bluuebunny/crossref_metadata_2025 huggingface dataset:
Transumbilical laparoendoscopic single‐site surgery versus conventional laparoscopy for the resection of retroperitoneal paragangliomas
Authors: Xu Weifeng , Li Hanzhong , Ji Zhigang , Yan Weigang , Zhang Yushi , Zhang Xuebin , Li Qian
Published: June 2015

Objectives

To compare transumbilical laparoendoscopic single‐site surgery with conventional laparoscopy for the resection of retroperitoneal paragangliomas.

Methods

In the present case–control study, we compared 11 transumbilical laparoendoscopic single‐site surgery procedures with 22 conventional laparoscopy procedures carried out to treat retroperitoneal paragangliomas between June 2004 and October 2013 at Peking Union Medical Hospital, Beijing, China. Operative time, estimated intraoperative blood loss, blood transfusions, intraoperative hypertension, intraoperative hypotension, highest intraoperative systolic blood pressure, lowest intraoperative systolic blood pressure, postoperative fatigue time, postoperative systematic inflammation reaction syndrome, 24‐h postoperative visual analog scale scores, postoperative hospital stay duration, and postoperative complications were recorded and analyzed.

Results

There were no significant differences in patient characteristics. All surgical procedures were successfully completed in both groups. Minor complications occurred in one case in the laparoendoscopic single‐site surgery group and in two cases in the conventional laparoscopy group. In the laparoendoscopic single‐site surgery group, the operative time was longer than that in the conventional laparoscopy group (P = 0.001). There were no significant differences in terms of intraoperative hypertension, intraoperative hypotension, highest intraoperative systolic blood pressure, lowest intraoperative systolic blood pressure, estimated blood loss, postoperative fatigue time, postoperative hospital stay or systematic inflammation reaction syndrome between the two groups. The 24‐h postoperative visual analog scale score was lower in the laparoendoscopic single‐site surgery group (P = 0.002). No recurrence or metastases were observed over the duration of the postoperative follow up.

Conclusions

In properly selected patients, transumbilical laparoendoscopic single‐site surgery is a feasible, safe and effective procedure for the surgical treatment of retroperitoneal paragangliomas.
Long‐distance dispersal during the middle–late Pleistocene explains the bipolar disjunction of Carex maritima (Cyperaceae)
Authors: Villaverde Tamara , Escudero Marcial , Luceño Modesto , Martín‐Bravo Santiago
Published: June 2015

Aim

We set out to explain the bipolar distribution of Carex maritima, clarifying the direction and timing of dispersal. We also tested mountain‐hopping and direct long‐distance dispersal hypotheses, as well as the relationship of C. maritima with biotic and abiotic factors that could explain the bipolar distribution.

Location

Arctic/boreal latitudes of both hemispheres.

Methods

Molecular and bioclimatic data were obtained for C. maritima and related species from section Foetidae. We sequenced two (rps16 and 5′trnK intron) plastid DNA regions (cpDNA) and the external and internal transcribed spacers (ETS and ITS) of the nuclear ribosomal gene region (nrDNA) and inferred phylogenetic relationships, divergence time estimates and biogeographical patterns using maximum likelihood, statistical parsimony, Bayesian inference and ecological niche modelling.

Results

Carex maritima populations from the Southern Hemisphere were genetically and ecologically differentiated from their northern counterparts and formed a monophyletic group nested within a paraphyletic C. maritima. Divergence time analysis estimated a middle–late Pleistocene divergence of the southern lineage (0.23 Ma; 95% highest posterior density: 0.03–0.51 Ma). Southern Hemisphere populations are more stenotopic than the Northern Hemisphere ones, which tolerate harsher conditions.

Main conclusions

Our results point to a middle–late Pleistocene migration of C. maritima by long‐distance dispersal, either directly or via mountain‐hopping, from the Northern Hemisphere to the Southern Hemisphere.
Astaxanthin prevents pulmonary fibrosis by promoting myofibroblast apoptosis dependent on Drp1‐mediated mitochondrial fission
Authors: Zhang Jinjin , Xu Pan , Wang Youlei , Wang Meirong , Li Hongbo , Lin Shengcui , Mao Cuiping , Wang Bingsi , Song Xiaodong , Lv Changjun
Published: June 2015

Promotion of myofibroblast apoptosis is a potential therapeutic strategy for pulmonary fibrosis. This study investigated the antifibrotic effect of astaxanthin on the promotion of myofibroblast apoptosis based on dynamin‐related protein‐1 (Drp1)‐mediated mitochondrial fission in vivo and in vitro. Results showed that astaxanthin can inhibit lung parenchymal distortion and collagen deposition, as well as promote myofibroblast apoptosis. Astaxanthin demonstrated pro‐apoptotic function in myofibroblasts by contributing to mitochondrial fission, thereby leading to apoptosis by increasing the Drp1 expression and enhancing Drp1 translocation into the mitochondria. Two specific siRNAs were used to demonstrate that Drp1 is necessary to promote astaxanthin‐induced mitochondrial fission and apoptosis in myofibroblasts. Drp1‐associated genes, such as Bcl‐2‐associated X protein, cytochrome c, tumour suppressor gene p53 and p53‐up‐regulated modulator of apoptosis, were highly up‐regulated in the astaxanthin group compared with those in the sham group. This study revealed that astaxanthin can prevent pulmonary fibrosis by promoting myofibroblast apoptosis through a Drp1‐dependent molecular pathway. Furthermore, astaxanthin provides a potential therapeutic value in pulmonary fibrosis treatment.
Shp‐2 contributes to anti‐RSV activity in human pulmonary alveolar epithelial cells by interfering with the IFN‐α‐induced Jak/Stat1 pathway
Authors: Wang Saisai , Zheng Gang , Zhao Lifang , Xu Feng , Qian Jing
Published: June 2015

Src homology phosphotyrosyl phosphatase 2 (Shp‐2) is a ubiquitously expressed protein that is involved in a variety of cellular processes, including antiviral interferon signalling pathways. In this study, we investigated the role of Shp‐2 in the host cell interactions of human respiratory syncytial virus (RSV). We report significant changes in the expression of Shp‐2 in human pulmonary alveolar epithelial cells (A549) upon RSV infection. We also report that blocking Shp‐2 does not affect viral replication or virus‐induced interferon‐alpha (IFN‐α) production. Interestingly, whereas A549 cells were activated by IFN‐α, the blocking of Shp‐2 resulted in increased viral replication that was associated with the reduced expression of the IFN‐stimulated genes of 2′,5′‐oligoadenylate synthetases and Mx1, and the concomitant inhibition of Stat1 tyrosine phosphorylation. Our findings suggest that Shp‐2 contributes to the control of RSV replication and progeny production in pulmonary alveolar epithelial cells by interfering with IFN‐α‐induced Jak/Stat1 pathway activation rather than by affecting the production of IFN‐α itself.
Feasibility of immediate placement of single‐tooth implants in the aesthetic zone: a 1‐year randomized controlled trial
Authors: Slagter Kirsten W. , Meijer Henny J.A. , Bakker Nicolaas A. , Vissink Arjan , Raghoebar Gerry M.
Published: June 2015

Aim

To assess whether outcome of immediate implant placement and immediate provisionalization after 1 year was non‐inferior to immediate implant placement and delayed provisionalization regarding Marginal Bone Level (MBL).

Materials and Methods

Forty patients with a failing tooth in the aesthetic zone were randomly assigned for immediate implant placement with immediate (n = 20) or delayed (n = 20) provisionalization. Follow‐up was at 1 month and after 1 year. The study was powered to detect a difference in MBL of <0.9 mm. Apart from MBL, soft tissue peri‐implant parameters, aesthetic indexes and patient satisfaction were assessed.

Results

After 1 year, MBL changes were −0.75 ± 0.69 mesially and −0.68 ± 0.65 distally mm for the immediate group and −0.70 ± 0.64 and −0.68 ± 0.64 mm for the delayed group respectively (NS). Regarding differences in means, non‐inferiority was observed after 1 year (mesially: Group A versus B: difference in mean 0.08 mm (95% CI −0.38 to 0.53, p = 0.71 distally: Group A versus B: difference in mean 0.09 mm (95% CI −0.37 to 0.56 mm, p = 0.66).No significant differences in the other outcome variables were observed.

Conclusions

This study showed that immediate placement and immediate provisionalization was non‐inferior to immediate placement with delayed provisionalization. In addition, although not powered for these outcome variables, no clinically relevant differences in other outcomes were observed (www.isrtcn.com: ISRCTN57251089).
Heterogeneity of Notch signaling in astrocytes and the effects of GFAP and vimentin deficiency
Authors: Lebkuechner Isabell , Wilhelmsson Ulrika , Möllerström Elin , Pekna Marcela , Pekny Milos
Published: June 2015

Astrocytes have multiple roles in the CNS including control of adult neurogenesis. We recently showed that astrocyte inhibition of neurogenesis through Notch signaling depends on the intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin. Here, we used real‐time quantitative PCR to analyze gene expression in individual mouse astrocytes in primary cultures and in GFAPPOS or Aldh1L1POS astrocytes freshly isolated from uninjured, contralesional and lesioned hippocampus 4 days after entorhinal cortex lesion. To determine the Notch signaling competence of individual astrocytes, we measured the mRNA levels of Notch ligands and Notch1 receptor. We found that whereas most cultured and freshly isolated astrocytes were competent to receive Notch signals, only a minority of astrocytes were competent to send Notch signals. Injury increased the fraction of astrocyte subpopulation unable to send and receive Notch signals, thus resembling primary astrocytes in vitro. Astrocytes deficient of GFAP and vimentin showed decreased Notch signal sending competence and altered expression of Notch signaling pathway‐related genes Dlk2, Notch1, and Sox2. Furthermore, we identified astrocyte subpopulations based on their mRNA and protein expression of nestin and HB‐EGF. This study improves our understanding of astrocyte heterogeneity, and points to astrocyte cytoplasmic intermediate filaments as targets for neural cell replacement strategies.

image

We previously demonstrated that Notch signaling from astrocytes to neural stem cells, that inhibits neurogenesis, depends on the intermediate filament (nanofilament) system of astrocytes. Here we report the existence of four subpopulations of astrocytes with respect to their Notch signaling competence. We show that the fraction of astrocytes that are Notch signaling incompetent increases after brain injury and corresponds to the fraction of Notch signaling incompetent astrocytes in primary astrocyte cultures. We also demonstrate that the subpopulation of Notch signal sending competent astrocytes decreases when their intermediate filament system is genetically ablated.
Glucose is a positive modulator for the activation of human recombinant glycine receptors
Authors: Breitinger Ulrike , Raafat Karim M. , Breitinger Hans‐Georg
Published: June 2015

The inhibitory glycine receptor (GlyR), a cys–loop ion channel receptor, mediates rapid synaptic inhibition in spinal cord, brainstem and higher centres of the mammalian central nervous system. Here, modulation of GlyR function by glucose and fructose was examined in recombinant alpha1 and alpha1/beta GlyRs using patch‐clamp methods. Glucose was a positive modulator of the receptor, reducing the average EC50 for glycine up to 4.5‐fold. Glucose reduced cell‐to‐cell variability of glycine‐mediated currents by stabilizing receptors with low EC50. Pre‐incubation with sugars for several hours also produced augmentation of current responses that persisted after sugar removal. Potentiation by sugars was most significant in the range between 5 and 20 mM, with EC50 values ~ 10 mM, i.e. at physiological levels. Addition of glucose had no significant influence on responses mediated by the other GlyR agonists like taurine, β‐alanine or ivermectin, indicating that glucose specifically augmented glycine receptor‐mediated responses, and did not act through indirect metabolic effects. Receptor modulation by glucose may account for differences in constants reported in the literature and may be clinically relevant for disorders with elevated blood glucose levels.

image

Glucose and related sugars are essential metabolites. We identified glucose and fructose as positive modulators of the human inhibitory glycine receptor, a neuronal ligand‐gated ion channel. Receptor‐mediated currents were enhanced at physiological concentrations (~ 10 mM of sugar). Direct modulation of a synaptic receptor by glucose is relevant in clinical cases of elevated blood glucose, and may be considered in experimental protocols.
Dickkopf‐related protein 3 is a potential Aβ‐associated protein in Alzheimer's Disease
Authors: Bruggink Kim A. , Kuiperij H. Bea , Gloerich Jolein , Otte‐Höller Irene , Rozemuller Annemieke J.M. , Claassen Jurgen A.H.R. , Küsters Benno , Verbeek Marcel M.
Published: June 2015

Amyloid‐β (Aβ) is the most prominent protein in Alzheimer's disease (AD) senile plaques. In addition, Aβ interacts with a variety of Aβ‐associated proteins (AAPs), some of which can form complexes with Aβ and influence its clearance, aggregation or toxicity. Identification of novel AAPs may shed new light on the pathophysiology of AD and the metabolic fate of Aβ. In this study, we aimed to identify new AAPs by searching for proteins that may form soluble complexes with Aβ in CSF, using a proteomics approach. We identified the secreted Wnt pathway protein Dickkopf‐related protein 3 (Dkk‐3) as a potential Aβ‐associated protein. Using immunohistochemistry on human AD brain tissue, we observed that (i) Dkk‐3 co‐localizes with Aβ in the brain, both in diffuse and classic plaques. (ii) Dkk‐3 is expressed in neurons and in blood vessel walls in the brain and (iii) is secreted by leptomeningeal smooth muscle cells in vitro. Finally, measurements using ELISA revealed that (iv) Dkk‐3 protein is abundantly present in both cerebrospinal fluid and serum, but its levels are similar in non‐demented controls and patients with AD, Lewy body dementia, and frontotemporal dementia. Our study demonstrates that Dkk‐3 is a hitherto unidentified Aβ‐associated protein which, given its relatively high cerebral concentrations and co‐localization with Aβ, is potentially involved in AD pathology.

image

In this study, we propose that Dickkopf‐related protein‐3 (Dkk‐3) might be a novel Amyloid‐β (Aβ) associated protein. We demonstrate that Dkk‐3 is expressed in the brain, especially in vessel walls, and co‐localizes with Aβ in senile plaques. Furthermore, Dkk‐3 levels in cerebrospinal fluid strongly correlate with Aβ40 levels, but were not suitable to discriminate non‐demented controls and patients with dementia.
The pathogenic role of the inflammasome in neurodegenerative diseases
Authors: Freeman Leslie C. , Ting Jenny P.‐Y.
Published: June 2015

The inflammasome is a large macromolecular complex that contains multiple copies of a receptor or sensor of pathogen‐derived or damage‐derived molecular patterns, pro‐caspase‐1, and an adaptor called ASC (apoptotic speck containing protein with a CARD), which results in caspase‐1 maturation. Caspase‐1 then mediates the release of pro‐inflammatory cytokines such as IL‐1β and IL‐18. These cytokines play critical roles in mediating immune responses during inflammation and innate immunity. Broader studies of the inflammasome over the years have implicated their roles in the pathogenesis of a variety of inflammatory diseases. Recently, studies have shown that the inflammasome modulates neuroinflammatory cells and the initial stages of neuroinflammation. A secondary cascade of events associated with neuroinflammation (such as oxidative stress) has been shown to activate the inflammasome, making the inflammasome a promising therapeutic target in the modulation of neurodegenerative diseases. This review will focus on the pathogenic role that inflammasomes play in neurologic diseases such as Alzheimer's disease, traumatic brain injury, and multiple sclerosis.

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We here review the role of the inflammasome in the pathogenesis of traumatic brain injury (TBI). TBI is initiated by physical force exerted to head, resulting in neuronal injury and death. Primary insult is followed by a secondary cascade of events following neuroinflammation such as mitochondrial dysfunction, production of reactive oxygen species, potassium effluxes, and release of circulating DNA. These events can potentially trigger the activation of NLRP3, NLRP1, and AIM2 during TBI but have yet to be confirmed (dashed lines). NLRP3, NLRP1, and AIM2 associate with the adaptor protein ASC, which initiates the cleavage of pro‐caspase‐1 to the mature form of caspase‐1 which cleaves pro‐IL‐1β and pro‐IL‐18 into their mature forms of IL‐1β and IL‐18.
Mutual induction of transcription factorPPARγ and microRNAs miR‐145 and miR‐329
Authors: Dharap Ashutosh , Pokrzywa Courtney , Murali Shruthi , Kaimal Balarama , Vemuganti Raghu
Published: June 2015

MicroRNAs (miRNAs) are small non‐codingRNAs that are known to controlmRNAtranslation. Most miRNAs are transcribed from specific genes with well‐defined promoters located throughout the genome. The mechanisms that control miRNAexpression under normal and pathological conditions are not yet understood clearly. Peroxisome proliferator‐activated receptor (PPAR) γ is a ligand‐activated transcription factor that is extensively distributed in theCNS.PPARγ activation induces neuroprotection by modulating genes that contain peroxisome proliferator response elements (PPREs) in their promoters. We presently evaluated ifPPARγ modulates miRNAexpression. When adult rats were treated withPPARγ agonist rosiglitazone, expression of 28 miRNAs altered significantly (12 up‐ and 16 down‐regulated; 3–119 fold) in the cerebral cortex compared to vehicle‐treated controls.In silicoanalysis showed 1–5PPREs in the putative promoter regions (within 1 Kb upstream of the transcription start site) of these miRNAgenes. Cotransfection with aPPARγ constitutively expressing vector significantly induced the miR‐145 and miR‐329 promoter vectors (each have fourPPREs), which was curtailed by point mutations ofPPREs in their promoters. Interestingly, thePPARγ promoter has binding sites for both these miRNAs and transfection with miR‐329 mimic and miR‐145 mimic induced thePPARγ expression. Thus, these studies show a cyclical induction of miRNAs andPPARγ, indicating that the pleiotropic beneficial effects ofPPARγ agonists might be modulated in part by miRNAs and their down‐streammRNAs.

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We proposed that promoters of many microRNAs contain the binding sites for the transcription factor PPARγ. Activation of PPARγ modulates the expression of these microRNAs. Two such PPARγ‐responsive microRNAs (miR‐145 and miR‐329) bind to PPARγ promoter to induce its expression. This indicates the presence of a feedback loop by which transcription factors and microRNAs can modulate each other.
Management of intestinal bleeding with single‐dose cyclophosphamide in Henoch–Schönlein purpura
Authors: Uluca Ünal , Ece Aydın , Şen Velat , Yel Servet , Tan İlhan , Karabel Duran
Published: June 2015

In these case series, we report on six children (3 girls, 3 boys) aged 5–13 years with Henoch–Schönlein purpura (HSP) who developed severe gastrointestinal (GI) bleeding resistant to both 2 mg/kg or pulse (10–30 mg/kg) i.v. methylprednisolone. All patients responded to single‐dose (500 mg/m2) i.v. cyclophosphamide (CPA) and none of them developed new GI bleeding after CPA treatment. No patients required surgical intervention. Single high‐dose CPA may be beneficial in HSP with severe GI involvement, in which bleeding is non‐responsive to high‐dose steroids.
Planning tiger recovery: Understanding intraspecific variation for effective conservation
Authors: Wilting Andreas , Courtiol Alexandre , Christiansen Per , Niedballa Jürgen , Scharf Anne K. , Orlando Ludovic , Balkenhol Niko , Hofer Heribert , Kramer-Schadt Stephanie , Fickel Jörns , Kitchener Andrew C.
Published: June 2015

Radical revision of tiger taxonomy for a pragmatic and scientifically sound approach to tiger conservation management.
Responses of Bacterial Communities to Simulated Climate Changes in Alpine Meadow Soil of the Qinghai-Tibet Plateau
Authors: Rui Junpeng , Li Jiabao , Wang Shiping , An Jiaxing , Liu Wen-tso , Lin Qiaoyan , Yang Yunfeng , He Zhili , Li Xiangzhen
Published: June 2015

The soil microbial community plays an important role in terrestrial carbon and nitrogen cycling. However, microbial responses to climate warming or cooling remain poorly understood, limiting our ability to predict the consequences of future climate changes. To address this issue, it is critical to identify microbes sensitive to climate change and key driving factors shifting microbial communities. In this study, alpine soil transplant experiments were conducted downward or upward along an elevation gradient between 3,200 and 3,800 m in the Qinghai-Tibet plateau to simulate climate warming or cooling. After a 2-year soil transplant experiment, soil bacterial communities were analyzed by pyrosequencing of 16S rRNA gene amplicons. The results showed that the transplanted soil bacterial communities became more similar to those in their destination sites and more different from those in their “home” sites. Warming led to increases in the relative abundances in
Alphaproteobacteria
,
Gammaproteobacteria
, and
Actinobacteria
and decreases in
Acidobacteria
,
Betaproteobacteria
, and
Deltaproteobacteria
, while cooling had opposite effects on bacterial communities (symmetric response). Soil temperature and plant biomass contributed significantly to shaping the bacterial community structure. Overall, climate warming or cooling shifted the soil bacterial community structure mainly through species sorting, and such a shift might correlate to important biogeochemical processes such as greenhouse gas emissions. This study provides new insights into our understanding of soil bacterial community responses to climate warming and cooling.
Molecular and Physical Factors That Influence Attachment of Vibrio vulnificus to Chitin
Authors: Williams Tiffany C. , Ayrapetyan Mesrop , Oliver James D.
Published: June 2015

The human pathogen
Vibrio vulnificus
is the leading cause of seafood-related deaths in the United States. Strains are genotyped on the basis of alleles that correlate with isolation source, with clinical (C)-genotype strains being more often implicated in disease and environmental (E)-genotype strains being more frequently isolated from oysters and estuarine waters. Previously, we have shown that the ecologically distinct C- and E-genotype strains of
V. vulnificus
display different degrees of chitin attachment, with C-genotype strains exhibiting reduced attachment relative to their E-genotype strain counterparts. We identified type IV pili to be part of the molecular basis for this observed genotypic variance, as E-genotype strains exhibit higher levels of expression of these genes than C-genotype strains. Here, we used a C-genotype quorum-sensing (QS) mutant to demonstrate that quorum sensing is a negative regulator of type IV pilus expression, which results in decreased chitin attachment. Furthermore, calcium depletion reduced E-genotype strain attachment to chitin, which suggests that calcium is necessary for proper functioning of the type IV pili in E-genotype strains. We also found that starvation or dormancy can alter the efficiency of chitin attachment, which has significant implications for the environmental persistence of
V. vulnificus
. With the increasing incidence of wound infections caused by
V. vulnificus
, we investigated a subset of E-genotype strains isolated from human wound infections and discovered that they attached to chitin in a manner more similar to that of C-genotype strains. This study enhances our understanding of the molecular and physical factors that mediate chitin attachment in
V. vulnificus
, providing insight into the mechanisms that facilitate the persistence of this pathogen in its native environment.
Polar Fixation of Plasmids during Recombinant Protein Production in Bacillus megaterium Results in Population Heterogeneity
Authors: Münch Karin M. , Müller Johannes , Wienecke Sarah , Bergmann Simone , Heyber Steffi , Biedendieck Rebekka , Münch Richard , Jahn Dieter
Published: June 2015

During the past 2 decades,
Bacillus megaterium
has been systematically developed for the gram-per-liter scale production of recombinant proteins. The plasmid-based expression systems employed use a xylose-controlled promoter. Protein production analyses at the single-cell level using green fluorescent protein as a model product revealed cell culture heterogeneity characterized by a significant proportion of less productive bacteria. Due to the enormous size of
B. megaterium
, such bistable behavior seen in subpopulations was readily analyzed by time lapse microscopy and flow cytometry. Cell culture heterogeneity was not caused simply by plasmid loss: instead, an asymmetric distribution of plasmids during cell division was detected during the exponential-growth phase. Multicopy plasmids are generally randomly distributed between daughter cells. However,
in viv
o and
in vitro
experiments demonstrated that under conditions of strong protein production, plasmids are retained at one of the cell poles. Furthermore, it was found that cells with accumulated plasmids and high protein production ceased cell division. As a consequence, the overall protein production of the culture was achieved mainly by the subpopulation with a sufficient plasmid copy number. Based on our experimental data, we propose a model whereby the distribution of multicopy plasmids is controlled by polar fixation under protein production conditions. Thereby, cell lines with fluctuating plasmid abundance arise, which results in population heterogeneity. Our results provide initial insights into the mechanism of cellular heterogeneity during plasmid-based recombinant protein production in a
Bacillus
species.
Whole-Genome Sequencing Allows for Improved Identification of Persistent Listeria monocytogenes in Food-Associated Environments
Authors: Stasiewicz Matthew J. , Oliver Haley F. , Wiedmann Martin , den Bakker Henk C.
Published: June 2015

While the food-borne pathogen
Listeria monocytogenes
can persist in food associated environments, there are no whole-genome sequence (WGS) based methods to differentiate persistent from sporadic strains. Whole-genome sequencing of 188 isolates from a longitudinal study of
L. monocytogenes
in retail delis was used to (i) apply single-nucleotide polymorphism (SNP)-based phylogenetics for subtyping of
L. monocytogenes
, (ii) use SNP counts to differentiate persistent from repeatedly reintroduced strains, and (iii) identify genetic determinants of
L. monocytogenes
persistence. WGS analysis revealed three prophage regions that explained differences between three pairs of phylogenetically similar populations with pulsed-field gel electrophoresis types that differed by ≤3 bands. WGS-SNP-based phylogenetics found that putatively persistent
L. monocytogenes
represent SNP patterns (i) unique to a single retail deli, supporting persistence within the deli (11 clades), (ii) unique to a single state, supporting clonal spread within a state (7 clades), or (iii) spanning multiple states (5 clades). Isolates that formed one of 11 deli-specific clades differed by a median of 10 SNPs or fewer. Isolates from 12 putative persistence events had significantly fewer SNPs (median, 2 to 22 SNPs) than between isolates of the same subtype from other delis (median up to 77 SNPs), supporting persistence of the strain. In 13 events, nearly indistinguishable isolates (0 to 1 SNP) were found across multiple delis. No individual genes were enriched among persistent isolates compared to sporadic isolates. Our data show that WGS analysis improves food-borne pathogen subtyping and identification of persistent bacterial pathogens in food associated environments.
Type III Secretion System Translocon Component EseB Forms Filaments on and Mediates Autoaggregation of and Biofilm Formation by Edwardsiella tarda
Authors: Gao Zhi Peng , Nie Pin , Lu Jin Fang , Liu Lu Yi , Xiao Tiao Yi , Liu Wei , Liu Jia Shou , Xie Hai Xia
Published: June 2015

The type III secretion system (T3SS) of
Edwardsiella tarda
plays an important role in infection by translocating effector proteins into host cells. EseB, a component required for effector translocation, is reported to mediate autoaggregation of
E. tarda
. In this study, we demonstrate that EseB forms filamentous appendages on the surface of
E. tarda
and is required for biofilm formation by
E. tarda
in Dulbecco's modified Eagle's medium (DMEM). Biofilm formation by
E. tarda
in DMEM does not require FlhB, an essential component for assembling flagella. Dynamic analysis of EseB filament formation, autoaggregation, and biofilm formation shows that the formation of EseB filaments occurs prior to autoaggregation and biofilm formation. The addition of an EseB antibody to
E. tarda
cultures before bacterial autoaggregation prevents autoaggregation and biofilm formation in a dose-dependent manner, whereas the addition of the EseB antibody to
E. tarda
cultures in which biofilm is already formed does not destroy the biofilm. Therefore, EseB filament-mediated bacterial cell-cell interaction is a prerequisite for autoaggregation and biofilm formation.
Composition of Bacterial Communities Associated with Aurelia aurita Changes with Compartment, Life Stage, and Population
Authors: Weiland-Bräuer Nancy , Neulinger Sven C. , Pinnow Nicole , Künzel Sven , Baines John F. , Schmitz Ruth A.
Published: June 2015

The scyphozoan
Aurelia aurita
is recognized as a key player in marine ecosystems and a driver of ecosystem change. It is thus intensely studied to address ecological questions, although its associations with microorganisms remain so far undescribed. In the present study, the microbiota associated with
A. aurita
was visualized with fluorescence
in situ
hybridization (FISH) analysis, and community structure was analyzed with respect to different life stages, compartments, and populations of
A. aurita
by 16S rRNA gene amplicon sequencing. We demonstrate that the composition of the
A. aurita
microbiota is generally highly distinct from the composition of communities present in ambient water. Comparison of microbial communities from different developmental stages reveals evidence for life stage-specific community patterns. Significant restructuring of the microbiota during strobilation from benthic polyp to planktonic life stages is present, arguing for a restructuring during the course of metamorphosis. Furthermore, the microbiota present in different compartments of the adult medusa (exumbrella mucus and gastric cavity) display significant differences, indicating body part-specific colonization. A novel
Mycoplasma
strain was identified in both compartment-specific microbiota and is most likely present inside the epithelium as indicated by FISH analysis of polyps, indicating potential endosymbiosis. Finally, comparison of polyps of different populations kept under the same controlled laboratory conditions in the same ambient water showed population-specific community patterns, most likely due the genetic background of the host. In conclusion, the presented data indicate that the associated microbiota of
A. aurita
may play important functional roles, e.g., during the life cycle.
Neuroborreliosis: the Guillain-Barré mimicker
Authors: Tyagi Niharika , Maheswaran Tim , Wimalaratna Sunil
Published: June 2015

A 34-year-old woman presented to the medical admissions unit with progressive ascending weakness of her limbs and areflexia. Diagnosis of Guillain-Barré syndrome was suspected and she was started on intravenous immunoglobulins. Owing to a poor initial response, further exploratory history revealed travel to the New Forest and a possible tick bite; subsequent investigations confirmed positive serology for antibodies againstBorrelia.The patient's weakness improved with intravenous ceftriaxone for neuroborreliosis, a manifestation of Lyme disease. With inpatient neurorehabilitation, she made good recovery and was able to mobilise with a stick from being completely bed bound 6 weeks after completion of her antibiotics.
Giant cell tumour—a very rare differential for a lytic lesion of the medial condyle of the humerous
Authors: Prakash Jatin , Mehtani Anil , Baruah Tankeshwar
Published: June 2015

Tumours are rare around the elbow joint, and giant cell tumours are especially rare in this region. A single case report of a giant cell involving the distal humerous was found in the literature and none were found involving the isolated medial condyle. We present a rare case of a 22-year-old woman with progressively increasing painful swelling in her left elbow over a period of 6 months. A plain radiograph revealed an expansile epiphyseometaphyseal, radiolucent lesion in the medial end of the distal humerous, with the rim being thin but still intact. The MRI of the elbow revealed a solid lesion in the medial aspect of the elbow with no breach of cortex. Biopsy of the lesion revealed multinucleated giant cells along with mononuclear cells consistent with a diagnosis of giant cell tumour. Extended curettage with bone cement was performed through an anterior approach. There has been no recurrence of the tumour in 2 years of follow-up; the patient has a good range of elbow movements of 20–110°.
Cerebral vascular findings in PAPA syndrome: cerebral arterial vasculopathy or vasculitis and a posterior cerebral artery dissecting aneurysm
Authors: Khatibi Kasra , Heit Jeremy J , Telischak Nicholas A , Elbers Jorina M , Do Huy M
Published: June 2015

A young patient with PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome developed an unusual cerebral arterial vasculopathy/vasculitis (CAV) that resulted in subarachnoid hemorrhage from a ruptured dissecting posterior cerebral artery (PCA) aneurysm. This aneurysm was successfully treated by endovascular coil sacrifice of the affected segment of the PCA. The patient made an excellent recovery with no significant residual neurologic deficit.
Hodgkin's lymphoma in an adolescent previously treated with surgical resection of third ventricular juvenile pilocytic astrocytoma
Authors: Chen Dillon Y , Crawford John Ross
Published: June 2015

We present a case of a 19-year-old man with cervical lymphadenopathy diagnosed with classical Hodgkin's lymphoma 9 years after gross total resection of a third ventricular juvenile pilocytic astrocytoma (JPA). Chemotherapy or radiation therapy was not a part of his initial JPA treatment. Owing to his two primary neoplasms, genetic testing was performed, which revealed heterozygous polymorphisms of unknown significance for CDH1 and p53, and negative BRAF mutation analysis. Our case reports development of classical Hodgkin's lymphoma after JPA in the absence of antecedent radiation and/or chemotherapy, and identifiable genetic predisposition.
A rare case of subcapsular liver haematoma following laparoscopic cholecystectomy
Authors: Brown Victoria , Martin Jennifer , Magee Damian
Published: June 2015

Laparoscopic cholecystectomy is a commonly performed surgical procedure for the treatment of symptomatic cholelithiasis. As with all surgical procedures, it carries risk, with the most commonly reported complications including infection, bile leak and bleeding. One unusual complication is subcapsular liver haematoma, the diagnosis presented here. This is a rare occurrence; only a small number of cases have been reported in the literature and as yet no conclusive cause or management plan has been found. Iatrogenic liver trauma, the use of oral and intravenous non-steroidal anti-inflammatory drugs (NSAIDs) and anticoagulants have all been named as possible contributing factors. Particularly, the use of ketorolac has been associated with four reported cases of subcapsular haematoma following laparoscopic cholecystectomy. The case reported here refutes that hypothesis, as neither NSAIDs nor anticoagulants were used during the treatment of this patient.
Nodular trachea: tracheobronchopathia osteochondroplastica
Authors: Agarwal Abhishek , Klair Jagpal , Joiner Amy , Meena Nikhil K
Published: June 2015

Tracheobronchopathia osteochondroplastica (TPO) is a rare disorder characterised by development of cartilaginous and bony nodules in the trachea. It usually affects elderly males with total prevalence of disease reported to be around 0.1%. Even though multiple theories and associations have been described, the exact cause of the disease remains unknown. Its presentation is non-specific with many cases being diagnosed incidentally. Chronic cough and dyspnoea are the most common presenting symptoms, but some cases may present with severe airway compromise. We present a case of a 70-year-old man with IgA λ multiple myeloma, who was diagnosed with TPO by flexible bronchoscopy.
Hemosuccus pancreaticus: a rare complication of chronic pancreatitis
Authors: Ferreira Joana , Tavares Amelia Brandao , Costa Elsa , Maciel Jorge
Published: June 2015

Hemosuccus pancreaticus is a very rare cause of gastrointestinal bleeding and it should be considered in every patient with history of chronic pancreatitis who presents with acute or intermittent gastrointestinal haemorrhage. A 54-year-old man with a history of chronic alcoholic pancreatitis was admitted to hospital for an acute exacerbation. During hospital stay, he presented with haematemesis and haemodynamic instability. Upper gastrointestinal endoscopy revealed a blood clot on Vater papilla. CT investigation showed a 4 cm cephalopancreatic pseudocyst and angiography identified a large pseudoaneurysm of the right gastroepiploic artery, bleeding into the pseudocyst–hemosuccus pancreaticus. Microcoil transcatheter embolisation was performed with success.
Osteolipoma of floor of the mouth
Authors: Raghunath Vandana , Manjunatha Bhari Sharanesha
Published: June 2015

Lipomas are benign soft tissue tumours composed mainly of mature adipose tissue. Histological variants of lipomas have been named according to the type of tissue present and they include fibrolipoma, angiolipoma, osteolipoma, chondrolipoma and others. Osteolipoma, a classic lipoma with osseous metaplasia, is a very rare histological variant. Owing to the rarity of oral osteolipomas, we report an uncommon case of osteolipoma located on the floor of the mouth of a 20-year-old female patient and include a review of the literature.
Clear cell adenocarcinoma of the bladder with intravesical cervical invasion
Authors: Marchalik Daniel , Krishnan Jayashree , Verghese Mohan , Venkatesan Krishnan
Published: June 2015

A 26-year-old woman with a complicated urological and gynecological history with uterine didelphys with bilaterally inserting intravesical cervical oses presented with cyclical haematuria. Work up revealed a mass in the ectopic cervical os and adjacent bladder wall. Subsequent resection confirmed a clear cell adenocarcinoma of urological origin with invasion into neighbouring os.
Intravenous immunoglobulin for antibody-mediated keratolimbal allograft rejection
Authors: Squissato Victoria , Schiff Jeffrey , Chan Clara C
Published: June 2015

A 33-year-old woman with congenital aniridia presented with decreased vision in her right eye. Slit lamp examination revealed diffuse conjunctivalisation of the ocular surface with mild subepithelial fibrosis consistent with aniridic keratopathy secondary to limbal stem cell deficiency. She underwent limbal stem cell transplantation with cadaver donor tissue (keratolimbal allograft (KLAL) surgery) and received systemic immunosuppression. Despite optimal combination immunosuppressive therapy managed by a renal transplant specialist, 2 weeks after the KLAL, the patient developed intractable eye pain, conjunctival injection, dilation of the KLAL graft blood vessels and limbal haemorrhages. There were no epithelial defects noted. Donor-specific antibody testing was positive, and intravenous immunoglobulin therapy was initiated. There was immediate symptomatic and objective improvement. Fifteen months postoperatively, the patient's vision was 20/400 with a stable corneal epithelium and no evidence of inflammation.
FAST CP:protocol of a randomised controlled trial of the efficacy of a 12-week combined Functional Anaerobic and Strength Training programme on muscle properties and mechanical gait deficiencies in adolescents and young adults with spastic-type cerebral palsy
Authors: Gillett Jarred G , Lichtwark Glen A , Boyd Roslyn N , Barber Lee A
Published: June 2015

Introduction

Individuals with cerebral palsy (CP) have muscles that are smaller, weaker and more resistant to stretch compared to typically developing people. Progressive resistance training leads to increases in muscle size and strength. In CP, the benefits of resistance training alone may not transfer to improve other activities such as walking; however, the transfer of strength improvements to improved mobility may be enhanced by performing training that involves specific functional tasks or motor skills. This study aims to determine the efficacy of combined functional anaerobic and strength training in (1) influencing muscle strength, structure and function and (2) to determine if any changes in muscle strength and structure following training impact on walking ability and gross motor functional capacity and performance in the short (following 3 months of training) and medium terms (a further 3 months post-training).

Methods and analysis

40 adolescents and young adults with CP will be recruited to undertake a 12-week training programme. The training programme will consist of 3×75 min sessions per week, made up of 5 lower limb resistance exercises and 2–3 functional anaerobic exercises per session. The calf muscles will be specifically targeted, as they are the most commonly impacted muscles in CP and are a key muscle group involved in walking. If, as we believe, muscle properties change following combined strength and functional training, there may be long-term benefits of this type of training in slowing the deterioration of muscle function in people with spastic-type CP.

Ethics and dissemination

Ethical approval has been obtained from the ethics committees at The University of Queensland (2014000066) and Children's Health Queensland (HREC/15/QRCH/30). The findings will be disseminated by publications in peer-reviewed journals, conferences and local research organisations’ media.

Trial registration number

Australian and New Zealand Clinical Trials Registry (ACTRN12614001217695).
Systems modelling and simulation in health service design, delivery and decision making
Authors: Pitt Martin , Monks Thomas , Crowe Sonya , Vasilakis Christos
Published: June 2015

The ever increasing pressures to ensure the most efficient and effective use of limited health service resources will, over time, encourage policy makers to turn to system modelling solutions. Such techniques have been available for decades, but despite ample research which demonstrates potential, their application in health services to date is limited. This article surveys the breadth of approaches available to support delivery and design across many areas and levels of healthcare planning. A case study in emergency stroke care is presented as an exemplar of an impactful application of health system modelling. This is followed by a discussion of the key issues surrounding the application of these methods in health, what barriers need to be overcome to ensure more effective implementation, as well as likely developments in the future.
Fetuin-A is related to infarct size, left ventricular function and remodelling after acute STEMI
Authors: Feistritzer Hans-Josef , Klug Gert , Reinstadler Sebastian J , Gröber Marie-Therese , Mair Johannes , Kirchmair Rudolf , Henninger Benjamin , Franz Wolfgang-Michael , Metzler Bernhard
Published: June 2015

Objective

To investigate the relationship between plasma fetuin-A, an anti-inflammatory glycoprotein which might be involved in myocardial healing after acute infarction, and infarct size, left ventricular (LV) function and dimensions as well as the occurrence of adverse remodelling at 4 months after acute ST segment elevation myocardial infarction (STEMI).

Methods

In this single-centre prospective, observational study, 89 patients underwent cardiac MR within the first week and 4 months after mechanical reperfusion for first STEMI. Infarct size, LV function and dimensions were assessed at both time points. Fetuin-A levels were determined from blood samples drawn at a median of 49 h (IQR 30–59 h) after STEMI by an immunofluorescent assay.

Results

Fetuin-A levels (median 568 µg/mL, IQR 478–763 µg/mL) were significantly correlated with infarct size and LV ejection fraction at baseline and follow-up (all p<0.05). Moreover, fetuin-A was related to the increase in the end-diastolic volume index (r=−0.383, p<0.001). According to multivariate logistic regression analysis, fetuin-A concentrations (HR=0.17, 95% CI 0.03 to 0.89, p=0.036) besides the presence of late microvascular obstruction (HR=10.03, 95% CI 0.98 to 102.43, p=0.05) were significantly related to the occurrence of adverse LV remodelling at 4 months.

Conclusions

Circulating fetuin-A at day 2 after STEMI is related to acute and chronic infarct size, LV function and dimensions. In addition, it might be useful to identify patients at increased risk for adverse LV remodelling.
Effect of the adult pneumococcal polysaccharide vaccine on cardiovascular disease: a systematic review and meta-analysis
Authors: Ren Shu , Newby David , Li Shu Chuen , Walkom Emily , Miller Peter , Hure Alexis , Attia John
Published: June 2015

Animal models and clinical studies suggest a mechanistic link between the pneumococcal polysaccharide vaccine (PPV) and a cardiovascular protective effect. However, conflicting results exist from several large observational studies in humans. We set out to systematically review current literature and conduct meta-analyses of studies on PPV and cardiovascular outcomes. Medline, Embase and CENTRAL were searched for randomised controlled trials (RCTs) and observational studies in adults, using PPV as the intervention, up to 30 April 2014. Studies that compared PPV with a control (another vaccine, no vaccine or placebo) and recorded ischaemic events were included in this review. Two investigators extracted data independently on study design, baseline characteristics and summary outcomes. Study quality was examined using the Newcastle-Ottawa Quality Assessment Scale. Pooled estimates using random effects models and their 95% CIs were calculated separately for the outcomes of acute coronary syndrome (ACS) events and stroke. No RCT data were available. A total of 230 426 patients were included in eight observational studies and recorded as ACS events. PPV was associated with significantly lower odds of ACS events in patients 65 years and older (pooled OR=0.83 (95% CI 0.71 to 0.97), I2=77.0%). However, there was no significant difference in ACS events when younger people were included (pooled OR=0.86 (95% CI 0.73 to 1.01), I2=81.4%). Pooling of four studies, covering a total of 192 210 patients, did not find a significantly reduced risk of stroke in all patients (pooled OR=1.00 (95% CI 0.89 to 1.12), I2=55.3%), or when restricted to those 65 years and older (pooled OR=0.96 (95% CI 0.87 to 1.05), I2=22.5%). In this meta-analysis of observational studies, the use of PPV was associated with a significantly lower risk of ACS events in the older population, but not stroke. An adequately powered and blinded RCT to confirm these findings is warranted.