bluuebunny/crossref_metadata_2025 huggingface dataset:
Roles of brain and muscle ARNT‐like 1 and Wnt antagonist Dkk1 during osteogenesis of bone marrow stromal cells
Authors: He Y. , Chen Y. , Zhao Q. , Tan Z.
Published: October 2013

Objectives

Many studies have demonstrated that the clock gene, brain and muscle ARNT‐like 1 (Bmal1), is directly related to bone ageing by affecting age‐related changes to mesenchymal stem cells (MSCs). As a main developmental signal, Wnt may play an important role in this process. Here, we have aimed to elucidate whether Bmal1 positively regulates osteogenesi via Wnt pathways.

Materials and methods

Bone marrow stromal cells were cultured in basic and in osteo‐induction medium with Wnt signalling inhibitor Dkk1 and Bmal1 transfection. Proliferation and osteogenesis of MSCs, expression of Bmal1 and activation of Wnt signalling were investigated by flow cytometry, senescence‐associated β‐galactosidase (SA‐β‐gal) staining, real‐time quantitative PCR and western blot analysis.

Results

Expression of Bmal1 (specially after 7 days osteo‐induction), activation of Wnt signalling and osteo‐related factors fell significantly during osteo‐induction after Dkk1 addition. When cellular Bmal1 was increased by transfection, osteogenesis inhibition by Dkk1 was rescued to a certain extent with activation of Wnt signalling. However, Dkk1 did not significantly affect proliferation or senescence of MSCs during early periods of culture.

Conclusion

These findings demonstrated that Bmal1 and Wnt signalling may have a synergistic effect at a particular stage of osteogenesis. Inhibition of Wnt signalling did not greatly affect ageing of MSCs through early passages.
Behavioural sensitivity to binaural spatial cues in ferrets: evidence for plasticity in the duplex theory of sound localization
Authors: Keating Peter , Nodal Fernando R. , King Andrew J.
Published: October 2013

For over a century, the duplex theory has guided our understanding of human sound localization in the horizontal plane. According to this theory, the auditory system uses interaural time differences (ITDs) and interaural level differences (ILDs) to localize low‐frequency and high‐frequency sounds, respectively. Whilst this theory successfully accounts for the localization of tones by humans, some species show very different behaviour. Ferrets are widely used for studying both clinical and fundamental aspects of spatial hearing, but it is not known whether the duplex theory applies to this species or, if so, to what extent the frequency range over which each binaural cue is used depends on acoustical or neurophysiological factors. To address these issues, we trained ferrets to lateralize tones presented over earphones and found that the frequency dependence of ITD and ILD sensitivity broadly paralleled that observed in humans. Compared with humans, however, the transition between ITD and ILD sensitivity was shifted toward higher frequencies. We found that the frequency dependence of ITD sensitivity in ferrets can partially be accounted for by acoustical factors, although neurophysiological mechanisms are also likely to be involved. Moreover, we show that binaural cue sensitivity can be shaped by experience, as training ferrets on a 1‐kHz ILD task resulted in significant improvements in thresholds that were specific to the trained cue and frequency. Our results provide new insights into the factors limiting the use of different sound localization cues and highlight the importance of sensory experience in shaping the underlying neural mechanisms.
Site‐specific effects of gastrin‐releasing peptide in the suprachiasmatic nucleus
Authors: Kallingal George J. , Mintz Eric M.
Published: October 2013

The effects of gastrin‐releasing peptide (GRP) on the circadian clock in the suprachiasmatic nucleus (SCN) are dependent on the activation of N‐methyl‐d‐aspartate (NMDA) receptors in the SCN. In this study, the interaction between GRP, glutamate and serotonin in the regulation of circadian phase in Syrian hamsters was evaluated. Microinjection of GRP into the third ventricle induced c‐fos and p‐ERK expression throughout the SCN. Coadministration of an NMDA antagonist or 8‐hydroxy‐2‐di‐n‐propylamino‐tetralin [a serotonin (5‐HT)1A,7 agonist, DPAT] with GRP limited c‐fos expression in the SCN to a region dorsal to GRP cell bodies. Similar to the effects of NMDA antagonists, DPAT attenuated GRP‐induced phase shifts in the early night, suggesting that the actions of serotonin on the photic phase shifting mechanism occur downstream from retinorecipient cells. c‐fos and p‐ERK immunoreactivity in the supraoptic (SON) and paraventricular hypothalamic nuclei also increased following ventricular microinjection of GRP. Because of this finding, a second set of experiments was designed to test a potential role for the SON in the regulation of clock function. Syrian hamsters were given microinjections of GRP into the peri‐SON during the early night. GRP‐induced c‐fos activity in the SCN was similar to that following ventricular administration of GRP. GRP or bicuculline (a γ‐aminobutyric acidA antagonist) administered near the SON during the early night elicited phase delays of circadian activity rhythms. These data suggest that GRP‐induced phase‐resetting is dependent on levels of glutamatergic and serotonergic neurotransmission in the SCN and implicate activity in the SON as a potential regulator of photic signaling in the SCN.
Medication Usage Patterns for Headache Treatment After Mild Traumatic Brain Injury
Authors: DiTommaso Craig , Hoffman Jeanne M. , Lucas Sylvia , Dikmen Sureyya , Temkin Nancy , Bell Kathleen R.
Published: October 2013

Objective

To describe patient self‐report of headache treatment in the first year following mild traumatic brain injury (TBI).

Background

An understanding of appropriate management of symptoms after mild TBI is crucial for improving acute care and long‐term outcomes. This is particularly true for post‐traumatic headaches as recent studies suggest that headaches after mild TBI are common with multiple phenotypes. In addition, symptoms such as headache after mild TBI are often managed by primary care providers without specialty training, and often in medically underserved areas. Outside of previous opinion papers, few studies have guided the treatment or examined the effectiveness of the interventions for post‐traumatic headache.

Methods

One hundred sixty‐seven participants admitted to a level 1 trauma hospital with mild TBI who were prospectively enrolled and reported new or worse headache at 3, 6, or 12 months after injury.

Results

Participants were primarily male (75%), white (75%), injured in vehicle crashes (62%), and had completed high school (83%). The majority of headaches met International Classification of Headache Disorders – 2nd edition criteria for migraine/probable migraine, followed by tension‐type headache. Despite the diverse nature of headaches, more than 70% of those with headache at each time period used acetaminophen or a nonsteroidal anti‐inflammatory drug for headache control. Only 8% of those with the migraine/probable migraine phenotype used triptans. Of those individuals who used medication, 26% of those with migraine/probable migraine phenotype and 70% of those with tension headache phenotype endorsed complete relief (vs partial or no relief) because of medication use. The majority of individuals with tension headache reported never taking medication.

Conclusions

Headaches after mild TBI are frequent and are not optimally treated. Results suggest that many individuals with mild TBI may be self‐treating their headaches by utilizing over‐the‐counter pain relief medications. These medications, however, are only providing effective treatment for a minority of this population. Further research must be conducted to develop evidence‐guided treatment and educate providers.
Therapeutic reversal of chronic alcohol‐related steatohepatitis with the ceramide inhibitor myriocin
Authors: Tong Ming , Longato Lisa , Ramirez Teresa , Zabala Valerie , Wands Jack R. , de la Monte Suzanne M.
Published: October 2013

Alcohol‐related liver disease (ALD) is associated with steatohepatitis and insulin resistance. Insulin resistance impairs growth and disrupts lipid metabolism in hepatocytes. Dysregulated lipid metabolism promotes ceramide accumulation and oxidative stress, leading to lipotoxic states that activate endoplasmic reticulum (ER) stress pathways and worsen inflammation and insulin resistance. In a rat model of chronic alcohol feeding, we characterized the effects of a ceramide inhibitor, myriocin, on the histopathological and ultrastructural features of steatohepatitis, and the biochemical and molecular indices of hepatic steatosis, insulin resistance and ER stress. Myriocin reduced the severity of alcohol‐related steatohepatitis including the abundance and sizes of lipid droplets and mitochondria, inflammation and architectural disruption of the ER. In addition, myriocin‐mediated reductions in hepatic lipid and ceramide levels were associated with constitutive enhancement of insulin signalling through the insulin receptor and IRS‐2, reduced hepatic oxidative stress and modulation of ER stress signalling mechanisms. In conclusion, ceramide accumulation in liver mediates tissue injury, insulin resistance and lipotoxicity in ALD. Reducing hepatic ceramide levels can help restore the structural and functional integrity of the liver in chronic ALD due to amelioration of insulin resistance and ER stress. However, additional measures are needed to protect the liver from alcohol‐induced necroinflammatory responses vis‐à‐vis continued alcohol abuse.
Frequency, pattern, and extent of skin diseases in relation to CD4+ cell count among adults with human immunodeficiency virus infection or acquired immunodeficiency syndrome in Osogbo, southwestern Nigeria
Authors: Akinboro Adeolu Oladayo , Onayemi Olaniyi , Mejiuni Ayodele D.
Published: October 2013

Background

Skin diseases characterize all stages of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) and contribute significantly to associated morbidity and mortality.

Objectives

The aim of this study was to document the prevalences, patterns, and extents (severity) of skin diseases and their relationships with immunologic status in HIV/AIDS patients.

Methods

A total of 140 HIV/AIDS patients in different stages of HIV infection and 140 controls were recruited. Skin diseases were documented and CD4+ cell counts determined in all subjects. Severity was assessed according to the body surface area affected (using the Wallace rule of nines and the rule of palm) for lesions that tended to be widespread. The number of digits involved was counted for lesions involving the nails. Intensity of pain was graded for specific conditions such as herpes zoster. Chi‐squared statistics and Pearson correlations were determined.

Results

Mean ± standard deviation age was 35.04 ± 8.83 years in the patient group and 32.21 ± 8.30 years in the control group. The prevalences and patterns of skin diseases in HIV/AIDS patients were similar to those reported in previous studies. Most commonly found dermatoses were oral candidiasis (n = 28, 20.0%), pruritic papular eruption (n = 27, 19.3%), xeroderma (n = 23, 16.4%), dermatophytosis (n = 22, 15.7%), and fluffy hair (n = 19, 13.6%). The presence of specific skin lesions represented a better correlate with immunosuppression than cutaneous extents. However, the extents of viral warts and multiple blue–black nails correlated significantly with CD4+ cell count. The presence of a lighter hair color phenotype signifies a lower CD4+ cell count than a softer hair phenotype.

Conclusions

The presence of specific skin lesions correlates more strongly with a low CD4+ cell count than does the extent of their distribution, except in cases of viral warts. The presence of and higher numbers of nails affected with blue–black nail hyperpigmentation suggest severe immunosuppression.
Music, identity, and musical ethnocentrism of young people in sixAsian,LatinAmerican, andWestern cultures
Authors: Boer Diana , Fischer Ronald , González Atilano Ma Luisa , de Garay Hernández Jimena , Moreno García Luz Irene , Mendoza Socorro , Gouveia Valdiney V. , Lam Jason , Lo Eva
Published: October 2013

Ethnomusicologists and sociologists have extensively discussed the symbolic role of music in the creation, maintenance, and expression of cultural and national identity, while the underlying social psychological processes remain unexplored. We elaborate psychological mechanisms of identity construction and identity expression through culture‐specific music preferences. We propose and test a model linking music preferences to national identity via musical ethnocentrism in six student samples fromBrazil,Germany,HongKong,Mexico,NewZealand, and thePhilippines. In each context, culture‐specific music styles were related to national identity of its listeners and musical ethnocentrism mediated these effects. This paper bridges culture‐specific and universal perspectives on music and identity by examining the underlying psychological processes inAsian,Latin, andWestern cultures.
Low Prolactin Is Associated with Sexual Dysfunction and Psychological or Metabolic Disturbances in Middle-Aged and Elderly Men: The European Male Aging Study (EMAS)
Authors: Corona Giovanni , Wu Frederick C. , Rastrelli Giulia , Lee David M. , Forti Gianni , O'Connor Daryl B. , O'Neill Terence W. , Pendleton Neil , Bartfai Gyorgy , Boonen Steven , Casanueva Felipe F. , Finn Joseph D. , Huhtaniemi Ilpo T. , Kula Krzysztof , Punab Margus , Vanderschueren Dirk , Rutter Martin K. , Maggi Mario
Published: October 2013

Introduction

We previously reported that in male patients consulting for sexual dysfunction, low prolactin (PRL) levels were associated with metabolic syndrome (MetS), arteriogenic erectile dysfunction, and incident major cardiovascular events.

Aim

The aim of this study is to assess the clinical associations of PRL levels in the European Male Ageing Study (EMAS).

Methods

EMAS is a prospective, observational cohort of community-dwelling men aged 40–79 years old (mean age 60 ± 11 years old). PRL was available for 2,948 men.

Main Outcome Measures

Different parameters were evaluated including the Short Form-36 questionnaire, Becks Depression Inventory, the Adverse Life Events Scale, the Physical Activity Scale for the Elderly, and the EMAS sexual function questionnaire (EMAS-SFQ).

Results

After the adjustment for confounders, PRL levels were inversely related with worsening of sexual function as compared with the previous year, as derived from change in sexual functioning domain of the EMAS-SFQ (adj. r = −0.043; P = 0.029). The strongest correlation (Wald = 6.840; P = 0.009) was observed between lower PRL levels and reduced enjoyment of orgasmic experiences. Furthermore, an inverse relationship between PRL levels and stressful life events or depressive symptoms was observed. Low PRL was also negatively associated with an unhealthy metabolic phenotype as well as with the MetS (Wald = 5.229; P = 0.022). In line with these data, low PRL was associated with a lower level of physical activity and feeling unhealthier.

Conclusions

Low PRL is related to several metabolic, psychological, and sexual unhealthy characteristics in European men. Checking PRL might be useful to stratify men for cardiovascular risk and to encourage appropriate lifestyle changes.
Does competition for pollinators contribute to structuring Erica communities?
Authors: Heystek A. , Pauw A.
Published: October 2013

Question

Pollinators are often implicated in the origin of plant species, but their role during the assembly of diverse plant communities has only rarely been investigated. Intra‐specific competition for pollinators can theoretically facilitate plant species co‐occurrence by limiting the density of any one species, while inter‐specific competition can potentially structure communities through the exclusion of inferior competitors. We analyse plant community composition and use field experiments to test whether intra‐ and inter‐specific competition for pollinators structures communities of co‐occurring Erica species.

Location

Cape Floral Region, southwestern South Africa (ca. 34° S, 18° E).

Methods and Results

In the study area, the genus Erica has diversified into ca. 680 species that differ primarily in their floral morphologies, reflecting insect, bird and wind pollination syndromes. Vegetation plot data from nine regions throughout the Fynbos Biome were used to test whether the frequency of co‐occurrence of species with the same pollination syndrome differs from a null model of random community assembly. We found that Erica communities were assembled randomly with respect to pollination in six regions, but that pollination syndrome co‐occurrence was significantly lower than expected in three regions. This over‐dispersion of syndromes across communities is consistent with communities being structured by inter‐specific competition for pollinators. To better understand the processes generating these patterns, we conducted competition experiments with six Erica species that share the Orange‐breasted sunbird (Anthobaphes violacea) as pollinator. We transplanted inflorescences of a focal Erica species into communities containing another resident Orange‐breasted sunbird bird‐pollinated Erica species and recorded pollination and nectar robbing rates in both the resident and the transplanted species in relation to the floral density of the resident species. Consistent with the observed community structure, pollination rate in both the resident and the introduced species declined with increasing density of the resident species, but the effect was not consistent among all populations. Nectar robbing rates of the resident species were negatively related to its own density.

Conclusion

Our analyses concur that both intra‐ and inter‐specific competition for pollination can contribute to structuring plant communities, but it is not the dominant factor structuring Erica communities.
Diet of mussels Mytilus trossulus and Dreissena polymorpha in a brackish nontidal environment
Authors: Lauringson Velda , Kotta Jonne , Orav‐Kotta Helen , Kaljurand Kaire
Published: October 2013

Benthic suspension feeders have traditionally been considered an important link between pelagic and benthic food webs in shallow seas. Their ecological impact depends highly on the removal rate of pelagic production from the water column. Besides phytoplankton, benthic suspension feeders can feed on microphytobenthos and detritus suspended in the water column by wind‐waves or tidal forces. The share of the pelagic component in the diet of benthic suspension feeders is poorly studied in the non‐tidal environment. We examined the diatom food items of two bivalve species, Mytilus trossulus Gould and Dreissena polymorpha Pallas, at four shallow locations in the Gulf of Riga basin, in the Baltic Sea, differing in hydrographic characteristics. The share of pennate benthic diatoms was always higher in mussel food than in ambient water, whereas pelagic species were under‐represented. Mussels never consumed the dominant genera that were in the water column, Cylindrotheca and Leptocylindrus. There were no differences in the main food source between the two mussel species. Our results suggest that the impact of benthic suspension feeders on pelagic foodwebs and their role in promoting benthic–pelagic coupling is of a minor importance in the study area, whereas the impact on benthic food webs may be mainly by the re‐arrangement of energy within benthic pathways.
Complex formation and processing of the minor transformation pilins of Bacillus subtilis
Authors: Mann Jessica M. , Carabetta Valerie J. , Cristea Ileana M. , Dubnau David
Published: October 2013

Transformation in most bacteria is dependent on orthologues of Type 2 secretion and Type 4 pilus system proteins. In each system, pilin proteins (major and minor) are required to make the pilus structure and are essential to the process, although the precise roles of the minor pilins remain unclear. We have explored protein–protein interactions among the competence minor pilins of Bacillus subtilis through in vitro binding studies, immunopurification and mass spectrometry. We demonstrate that the minor pilins directly interact, and the minor pilin ComGG interacts with most of the known proteins required for transformation. We find that ComGG requires other ComG proteins for its stabilization and for processing by the pre‐pilin peptidase. These observations, C‐terminal mutations in ComGG that prevent processing and the inaccessibility of pre‐ComGG to externally added protease suggest a model in which pre‐ComGG must be associated with other minor pilins for processing to take place. We propose that ComGG does not become a transmembrane protein until after processing. These behaviours contrast with that of pre‐ComGC, the major pilin, which is accessible to externally added protease and requires only the peptidase to be processed. The roles of the pilins and of the pilus in transformation are discussed.
Essential role of the plasmidhik31operon in regulating central metabolism in the dark inSynechocystissp.PCC6803
Authors: Nagarajan Sowmya , Srivastava Sanvesh , Sherman Louis A.
Published: October 2013

The plasmidhik31operon (P3, slr6039‐slr6041) is located on thepSYSXplasmid inSynechocystissp.PCC6803. AP3 mutant (ΔP3) had a growth defect in the dark and a pigment defect that was worsened by the addition of glucose. The glucose defect was from incomplete metabolism of the substrate, was pH dependent, and completely overcome by the addition of bicarbonate. Addition of organic carbon and nitrogen sources partly alleviated the defects of the mutant in the dark. Electron micrographs of the mutant revealed larger cells with division defects, glycogen limitation, lack of carboxysomes, deteriorated thylakoids and accumulation of polyhydroxybutyrate and cyanophycin. A microarray experiment over two days of growth in light‐dark plus glucose revealed downregulation of several photosynthesis, amino acid biosynthesis, energy metabolism genes; and an upregulation of cell envelope and transport and binding genes in the mutant. ΔP3had an imbalance in carbon and nitrogen levels and many sugar catabolic and cell division genes were negatively affected after the first dark period. The mutant suffered from oxidative and osmotic stress, macronutrient limitation, and an energy deficit. Therefore, theP3 operon is an important regulator of central metabolism and cell division in the dark.
Oxygen removal during pathogen inactivation with riboflavin and UV light preserves protein function in plasma for transfusion
Authors: Feys H. B. , Van Aelst B. , Devreese K. , Devloo R. , Coene J. , Vandekerckhove P. , Compernolle V.
Published: October 2013

Background and Objective

Photochemical pathogen inactivation technologies (PCT) for individual transfusion products act by inhibition of replication through irreversibly damaging nucleic acids. Concern on the collateral impact of PCT on the blood component's integrity has caused reluctance to introduce this technology in routine practice. This work aims to uncover the mechanism of damage to plasma constituents by riboflavin pathogen reduction technology (RF‐PRT).

Methods

Activity and antigen of plasma components were determined following RF‐PRT in the presence or absence of dissolved molecular oxygen.

Results

Employing ADAMTS13 as a sentinel molecule in plasma, our data show that its activity and antigen are reduced by 23 ± 8% and 29 ± 9% (n = 24), respectively, which corroborates with a mean decrease of 25% observed for other coagulation factors. Western blotting of ADAMTS13 shows decreased molecular integrity, with no obvious indication of additional proteolysis nor is riboflavin able to directly inhibit the enzyme. However, physical removal of dissolved oxygen prior to RF‐PRT protects ADAMTS13 as well as FVIII and fibrinogen from damage, indicating a direct role for reactive oxygen species. Redox dye measurements indicate that superoxide anions are specifically generated during RF‐PRT. Protein carbonyl content as a marker of disseminated irreversible biomolecular damage was significantly increased (3·1 ± 0·8 vs. 1·6 ± 0·5 nmol/mg protein) following RF‐PRT, but not in the absence of dissolved molecular oxygen (1·8 ± 0·4 nmol/mg).

Conclusions

RF‐PRT of single plasma units generates reactive oxygen species that adversely affect biomolecular integrity of relevant plasma constituents, a side‐effect, which can be bypassed by applying hypoxic conditions during the pathogen inactivation process.
Allowing blood donation from men who had sex with men more than 5 years ago: a model to evaluate the impact on transfusion safety in Canada
Authors: Germain M. , Robillard P. , Delage G. , Goldman M.
Published: October 2013

Canada now allows donations from men who had sex with men (MSM) if their last sexual contact with a man was more than 5 years ago. We modelled the impact of this policy on supply and safety. Approximately 4500 new donors will be added and assuming compliance to the new policy remains unchanged, the worst‐case scenario predicts the introduction of one HIV‐contaminated unit in the inventory every 1072 years. This change will entail negligible additional HIV risk to recipients. A five‐year deferral will also protect recipients against the theoretical concern that MSM may represent a group at higher risk of sexually transmitted, emerging blood borne pathogens.
Designing Folding Rings Using Polynomial Continuation
Authors: Viquerat Andrew D. , Guest Simon D.
Published: October 2013

Two types of foldable rings are designed using polynomial continuation. The first type of ring, when deployed, forms regular polygons with an even number of sides and is designed by specifying a sequence of orientations which each bar must attain at various stages throughout deployment. A design criterion is that these foldable rings must fold with all bars parallel in the stowed position. At first, all three Euler angles are used to specify bar orientations, but elimination is also used to reduce the number of specified Euler angles to two, allowing greater freedom in the design process. The second type of ring, when deployed, forms doubly plane-symmetric (irregular) polygons. The doubly symmetric rings are designed using polynomial continuation, but in this example a series of bar end locations (in the stowed position) is used as the design criterion with focus restricted to those rings possessing eight bars.
Guardian of the Gut
Authors: Pickersgill Helen
Published: October 2013

Mucus not only forms a physical barrier in the intestine but also promotes immunological tolerance of bacteria and foods.
Are Vancomycin Trough Concentrations Adequate for Optimal Dosing?
Authors: Neely Michael N. , Youn Gilmer , Jones Brenda , Jelliffe Roger W. , Drusano George L. , Rodvold Keith A. , Lodise Thomas P.
Published: October 2013

The current vancomycin therapeutic guidelines recommend the use of only trough concentrations to manage the dosing of adults with
Staphylococcus aureus
infections. Both vancomycin efficacy and toxicity are likely to be related to the area under the plasma concentration-time curve (AUC). We assembled richly sampled vancomycin pharmacokinetic data from three studies comprising 47 adults with various levels of renal function. With Pmetrics, the nonparametric population modeling package for R, we compared AUCs estimated from models derived from trough-only and peak-trough depleted versions of the full data set and characterized the relationship between the vancomycin trough concentration and AUC. The trough-only and peak-trough depleted data sets underestimated the true AUCs compared to the full model by a mean (95% confidence interval) of 23% (11 to 33%;
P
= 0.0001) and 14% (7 to 19%;
P
< 0.0001), respectively. In contrast, using the full model as a Bayesian prior with trough-only data allowed 97% (93 to 102%;
P
= 0.23) accurate AUC estimation. On the basis of 5,000 profiles simulated from the full model, among adults with normal renal function and a therapeutic AUC of ≥400 mg · h/liter for an organism for which the vancomycin MIC is 1 mg/liter, approximately 60% are expected to have a trough concentration below the suggested minimum target of 15 mg/liter for serious infections, which could result in needlessly increased doses and a risk of toxicity. Our data indicate that adjustment of vancomycin doses on the basis of trough concentrations without a Bayesian tool results in poor achievement of maximally safe and effective drug exposures in plasma and that many adults can have an adequate vancomycin AUC with a trough concentration of <15 mg/liter.
Efficacy of an Experimental Azithromycin Cream for Prophylaxis of Tick-Transmitted Lyme Disease Spirochete Infection in a Murine Model
Authors: Piesman Joseph , Hojgaard Andrias , Ullmann Amy J. , Dolan Marc C.
Published: October 2013

As an alternative to oral prophylaxis for the prevention of tick transmission ofBorrelia burgdorferi, we tested antibiotic cream prophylactic formulations in a murine model of spirochete infection. A 4% preparation of doxycycline cream afforded no protection, but a single application of 4% azithromycin cream was 100% protective when applied directly to the tick bite site at the time of tick removal. Indeed, the azithromycin cream was 100% effective when applied at up to 3 days after tick removal and protected 74% of mice exposed to tick bite when applied at up to 2 weeks after tick removal. Azithromycin cream was also protective when applied at a site distal to the tick bite site, suggesting that it was having a systemic effect in addition to a local transdermal effect. Mice that were protected from tick-transmitted infection did not seroconvert and did not infect larval ticks on xenodiagnosis. Azithromycin cream formulations appear to hold promise for Lyme disease prophylaxis.
Characterizing
In Vivo
Pharmacodynamics of Carbapenems against Acinetobacter baumannii in a Murine Thigh Infection Model To Support Breakpoint Determinations
Authors: MacVane Shawn H. , Crandon Jared L. , Nicolau David P.
Published: October 2013

Pharmacodynamic profiling data of carbapenems for
Acinetobacter
spp. are sparse. This study aimed to determine the pharmacodynamic targets of carbapenems for
Acinetobacter baumannii
based on a range of percentages of the dosing interval in which free drug concentrations remained above the MIC (
f
T>MIC) in the neutropenic murine thigh infection model.
f
T>MIC values of 23.7%, 32.8%, and 47.5% resulted in stasis, 1-log reductions, and 2-log reductions in bacterial density after 24 h, respectively. The pharmacodynamic targets of carbapenems for
A. baumannii
demonstrated
in vivo
are similar to those of other Gram-negative bacteria.
Candida albicans Airway Exposure Primes the Lung Innate Immune Response against Pseudomonas aeruginosa Infection through Innate Lymphoid Cell Recruitment and Interleukin-22-Associated Mucosal Response
Authors: Mear Jean Baptiste , Gosset Philippe , Kipnis Eric , Faure Emmanuel , Dessein Rodrigue , Jawhara Samir , Fradin Chantal , Faure Karine , Poulain Daniel , Sendid Boualem , Guery Benoit
Published: October 2013

Pseudomonas aeruginosaandCandida albicansare two pathogens frequently encountered in the intensive care unit microbial community. We have demonstrated thatC. albicansairway exposure protected againstP. aeruginosa-induced lung injury. The goal of the present study was to characterize the cellular and molecular mechanisms associated withC. albicans-induced protection. Airway exposure byC. albicansled to the recruitment and activation of natural killer cells, innate lymphoid cells (ILCs), macrophages, and dendritic cells. This recruitment was associated with the secretion of interleukin-22 (IL-22), whose neutralization abolishedC. albicans-induced protection. We identified, by flow cytometry, ILCs as the only cellular source of IL-22. Depletion of ILCs by anti-CD90.2 antibodies was associated with a decreased IL-22 secretion and impaired survival afterP. aeruginosachallenge. Our results demonstrate that the production of IL-22, mainly by ILCs, is a major and inducible step in protection againstP. aeruginosa-induced lung injury. This cytokine may represent a clinical target inPseudomonas aeruginosa-induced lung injury.
High dose of prokinetics for refractory hiccups after chemotherapy or the return to a simple drug
Authors: Uña Esther , Alonso Pilar
Published: October 2013

Hiccups in patients with cancer might be difficult to treat, impacting negatively on the quality of life. Many therapies are available, but they are usually started empirically, and often they are unsuccessful. We report a case of a man with metastatic colon cancer who after the first cycle of chemotherapy developed persistent hiccups refractory to neuroleptics and low dose of metoclopramide. After searching for the potential cause, a high dose of prokinetics was initiated in the hospital and his symptoms disappeared. This case shows how searching for potential causes helps start the right treatment immediately, and therefore it is relevant for the prompt relief from this bothersome symptom. So far, no cases reporting high doses of prokinetics to treat persistent hiccups after chemotherapy have been published. This option should be taken into account when developing hiccups and gastro-oesophageal reflux after chemotherapy, especially if low doses of prokinetics have already been tried.
CSF xanthochromia analysis takes longer following centralisation of the laboratories testing samples - how can we improve the time to result?
Authors: Martin Sean , Page Melanie , Godber Ian , McGregor Calum
Published: October 2013

Lumbar puncture is an essential tool for excluding subarachnoid haemorrhage. In August 2012, the laboratory at which cerebrospinal fluid (CSF) is analysed for xanthochromia in Lanarkshire was centralised at Hairmyres (East Kilbride, UK). Prior to this, each of the three hospitals analysed their own specimens.

We aim to assess whether or not the change in xanthochromia processing has resulted in diagnostic delay at Wishaw General Hospital in the assessment of CT negative possible subarachnoid haemorrhage. We subsequently assessed the impact of a strategy to minimise any delay, i.e. increasing laboratory processing hours.

Patients undergoing CSF analysis for xanthochromia were identified directly from the laboratory database. Time of lumbar puncture, and time of xanthochromia results were obtained from the hospital's laboratory computer system. Data were analysed using a commercially available statistical software programme (Microsoft Excel). Audit was repeated after the change to a centralised laboratory, and again following the increased laboratory working hours.

Mean time from lumbar puncture to availability of xanthochromia result was significantly longer following the laboratory change (20.8±3.5 hours post [n=35] vs. 12.5±3.0 pre, p=0.01 [n=17]). However, following a change in the laboratory's practice, there was no improvement (19.8±3.4 hours post practice change [n=35]), and this remained significantly longer when compared to the original laboratory set-up (p=0.025).

The change in laboratory processing CSF samples for xanthochromia in Lanarkshire resulted in a significant delay in analysing the samples. Attempts by the laboratory to extend processing hours did not make any significant improvement, but having expanded our knowledge of the issues, further measures are now planned to minimise delays in the future.

Centralisation of laboratory services for CSF analysis, whilst cheaper, may impact negatively on clinical care.
Warfarin Management Pathway: A clear and safe algorithm, from admission to discharge.
Authors: Hart-George Alice
Published: October 2013

Warfarin is the most commonly prescribed anticoagulant in the UK and the one most frequently associated with both fatal medication errors and litigation claims [1]. Its life-threatening interactions and side effects are a concern for all doctors. Identifying and implementing solutions to achieve safer prescribing and monitoring is imperative to improve patient safety. The National Patient Safety Agency (NPSA) has outlined the major risks associated with anticoagulant therapy and sought to establish safer practice [1]. The monitoring of safety indicators has been highlighted as a solution. This quality improvement project (QIP) introduces a management algorithm for oral anticoagulant therapy in hospital patients, validated through a completed audit cycle. It was completed at one district general hospital (DGH) in England and involved all inpatient wards.

Doctors and pharmacists were interviewed to assess their knowledge of the correct pathways for management of patients on warfarin. The number of errors on hospital warfarin charts was audited over three weeks. These results, coupled with senior haematological advice led to the production of an algorithm illustrating the gold-standard pathway for warfarin management from admission to discharge. It was emailed to all doctors in the Trust and a laminated copy attached to hospital Pneumatic Tube System (PTS) machines. The warfarin charts were re-audited over the following three weeks. The results showed a marked decrease in errors and incomplete anticoagulation referrals as well as a reduction in doctors’ anxiety around prescribing warfarin.
CHARMING MESONS WITH BARYONS AND NUCLEI
Authors: TOLOS LAURA
Published: October 2013

The properties of charmed mesons in nuclear matter and nuclei are reviewed. Different frameworks are discussed paying a special attention to unitarized coupled-channel approaches which incorporate heavy-quark spin symmetry. Several charmed baryon states with negative parity are generated dynamically by the s-wave interaction between pseudoscalar and vector meson multiplets with 1/2+ and 3/2+ baryons. These states are compared to experimental data. Moreover, the properties of open-charm mesons in matter are analyzed. The in-medium solution accounts for Pauli blocking effects, and for the meson self-energies in a self-consistent manner. The behavior in the nuclear medium of the rich spectrum of dynamically-generated baryon states is studied as well as their influence in the self-energy and, hence, the spectral function of open charm. The possible experimental signatures of the in-medium properties of open charm are finally addressed, such as the formation of charmed nuclei, in connection with the future FAIR facility.
A BOTTOM-UP METHOD TO BUILD 3D SCAFFOLDS WITH PREDEFINED VASCULAR NETWORK
Authors: WANG LU , CHEN YANNI , QIAN JUN , TAN YANYAN , HUANGFU SHAOHUA , DING YIJIANG , DING SHUQING , JIANG BIN
Published: October 2013

Tissue engineering is a promising approach to regenerate transplantable tissue or organ substitutes in vitro. However, the existing methods are based on seeding cells on macroscale polymer scaffolds, which are associated with several challenges including limited control over cell microenvironment, limited nutrient diffusion, directed cell alignment. The emerging bottom-up tissue engineering methods hold great potential to address these challenges by assembling building blocks into complex 3D tissue constructs. In this study, we developed a layer-by-layer assembly approach to recreate 3D cell-laden constructs. Our experiment showed the predefined channels form a vascular system and help the transplant cells to transport the requirement of culture cells in early case of cells attaching and growing up. It is an original concept to demonstrate the feasibility of forming a network with a vascular geometry in a biocompatible polymer and fabricated different scaffold with different cells. The concept was developed to create a complete branching vascular circulation in 3D on surface of mixture of chitosan and gelatin structures and pre-define the structure of channel for culturing smooth muscle for controlling the SMC growing up as smooth muscle fiber.
MECHANISMS OF LEARNING AND INNOVATION PERFORMANCE: THE RELEVANCE OF KNOWLEDGE SHARING AND CREATIVITY FOR NON-TECHNOLOGICAL INNOVATION
Authors: TRIGO ALEXANDRE
Published: October 2013

This paper examines the role of several learning mechanisms for innovation performance, particularly their relevance for different types of innovation. Although the innovation drivers have been extensively discussed in the literature, more evidence is needed to verify that specific innovation outputs rely on specific knowledge sources. Based on the European Innobarometer Survey 2009, the empirical analysis reveals different profiles among innovating firms. Non-technological innovators, in particular firms highly intensive in organizational innovation, show a high propensity to perform knowledge sharing practices, to introduce knowledge management systems and to apply alternative mechanisms to promote creative ideas. The findings also prove a strong connection between product and process innovation, R&D activities and cooperation with scientific partners. The analysis concludes that firms with highest probabilities of engagement in learning mechanisms show the highest innovative performance. Moreover, the most innovative firms are characterized by the combination of different learning initiatives.
Parabolic Spiral Search Plan for a Randomly Located Target in the Plane
Authors: Beltagy Mohamed , Abd Allah El-Hadidy Mohamed
Published: October 2013

This paper addresses the problem of searching for a located target in the plane by using one searcher starting its motion from the point . The searcher moves along parabolic spiral curve. The position of the target has a known distribution.
We show that the distance between the target position and the searcher starting point
depends on the number of revolutions, where the complete revolution is done when .
Furthermore, we study this technique in the one-dimensional case (i.e., when the searcher
moves with linear search technique). It is desired to get the expected value of the time for
detecting the target. Illustrative examples are given to demonstrate the applicability of this
technique assuming circular normal distributed estimates of the target position.
Comparison of VIDAS and Radioimmunoassay Methods for Measurement of Cortisol Concentration in Bovine Serum
Authors: Proverbio Daniela , Perego Roberta , Spada Eva , Bagnagatti de Giorgi Giada , Belloli Angelo , Pravettoni Davide
Published: October 2013

Radioimmunoassay (RIA) is the “gold standard” method for evaluation of serum cortisol concentration. The VIDAS cortisol test is an enzyme‐linked fluorescent assay designed for the MiniVidas system. The aim of this study was to compare the VIDAS method with RIA for measurement of bovine serum cortisol concentration. Cortisol concentrations were evaluated in 40 cows using both VIDAS and RIA methods, the latter as the reference method. A paired Student’s t‐test, Pearson’s correlation analysis, Bland‐Altman plot, and Deming regression analysis were used to compare the two methods. There was no statistically significant difference between mean serum cortisol concentrations measured by VIDAS or RIA methods (P = 0.6570). Both methods were able to detect significant differences in mean low and high cortisol concentrations (P < 0.00014 RIA and P < 0.0016 VIDAS). The correlation coefficient was low, but a Bland‐Altman plot and Deming regression analysis show neither constant nor proportional error. The VIDAS method produced slightly higher values than RIA, but the difference was small and in no case did the mean value move the normal range. Results suggest that VIDAS method is suitable for the determination of bovine serum cortisol concentration in studies of large numbers of animals.
Marker Identification Technique for Deformation Measurement
Authors: Wang Huaiwen
Published: October 2013

A technique for noncontact optical measurement of in-plane displacement based on correlation analysis is presented. This approach can be used to identify the position of a marker before and after deformation of a specimen or plane test object. Some mechanical parameters of materials and strains can be calculated using information from several markers' displacement. The method is simpler than other optical techniques in experimental processing and can be efficiently used to measure large deformations. Two applications of this method are illustrated. One application of this method is to test the mechanical behavior of polymer film material. Another application of this method is to measure the displacement field in a strata movement simulation experiment.
Synthesis and Biological Evaluation of 2‐Hydroxy‐3‐[(2‐aryloxyethyl)amino]propyl 4‐[(Alkoxycarbonyl)amino]benzoates
Authors: Tengler Jan , Kapustíková Iva , Peško Matúš , Govender Rodney , Keltošová Stanislava , Mokrý Petr , Kollár Peter , O′Mahony Jim , Coffey Aidan , Král′ová Katarína , Jampílek Josef
Published: October 2013

A series of twenty substituted 2‐hydroxy‐3‐[(2‐aryloxyethyl)amino]propyl 4‐[(alkoxycarbonyl)amino]benzoates were prepared and characterized. As similar compounds have been described as potential antimycobacterials, primary in vitro screening of the synthesized carbamates was also performed against two mycobacterial species. 2‐Hydroxy‐3‐[2‐(2,6‐dimethoxyphenoxy)ethylamino]‐propyl 4‐(butoxycarbonylamino)benzoate hydrochloride, 2‐hydroxy‐3‐[2‐(4‐methoxyphenoxy)ethylamino]‐propyl 4‐(butoxycarbonylamino)benzoate hydrochloride, and 2‐hydroxy‐3‐[2‐(2‐methoxyphenoxy)ethylamino]‐propyl 4‐(butoxycarbonylamino)benzoate hydrochloride showed higher activity against M. avium subsp. paratuberculosis and M. intracellulare than the standards ciprofloxacin, isoniazid, or pyrazinamide. Cytotoxicity assay of effective compounds was performed using the human monocytic leukaemia THP‐1 cell line. Compounds with predicted amphiphilic properties were also tested for their effects on the rate of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. All butyl derivatives significantly stimulated the rate of PET, indicating that the compounds can induce conformational changes in thylakoid membranes resulting in an increase of their permeability and so causing uncoupling of phosphorylation from electron transport.
Prognostic Significance of Serum Free Light Chains in Chronic Lymphocytic Leukemia
Authors: Sarris Katerina , Maltezas Dimitrios , Koulieris Efstathios , Bartzis Vassiliki , Tzenou Tatiana , Sachanas Sotirios , Nikolaou Eftychia , Efthymiou Anna , Bitsani Katerina , Dimou Maria , Vassilakopoulos Theodoros P. , Siakantaris Marina , Angelopoulou Maria K. , Kontopidou Flora , Tsaftaridis Panagiotis , Kafasi Nikolitsa , Pangalis Gerasimos A. , Panayiotidis Panayiotis P. , Harding Stephen , Kyrtsonis Marie-Christine
Published: October 2013

Background. Serum free light chains (sFLC), the most commonly detected paraprotein in CLL, were recently proposed as useful tools for the prognostication of CLL patients.Objective. To investigate the prognostic implication of sFLC and the summated FLC-kappa plus FLC-lambda in a CLL patients’ series.Patients and Methods. We studied 143 CLL patients of which 18 were symptomatic and needed treatment, while 37 became symptomatic during follow-up. Seventy-two percent, 18%, and 10% were in Binet stage A, B and C, respectively. Median patients’ followup was 32 months (range 4–228).Results. Increased involved (restricted) sFLC (iFLC) was found in 42% of patients, while the summated FLC-kappa plus FLC-lambda was above 60 mg/dL in 14%. Increased sFLC values as well as those of summated FLC above 60 were related to shorter time to treatment (P=0.0005andP=0.000003, resp.) and overall survival (P=0.05andP=0.003, resp.). They also correlated withβ2-microglobulin (P=0.009andP=0.03, resp.), serum albumin (P=0.009for summated sFLC), hemoglobin (P<0.001), abnormal LDH (P=0.037andP=0.001, resp.), Binet stage (P<0.05) and with the presence of beta symptoms (P=0.004for summated sFLC).Conclusion. We confirmed the prognostic significance of sFLC in CLL regarding both time to treatment and survival and showed their relationship with other parameters.