bluuebunny/crossref_metadata_2025 huggingface dataset:
Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice
Authors: Dolejší Eva , Liraz Ori , Rudajev Vladimír , Zimčík Pavel , Doležal Vladimír , Michaelson Daniel M.
Published: November 2015

Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease. We utilized apoE4‐targeted replacement mice (approved by the Tel Aviv University Animal Care Committee) to investigate whether cholinergic dysfunction, which increases during aging and is a hallmark of Alzheimer's disease, is accentuated by apoE4. This revealed that levels of the pre‐synaptic cholinergic marker, vesicular acetylcholine transporter in the hippocampus and the corresponding electrically evoked release of acetylcholine, are similar in 4‐month‐old apoE4 and apolipoprotein E3 (apoE3) mice. Both parameters decrease with age. This decrease is, however, significantly more pronounced in the apoE4 mice. The levels of cholinacetyltransferase (ChAT), acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) were similar in the hippocampus of young apoE4 and apoE3 mice and decreased during aging. For ChAT, this decrease was similar in the apoE4 and apoE3 mice, whereas it was more pronounced in the apoE4 mice, regarding their corresponding AChE and BuChE levels. The level of muscarinic receptors was higher in the apoE4 than in the apoE3 mice at 4 months and increased to similar levels with age. However, the relative representation of the M1 receptor subtype decreased during aging in apoE4 mice. These results demonstrate impairment of the evoked release of acetylcholine in hippocampus by apoE4 in 12‐month‐old mice but not in 4‐month‐old mice. The levels of ChAT and the extent of the M2 receptor‐mediated autoregulation of ACh release were similar in the adult mice, suggesting that the apoE4‐related inhibition of hippocampal ACh release in these mice is not driven by these parameters.

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Evoked ACh release from hippocampal and cortical slices is similar in 4‐month‐old apoE4 and apoE3 mice but is specifically and significantly reduced in hippocampus, but not cortex, of 12‐month‐old apoE4 mice. This effect is accompanied by decreased VAChT levels. These findings show that the hipocampal cholinergic nerve terminals are specifically affected by apoE4 and that this effect is age dependent.
Plasmatic retinol‐binding protein 4 and glial fibrillary acidic protein as biomarkers to differentiate ischemic stroke and intracerebral hemorrhage
Authors: Llombart Víctor , García‐Berrocoso Teresa , Bustamante Alejandro , Giralt Dolors , Rodriguez‐Luna David , Muchada Marian , Penalba Anna , Boada Cristina , Hernández‐Guillamon Mar , Montaner Joan
Published: November 2015

A rapid differentiation of acute ischemic stroke and intracerebral hemorrhage (ICH) is essential for an adequate treatment and to promote a better outcome. Our aim was to identify new plasma biomarkers to differentiate stroke subtypes and to combine their diagnostic ability with other biomarkers already described for this clinical indication.

Plasma samples of ischemic stroke patients (36) and ICH patients (10) were screened using a 177 antibodies library, and 11 showed different concentrations among stroke subtypes (p < 0.05), mainly chemokines, growth factors and angiogenic factors. Five proteins were selected for replication in 16 ischemic stroke patients and 16 ICH patients, and retinol‐binding protein 4 (RPB4), apolipoprotein B100 and pigment epithelial–derived factor were replicated (p < 0.05). These proteins, together with glial fibrillary acidic protein (GFAP) and receptor for advanced glycation end product, were tested in 38 ischemic stroke and 28 ICH samples. Finally, RBP4 >61 μg/mL and GFAP <0.07 ng/mL showed a specificity of 100% for both subtypes. Moreover, after multivariate logistic regression analysis, RBP4 >48.75 μg/mL (ORadj: 6.09 (1.3–28.57), p = 0.02) and GFAP <0.07 ng/mL (ORadj: 0.03 (0.003–0.31), p = 0.003) resulted in independent predictors of stroke subtype, improving discrimination by 29% (p < 0.0001). Both biomarkers might be useful as diagnostic biomarkers to differentiate ischemic stroke and ICH.

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A rapid differentiation of ischemic stroke from intracerebral hemorrhage is essential to provide the appropriate treatment. We describe the discovery and subsequent replications of RBP4 and its combination with circulating GFAP as plasmatic biomarkers for hyperacute stroke subtype differentiation. The combination of these biomarkers and others might aid to speed up the discrimination of both stroke subtypes improving the outcome of patients.
Land Registration and Gender Equality in Ethiopia: How State–Society Relations Influence the Enforcement of Institutional Change
Authors: Lavers Tom
Published: November 2015

In recent years, the Ethiopian government has introduced reforms to promote gender equality in land rights, including legislative changes and a land registration programme that requires the names of both husbands and wives on certificates. This paper examines implementation of these reforms through a case‐based approach that links national policy processes to analysis of two village‐level case studies, based on fieldwork conducted in 2009–10. In both cases, government initiatives do appear to have enhanced women's land rights to a certain degree. However, the causal process involved is considerably more complex than the direct link between titling and women's land rights that is assumed in much of the existing literature. The cases suggest that government initiatives are contingent upon state–society relations, and that change to informal institutions and power relations within society can constitute an important complement to land registration.
Enjoyment in nursing – experiences from the clinical milieu
Authors: Wilkes Lesley , Doull Michelle , Ng Chok Harrison , Mashingaidze Gladys
Published: November 2015

Aims and objectives

To present findings from a qualitative study which aimed to explore and describe experiences of enjoyment in nursing.

Background

The topic of ‘enjoying nursing’ is often part of job satisfaction surveys conducted in the workplace and in some studies it has been found to be the prime reason that nurses stay in the workforce. However, there is little research which explores the concept fully.

Design

Qualitative in‐depth interviews.

Method

Semi‐structured individual interviews were conducted with 17 nurses in a local health district in Sydney, Australia. Data from digitally recorded individual interviews were transcribed and the content was analysed for themes relating to aspects of nursing that were enjoyable and others that were not.

Results

The major themes to emerge from the data describing enjoyment of nursing were: doing for others, supporting others and educating others. Themes that identified not enjoying nursing were related to the aggression of others, i.e. patients/clients, families or other staff in the workplace, as well as system issues. System issues referred mainly to the need for support from other nurses and management.

Conclusion

Nurses still enjoy caring for patients and teaching others to care. This is the reason they remain in nursing even though the system and people are not always supportive or encouraging.

Relevance to clinical practice

Managers and educators can use these results to assist them to understand the importance of giving support to nursing staff to optimise their enjoyment of caring for their patients/clients.
Nursing assessment of continuous vital sign surveillance to improve patient safety on the medical/surgical unit
Authors: Watkins Terri , Whisman Lynn , Booker Pamela
Published: November 2015

Aims and objectives

Evaluate continuous vital sign surveillance as a tool to improve patient safety in the medical/surgical unit.

Background

Failure‐to‐rescue is an important measure of hospital quality. Patient deterioration is often preceded by changes in vital signs. However, continuous multi‐parameter vital sign monitoring may decrease patient safety with an abundance of unnecessary alarms.

Design

Prospective observational study at two geographically disperse hospitals in a single hospital system.

Methods

A multi‐parameter vital sign monitoring system was installed in a medical/surgical unit in Utah and one in Alabama providing continuous display of SpO2, heart rate, blood pressure and respiration rate on a central station. Alarm thresholds and time to alert annunciations were set based on prior analysis of the distribution of each vital sign. At the end of 4 weeks, nurses completed a survey on their experience. An average alert per patient, per day was determined retrospectively from the saved vital signs data and knowledge of the alarm settings.

Results

Ninety‐two per cent of the nurses agreed that the number of alarms and alerts were appropriate; 54% strongly agreed. On average, both units experienced 10·8 alarms per patient, per day. One hundred per cent agreed the monitor provided valuable patient data that increased patient safety; 79% strongly agreed.

Conclusions

Continuous, multi‐parameter patient monitoring could be performed on medical/surgical units with a small and appropriate level of alarms. Continuous vital sign assessment may have initiated nursing interventions that prevented failure‐to‐rescue events. Nurses surveyed unanimously agreed that continuous vital sign surveillance will help enhance patient safety.

Relevance to clinical practice

Nursing response to abnormal vital signs is one of the most important levers in patient safety, by providing timely recognition of early clinical deterioration. This occurs through diligent nursing surveillance, involving assessment, interpretation of data, recognition of a problem and meaningful response.
Spillover in the Home: The Effects of Family Conflict on Parents' Behavior
Authors: Sears Meredith S. , Repetti Rena L. , Reynolds Bridget M. , Robles Theodore F. , Krull Jennifer L.
Published: November 2015

Conflict with a spouse or child may generate spillover, defined as short‐term affective changes in parents that affect their behavior with other family members. In a diverse sample of 86 parents, this 56‐day diary study examined daily bidirectional spillover between conflict in the marital or parent–child dyad and parents' irritable, frictional behavior with their child or spouse, respectively. Tests of daily associations between conflict and parent behavior revealed robust spillover effects according to parent as well as spouse and child reports. Parents' daily negative mood and child externalizing behavior contributed to several but not all of these associations. Daily spillover findings were largely unaffected by parents' neuroticism, suggesting that parents' day‐to‐day fluctuations in negative mood, not average levels of negative affectivity, promoted spillover. Significant direct effects of conflict on parent behavior even when controlling for negative mood, however, implicate additional cognitive or social processes as contributors to conflict spillover in families.
The Porphyromonas gingivalis O antigen is required for inhibition of apoptosis in gingival epithelial cells following bacterial infection
Authors: Soto C. , Bugueño I. , Hoare A. , Gonzalez S. , Venegas D. , Salinas D. , Melgar‐Rodríguez S. , Vernal R. , Gamonal J. , Quest A. F. G. , Pérez‐Donoso J. M. , Bravo D.
Published: November 2015

Background and Objective

Porphyromonas gingivalis infection induces apoptosis inhibition in gingival epithelial cells; however, it is not fully understood which bacterial effectors are involved in this process. The aim of this study is to evaluate whether the P. gingivalis lipopolysaccharide (LPS), specifically the O‐antigen region, affects adherence, invasion, viability and apoptosis of gingival epithelial cells.

Material and Methods

Gingival epithelial cells (OKF6/TERT2 line) were infected by different freshly prepared P. gingivalis clinical isolates, obtained from subjects with chronic periodontitis (CP3 and CP4) and healthy individuals (H1 and H3). Periodontitis and healthy isolates show differences in O‐antigen production, as healthy isolates lack the O‐antigen region. In addition, cells were infected by a site‐specific mutant lacking the O‐antigen portion. After 24 h postinfection, cell proliferation, viability and apoptosis were evaluated by Trypan blue, MTS and annexin V assays, respectively. Bacterial invasion, adhesion and proliferation were measured by gentamicin/metronidazole protection assays. Finally, toll‐like receptor (TLR)2 and TLR4 mRNA expression was evaluated by quantitative reverse transcription–polymerase chain reaction. Statistical analysis was performed using ANOVA, Tukey's or Dunnett's tests (p < 0.05).

Results

At 24 h postinfection, strains lacking the O‐antigen region (healthy isolates and O‐antigen ligase‐deficient strain) were unable to increase proliferation and viability, or decrease apoptosis as compared with strains producing intact LPS (periodontitis isolates and reference strain). However, the presence of the O‐antigen neither contributed to changes in the ability of the bacteria to adhere to or invade cells, nor to intracellular survival. The presence of O‐antigen also increased the expression of TLR4 (nearly sixfold), which correlated with inhibition of apoptosis.

Conclusion

The O‐antigen region of P. gingivalis LPS is required to increase gingival epithelial cell viability upon infection by bacteria and this increase is attributable to a reduction in apoptosis. Moreover, although bacterial internalization is required, the effects observed are not due to alterations in P. gingivalis adherence, invasion or intracellular survival. Interestingly, inhibition of apoptosis correlates with increased TLR4 expression, suggesting a role for TLR4 in this process.
14,15‐epoxyeicosatrienoic acid promotes production of brain derived neurotrophic factor from astrocytes and exerts neuroprotective effects during ischaemic injury
Authors: Yuan L. , Liu J. , Dong R. , Zhu J. , Tao C. , Zheng R. , Zhu S.
Published: November 2015

Aims

14,15‐Epoxyeicosatrienoic acid (14,15‐EET) is abundantly expressed in brain and exerts protective effects against ischaemia. 14,15‐EET is hydrolysed by soluble epoxide hydrolase (sEH). sEH−/− mice show a higher level of 14,15‐EET in the brain. Astrocytes play a pivotal role in neuronal survival under ischaemic conditions. However, it is unclear whether the neuroprotective effect of 14,15‐EET is associated with astrocytes.

Methods

A mouse model of focal cerebral ischaemia was induced by middle cerebral artery occlusion. Oxygen–glucose deprivation/reoxygenation (OGD/R) was performed on cultured murine astrocytes, neurons and a human cell line. Cell viabilities were measured by 3‐(4, 5‐dimethyl‐2‐thiazolyl)‐2, 5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay. The mRNA expressions were quantified by real‐time PCR. Brain derived neurotrophic factor (BDNF) concentration was measured by ELISA. Protein expressions were quantified by Western blotting. BDNF and peroxisome proliferators‐activated receptor gamma (PPAR‐γ) expressions were analysed by confocal microscopy.

Results

Decreased infarct volumes, elevated BDNF expression and increased numbers of BDNF/GFAP Glial Fibrillary Acidic Protein double‐positive cells were observed in the ischaemic penumbra of sEH−/− mice. The decreased infarct volumes of sEH−/− mice were diminished by intracerebroventricular injection of a blocker of BDNF receptor. 14,15‐EET increases BDNF expression and cell viability of murine astrocytes and U251 cells by BDNF‐TrkB Tyrosine receptor kinase‐B‐extracellular signal‐regulated kinase 1/2 signalling during OGD/R. 14,15‐EET protects neurons from OGD/R by stimulating the production of astrocyte‐derived BDNF. 14,15‐EET stimulates the production of astrocyte‐derived BDNF through PPAR‐γ/p‐cAMP‐response element binding protein signal pathways.

Conclusions

Our study demonstrates the importance of 14,15‐EET‐mediated production of astrocyte‐derived BDNF for enhancing viability of astrocytes and protecting neurons from the ischaemic injury and provides insights into the mechanism by which 14,15‐EET is involved in neuroprotection.
Cortical Lewy bodies and Aβ burden are associated with prevalence and timing of dementia in Lewy body diseases
Authors: Ruffmann C. , Calboli F. C. F. , Bravi I. , Gveric D. , Curry L. K. , de Smith A. , Pavlou S. , Buxton J. L. , Blakemore A. I. F. , Takousis P. , Molloy S. , Piccini P. , Dexter D. T. , Roncaroli F. , Gentleman S. M. , Middleton L. T.
Published: November 2015

Aims

Our main objective was to determine the neuropathological correlates of dementia in patients with Lewy body disease (LBD). Furthermore, we used data derived from clinical, neuropathological and genetic studies to investigate boundary issues between Dementia with Lewy bodies (DLB) and Parkinson's disease with (PDD) and without (PDND) dementia.

Methods

One hundred and twenty‐one cases with a neuropathological diagnosis of LBD and clinical information on dementia status were included in the analysis (55 PDD, 17 DLB and 49 PDND). We carried out topographical and semi‐quantitative assessment of Lewy bodies (LB), Aβ plaques and tau‐positive neuropil threads (NT). The APOE genotype and MAPT haplotype status were also determined.

Results

The cortical LB (CLB) burden was the only independent predictor of dementia (OR: 4.12, P < 0.001). The total cortical Aβ plaque burden was an independent predictor of a shorter latency to dementia from onset of motor signs (P = 0.001). DLB cases had a higher LB burden in the parietal and temporal cortex, compared to PDD. Carrying at least one APOE ϵ4 allele was associated with a higher cortical LB burden (P = 0.02), particularly in the neocortical frontal, parietal and temporal regions.

Conclusions

High CLB burden is a key neuropathological substrate of dementia in LBD. Elevated cortical LB pathology and Aβ plaque deposition are both correlated with a faster progression to dementia. The higher CLB load in the temporal and parietal regions, which seems to be a distinguishing feature of DLB, may account for the shorter latency to dementia and could be mediated by the APOE ϵ4 allele.
Ethnonationalism and attitudes towards gay and lesbian rights in Northern Ireland
Authors: Hayes Bernadette C. , Nagle John
Published: November 2015

Disputes over gay and lesbian rights occupy a central place on both national and international agendas in recent years. This is also the case in societies emerging from chronic ethnonational conflict where debates over gay and lesbian rights vs. ethnic‐based rights predominate. While much scholarly work focuses on the influence of socio‐demographic factors in determining attitudes toward gay and lesbian rights in postconflict societies, to date, the role of political influences, such as ethnonationalism, is noticeably under‐researched. It is with this omission in mind that this paper focuses on the influence of ethnonationalism, or congruency in religious, national and communal identity, on attitudes towards gay and lesbian rights issues. Using nationally representative data from Northern Ireland, the results suggest that while ethnonationalism is a key predictor of attitudes among Protestants, it is socio‐demographic factors, such as gender, age and educational attainment, that are the primary determinants of Catholic views.
Altered brain responses in subjects with irritable bowel syndrome during cued and uncued pain expectation
Authors: Hong J.‐Y. , Naliboff B. , Labus J. S. , Gupta A. , Kilpatrick L. A. , Ashe‐McNalley C. , Stains J. , Heendeniya N. , Smith S. R. , Tillisch K. , Mayer E. A.
Published: November 2015

Background

A majority of the subjects with irritable bowel syndrome (IBS) show increased behavioral and brain responses to expected and delivered aversive visceral stimuli during controlled rectal balloon distension, and during palpation of the sigmoid colon. We aimed to determine if altered brain responses to cued and uncued pain expectation are also seen in the context of a noxious somatic pain stimulus applied to the same dermatome as the sigmoid colon.

Methods

A task‐dependent functional magnetic resonance imaging technique was used to investigate the brain activity of 37 healthy controls (18 females) and 37 IBS subjects (21 females) during: (i) a cued expectation of an electric shock to the abdomen vs a cued safe condition; and (ii) an uncued cross‐hair condition in which the threat is primarily based on context vs a cued safe condition.

Key Results

Regions within the salience, attention, default mode, and emotional arousal networks were more activated by the cued abdominal threat condition and the uncued condition than in the cued safe condition. During the uncued condition contrasted to the cued safe condition, IBS subjects (compared to healthy control subjects) showed greater brain activations in the affective (amygdala, anterior insula) and attentional (middle frontal gyrus) regions, and in the thalamus and precuneus. These disease‐related differences were primarily seen in female subjects.

Conclusions & Inferences

The observed greater engagement of cognitive and emotional brain networks in IBS subjects during contextual threat may reflect the propensity of IBS subjects to overestimate the likelihood and severity of future abdominal pain.
Landscape genetics, adaptive diversity and population structure in Phaseolus vulgaris
Authors: Rodriguez Monica , Rau Domenico , Bitocchi Elena , Bellucci Elisa , Biagetti Eleonora , Carboni Andrea , Gepts Paul , Nanni Laura , Papa Roberto , Attene Giovanna
Published: November 2015

Here we studied the organization of genetic variation of the common bean (Phaseolus vulgaris) in its centres of domestication.

We used 131 single nucleotide polymorphisms to investigate 417 wild common bean accessions and a representative sample of 160 domesticated genotypes, including Mesoamerican and Andean genotypes, for a total of 577 accessions.

By analysing the genetic spatial patterns of the wild common bean, we documented the existence of several genetic groups and the occurrence of variable degrees of diversity in Mesoamerica and the Andes. Moreover, using a landscape genetics approach, we demonstrated that both demographic processes and selection for adaptation were responsible for the observed genetic structure.

We showed that the study of correlations between markers and ecological variables at a continental scale can help in identifying local adaptation genes. We also located putative areas of common bean domestication in Mesoamerica, in the Oaxaca Valley, and the Andes, in southern Bolivia‐northern Argentina. These observations are of paramount importance for the conservation and exploitation of the genetic diversity preserved within this species and other plant genetic resources.
Preface Writers are Consistent
Authors: Clarke Roger
Published: November 2015

The preface paradox does not show that it can be rational to have inconsistent beliefs, because preface writers do not have inconsistent beliefs. I argue, first, that a fully satisfactory solution to the preface paradox would have it that the preface writer's beliefs are consistent. The case here is on basic intuitive grounds, not the consequence of a theory of rationality or of belief. Second, I point out that there is an independently motivated theory of belief – sensitivism – which allows such a solution. I sketch a sensitivist account of the preface writer's (consistent) doxastic state.
Prenatal Triptan Exposure and Internalising and Externalising Behaviour Problems in 3‐Year‐Old Children: Results from the Norwegian Mother and Child Cohort Study
Authors: Wood Mollie E. , Lapane Kate , Frazier Jean A. , Ystrom Eivind , Mick Eric O. , Nordeng Hedvig
Published: November 2015

Background

Triptans are commonly prescribed for migraine, a pain condition that is highly prevalent in women of childbearing age. No prior studies have investigated associations between exposure to triptans during fetal life and risk of externalising and internalising behaviours in children.

Methods

This study was set in the Norwegian Mother and Child Cohort study, a prospective birth cohort. A total of 41 173 live, singleton births without major malformations present at 36‐month post‐partum follow‐up were included in this study; 396 used a triptan during pregnancy, 798 used a triptan prior to pregnancy only, 3291 reported migraine without triptan use, and 36 688 reported no history of migraine or triptan use. Marginal structural models were used to analyse the association between timing of triptan exposure and neurodevelopmental outcome.

Results

Children exposed to triptans during pregnancy had a 1.39‐fold increased risk of externalising behaviours compared with those whose mothers used triptans prior to pregnancy only (95% CI 0.97, 1.97), a 1.36‐fold increased risk compared with the unmedicated migraine group (95% CI 1.02, 1.81), and a 1.41‐fold increased risk compared with the population comparison group (95% CI 1.08, 1.85). The greatest risk was associated with first trimester exposure (RR 1.77, 95% CI 0.98, 3.14). Risk differences were small, ranging from 3–6%.

Conclusions

This study found an increased risk of clinically relevant externalising behaviours in children with prenatal exposure to triptans, and this risk was highest for first trimester exposure. Absolute risks were small, and the results may be due to confounding by underlying migraine severity.
Gender differences in scalp hair growth rates are maintained but reduced in pattern hair loss compared to controls
Authors: Van Neste D. J. J. , Rushton D. H.
Published: November 2015

Background

Hair loss is related to follicular density, programmed regrowth and hair productivity.

Objective

The dissatisfaction with hair growth in patients experiencing hair loss might be due to slower linear hair growth rate (LHGR).

Methods

LHGR and hair diameter was evaluated in Caucasian controls and patients with patterned hair loss employing the validated non‐invasive, contrast‐enhanced‐phototrichogram with exogen collection.

Results

We evaluated 59,765 anagen hairs (controls 24,609, patients 35,156) and found thinner hairs grew slower than thicker hairs. LHGR in normal women was generally higher than in normal men. LHGR correlates with hair diameter (P < 0.006) and global thinning is associated with slower growth rates. Compared with hair of equal thickness in controls, subjects affected with patterned hair loss showed reduced hair growth rates, an observation found in both male and female patients. Males with pattern hair loss showed further reduction in growth rates as clinical severity worsened. However, sample size limitations prevented statistical evaluation of LHGR in severely affected females.

Limitations

Caucasian ethnicity.

Conclusion

In pattern hair loss, LHGR significantly contributes to the apparent decrease in hair volume in affected areas. In early onset, LHRG might have a prognostic value in females but not in males.
A Dynamic Analysis of Exchange Rate Exposure: The impact of China's Renminbi
Authors: Chen Pei‐Fen , Lee Chien‐Chiang , Lee Chi‐Chuan , Huang Jing‐Xuan
Published: November 2015

This study examines the impacts of unexpected exchange rate movements of Chinese renminbi (CNY/USD) on stock returns of Standard & Poor's 500 corporations. To gain better insight into the long‐standing exposure puzzle concerning the divergence between theoretical and empirical investigation and the critical issue regarding the determinants of exposure, the time variation and asymmetry property associated with foreign exchange exposure are further taking into account. We also broaden the scope of analysis to investigate unexpected risk exposure at 10 economic sectors in compliance with Global Industry Classification Standard. Unlike those from the static analysis or dynamic ones with the ordinary least squares model, the empirical findings provide additional concrete evidence that unexpected exchange rate exposure varies substantially across time and market circumstances when using the quantile regression with a rolling method. Furthermore, our dynamic analysis not only supports the existence of industrial effects across different economic sectors, but also provides strong evidence that financial factors, such as size, debt ratio and book to market ratio, have a significant impact on exposure.
ABO‐immune complex formation and impact on platelet function, red cell structural integrity and haemostasis: an in vitro model of ABO non‐identical transfusion
Authors: Zaffuto B. J. , Conley G. W. , Connolly G. C. , Henrichs K. F. , Francis C. W. , Heal J. M. , Blumberg N. , Refaai M. A.
Published: November 2015

Background

Transfusion of ABO non‐identical platelets has been associated with fatal haemolytic reactions, increased red cell transfusion needs and other adverse effects, but the practice of ABO matching in platelet transfusion is controversial. Immune complexes can be formed from the anti‐A and/or anti‐B antibodies and ABO soluble antigen(s) present in donor and recipient plasma after ABO non‐identical transfusions. We hypothesized that these immune complexes affect recipient red cell structural integrity, platelet function and haemostasis.

Study Design and Methods

Haemolysis, platelet function and haemostatic function were assessed before and after incubation of recipient red cells, platelets and whole blood with normal saline controls, ABO‐identical plasma controls or in vitro‐generated ABO‐immune complexes.

Results

ABO‐immune complexes caused significantly increased haemolysis (P < 0·001), inhibition of platelet function (P = 0·001) and disruption of clot formation kinetics (P < 0·005) in both group A and O recipient samples.

Conclusions

Substantial changes in platelet function, red cell integrity and haemostasis occur after in vitro exposure to immune complexes. These in vitro findings may explain, in part, previously observed associations of ABO non‐identical platelet transfusions with adverse effects including increased red cell transfusion needs, organ failure and mortality.
Genetic variations of CD36 and low platelet CD36 expression – a risk factor for lipemic plasma donation in Taiwanese apheresis donors
Authors: Lo S.‐C. , Lin K.‐H. , Hsieh H.‐H. , Lin D.‐T. , Hu C.‐Y.
Published: November 2015

Background

New CD36 mutations are constantly being identified, although no study has specifically targeted a Taiwanese population. CD36 deficiency can result in dyslipid state and slow clearance of chylomicron. This could be linked to more frequent lipemic donations.

Study Design and Methods

We used flow cytometric methods to study the CD36 deficiency in 640 regular volunteer platelet apheresis donors from Taipei blood centre. The coding exons of CD36 gene were sequenced in CD36‐deficient individuals, and the allele frequencies of CD36 variants were determined in the larger population by mutation‐specific PCR and oligonucleotide hybridization. Visual inspection of lipemic plasma was routinely performed on samples taken before commencement of apheresis. Individuals found to have lipemic plasma are deferred until next donation. We investigated the link between positive lipemic deferral record and low platelet CD36 expression status.

Results

We found four donors (0·6%) with type I CD36 deficiency (both platelets and monocytes CD36null) and six (1·0%) with type II CD36 deficiency (PLT: CD36null, monocyte: CD36low). Six CD36 genetic variants were identified, two of them were novel, all but one are found exclusively in CD36null and CD36low expressors. Subjects with CD36 genetic variants also displayed deficient or reduced CD36 on monocytes. Donors with null or low PLT CD36 expression were more likely to have a lipemic deferral record than control subjects with normal PLT CD36 expression (X2 = 27·36, odds ratio = 2·6, 95% conference interval: 1·8–3·8, P < 0·0001).

Conclusion

Through this study, we established a donor registry to supply CD36‐negative platelets for patients in need.
No evidence of asymptomatic variant CJD infection in immunodeficiency patients treated with UK‐sourced immunoglobulin
Authors: Helbert M. R. , Bangs C. , Bishop M. , Molesworth A. , Ironside J.
Published: November 2015

Surveillance of 75 immunodeficiency patients exposed to UK‐sourced immunoglobulin, including batches derived from donors who went on to develop vCJD, has not detected any clinical cases of vCJD, or of asymptomatic infection in 15 patients with available tissue samples of sufficient quality for testing.
Two compact incremental prime sieves
Authors: Sorenson Jonathan P.
Published: November 2015

A prime sieve is an algorithm that finds the primes up to a bound $n$. We say that a prime sieve is incremental, if it can quickly determine if $n+1$ is prime after having found all primes up to $n$. We say a sieve is compact if it uses roughly $\sqrt{n}$ space or less. In this paper, we present two new results.

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We describe the rolling sieve, a practical, incremental prime sieve that takes $O(n\log \log n)$ time and $O(\sqrt{n}\log n)$ bits of space.

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We also show how to modify the sieve of Atkin and Bernstein from 2004 to obtain a sieve that is simultaneously sublinear, compact, and incremental.

The second result solves an open problem given by Paul Pritchard in 1994.
Three-dimensional localization of polymer nanoparticles in cells using ToF-SIMS
Authors: Graham Daniel J. , Wilson John T. , Lai James J. , Stayton Patrick S. , Castner David G.
Published: November 2015

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) three-dimensional (3D) depth profiling and a novel background subtraction method were used to localize polymeric nanoparticles within cells. Results showed that ToF-SIMS 3D depth profiling is capable of localizing polymer nanoparticles within HeLa cells. ToF-SIMS results compared well with optical images of cells incubated with fluorescently labeled polymer nanoparticles, with both imaging techniques demonstrating clustering of nanoparticles in punctate regions consistent with endosomal localization as anticipated based on the nanoparticle design.
Dynamic acousto-elastic testing applied to a highly dispersive medium and evidence of shell buckling of lipid-coated gas microbubbles
Authors: Renaud Guillaume , Bosch Johan G. , van der Steen Antonius F. W. , de Jong Nico
Published: November 2015

Dynamic acousto-elastic testing is applied to a mixture of lipid-coated microbubbles in water. A dynamic change of ambient pressure is produced by a 16 kHz pressure wave having a peak pressure amplitude of 28 kPa. The induced changes of phase velocity and attenuation are captured by a sequence of short ultrasound pulses with a center frequency of 4 MHz. As a consequence of the dispersion brought about by the resonance of microbubbles at a frequency close to 2 MHz, time-domain approaches like the cross-correlation method are shown to be unsuited to determine the variation in ultrasound wavespeed. A frequency-domain analysis shows that the acousto-elastic effect (first order pressure derivative of ultrasound phase velocity) depends on the ultrasound frequency. The acousto-elastic effect tends to that measured in water for an ultrasound frequency above the resonance frequency of microbubbles, while it is two orders of magnitude larger for an ultrasound frequency close to or below the resonance frequency of microbubbles. Besides the large magnitude of the acousto-elastic effect observed for an ultrasound frequency below the resonance frequency of microbubbles, the first order pressure derivative of ultrasound phase velocity is negative. This supports the occurrence of shell buckling of lipid-coated microbubbles induced by the 16 kHz pressure wave.
Extensional-wave stopband broadening across the joint of pipes of different thickness
Authors: Su Yuanda , Tang Xiaoming , Liu Yukai , Xu Song , Zhuang Chunxi
Published: November 2015

The stopband of pipe extensional waves is an interesting natural phenomenon. This study demonstrates an important extension of this phenomenon. That is, the stopband can be effectively broadened by transmitting the waves across the joint of pipes of different thickness. The theoretical and experimental results reveal the detailed process of stopband forming along the pipe and the band broadening across the pipe joint. The result can be utilized to provide a method for logging while drilling acoustic isolation design.
Force–Velocity Relationship of Upper Body Muscles: Traditional Versus Ballistic Bench Press
Authors: García-Ramos Amador , Jaric Slobodan , Padial Paulino , Feriche Belén
Published: November 2015

This study aimed to (1) evaluate the linearity of the force–velocity relationship, as well as the reliability of maximum force (F0), maximum velocity (V0), slope (a), and maximum power (P0); (2) compare these parameters between the traditional and ballistic bench press (BP); and (3) determine the correlation of F0 with the directly measured BP 1-repetition maximum (1RM). Thirty-two men randomly performed 2 sessions of traditional BP and 2 sessions of ballistic BP during 2 consecutive weeks. Both the maximum and mean values of force and velocity were recorded when loaded by 20–70% of 1RM. All force–velocity relationships were strongly linear (r > .99). While F0 and P0 were highly reliable (ICC: 0.91–0.96, CV: 3.8–5.1%), lower reliability was observed for V0 and a (ICC: 0.49–0.81, CV: 6.6–11.8%). Trivial differences between exercises were found for F0 (ES: < 0.2), however the a was higher for the traditional BP (ES: 0.68–0.94), and V0 (ES: 1.04–1.48) and P0 (ES: 0.65–0.72) for the ballistic BP. The F0 strongly correlated with BP 1RM (r: 0.915–0.938). The force–velocity relationship is useful to assess the upper body maximal capabilities to generate force, velocity, and power.
The Influence of Risk Perceptions and Efficacy Beliefs on Leisure-Time Physical Activity During Pregnancy
Authors: Connolly Christopher P. , Pivarnik James M. , Mudd Lanay M. , Feltz Deborah L. , Schlaff Rebecca A. , Lewis Mark G. , Silver Robert M. , Lapinski Maria K.
Published: November 2015

Background:

Pregnancy risk perceptions and physical activity efficacy beliefs may facilitate or impede pregnancy leisure-time physical activity (LTPA). We examined the separate and joint influence of these variables on LTPA behavior among pregnant women.

Methods:

Pregnant women (n = 302) completed a survey containing questions on LTPA efficacy beliefs and behavior, as well as pregnancy risk perceptions with respect to the health of the unborn baby. As stipulated by the Risk Perception Attitude (RPA) Framework, 4 attitudinal groups were created: Responsive (High Risk+High Efficacy), Proactive (Low+High), Avoidant (High+Low), and Indifferent (Low+Low). Moderate LTPA and vigorous LTPA were dichotomized for study analyses.

Results:

A total of 82 women (27.2%) met the moderate physical activity guideline and 90 women (30.1%) performed any vigorous LTPA. Responsive and proactive pregnant women (those with high efficacy) were most likely to meet the moderate guideline and participate in vigorous LTPA. Hierarchical logistic regression did not reveal an interactive effect of pregnancy risk perceptions and LTPA efficacy beliefs for meeting the moderate guideline (OR = 0.94, 95% CI = 0.66–1.36) or any vigorous LTPA participation (OR = 1.41, 95% CI = 0.86–2.29).

Conclusions:

LTPA efficacy beliefs appear important in facilitating greater levels of pregnancy LTPA. Significant interactive effects between pregnancy risk perceptions and LTPA efficacy beliefs were not found.
Science Signaling
Podcast for 3 November 2015: Ligands control GPCR voltage sensitivity
Authors: Bünemann Moritz , Kolb Peter , VanHook Annalisa M.
Published: November 2015

How a ligand binds to a G protein–coupled receptor determines whether changes in membrane potential enhance or attenuate signaling.
Viral oncogenes remove the host's STING
Authors: Mueller Kristen L.
Published: November 2015

Oncoproteins encoded by DNA tumor viruses subvert antiviral immunity by binding to a key component of an intracellular DNA-sensing pathway.
Pyroptosis mediator identified
Authors: Gough Nancy R.
Published: November 2015

Caspase-mediated cleavage of gasdermin D triggers death by pyroptosis.
Immunotherapy: Reduce, reuse, recycle
Authors: Colmone Angela
Published: November 2015

IL-2Rα sustains IL-2 immunotherapy response after cytokine withdrawal by recycling and cell surface reservoirs.
Treatment Outcomes with Fluoroquinolone-Containing Regimens for Isoniazid-Resistant Pulmonary Tuberculosis
Authors: Lee Hyun , Jeong Byeong-Ho , Park Hye Yun , Jeon Kyeongman , Huh Hee Jae , Lee Nam Yong , Koh Won-Jung
Published: November 2015

Resistance to isoniazid (INH) is the most common form of drug resistance in pulmonary tuberculosis (TB). Although fluoroquinolones (FQs) are recommended to strengthen treatment regimens for INH-resistant pulmonary TB, few studies have evaluated the clinical efficacy of FQ-containing regimens in patients with INH-resistant pulmonary TB. A retrospective cohort study of 140 patients with INH-resistant pulmonary TB was performed between 2005 and 2012. We evaluated whether FQ-containing regimens yielded improved treatment outcomes for patients with INH-resistant pulmonary TB. Overall, favorable outcomes were achieved in 128 (91.4%) patients. Unfavorable outcomes occurred in 12 patients (8.6%), including 7 with treatment failure (5.0%) and 5 with relapse after initial treatment completion (3.6%). FQs, such as levofloxacin and moxifloxacin, were given to 75 (53.6%) patients. Favorable treatment outcomes were more frequent for patients who received FQs (97.3% [73/75 patients]) than for those who did not receive FQs (84.6% [55/65 patients]) (
P
= 0.007). Patients who did not receive FQs were more likely to develop treatment failure (9.2% [6/65 patients] versus 1.3% [1/75 patients]) (
P
= 0.049) than patients who received FQs. The adjusted proportion of unfavorable outcomes was significantly higher among patients who did not receive FQs (8.8%; 95% confidence interval [CI], 3.3 to 21.5%) than among those who did receive FQs (1.5%; 95% CI, 0.3 to 7.7%) (
P
= 0.037). These results suggest that the addition of FQs can improve treatment outcomes for patients with INH-resistant pulmonary TB.
Complete Sequences of IncU Plasmids Harboring Quinolone Resistance Genes
qnrS2
and
aac(6
′
)-Ib-cr
in Aeromonas spp. from Ornamental Fish
Authors: Dobiasova Hana , Videnska Petra , Dolejska Monika
Published: November 2015

The nucleotide sequences of three IncU plasmids from
Aeromonas
spp. isolated from ornamental fish are described. They had a typical IncU backbone for plasmid replication and maintenance functions, but conjugative transfer modules were disrupted. The gene
qnrS2
was inserted into
mpR
as a mobile insertion cassette. Novel Tn
3
family transposons carrying putative toxin-antitoxin and plasmid stability genes were identified. The study demonstrates high plasticity of IncU plasmids from aquatic environments.
Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis
Authors: Zhao Ying Jiao , Khoo Ai Leng , Tan Gloria , Teng Monica , Tee Caroline , Tan Ban Hock , Ong Benjamin , Lim Boon Peng , Chai Louis Yi Ann
Published: November 2015

Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care setting.
Characterization of a
cfr
-Carrying Plasmid from Porcine Escherichia coli That Closely Resembles Plasmid pEA3 from the Plant Pathogen Erwinia amylovora
Authors: Zhang Rongmin , Sun Bin , Wang Yang , Lei Lei , Schwarz Stefan , Wu Congming
Published: November 2015

The multiresistance gene
cfr
was found in two porcine
Escherichia coli
isolates, one harboring it on the conjugative 33,885-bp plasmid pFSEC-01, the other harboring it in the chromosomal DNA. Sequence analysis of pFSEC-01 revealed that a 6,769-bp fragment containing the
cfr
gene bracketed by two IS
26
elements was inserted into a plasmid closely related to pEA3 from the plant pathogen
Erwinia amylovora
, suggesting that pFSEC-01 may be transferred between different bacterial genera of both animal and plant origin.
Expression of Plasmodium vivax
crt-o
Is Related to Parasite Stage but Not
Ex Vivo
Chloroquine Susceptibility
Authors: Pava Zuleima , Handayuni Irene , Wirjanata Grennady , To Sheren , Trianty Leily , Noviyanti Rintis , Poespoprodjo Jeanne Rini , Auburn Sarah , Price Ric N. , Marfurt Jutta
Published: November 2015

Chloroquine (CQ)-resistant
Plasmodium vivax
is present in most countries where
P. vivax
infection is endemic, but the underlying molecular mechanisms responsible remain unknown. Increased expression of
P. vivax
crt-o
(
pvcrt-o
) has been correlated with
in vivo
CQ resistance in an area with low-grade resistance. We assessed
pvcrt-o
expression in isolates from Papua (Indonesia), where
P. vivax
is highly CQ resistant.
Ex vivo
drug susceptibilities to CQ, amodiaquine, piperaquine, mefloquine, and artesunate were determined using a modified schizont maturation assay. Expression levels of
pvcrt-o
were measured using a novel real-time quantitative reverse transcription-PCR method. Large variations in
pvcrt-o
expression were observed across the 51 isolates evaluated, with the fold change in expression level ranging from 0.01 to 59 relative to that seen with the
P. vivax
β-tubulin gene and from 0.01 to 24 relative to that seen with the
P. vivax
aldolase gene. Expression was significantly higher in isolates with the majority of parasites at the ring stage of development (median fold change, 1.7) compared to those at the trophozoite stage (median fold change, 0.5;
P
< 0.001). Twenty-nine isolates fulfilled the criteria for
ex vivo
drug susceptibility testing and showed high variability in CQ responses (median, 107.9 [range, 6.5 to 345.7] nM). After controlling for the parasite stage, we found that
pvcrt-o
expression levels did not correlate with the
ex vivo
response to CQ or with that to any of the other antimalarials tested. Our results highlight the importance of development-stage composition for measuring
pvcrt-o
expression and suggest that
pvcrt-o
transcription is not a primary determinant of
ex vivo
drug susceptibility. A comprehensive transcriptomic approach is warranted for an in-depth investigation of the role of gene expression levels and
P. vivax
drug resistance.