bluuebunny/crossref_metadata_2025 huggingface dataset:
Hematopoietic stem cell transplant for hyper‐IgM syndrome due to CD40L defects: A single‐center experience
Authors: Al‐Saud Bandar , Al‐Mousa Hamoud , Al‐Ahmari Ali , Al‐Ghonaium Abdulaziz , Ayas Mouhab , Alhissi Safa , Al‐Muhsen Saleh , Al‐Seraihy Amal , Arnaout Rand , Al‐Dhekri Hasan , Hawwari Abbas
Published: June 2015

HIGMI is a disease with a high risk for morbidity and mortality. HSCT has been shown to be a curative option. This study retrospectively reviewed and analyzed data from five patients who received HSCT at King Faisal Specialist Hospital & Research Centre (KFSH&RC) in Riyadh, Saudi Arabia, between 2005 and 2013. Five patients with HIGMI syndrome underwent HSCT at a median age of 41 months (range, 9–72 months). The median time from diagnosis to transplantation was 30 months (range, 5–58 months). For all five patients, the donors were HLA‐identical siblings. In three patients, the conditioning regimen was composed of BU and CY. Fludarabine and melphalan with either ATG or alemtuzumab was used in two patients. For GVHD prophylaxis, cyclosporine was used in two patients, and the combination of cyclosporine and MTX was used in three patients. The survival rate was 100%, with a median follow‐up of 69 months (range, 13–100 months). All patients engrafted. Two patients developed acute GVHD. Four patients showed complete immune recovery with positive CD40L expression in activated T cells and discontinued IVIG replacement. HSCT in early stage from an HLA‐matched sibling donor is potentially effective at curing the disease.
Reclamation of Water Polluted with Flubendiamide Residues by Photocatalytic Treatment with Semiconductor Oxides
Authors: Fenoll José , Vela Nuria , Garrido Isabel , Navarro Ginés , Pérez‐Lucas Gabriel , Navarro Simón
Published: June 2015

The photodegradation of flubendiamide (benzenedicarboxamide insecticide), a relatively new insecticide was investigated in aqueous suspensions binary (ZnO of and TiO2) and ternary (Zn2TiO4 and ZnTiO3) oxides under artificial light (300–460 nm) irradiation. Photocatalytic experiments showed that the addition of semiconductors, especially ZnO and TiO2, in tandem with an electron acceptor (Na2S2O8) enhances the degradation rate of this compound in comparison with those carried out with catalyst alone and photolytic tests. The photocatalytical degradation of flubendiamide using ZnO/Na2S2O8 and TiO2/Na2S2O8 followed first‐order kinetics. In addition, desiodo‐flubendiamide was identified during the degradation of flubendiamide. Finally, application of these reaction systems in different waters (tap, leaching and watercourse) showed the validity of the treatments, which allowed the removal of flubendiamide residues in these drinking and environmental water samples.
Curative drug treatment of trypanosomosis leads to the restoration of B‐cell lymphopoiesis and splenic B‐cell compartments
Authors: Cnops J. , Bockstal V. , De Trez C. , Miquel M.C. , Radwanska M. , Magez S.
Published: June 2015

African trypanosomosis is a parasitic disease affecting both humans (sleeping sickness) and animals (nagana). In murine trypanosomosis, the B‐cell compartment is rapidly destroyed after infection. In addition, B‐cell lymphopoiesis in the bone marrow is abrogated, B‐cell subsets in the spleen are irreversibly depleted, and B‐cell memory is destroyed. Here, we investigated the effect of cure of infection on the B‐cell compartment. Suramin and diminazene aceturate were used in this study as these drugs exhibit different modes of uptake and different mechanisms of trypanocidal action. Curative drug treatment of trypanosomosis infection led to the re‐initiation of B‐cell lymphopoiesis in the bone marrow, and to the repopulation of splenic B‐cell subsets, independent of the drug used. Neither of these drugs by itself induced measurable effects on B‐cell lymphopoiesis in the bone marrow or B‐cell homoeostasis in the spleen in healthy, naïve animals.
Simultaneous monitoring and quantification of Melampsora allii‐populina and Melampsora larici‐populina on infected poplar leaves using a duplex real‐time PCR assay
Authors: Guinet C. , Boutigny A. L. , Vialle A. , Hamelin R. C. , Frey P. , Ioos R.
Published: June 2015

The rust fungi Melampsora larici‐populina (Mlp) and Melampsora allii‐populina (Map) are the main phytosanitary constraints for commercial poplar cultivation in Europe. Although Mlp is more aggressive and prevalent than Map, the two species may co‐infect the same poplar tree or even the same poplar leaf, making the epidemiological surveys of each species difficult to achieve. In this study, a new duplex real‐time PCR assay targeting each species was developed, based on single‐copy genes. This test proved to be specific, inclusive and was successfully used to detect and quantify each species, starting from urediniospore samples or directly from infected poplar leaves, with or without visible symptoms. This new molecular tool was also assessed for comparative studies of time‐course infection experiments on artificially inoculated poplar leaf discs. These studies showed that the growth dynamics of Map were significantly slower when the two species were co‐inoculated on the same leaf disc, confirming that Map is less aggressive than Mlp.
Derivation of Canine Induced Pluripotent Stem Cells
Authors: Baird AEG , Barsby T , Guest DJ
Published: June 2015

Contents

Dogs and humans have many inherited genetic diseases in common and conditions that are increasingly prevalent in humans also occur naturally in dogs. The use of dogs for the experimental and clinical testing of stem cell and regenerative medicine products would benefit canine health and welfare and provide relevant animal models for the translation of therapies to the human field. Induced pluripotent stem cells (iPSCs) have the capacity to turn into all cells of the body and therefore have the potential to provide cells for therapeutic use and for disease modelling. The objective of this study was to derive and characterize iPSCs from karyotypically abnormal adult canine cells. Aneuploid adipose‐derived mesenchymal stromal cells (AdMSCs) from an adult female Weimeraner were re‐programmed into iPSCs via overexpression of four human pluripotency factors (Oct 4, Sox2, Klf4 and c‐myc) using retroviral vectors. The iPSCs showed similarity to human ESCs with regard to morphology, pluripotency marker expression and the ability to differentiate into derivatives of all three germ layers in vitro (endoderm, ectoderm and mesoderm). The iPSCs also demonstrated silencing of the viral transgenes and re‐activation of the silent X chromosome, suggesting full reprogramming had occurred. The levels of aneuploidy observed in the AdMSCs were maintained in the iPSCs. This finding demonstrates the potential for generating canine induced pluripotent stem cells for use as disease models in addition to regenerative medicine and pharmaceutical testing.
Women's Organizations, Social Learning, and the Federal State: A Case Study of Canadian Pension Policy
Authors: Cooper Christopher A.
Published: June 2015

The various ways which federalism influences gender policies has recently received a surge of academic interest. This article contributes to this literature by moving beyond formally adopted policies to study the influence of federalism on social learning amongst women's organizations. Using a most‐likely case study design, this exploratory work traces the policy positions held by women's organizations in Canada during a seven‐year period now known as the Great Pension Debate. Focusing on four empirical indicators of issue attention, participation in policy discussions, specificity of policy proposals, and consensus for reform, the findings suggest that the plurality and temporal proximity of successive policy venues – such as royal commissions and parliamentary committees – created by various governments offered women's organizations an optimum environment to engage in ongoing exchanges leading to the development, and greater specification, of policy positions.
Regional provenance from southwestern Colombia fore‐arc and intra‐arc basins: implications for Middle to Late Miocene orogeny in the Northern Andes
Authors: Echeverri Sebastián , Cardona Agustín , Pardo Andrés , Monsalve Gaspar , Valencia Victor A. , Borrero Carlos , Rosero Sebastián , López Sergio
Published: June 2015

Andean orogenic processes controlled the spatial and temporal distribution of the magmatic and sedimentary record. This contribution integrates new U/Pb zircon ages, heavy mineral analyses and biostratigraphic constraints from the Neogene sedimentary record of the fore‐arc and intra‐arc basins and volcano‐plutonic rocks of southwestern Colombia, to reconstruct these orogenic processes. The results reveal continuous arc magmatism since the Late Oligocene, with a major post‐Middle Miocene magmatic peak and exhumation. When integrated with other geological constraints, the tectonic evolution of the margin includes Eocene‐Oligocene oblique convergence with limited magmatic activity, followed by the initiation of a Late Oligocene‐Early Miocene arc that migrated to the east in the Middle Miocene, when it experienced a major increase in magmatic activity, crustal deformation, exhumation and thickening. This orogenic evolution is related to the shallowing of the slab dip due to the subduction of the Neogene Nazca Plate.
C‐reactive protein and high mobility group box 1 in dogs with gastric dilatation and volvulus
Authors: Uhrikova Ivana , Rauserova‐Lexmaulova Leona , Rehakova Kristina , Scheer Peter , Doubek Jaroslav
Published: June 2015

Objective

To (1) measure C‐reactive protein (CRP) and high mobility group box 1 (HMGB1) and (2) evaluate their prognostic value and relationship to severity of systemic inflammatory response syndrome, routine hematological and acid‐base parameters in dogs with gastric dilatation volvulus (GDV).

Design

Prospective observational study from September 2010 to June 2012.

Setting

Veterinary teaching hospital.

Animals

Forty‐one client‐owned dogs with GDV.

Interventions

None.

Measurements and Main Results

Blood was collected before surgery (baseline), postsurgery, 6–10 hours postsurgery, and 18–22 hours postsurgery. CRP and HMGB1 were measured in all samples, and routine hematological, biochemical, and acid‐base analyses were performed. Only baseline and postsurgery samples were used from nonsurvivors (n= 10). CRP increased significantly from postsurgery sampling to 18–22 hours postsurgery, while HMGB1 did not change over time. There was a significant difference in HMGB1 between survivors and nonsurvivors over time. Both proteins correlated with systemic inflammatory response syndrome severity, total leukocyte, segmented neutrophils, and band counts. HMGB1 correlated also with acid‐base parameters (pH, bicarbonate, base excess).

Conclusion

HMGB1 and CRP behaved differently in regards to their kinetic patterns, with HMGB1 appearing to better reflect the severity of tissue injury in dogs with GDV than CRP.
Testosterone biases the amygdala toward social threat approach
Authors: Radke Sina , Volman Inge , Mehta Pranjal , van Son Veerle , Enter Dorien , Sanfey Alan , Toni Ivan , de Bruijn Ellen R. A. , Roelofs Karin
Published: June 2015

Testosterone administration in human participants increased amygdala responses during threat approach and decreased it during threat avoidance.
Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics
Authors: Kadoch Cigall , Crabtree Gerald R.
Published: June 2015

New human genetic findings paired with biochemical studies are challenging current thinking on the function of chromatin remodeling complexes.
Sourcing niche cell populations: Techniques for isolating and characterizing progenitor cells
Authors: Phinney Donald G. , Da Sacco Stefano
Published: June 2015

Understanding stem/progenitor cells—which can develop into various types of tissue—are key to developing novel approaches for regenerative medicine. Techniques enabling the isolation of specific cell populations have advanced our ability to identify and characterize niche cell types which may be used to replace or engineer cells/tissue. The use of cell surface markers to isolate specific cell populations is one common method for separating cells; however, isolating live cells based on their RNA expression is a powerful new way enabling the study of small cell niches in nongenetically modified animal models and human tissue. In this webinar, we will hear from experts about different ways to isolate and characterize specific cell populations, including the nephrogenic progenitors that give rise to mature functional renal cells and mesenchymal stem cells which can differentiate into multiple cell types.
Response to Comment on “Early
Homo
at 2.8 Ma from Ledi-Geraru, Afar, Ethiopia”
Authors: Villmoare Brian , Kimbel William H. , Seyoum Chalachew , Campisano Christopher J. , DiMaggio Erin , Rowan John , Braun David R. , Arrowsmith J. Ramon , Reed Kaye E.
Published: June 2015

Hawks
et al
. argue that our analysis of
Australopithecus sediba
mandibles is flawed and that specimen LD 350-1 cannot be distinguished from this, or any other,
Australopithecus
species. Our reexamination of the evidence confirms that LD 350-1 falls outside of the pattern that
A. sediba
shares with
Australopithecus
and thus is reasonably assigned to the genus
Homo
.
Multilocus PCR Assays Elucidate Vegetative Incompatibility Gene Profiles of Cryphonectria parasitica in the United States
Authors: Short Dylan P. G. , Double Mark , Nuss Donald L. , Stauder Cameron M. , MacDonald William , Kasson Matthew T.
Published: June 2015

Chestnut blight is a devastating disease of
Castanea
spp. Mycoviruses that reduce virulence (hypovirulence) of the causative agent,
Cryphonectria parasitica
, can be used to manage chestnut blight. However, vegetative incompatibility (
vic
) barriers that restrict anastomosis-mediated virus transmission hamper hypovirulence efficacy. In order to effectively determine the vegetative incompatibility genetic structure of
C. parasitica
field populations, we have designed PCR primer sets that selectively amplify and distinguish alleles for each of the six known diallelic
C. parasitica
vic
genetic loci. PCR assay results were validated using a panel of 64 European tester strains with genetically determined
vic
genotypes. Analysis of 116
C. parasitica
isolates collected from five locations in the eastern United States revealed 39 unique
vic
genotypes and generally good agreement between PCR and tester strain coculturing assays in terms of
vic
diversity and genotyping. However, incongruences were observed for isolates from multiple locations and suggested that the coculturing assay can overestimate diversity at the six known
vic
loci. The availability of molecular tools for rapid and precise
vic
genotyping significantly improves the ability to predict and evaluate the efficacy of hypovirulence and related management strategies.
Acetylation Regulates Survival of Salmonella enterica Serovar Typhimurium under Acid Stress
Authors: Ren Jie , Sang Yu , Ni Jinjing , Tao Jing , Lu Jie , Zhao Mingwen , Yao Yu-Feng
Published: June 2015

The ability to acetylate lysine residues is conserved across organisms, and acetylation of lysine residues plays important roles in various cellular functions. Maintaining intracellular pH homeostasis is crucial for the survival of enteric bacteria in the acidic gastric tract. It has been shown that eukaryotes can stabilize the intracellular pH by histone deacetylation. However, it remains unknown whether bacteria can utilize a reversible protein acetylation system to adapt to an acidic environment. Here we demonstrate that protein acetylation/deacetylation is critical for
Salmonella enterica
serovar Typhimurium to survive in an acidic environment. We used RNA sequencing to analyze the transcriptome patterns under acid stress and found that the transcriptional levels of genes involved in NAD
+
/NADH metabolism were significantly changed, leading to an increase in the intracellular NAD
+
/NADH ratio. Moreover, acid stress downregulated the transcriptional level of
pat
, encoding acetyltransferase, and genes
cyaA
and
crp
, encoding adenylate cyclase and cyclic AMP receptor protein, respectively, which are positive regulators of
pat
. It was found that the acid signal alerts the tricarboxylic acid cycle to promote the consumption of acetyl coenzyme A (Ac-CoA), an acetyl group donor for the acetylation reaction. A lowered acetylation level not only was the bacterial response to acid stress but also increased the survival rate of
S
. Typhimurium under acid stress. The
pat
deletion mutant had a more stable intracellular pH, which paralleled the higher survival rate after acid treatment compared with that of both the wild-type strain and the
cobB
(encoding deacetylase) deletion mutant. Our data indicate that bacteria can downregulate the protein acetylation level to prevent the intracellular pH from further falling under acid stress, and this work may provide a new perspective to understand the bacterial acid resistance mechanism.
Protozoan Cysts Act as a Survival Niche and Protective Shelter for Foodborne Pathogenic Bacteria
Authors: Lambrecht Ellen , Baré Julie , Chavatte Natascha , Bert Wim , Sabbe Koen , Houf Kurt
Published: June 2015

The production of cysts, an integral part of the life cycle of many free-living protozoa, allows these organisms to survive adverse environmental conditions. Given the prevalence of free-living protozoa in food-related environments, it is hypothesized that these organisms play an important yet currently underinvestigated role in the epidemiology of foodborne pathogenic bacteria. Intracystic bacterial survival is highly relevant, as this would allow bacteria to survive the stringent cleaning and disinfection measures applied in food-related environments. The present study shows that strains of widespread and important foodborne bacteria (
Salmonella enterica
,
Escherichia coli
,
Yersinia enterocolitica
, and
Listeria monocytogenes
) survive inside cysts of the ubiquitous amoeba
Acanthamoeba castellanii
, even when exposed to either antibiotic treatment (100 μg/ml gentamicin) or highly acidic conditions (pH 0.2) and resume active growth in broth media following excystment. Strain- and species-specific differences in survival periods were observed, with
Salmonella enterica
surviving up to 3 weeks inside amoebal cysts. Up to 53% of the cysts were infected with pathogenic bacteria, which were located in the cyst cytosol. Our study suggests that the role of free-living protozoa and especially their cysts in the persistence and epidemiology of foodborne bacterial pathogens in food-related environments may be much more important than hitherto assumed.
World Health Organization International Standard To Harmonize Assays for Detection of Mycoplasma DNA
Authors: Nübling C. Micha , Baylis Sally A. , Hanschmann Kay-Martin , Montag-Lessing Thomas , Chudy Michael , Kreß Julia , Ulrych Ursula , Czurda Stefan , Rosengarten Renate ,   the Mycoplasma Collaborative Study Group
Published: June 2015

Nucleic acid amplification technique (NAT)-based assays (referred to here as NAT assays) are increasingly used as an alternative to culture-based approaches for the detection of mycoplasma contamination of cell cultures. Assay features, like the limit of detection or quantification, vary widely between different mycoplasma NAT assays. Biological reference materials may be useful for harmonization of mycoplasma NAT assays. An international feasibility study included lyophilized preparations of four distantly related mycoplasma species (
Acholeplasma laidlawii
,
Mycoplasma fermentans
,
M. orale
,
M. pneumoniae
) at different concentrations which were analyzed by 21 laboratories using 26 NAT assays with a qualitative, semiquantitative, or quantitative design. An
M. fermentans
preparation was shown to decrease the interassay variation when used as a common reference material. The preparation was remanufactured and characterized in a comparability study, and its potency (in NAT-detectable units) across different NATs was determined. The World Health Organization (WHO) Expert Committee on Biological Standardization (ECBS) established this preparation to be the “1st World Health Organization international standard for mycoplasma DNA for nucleic acid amplification technique-based assays designed for generic mycoplasma detection” (WHO Tech Rep Ser 987:42, 2014) with a potency of 200,000 IU/ml. This WHO international standard is now available as a reference preparation for characterization of NAT assays, e.g., for determination of analytic sensitivity, for calibration of quantitative assays in a common unitage, and for defining regulatory requirements in the field of mycoplasma testing.
Microbial Diversity and Putative Diazotrophy in High- and Low-Microbial-Abundance Mediterranean Sponges
Authors: Ribes Marta , Dziallas Claudia , Coma Rafel , Riemann Lasse
Published: June 2015

Microbial communities associated with marine sponges carry out nutrient transformations essential for benthic-pelagic coupling; however, knowledge about their composition and function is still sparse. We evaluated the richness and diversity of prokaryotic assemblages associated with three high-microbial-abundance (HMA) and three low-microbial-abundance (LMA) sympatric Mediterranean sponges to address their stability and uniqueness. Moreover, to examine functionality and because an imbalance between nitrogen ingestion and excretion has been observed for some of these species, we sequenced nitrogenase genes (
nifH
) and measured N
2
fixation. The prokaryotic communities in the two sponge types did not differ in terms of richness, but the highest diversity was found in HMA sponges. Moreover, the discrete composition of the communities in the two sponge types relative to that in the surrounding seawater indicated that horizontal transmission and vertical transmission affect the microbiomes associated with the two sponge categories.
nifH
genes were found in all LMA species and sporadically in one HMA species, and about half of the
nifH
gene sequences were common between the different sponge species and were also found in the surrounding water, suggesting horizontal transmission.
15
N
2
-enriched incubations showed that N
2
fixation was measurable in the water but was not associated with the sponges. Also, the analysis of the isotopic ratio of
15
N to
14
N in sponge tissue indicated that N
2
fixation is not an important source of nitrogen in these Mediterranean sponges. Overall, our results suggest that compositional and functional features differ between the prokaryotic communities associated with HMA and LMA sponges, which may affect sponge ecology.
Relationship between the Presence of Bartonella Species and Bacterial Loads in Cats and Cat Fleas (Ctenocephalides felis) under Natural Conditions
Authors: Gutiérrez Ricardo , Nachum-Biala Yaarit , Harrus Shimon
Published: June 2015

Cats are considered the main reservoir of three zoonotic
Bartonella
species:
Bartonella henselae
,
Bartonella
clarridgeiae
, and
Bartonella
koehlerae
. Cat fleas (
Ctenocephalides felis
) have been experimentally demonstrated to be a competent vector of
B. henselae
and have been proposed as the potential vector of the two other
Bartonella
species. Previous studies have reported a lack of association between the
Bartonella
species infection status (infected or uninfected) and/or bacteremia levels of cats and the infection status of the fleas they host. Nevertheless, to date, no study has compared the quantitative distributions of these bacteria in both cats and their fleas under natural conditions. Thus, the present study explored these relationships by identifying and quantifying the different
Bartonella
species in both cats and their fleas. Therefore, EDTA-blood samples and fleas collected from stray cats were screened for
Bartonella
bacteria. Bacterial loads were quantified by high-resolution melt real-time quantitative PCR assays. The results indicated a moderate correlation between the
Bartonella
bacterial loads in the cats and their fleas when both were infected with the same
Bartonella
species. Moreover, a positive effect of the host infection status on the
Bartonella
bacterial loads of the fleas was observed. Conversely, the cat bacterial loads were not affected by the infection status of their fleas. Our results suggest that the
Bartonella
bacterial loads of fleas are positively affected by the presence of the bacteria in their feline host, probably by multiple acquisitions/accumulation and/or multiplication events.
Sharply Tuned pH Response of Genetic Competence Regulation in Streptococcus mutans: a Microfluidic Study of the Environmental Sensitivity of
comX
Authors: Son Minjun , Ghoreishi Delaram , Ahn Sang-Joon , Burne Robert A. , Hagen Stephen J.
Published: June 2015

Genetic competence in
Streptococcus mutans
is a transient state that is regulated in response to multiple environmental inputs. These include extracellular pH and the concentrations of two secreted peptides, designated CSP (competence-stimulating peptide) and XIP (
comX
-inducing peptide). The role of environmental cues in regulating competence can be difficult to disentangle from the effects of the organism's physiological state and its chemical modification of its environment. We used microfluidics to control the extracellular environment and study the activation of the key competence gene
comX
. We find that the
comX
promoter (P

comX

) responds to XIP or CSP only when the extracellular pH lies within a narrow window, about 1 pH unit wide, near pH 7. Within this pH range, CSP elicits a strong P

comX

response from a subpopulation of cells, whereas outside this range the proportion of cells expressing
comX
declines sharply. Likewise, P

comX

is most sensitive to XIP only within a narrow pH window. While previous work suggested that
comX
may become refractory to CSP or XIP stimulus as cells exit early exponential phase, our microfluidic data show that extracellular pH dominates in determining sensitivity to XIP and CSP. The data are most consistent with an effect of pH on the ComR/ComS system, which has direct control over transcription of
comX
in
S. mutans
.
Targeting Importin-α7 as a Therapeutic Approach against Pandemic Influenza Viruses
Authors: Resa-Infante Patricia , Paterson Duncan , Bonet Jaume , Otte Anna , Oliva Baldo , Fodor Ervin , Gabriel Gülsah
Published: June 2015

Viral drug resistance is believed to be less likely to occur if compounds are directed against cellular rather than viral proteins. In this study, we analyzed the feasibility of a crucial viral replication factor, namely, importin-α7, as a cellular drug target to combat pandemic influenza viruses. Surprisingly, only five viral lung-to-lung passages were required to achieve 100% lethality in importin-α7
−/−
mice that otherwise are resistant. Viral escape from importin-α7 requirement was mediated by five mutations in the viral ribonucleoprotein complex and the surface glycoproteins. Moreover, the importin-α7
−/−
mouse-adapted strain became even more virulent for wild-type mice than the parental strain. These studies show that targeting host proteins may still result in viral escape by alternative pathways, eventually giving rise to even more virulent virus strains. Thus, therapeutic intervention strategies should consider a multitarget approach to reduce viral drug resistance.

IMPORTANCE
Here, we investigated the long-standing hypothesis based on
in vitro
studies that viral drug resistance occurrence is less likely if compounds are directed against cellular rather than viral proteins. Here, we challenged this hypothesis by analyzing, in an
in vivo
animal model, the feasibility of targeting the cellular factor importin-α7, which is crucial for human influenza virus replication and pathogenesis, as an efficient antiviral strategy against pandemic influenza viruses. In summary, our studies suggest that resistance against cellular factors is possible
in vivo
, and the emergence of even more virulent viral escape variants calls for particular caution. Thus, therapeutic intervention strategies should consider a multitarget approach using compounds against viral as well as cellular factors to reduce the risk of viral drug resistance and potentially increased virulence.
Preliminary Evaluation of a Bunyavirus Vector for Cancer Immunotherapy
Authors: Oreshkova N. , Spel L. , Vloet R. P. M. , Wichgers Schreur P. J. , Moormann R. J. M. , Boes M. , Kortekaas J.
Published: June 2015

Replicon particles of Rift Valley fever virus, referred to as nonspreading Rift Valley fever virus (NSR), are intrinsically safe and highly immunogenic. Here, we demonstrate that NSR-infected human dendritic cells can activate CD8
+
T cells
in vitro
and that prophylactic and therapeutic vaccinations of mice with NSR encoding a tumor-associated CD8 peptide can control the outgrowth of lymphoma cells
in vivo
. These results suggest that the NSR system holds promise for cancer immunotherapy.
Schwannoma in the anterior orbita
Authors: Comez Arzu Taskiran , Muratli Asli
Published: June 2015

A schwannoma is a rare benign tumour of peripheral nerve origin. We present a case of a 65-year-old woman with a 1-year history of a slowly enlarging, painless and movable mass, palpable by fingers in her right lower eyelid, adjacent to the inferior orbital rim. No apparent mass was present by macroscopic examination. A subciliary incision and blunt dissection through the septum revealed a pearl-like round and encapsulated cystic mass between the fat pads just below the septum. A total excision of the tumour was performed. Histopathology and immunohistochemistry led to the diagnosis of schwannoma. Although rare, schwannoma should be considered in the differential diagnosis of well-capsulated masses in the periorbital region.
Epilepsy emergency rescue training
Authors: Shankar Rohit , Jory Caryn , ashton juliet , McLean Brendan , Walker Matthew
Published: June 2015

The NICE audit of epilepsy related deaths revealed that 1200 epilepsy deaths occur every year in the UK, with 42% potentially avoidable.[1] Convulsive status epilepticus (SE) is a life-threatening condition with over 20% mortality rate, especially if early treatment is not initiated .[2] Ten percent of all UK emergency department (ED) admissions are due to epilepsy, usually over represented by cases of SE.[3] Six out of seven epilepsy cases seen in the ED are admitted into medical care.[4]

Patients with chronic and/or treatment resistant epilepsy carry a higher risk of premature death. When a seizure lasts for five minutes or more then the patient is at high risk of continuing to SE and this may result in causing brain damage or death.[2]

Buccal midazolam is an emergency rescue medication prescribed on a special named patient license to reduce the duration of an epileptic seizure and prevent SE.[2,5] It should be administered by a trained person and is widely used due to its effectiveness and social acceptability. In the UK, epilepsy education and training courses are expected to be conducted by epilepsy professionals in line with the agreed training guidelines of Joint Epilepsy Council (JEC) backed up by evidence from NICE.[6,7] Training should provide an overview of epilepsy to facilitate safe care and appropriate administration of rescue medication for people with epilepsy (PWE) when experiencing a prolonged seizure. The medication is prescribed on specialist advice by the GP or specialists directly.

Unfortunately the JEC guidelines are not robust enough to provide assurances of safe care. This problem had a myriad of complexities and an appropriate solution using web based resource was piloted, tested, and applied successfully using quality improvement methodology.
Cost and impoverishment 1 year after hospitalisation due to injuries: a cohort study in Thái Bình, Vietnam
Authors: Nguyen Ha , Ivers Rebecca , Jan Stephen , Martiniuk Alexandra , Segal Leonie , Pham Cuong
Published: June 2015

Background

Evidence on the economic impact on individuals and their families following an injury in Vietnam is limited. This study examines the costs and the risk of impoverishment due to hospitalised injuries at 12 months following hospital discharge and associated factors.

Method

Employing a prospective cohort design, 892 people hospitalised for injury were recruited from Thái Bình General Hospital in Vietnam in 2010 and followed up for 12 months. All out-of-pocket costs incurred and income lost by injured persons and their caregivers associated with care and treatment of their injuries were reported. To examine associated factors, we used generalised estimating equation models for costs and modified Poisson regression for the risk of impoverishment.

Results

The mean total costs by 12 months postdischarge were US$804, nearly 1.2 times the annual average income. Injuries that incurred highest costs were falls (US$950) and road traffic injuries (RTIs) (US$794). At 12-month follow-up, 181 persons (26.9%) became impoverished, with those injured in RTIs and falls at highest risk (26.1% and 35.4%, respectively). Factors associated with higher costs were also those associated with higher risk of impoverishment. These include those injured in RTIs or falls; having higher severity level; principal injured region as upper extremities, lower extremities or head; physical nature of injuries as fracture or concussion injuries; and longer hospitalisation.

Conclusions

Injuries impose significant economic burden on injured persons and their families during and beyond hospitalisation. In addition to prevention, there is a need to reform health financing system to protect injured persons from significant out-of-pocket expense for healthcare services.
Shared Reading: assessing the intrinsic value of a literature-based health intervention
Authors: Longden Eleanor , Davis Philip , Billington Josie , Lampropoulou Sofia , Farrington Grace , Magee Fiona , Walsh Erin , Corcoran Rhiannon
Published: June 2015

Public health strategies have placed increasing emphasis on psychosocial and arts-based strategies for promoting well-being. This study presents preliminary findings for a specific literary-based intervention, Shared Reading, which provides community-based spaces in which individuals can relate with both literature and one another. A 12-week crossover design was conducted with 16 participants to compare benefits associated with six sessions of Shared Reading versus a comparison social activity, Built Environment workshops. Data collected included quantitative self-report measures of psychological well-being, as well as transcript analysis of session recordings and individual video-assisted interviews. Qualitative findings indicated five intrinsic benefits associated with Shared Reading: liveness, creative inarticulacy, the emotional, the personal and the group (or collective identity construction). Quantitative data additionally showed that the intervention is associated with enhancement of a sense of ‘Purpose in Life’. Limitations of the study included the small sample size and ceiling effects created by generally high levels of psychological well-being at baseline. The therapeutic potential of reading groups is discussed, including the distinction between instrumental and intrinsic value within arts-and-health interventions.
ON COMPLEX MAPS WITH DELAY MEMORY
Authors: ALONSO-SANZ RAMÓN
Published: June 2015

An exploratory study is made on the dynamics of complex maps endowed with delay type memory of past states. Particular attention is paid to the quadratic map. Other maps, i.e. the cubic map, the map induced by the Newton–Raphson numerical method, and the purely real logistic map are also scrutinized.
Multimodal Imaging Spectroscopy of Tissue
Authors: Vogler Nadine , Heuke Sandro , Bocklitz Thomas W. , Schmitt Michael , Popp Jürgen
Published: June 2015

Advanced optical imaging technologies have experienced increased visibility in medical research, as they allow for a label-free and nondestructive investigation of tissue in either an excised state or living organisms. In addition to a multitude of ex vivo studies proving the applicability of these optical imaging approaches, a transfer of various modalities toward in vivo diagnosis is currently in progress as well. Furthermore, combining optical imaging techniques, referred to as multimodal imaging, allows for an improved diagnostic reliability due to the complementary nature of retrieved information. In this review, we provide a summary of ongoing multifold efforts in multimodal tissue imaging and focus in particular on in vivo applications for medical diagnosis. We also discuss the advantages and potential limitations of the imaging methods and outline opportunities for future developments.
Single-Cell Whole-Genome Amplification and Sequencing: Methodology and Applications
Authors: Huang Lei , Ma Fei , Chapman Alec , Lu Sijia , Xie Xiaoliang Sunney
Published: June 2015

We present a survey of single-cell whole-genome amplification (WGA) methods, including degenerate oligonucleotide–primed polymerase chain reaction (DOP-PCR), multiple displacement amplification (MDA), and multiple annealing and looping–based amplification cycles (MALBAC). The key parameters to characterize the performance of these methods are defined, including genome coverage, uniformity, reproducibility, unmappable rates, chimera rates, allele dropout rates, false positive rates for calling single-nucleotide variations, and ability to call copy-number variations. Using these parameters, we compare five commercial WGA kits by performing deep sequencing of multiple single cells. We also discuss several major applications of single-cell genomics, including studies of whole-genome de novo mutation rates, the early evolution of cancer genomes, circulating tumor cells (CTCs), meiotic recombination of germ cells, preimplantation genetic diagnosis (PGD), and preimplantation genomic screening (PGS) for in vitro–fertilized embryos.
Multilevel systems biology modeling characterized the atheroprotective efficiencies of modified dairy fats in a hamster model
Authors: Martin Jean-Charles , Berton Amélie , Ginies Christian , Bott Romain , Scheercousse Pierre , Saddi Alessandra , Gripois Daniel , Landrier Jean-François , Dalemans Daniel , Alessi Marie-Christine , Delplanque Bernadette
Published: June 2015

We assessed the atheroprotective efficiency of modified dairy fats in hyperlipidemic hamsters. A systems biology approach was implemented to reveal and quantify the dietary fat-related components of the disease. Three modified dairy fats (40% energy) were prepared from regular butter by mixing with a plant oil mixture, by removing cholesterol alone, or by removing cholesterol in combination with reducing saturated fatty acids. A plant oil mixture and a regular butter were used as control diets. The atherosclerosis severity (aortic cholesteryl-ester level) was higher in the regular butter-fed hamsters than in the other four groups ( P < 0.05). Eighty-seven of the 1,666 variables measured from multiplatform analysis were found to be strongly associated with the disease. When aggregated into 10 biological clusters combined into a multivariate predictive equation, these 87 variables explained 81% of the disease variability. The biological cluster “regulation of lipid transport and metabolism” appeared central to atherogenic development relative to diets. The “vitamin E metabolism” cluster was the main driver of atheroprotection with the best performing transformed dairy fat. Under conditions that promote atherosclerosis, the impact of dairy fats on atherogenesis could be greatly ameliorated by technological modifications. Our modeling approach allowed for identifying and quantifying the contribution of complex factors to atherogenic development in each dietary setup.
Optical projection tomography permits efficient assessment of infarct volume in the murine heart postmyocardial infarction
Authors: Zhao X. , Wu J. , Gray C. D. , McGregor K. , Rossi A. G. , Morrison H. , Jansen M. A. , Gray G. A.
Published: June 2015

The extent of infarct injury is a key determinant of structural and functional remodeling following myocardial infarction (MI). Infarct volume in experimental models of MI can be determined accurately by in vivo magnetic resonance imaging (MRI), but this is costly and not widely available. Experimental studies therefore commonly assess injury by histological analysis of sections sampled from the infarcted heart, an approach that is labor intensive, can be subjective, and does not fully assess the extent of injury. The present study aimed to assess the suitability of optical projection tomography (OPT) for identification of injured myocardium and for accurate and efficient assessment of infarct volume. Intact, perfusion-fixed, optically cleared hearts, collected from mice 7 days after induction of MI by coronary artery occlusion, were scanned by a tomograph for autofluorescence emission after UV excitation, generating >400 transaxial sections for reconstruction. Differential autofluorescence permitted discrimination between viable and injured myocardium and highlighted the heterogeneity within the infarct zone. Two-dimensional infarct areas derived from OPT imaging and Masson's trichrome staining of slices from the same heart were highly correlated (r2 = 0.99, P < 0.0001). Infarct volume derived from reconstructed OPT sections correlated with volume derived from in vivo late gadolinium enhancement MRI (r2 = 0.7608, P < 0.005). Tissue processing for OPT did not compromise subsequent immunohistochemical detection of endothelial cell and inflammatory cell markers. OPT is thus a nondestructive, efficient, and accurate approach for routine in vitro assessment of murine myocardial infarct volume.
BKCa channel activation increases cardiac contractile recovery following hypothermic ischemia/reperfusion
Authors: Cordeiro Brenda , Terentyev Dmitry , Clements Richard T.
Published: June 2015

Mitochondrial Ca2+-activated large-conductance K+ (BKCa) channels are thought to provide protection during ischemic insults in the heart. Rottlerin (mallotoxin) has been implicated as a potent BKCa activator. The purpose of this study was twofold: 1) to investigate the efficacy of BKCa channel activation as a cardioprotective strategy during ischemic cardioplegic arrest and reperfusion (CP/R) and 2) to assess the specificity of rottlerin for BKCa channels. Wild-type (WT) and BKCa knockout (KO) mice were subjected to an isolated heart model of ischemic CP/R. A mechanism of rottlerin-induced cardioprotection was also investigated using H9c2 cells subjected to in vitro CP/reoxygenation and assessed for mitochondrial membrane potential and reactive oxygen species (ROS) production. CP/R decreased left ventricular developed pressure, positive and negative first derivatives of left ventricular pressure, and coronary flow (CF) in WT mice. Rottlerin dose dependently increased the recovery of left ventricular function and CF to near baseline levels. BKCa KO hearts treated with or without 500 nM rottlerin were similar to WT CP hearts. H9c2 cells subjected to in vitro CP/R displayed reduced mitochondrial membrane potential and increased ROS generation, both of which were significantly normalized by rottlerin. We conclude that activation of BKCa channels rescues ischemic damage associated with CP/R, likely via effects on improved mitochondrial membrane potential and reduced ROS generation.
M2 macrophage accumulation in the aortic wall during angiotensin II infusion in mice is associated with fibrosis, elastin loss, and elevated blood pressure
Authors: Moore Jeffrey P. , Vinh Antony , Tuck Kellie L. , Sakkal Samy , Krishnan Shalini M. , Chan Christopher T. , Lieu Maggie , Samuel Chrishan S. , Diep Henry , Kemp-Harper Barbara K. , Tare Marianne , Ricardo Sharon D. , Guzik Tomasz J. , Sobey Christopher G. , Drummond Grant R.
Published: June 2015

Macrophages accumulate in blood vessels during hypertension. However, their contribution to vessel remodeling is unknown. In the present study, we examined the polarization state of macrophages (M1/M2) in aortas of mice during hypertension and investigated whether antagonism of chemokine receptors involved in macrophage accumulation reduces vessel remodeling and blood pressure (BP). Mice treated with ANG II (0.7 mg·kg−1·day−1, 14 days) had elevated systolic BP (158 ± 3 mmHg) compared with saline-treated animals (122 ± 3 mmHg). Flow cytometry revealed that ANG II infusion increased numbers of CD45+CD11b+Ly6Chi monocytes and CD45+CD11b+F4/80+ macrophages by 10- and 2-fold, respectively. The majority of macrophages were positive for the M2 marker CD206 but negative for the M1 marker inducible nitric oxide synthase. Expression of other M2 genes (arginase-1, Fc receptor-like S scavenger receptor, and receptor-1) was elevated in aortas from ANG II-treated mice, whereas M1 genes [TNF and chemokine (C-X-C motif) ligand 2] were unaltered. A PCR array to identify chemokine receptor targets for intervention revealed chemokine (C-C motif) receptor 2 (CCR2) to be upregulated in aortas from ANG II-treated mice, while flow cytometry identified Ly6Chi monocytes as the main CCR2-expressing cell type. Intervention with a CCR2 antagonist (INCB3344; 30 mg·kg−1·day−1), 7 days after the commencement of ANG II infusion, reduced aortic macrophage numbers. INCB334 also reduced aortic collagen deposition, elastin loss, and BP in ANG II-treated mice. Thus, ANG II-dependent hypertension in mice is associated with Ly6Chi monocyte and M2 macrophage accumulation in the aorta. Inhibition of macrophage accumulation with a CCR2 antagonist prevents ANG II-induced vessel fibrosis and elevated BP, highlighting this as a promising approach for the future treatment of vessel remodeling/stiffening in hypertension.
Cardiovascular and thermoregulatory dysregulation over 24 h following acute heat stress in rats
Authors: Quinn Carrie M. , Audet Gerald N. , Charkoudian Nisha , Leon Lisa R.
Published: June 2015

The influences of severe heat stroke (HS) on cardiovascular function during recovery are incompletely understood. We hypothesized that HS would elicit a heart rate (HR) increase persisting through 24 h of recovery due to hemodynamic, thermoregulatory, and inflammatory events, necessitating tachycardia to support mean arterial pressure (MAP). Core temperature (Tc), HR, and MAP were measured via radiotelemetry in conscious male Fischer 344 rats ( n = 22; 282.4 ± 3.5 g) during exposure to 37°C ambient temperature until a maximum Tc of 42.0°C, and during recovery at 20°C ambient temperature through 24 h. Rats were divided into Mild, Moderate, and Severe groups based on pathophysiology. HS rats exhibited hysteresis relative to Tc with HR higher for a given Tc during recovery compared with heating ( P < 0.0001). “Reverse” hysteresis occurred in MAP with pressure during cooling lower than heating per degree Tc ( P < 0.0001). Mild HS rats showed tachycardia [ P < 0.01 vs. control (Con)] through 8 h of recovery, elevated MAP ( P < 0.05 vs. Con) for the initial 5 h of recovery, with sustained hyperthermia ( P < 0.05 vs. Con) through 24 h. Moderate HS rats showed significant tachycardia ( P < 0.01 vs. Con), normal MAP ( P > 0.05 vs. Con), and rebound hyperthermia from 4 to 24 h post-HS ( P < 0.05 vs. Con). Severe HS rats showed tachycardia ( P < 0.05 vs. Con), hypotension ( P < 0.01 vs. Con), and hypothermia for 24 h ( P < 0.05 vs. Con). Severe HS rats showed 14- and 12-fold increase in heart and liver inducible nitric oxide synthase expression, respectively. Hypotension and hypothermia in Severe HS rats was consistent with inducible nitric oxide synthase-mediated systemic vasodilation. These findings provide mechanistic insight into hemodynamic and thermoregulatory impairments during 24 h of HS recovery.