent t-test with SPSS 16.0 software. Results: In Group N, there was a statistically significant shorter time to onset of sensory blockade (4.89 ± 1.5 vs. 14.62 ± 1.73 min, P = 0.000), longer duration of sensory block (373.17 ± 15.56 min vs. 157.82 ± 11.02 min, P = 0.000), shorter onset time to achieve motor block (8.83 ± 1.9 min vs. 18.76 ± 1.75 min, P = 0.000), longer duration of motor block (313.92 ± 16.22 min vs. 121.87 ± 16.62 min, P = 0.000), and prolonged analgesia (389.33 ± 14.52 min vs. 171.65 ± 19.79 min, P = 0.000). Conclusion: Nalbuphine when added to bupivacaine as an adjuvant in supraclavicular block significantly shortened the onset of sensory and motor block and enhanced the duration of sensory and motor block and DOA.

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Comparison between conventional and ultrasound-guided supraclavicular brachial plexus block in upper limb surgeries

Kiran Abhayakumar Honnannavar, Mahantesh Shivangouda Mudakanagoudar

Anesthesia: Essays and Researches 2017 11(2):467-471

Introduction: Brachial plexus blockade is a time-tested technique for upper limb surgeries. The classical approach using paresthesia technique is a blind technique and may be associated with a higher failure rate and injury to the nerves and surrounding structures. To avoid some of these problems, use of peripheral nerve stimulator and ultrasound techniques were started which allowed better localization of the nerve/plexus. Ultrasound for supraclavicular brachial plexus block has improved the success rate of the block with excellent localization as well as improved safety margin. Hence, this study was planned for comparing the efficacy of conventional supraclavicular brachial plexus block with ultrasound-guided technique. Subjects and Methods: After obtaining the Institutional ethical committee approval and patient consent total of 60 patients were enrolled in this prospective randomized study and were randomly divided into two groups: US (Group US) and C (Group C). Both groups received 0.5% bupivacaine. The amount of local anesthetic injected calculated according to the body weight and was not crossing the toxic dosage (injection bupivacaine 2 mg/kg). The parameters compared between the two groups were lock execution time, time of onset of sensory and motor block, quality of sensory and motor block success rates were noted. The failed blocks were supplemented with general anesthesia. Results: Demographic data were comparable in both groups. The mean time taken for the procedure to administer a block by eliciting paresthesia is less compared to ultrasound, and it was statistically significant. The mean time of onset of motor block, sensory blockade, the duration of sensory and motor blockade was not statistically significant. The success rate of the block is more in ultrasound group than conventional group which was not clinically significant. The incidence of complications was seen more in conventional method. Conclusion: Ultrasound guidance is the safe and effective method for the supraclavicular brachial plexus block. Incidence of complications are less as ultrasound provides real-time visulaization of underlying structures and the spread of local anaesthetic.

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Effect of pregabalin premedication on the requirement of anesthetic and analgesic drugs in laparoscopic cholecystectomy: Randomized comparison of two doses

Prasoon Gupta, Anudeep Saxena, Lalita Chaudhary

Anesthesia: Essays and Researches 2017 11(2):330-333

Background: Preoperative medication has a vital role in anesthesia. Pregabalin (PG) is a newer drug of gabapentinoid class and is six times more potent than gabapentin. Our study was designed to evaluate the effect of PG as premedication on the perioperative anesthetic requirement and analgesia. Materials and Methods: The study was conducted on ninety patients of American Society of Anesthesiologists Grade I and II of age group 20–60 years, allocated to one of the three groups of thirty patients each. Group I received tablet diazepam 10 mg HS and 5 mg 1 h before surgery, Group II received capsule PG 75 mg HS and 150 mg 1 h before surgery, and Group III received capsule PG 75 mg HS and 300 mg 1 h before surgery. Patients were induced with injection fentanyl citrate, thiopentone sodium, and rocuronium bromide and maintained by 66% N2O + 33% O2gas mixture with sevoflurane and intermittent boluses of fentanyl. Results: Perioperative consumption of thiopentone sodium was 5.59 ± 0.49 mg/kg in Group I, 4.29 ± 0.53 mg/kg in Group II, and 4.06 ± 0.59 mg/kg in Group III; fentanyl was 1.55 ± 0.42 μg/kg in Group I, 1.00 ± 0.00 μg/kg in Group II, and 1.05 ± 0.20 μg/kg in Group III; sevoflurane (%) was 1.20 ± 0.31 in Group I, 0.933 ± 0.25 in Group II, and 1.00 ± 0.00 in Group III. Perioperative requirement of thiopentone sodium, opioid, and inhalational agent was significantly less in Group II and III when compared with Group I. Maximum number of patients required postoperative rescue analgesia within 0–2 h of surgery in Group I, 2–4 h of surgery in Group II, and 6–8 h after surgery in Group III. Patients were more comfortable and asleep with a longer pain-free postoperative period in PG groups. Conclusion: PG premedication effectively reduced the consumption of all anesthetic agents during induction and maintenance of anesthesia as compared to diazepam. Patient's postoperative comfort and pain-free duration were also greater with PG premedication; more so with PG 300 mg as compared to PG 150 mg.

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Comparative Analysis of Tongue Indices between Patients with and without a Self-Reported Yin Deficiency: A Cross-Sectional Study

We investigated the hypothesis that Yin-deficient patients have a reddened tongue with less coating. We screened 189 participants aged 20 to 49 years, complaining of headache. To classify patients in terms of Yin deficiency, we used two self-reporting Yin-deficiency questionnaires (Yin-Deficiency Questionnaire and Yin-Deficiency Scale) and diagnosis by a doctor. Based on the tests, a total of 33 subjects were assigned to a Yin-deficient group and 33 subjects were assigned to a nondeficient control group. Tongue images were acquired using a computerized tongue diagnostic system, for evaluating tongue indices. The tongue coating percentage and tongue redness were calculated as the mean value of both the whole tongue area (WT ) and the tongue body area (TB ). The tongue coating percentage of the Yin-deficient group (34.79 ± 10.76) was lower than that of the nondeficient group (44.13 ± 14.08). The WT value of the Yin-deficient group (19.39 ± 1.52) was significantly higher than that of the nondeficient group (18.21 ± 2.06). However, the difference in the TB value between the two groups was not significant. In conclusion, we verified that Yin-deficient patients had less tongue coating and tended to have a more reddish tongue than nondeficient patients.

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The Loading Control Strategy of the Mobile Dynamometer Vehicle Based on Neural Network PID

To solve the problems of low loading precision, slow response speed, and poor adaptive ability of a mobile dynamometer in a tractor traction test, a PID control strategy based on a radial basis function neural network with self-learning and adaptive ability is proposed. The mathematical model of the loading system is established, the algorithm of adaptive control is described, and the loading control method is simulated with MATLAB software. The system, which uses the NN-PID (neural network PID) control strategy, is used to test a YTO-MF554 tractor. Then, the proposed control strategy is validated. Results show that when the traction increases from 0 to 10 kN, the response time of the test system is 1.5 s, the average traction force in the stability range is 10.13 kN, and the maximum relative error of traction force is 2.2%. This control strategy can improve the response speed and steady-state accuracy and enhance the adaptive ability of the mobile dynamometer vehicle loading system. This study provides a reference for designing the adaptive controller of the mobile dynamometer vehicle loading system.

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Oxidative Stress-Induced DNA Damage by Manganese Dioxide Nanoparticles in Human Neuronal Cells

Metal nanoparticles have been extensively used in industry as well as in biomedical application. In this work, we have evaluated the toxic potential of manganese dioxide (MnO2) nanoparticles (MNPs) on human neuronal (SH-SY5Y) cells. Cellular toxicity due to MNPs (0, 10, 30, and 60 μg/ml) on the SH-SY5Y cell was observed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red uptake (NRU) tests. MNPs produced reactive oxygen species (ROS) and declined in mitochondrial membrane potential in the SH-SY5Y cell in dose and duration dependent manner. Moreover, lipid peroxide (LPO), superoxide dismutase (SOD), and catalase (CAT) activities were increased and glutathione was reduced in dose and time dependent manner. A significant upgrade in Hoechst 33342 fluorescence intensity (chromosome condensation) and phosphatidylserine translocation (apoptotic cell) was visualized in cells treated with MNPs for 48 h. On the other hand, caspase-3 activity was increased due to MNPs in SH-SY5Y cells. DNA strand breaks were determined by alkaline single cell gel electrophoresis assay (Comet Assay) and maximum fragmentation of DNA produced due to MNPs (60 μg/ml) for 48 hours. This result provides a basic mechanism of induction of apoptosis and toxicity by MNPs in SH-SY5Y cells.

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Soluble Urokinase Receptor and the Kidney Response in Diabetes Mellitus

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide. DN typically manifests by glomerular hyperfiltration and microalbuminuria; then, the disease progresses to impaired glomerular filtration rate, which leads to ESRD. Treatment options for DN include the strict control of blood glucose levels and pressure (e.g., intraglomerular hypertension). However, the search for novel therapeutic strategies is ongoing. These include seeking specific molecules that contribute to the development and progression of DN to potentially interfere with these “molecular targets” as well as with the cellular targets within the kidney such as podocytes, which play a major role in the pathogenesis of DN. Recently, podocyte membrane protein urokinase receptor (uPAR) and its circulating form (suPAR) are found to be significantly induced in glomeruli and sera of DN patients, respectively, and elevated suPAR levels predicted diabetic kidney disease years before the occurrence of microalbuminuria. The intent of this review is to summarize the emerging evidence of uPAR and suPAR in the clinical manifestations of DN. The identification of specific pathways that govern DN will help us build a more comprehensive molecular model for the pathogenesis of the disease that can inform new opportunities for treatment.

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Physical Activity and Quality of Life in Retinitis Pigmentosa

Purpose. Aerobic exercise has been found to be neuroprotective in animal models of retinal degeneration. This study aims to report physical activity levels in patients with RP and investigate the relationship between physical activity and vision-related quality-of-life (QOL). Materials and Methods. A retrospective study of adult patients with RP examined in 2005–2014. Physical activity levels were assessed using the Godin Exercise Questionnaire. The NEI-Visual Function Questionaire-25 (VFQ-25), SF-36 General Health survey, and Pepper Assessment Tool for Disability (PAT-D) were administered. Results. 143 patients participated. 81 (56.6%) patients were classified as “active” and 62 (43.4%) as “insufficiently active” by Godin score. VFQ-25 revealed statistically significant differences between the active and insufficiently active patients, including overall visual function (53.3 versus 45.1, ), color vision (73.8 versus 52.9, ), and peripheral vision (34.3 versus 23.8, ). The physical component of the SF-36 and the PAT-D survey also demonstrated statistically significant differences (47.2 versus 52.9, ; 24.3 versus 30.0, ). Active patients had a higher initial Goldmann visual field (GVF) score (74.8 versus 60.1 degrees, ) and final GVF score (78.7 versus 47.1 degrees, ) but did not reach statistical significance. Conclusions. In RP, increased physical activity is associated with greater self-reported visual function and QOL.

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