bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical characterization of milk oligosaccharides of the common wombat (Vombatus ursinus)
Authors: Hirayama Kentaro , Taufik Epi , Kikuchi Megumi , Nakamura Tadashi , Fukuda Kenji , Saito Tadao , Newgrain Keith , Green Brian , Messer Michael , Urashima Tadasu
Published: November 2015

Previous structural characterizations of marsupial milk oligosaccharides have been performed in the tammar wallaby, red kangaroo, koala, common brushtail possum and the eastern quoll. To clarify the homology and heterogeneity of milk oligosaccharides among marsupial species, which could provide information on their evolution, the oligosaccharides of wombat milk carbohydrate were characterized in this study. Neutral and acidic oligosaccharides were isolated from the carbohydrate fractions of two samples of milk of the common wombat and characterized by 1H‐nuclear magnetic resonance spectroscopy. The structures of six neutral saccharides were found to be Gal(β1‐4)Glc (lactose), Gal(β1‐3)Gal(β1‐4)Glc (3'‐galactosyllactose), Gal(β1‐3)Gal(β1‐3)Gal(β1‐4)Glc (3',3”‐digalactosyllactose), Gal(β1‐3)Gal(β1‐3)Gal(β1‐3)Gal(β1‐4)Glc, Gal(β1‐3)Gal(β1‐3)[Gal(β1‐4)GlcNAc(β1‐6)]Gal(β1‐4)Glc (galactosyl lacto‐N‐novopentaose I) and Gal(β1‐3)[Gal(β1‐4)GlcNAc(β1‐6)]Gal(β1‐3)[Gal(β1‐4)GlcNAc(β1‐6)]Gal(β1‐4)Glc (lacto‐N‐novooctaose), while those of six acidic saccharides were Neu5Ac(α2‐3)Gal(β1‐3)Gal(β1‐4)Glc. (sialyl 3'‐galactosyllactose), Neu5Ac(α2‐3)Gal(β1‐3)Gal(β1‐3)Gal(β1‐4)Glc (sialyl 3',3”‐digalactosyllactose), Neu5Ac(α2‐3)Gal(β1‐3)[Gal(β1‐4)GlcNAc(β1‐6)]Gal(β1‐4)Glc (sialyl lacto‐N‐novopentaose a), Gal(β1‐3)[Neu5Ac(α2‐3)Gal(β1‐4)GlcNAc(β1‐6)]Gal(β1‐4)Glc (sialyl lacto‐N‐novopentaose c), Neu5Ac(α2‐3)Gal(β1‐3)Gal(β1‐3)Gal(β1‐3)Gal(β1‐4)Glc,, Neu5Ac(α2‐3)Gal(β1‐3)Gal(β1‐3)[Gal(β1‐4)GlcNAc(β1‐6)]Gal(β1‐4)Glc and Gal(β1‐3)Gal(β1‐3)[Neu5Ac(α2‐3)Gal(β1‐4)GlcNAc(β1‐6)]Gal(β1‐4)Glc. In addition, small amounts of sulfated oligosaccharides but no oligosaccharides containing Neu5Gc or α(2–6) linked Neu5Ac were detected.
Exenatide acutely increases heart rate in parallel with augmented sympathetic nervous system activation in healthy overweight males
Authors: Smits Mark M. , Muskiet Marcel H. A. , Tonneijck Lennart , Hoekstra Trynke , Kramer Mark H. H. , Diamant Michaela , van Raalte Daniël H.
Published: November 2015

Aim

Clinical use of glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) is consistently associated with heart rate (HR) acceleration in type 2 diabetes patients. We explored the mechanisms underlying this potential safety concern.

Methods

Ten healthy overweight males (aged 20–27 years) were examined in an open label, crossover study. Automated oscillometric blood pressure measurements and finger photoplethysmography were performed throughout intravenous administration of placebo (saline 0.9%), exenatide (targeting therapeutic concentrations) and a combination of exenatide and the nitric oxide synthase inhibitor L‐NG‐monomethyl arginine (L‐NMMA). Sympathetic nervous system (SNS) activity was measured by heart rate variability and rate‐pressure product.

Results

Exenatide increased HR by a mean maximum of 6.8 (95% CI 1.7, 11.9) beats min–1 (P < 0.05), systolic blood pressure (SBP) by 9.8 (95% CI 3.5, 16.1) mmHg (P < 0.01) and markers of SNS activity (P < 0.05). No changes in total peripheral resistance were observed. Increases in HR, SBP and sympathetic activity were preserved during concomitant L‐NMMA infusion.

Conclusions

Our data argue against exenatide‐induced reflex tachycardia as a response to vasodilation and rather suggest the involvement of SNS activation in humans.
Inter‐Role Conflict, Role Strain and Role Play in Chile's Relationship with Brazil
Authors: WEHNER LESLIE E.
Published: November 2015

This article assesses the relationship between Brazil and Chile, focusing on the fields of economic and security cooperation from Chile's perspective. Chile plays a number of different roles, the most salient of which is ‘global trader’. This role stretches beyond Brazil's expectations, but it converges with the social demands of Mexico and the United States as well as with the cues of the global market. Such a salient role – alongside that of mediator, bridge builder, and partner of Argentina in security cooperation issues – influences Chile's patterns of cooperation with and distance from Brazil as the regional power in South America.
Influence of race/ethnicity on cardiovascular risk factors in polycystic ovary syndrome, the Dallas Heart Study
Authors: Chang Alice Y. , Oshiro June , Ayers Colby , Auchus Richard J.
Published: November 2015

Objective

Polycystic ovarian syndrome (PCOS) is estimated to affect up to 20% of women. PCOS is associated with insulin resistance and cardiovascular (CV) risk factors. We aimed to evaluate the impact of race/ethnicity on the prevalence of CV risk factors and subclinical predictors of CV events.

Design

Cross‐sectional analysis of data collected by the Dallas Heart Study, an urban, population‐based cohort oversampled for blacks.

Patients

A previously described cohort of women with PCOS and control subjects of the same racial/ethnic group, matched for age and body mass index.

Measurements

Hormonal and clinical measures associated with PCOS and CV risk factors.

Results

The study included 117 women with PCOS and 204 controls. Women with PCOS had significant differences across racial/ethnic groups in the prevalence of hypertension, hypercholesterolaemia, hypertriglyceridaemia and impaired fasting glucose (P < 0·05). Controls showed significant racial/ethnic differences in the prevalence of hypertension and impaired fasting glucose (P < 0·05). The odds of hypertension were significantly greater among women with PCOS than controls after adjusting for race/ethnicity (odds ratio, 1·50 [95% CI, 1·03–2·30]; P = 0·04). However, we did not see an interaction of race/ethnicity that significantly changed CV risk factor prevalence between PCOS and controls. In addition, subclinical measures of CV disease were not different between women with PCOS vs controls, even among hypertensive women.

Conclusions

Race/ethnicity affects the prevalence of CV risk factors for women with and without PCOS. However, race/ethnicity does not interact with PCOS to additionally increase CV risk factor prevalence or subclinical CV disease.
Transforming child and family services in urban communities in South Africa: lessons from the South
Authors: Patel Leila , Schmid Jeanette Elizabeth , Venter Hendrik Jacobus
Published: November 2015

Post‐apartheid, South African agencies have been required to shift their services in fundamental ways, including offering services in previously un‐resourced areas, honouring the rights of children and families, ensuring that users, staff and governing bodies are representative of the population and providing developmental social welfare services in place of child protection‐oriented interventions only. A study of urban South African child welfare agencies provides insight into the complex task of managing and leading change. In view of overloaded change agenda and resource constraints, managers focused on effecting incremental change and prioritized the most ‘rewarding’ change efforts. Transforming practice towards a developmental approach was less successful. Structural interventions were also not prioritized. Child welfare agencies internationally face demands to transform in response to the effects of local change and globalization. The study's insights might resonate with agencies working for change in other societal contexts.
Solar urticaria
Authors: Goetze Steven , Elsner Peter
Published: November 2015

Solar urticaria is a rare IgE‐mediated and chromophore‐dependent photodermatosis. In some cases, these chromophores, designated as “serum factor”, may be detected in serum or plasma. To date, the exact pathogenesis of solar urticaria has, however, not been elucidated. Typical clinical features include the onset of urticarial lesions within a few minutes after light exposure, which already raises diagnostic suspicion. The most common triggers are UVA and visible light. Determination of the action spectrum as well as the minimal urticarial dose (MDU) is diagnostically crucial. Other photodermatoses such as polymorphic light eruption or porphyrias (especially erythropoietic protoporphyria) have to be ruled out. Apart from sunlight avoidance, which is always required, further therapeutic options used include nonsedating antihistamines as well as light hardening. Newer treatment modalities such as plasmapheresis or the anti‐IgE antibody omalizumab are reserved for severe, recalcitrant forms of solar urticaria.
MAL‐PDT mit Tageslicht – Aktuelle Datenlage und praxisorientierte Empfehlungen eines Expertentreffens
Authors: Philipp‐Dormston Wolfgang G. , Karrer Sigrid , Petering Holger , Ulrich Claas , Dirschka Thomas , Berking Carola , Lonsdorf Anke S. , Gerber Peter Arne , Radakovic Sonja , Hunger Robert E. , Szeimies Rolf‐Markus
Published: November 2015

Die photodynamische Therapie (PDT) gehört zu den Standardverfahren in der Therapie aktinischer Keratosen (AK). Bei der Tageslicht‐PDT (Daylight PDT, DL‐PDT) mit MAL‐Creme handelt es sich um eine neuere Entwicklung, bei der anstelle eines Belichtungssystems das Tageslicht zur Aktivierung des Photosensibilisators genutzt wird. Der vorliegende Review fasst die aktuelle Studienlage basierend auf einer selektiven Literaturrecherche zusammen, fokussiert auf praktische Aspekte in der Durchführung und reflektiert insbesondere auch die Expertenerfahrung der Autoren mit der DL‐PDT. Studiendaten zeigen, dass die DL‐PDT der konventionellen PDT in ihrer Wirksamkeit nicht unterlegen ist. Sie ist jedoch signifikant besser verträglich, da sie zu deutlich weniger Schmerzen während der Therapie führt. Sie kann in Mitteleuropa von März bis Oktober sowohl an bewölkten als auch an sonnigen Tagen durchgeführt werden. Hierbei ist auf UV‐Schutz auch der nicht behandelten Körperareale zu achten. Die Außentemperatur sollte 10°C nicht unterschreiten. An heißen Tagen sollte ein Aufenthalt im Schatten, soweit erforderlich, eingeplant werden. Die DL‐PDT mit MAL ist u. a. für Patienten mit Feldkanzerisierung und/oder negativer Schmerzerfahrung bei der cPDT geeignet und stellt eine sinnvolle Ergänzung der aktuellen Therapiemöglichkeiten dar.
Clinical implications of nonsarcomeric gene polymorphisms in hypertrophic cardiomyopathy
Authors: García‐Honrubia Antonio , Hernández‐Romero Diana , Orenes‐Piñero Esteban , Romero‐Aniorte Ana Isabel , Climent Vicente , García Miriam , Garrigos‐Gómez Noemí , Moro Concepción , Valdés Mariano , Marín Francisco
Published: November 2015

Background

Hypertrophic cardiomyopathy (HCM) is characterized by cardiomyocyte hypertrophy and fibrosis. Although is an autosomal dominant trait, a group of nonsarcomeric genes have been postulated as modifiers of the phenotypic heterogeneity.

Material and methods

We prospectively recruited 168 HCM patients and 136 healthy controls from three referral centres. Patients and controls were clinically stable at entry in the study. Nine polymorphisms previously associated with ventricular remodelling were determined: I/D ACE, AGTR1(A1666C), CYP11B2(C344T), PGC1‐α(G482S), COLIA1(G2046T), ADRB1(R389G), NOS3(G894T), RETN(‐420C>G) and CALM3(‐34T>A). Their potential influence on prognosis, assessed by hospital admissions, and their cause were recorded.

Results

The median follow‐up time was 49·5 months. Allele and genotype frequencies did not differ between patients and controls. Thirty‐six patients (21·5%) required urgent hospitalization (18·5% for heart failure, 22·2% for atrial arrhythmias, 11·1% for ventricular arrhythmias, 29·6% for ischaemic heart disease, 14·8% for stroke and 3·7% for other reasons) with a hospitalization rate of 8·75% per year. Multivariate analysis showed an independent predictive value for noncarriers of polymorphic COL1A1 allele [HR: 2·76(1·26–6·05), P = 0·011] and a trend in homozygous carriers of ADRB1 Arg389 variant [HR: 1·98(0·99–4·02); P = 0·057].

Conclusion

Our study suggests that COL1A1 polymorphism (2046G>T) is an independent predictor of prognosis in HCM patients supporting the importance of nonsarcomeric genes on clinical prognosis in HCM.
DOES THE PUBLIC SECTOR IMPLODE FROM BAUMOL'S COST DISEASE?
Authors: Andersen Torben M.
Published: November 2015

The root of the Baumol cost disease is higher productivity increases for manufactured goods than for services. The implied increase in relative costs of service production is widely claimed to have devastating implications for the public sector as a provider of tax‐financed services such as health, education, and care. To match the increasing costs it appears inevitable that tax rates would be ever increasing. It is shown that this inference does not follow under standard assumptions when accounting explicitly for service provision from both the private and public sectors. Strikingly under assumptions often made in the literature, the welfare maximizing tax rate for a utilitarian policy maker would remain constant despite the Baumol cost disease, and by implication the share of public employment in total employment will remain constant. (JEL H5, H11, O41)
Prospective study of signalling pathways in myeloma bone disease with regard to activity of the disease, extent of skeletal involvement and correlation to bone turnover markers
Authors: Minarik Jiri , Hermanova Zuzana , Petrova Pavla , Hrbek Jan , Zapletalova Jana , Krhovska Petra , Flodr Patrik , Pika Tomas , Bacovsky Jaroslav , Flodrova Pavla , Herman Miroslav , Scudla Vlastimil
Published: November 2015

Aims

The aim of our study was to address the utility of serum levels of selected parameters of myeloma bone disease (MBD) signalling with regard to the pathogenesis of multiple myeloma (MM), activity, markers of bone turnover and extent of skeletal changes.

Patients and methods

We assessed prospectively 77 individuals with monoclonal gammopathies – 46 patients with active MM (AMM), 12 patients with smouldering MM (SMM) and 19 individuals with monoclonal gammopathy of undetermined significance (MGUS) to determine the role of HGF, MIP‐1α, Syndecan‐1, osteoprotegerin, Activin A, DKK1, Annexin A2 and NF‐κB.

Results

We found significant differences of most of the parameters between MGUS and AMM, and with respect to the activity of MM assessed by International Staging System. Most of the parameters of MBD signalling correlated with traditional markers of bone turnover.

Conclusions

All the signalling pathways were activated in MM with more pronounced osteoclastogenesis in comparison with bone formation but not in MGUS regardless of its risk category, suggesting that MBD is not activated in MGUS until the process of transformation into MM. The parameters of MBD signalling might precede the increase of conventional parameters of bone turnover suggesting their possible role in early indication of anti‐resorption therapy.
Deoxycytidine kinase is downregulated under hypoxic conditions and confers resistance against cytarabine in acute myeloid leukaemia
Authors: Degwert Nicole , Latuske Emily , Vohwinkel Gabi , Stamm Hauke , Klokow Marianne , Bokemeyer Carsten , Fiedler Walter , Wellbrock Jasmin
Published: November 2015

Objectives

Leukaemia initiating cells reside within specialised niches in the bone marrow where they undergo complex interactions with different stromal cell types. The bone marrow niche is characterised by a low oxygen content resulting in high expression of hypoxia‐inducible factor 1 α in leukaemic cells conferring a negative prognosis to patients with acute myeloid leukaemia (AML).

Methods and Results

In the current study, we investigated the impact of hypoxic vs. normoxic conditions on the sensitivity of AML cell lines and primary AML blasts to cytarabine. AML cells cultured under 6% oxygen were significantly more resistant against cytarabine compared to cells cultured under normoxic conditions in proliferation and colony‐formation assays. Interestingly upon cultivation under hypoxia, the expression of the cytarabine‐activating enzyme deoxycytidine kinase was downregulated in all analysed AML cell lines and primary AML samples representing a possible mechanism for resistance to chemotherapy. Furthermore, the downregulation of deoxycytidine kinase could be associated with hypoxia‐inducible factor 1 α as treatment with its inhibitor BAY87‐2243 hampered the downregulation of deoxycytidine kinase expression under hypoxic conditions.

Conclusions

In conclusion, our data reveal that hypoxia‐induced downregulation of deoxycytidine kinase represents one stroma‐cell‐independent mechanism of drug resistance to cytarabine in acute myeloid leukaemia.
Subdivision of Broca's region based on individual‐level functional connectivity
Authors: Jakobsen Estrid , Böttger Joachim , Bellec Pierre , Geyer Stefan , Rübsamen Rudolf , Petrides Michael , Margulies Daniel S.
Published: November 2015

Broca's region is composed of two adjacent cytoarchitectonic areas, 44 and 45, which have distinct connectivity to superior temporal and inferior parietal regions in both macaque monkeys and humans. The current study aimed to make use of prior knowledge of sulcal anatomy and resting‐state functional connectivity, together with a novel visualization technique, to manually parcellate areas 44 and 45 in individual brains in vivo. One hundred and one resting‐state functional magnetic resonance imaging datasets from the Human Connectome Project were used. Left‐hemisphere surface‐based correlation matrices were computed and visualized in brainGL. By observation of differences in the connectivity patterns of neighbouring nodes, areas 44 and 45 were manually parcellated in individual brains, and then compared at the group‐level. Additionally, the manual labelling approach was compared with parcellation results based on several data‐driven clustering techniques. Areas 44 and 45 could be clearly distinguished from each other in all individuals, and the manual segmentation method showed high test‐retest reliability. Group‐level probability maps of areas 44 and 45 showed spatial consistency across individuals, and corresponded well to cytoarchitectonic probability maps. Group‐level connectivity maps were consistent with previous studies showing distinct connectivity patterns of areas 44 and 45. Data‐driven parcellation techniques produced clusters with varying degrees of spatial overlap with the manual labels, indicating the need for further investigation and validation of machine learning cortical segmentation approaches. The current study provides a reliable method for individual‐level cortical parcellation that could be applied to regions distinguishable by even the most subtle differences in patterns of functional connectivity.
De novo DNM1 mutations in two cases of epileptic encephalopathy
Authors: Nakashima Mitsuko , Kouga Takeshi , Lourenço Charles Marques , Shiina Masaaki , Goto Tomohide , Tsurusaki Yoshinori , Miyatake Satoko , Miyake Noriko , Saitsu Hirotomo , Ogata Kazuhiro , Osaka Hitoshi , Matsumoto Naomichi
Published: November 2015

Dynamin 1 (DNM1) is a large guanosine triphosphatase involved in clathrin‐mediated endocytosis. In recent studies, de novo mutations in DNM1 have been identified in five individuals with epileptic encephalopathy. In this study, we report two patients with early onset epileptic encephalopathy possessing de novo DNM1 mutations. Using whole exome sequencing, we detected the novel mutation c.127G>A (p.Gly43Ser) in a patient with Lennox‐Gastaut syndrome, and a recurrent mutation c.709C>T (p.Arg237Trp) in a patient with West syndrome. Structural consideration of DNM1 mutations revealed that both mutations would destabilize the G domain structure and impair nucleotide binding, dimer formation, and/or GTPase activity of the G domain. These and previous cases of DNM1 mutations were reviewed to verify the phenotypic spectrum. The main clinical features of DNM1 mutations include intractable seizures, intellectual disability, developmental delay, and hypotonia. Most cases showed development delay before the onset of seizures. A patient carrying p.Arg237Trp in this report showed a different developmental status from that of a previously reported case, together with characteristic extrapyramidal movement.
Chemical, microbial, and host‐related factors: effects on the integrity of dentin and the dentin–biomaterial interface
Authors: Carrilho Marcela T. , Piveta Fabiana , Tjäderhane Leo
Published: November 2015

Dentin is the largest substrate available whenever restorative procedures are implemented on the exposed crown or root of teeth. In endodontics, restorative/obturating procedures are practically restricted to dentin. It is well recognized that the incidence of fracture in endodontically treated teeth is intrinsically related to the amount of remaining dentin. Ideally, it is expected that a gap‐free, solid interface can be formed between the restorative/obturating materials and root dentin, providing an impervious seal and, simultaneously, fracture resistance to root‐filled teeth. Over the past years, a number of new obturating biomaterials have been launched in the market, bringing to endodontists the expectation of achieving consistent sealing/reinforcing of the root canal system. However, the successful sealing of root dentin remains one of the greatest challenges in restorative dentistry. This article will focus on reviewing some factors that affect the formation and integrity of dentin–biomaterial interfaces from the perspective of the dentin substrate. Because other articles in preceding issues of Endodontic Topics have already covered dentin structure and composition, the objective here is not to review these aspects. Specific attention is given, however, to depicting how chemical treatments affect existing root filling/restorative mechanisms and how some microbial and host‐related aspects can compromise the interaction of dentin with new biomaterials.
Contracted endodontic cavities: the foundation for less invasive alternatives in the management of apical periodontitis
Authors: Bóveda Carlos , Kishen Anil
Published: November 2015

Compromised structural or mechanical integrity of teeth results in different types of tooth fractures, which are known to be one of the most common causes for tooth extraction. Minimally invasive concepts and procedures are currently advocated as less invasive alternatives to traditional treatments. Recent advances in the available resources and technologies have made a significant impact on endodontic treatment procedures, allowing minimally invasive treatment procedures such as contracted endodontic cavities for preserving coronal and radicular tooth structure. The purpose of this article is to provide a framework for understanding the clinical reasoning for contracted endodontic cavities and their possible benefits in contemporary endodontics.
Rapid evolution of increased vulnerability to an insecticide at the expansion front in a poleward‐moving damselfly
Authors: Dinh Khuong Van , Janssens Lizanne , Therry Lieven , Gyulavári Hajnalka A. , Bervoets Lieven , Stoks Robby
Published: November 2015

Many species are too slow to track their poleward‐moving climate niche under global warming. Pesticide exposure may contribute to this by reducing population growth and impairing flight ability. Moreover, edge populations at the moving range front may be more vulnerable to pesticides because of the rapid evolution of traits to enhance their rate of spread that shunt energy away from detoxification and repair. We exposed replicated edge and core populations of the poleward‐moving damselfly Coenagrion scitulum to the pesticide esfenvalerate at low and high densities. Exposure to esfenvalerate had strong negative effects on survival, growth rate, and development time in the larval stage and negatively affected flight‐related adult traits (mass at emergence, flight muscle mass, and fat content) across metamorphosis. Pesticide effects did not differ between edge and core populations, except that at the high concentration the pesticide‐induced mortality was 17% stronger in edge populations. Pesticide exposure may therefore slow down the range expansion by lowering population growth rates, especially because edge populations suffered a higher mortality, and by negatively affecting dispersal ability by impairing flight‐related traits. These results emphasize the need for direct conservation efforts toward leading‐edge populations for facilitating future range shifts under global warming.
Stepwise evolution of Elk‐1 in early deuterostomes
Authors: Saxton Janice , Ferjentsik Zoltan , Ducker Charles , Johnson Andrew D. , Shaw Peter E.
Published: November 2015

Metazoans have multiple ETS paralogues with overlapping or indiscriminate biological functions. Elk‐1, one of three mammalian ternary complex factors (TCFs), is a well‐conserved, ETS domain‐containing transcriptional regulator of mitogen‐responsive genes that operates in concert with serum response factor (SRF). Nonetheless, its genetic role remains unresolved because the elk‐1 gene could be deleted from the mouse genome seemingly without adverse effect. Here we have explored the evolution of Elk‐1 to gain insight into its conserved biological role. We identified antecedent Elk‐1 proteins in extant early metazoans and used amino acid sequence alignments to chart the appearance of domains characteristic of human Elk‐1. We then performed biochemical studies to determine whether putative domains apparent in the Elk‐1 protein of a primitive hemichordate were functionally orthologous to those of human Elk‐1. Our findings imply the existence of primordial Elk‐1 proteins in primitive deuterostomes that could operate as mitogen‐responsive ETS transcription factors but not as TCFs. The role of TCF was acquired later, but presumably prior to the whole genome duplications in the basal vertebrate lineage. Thus its evolutionary origins link Elk‐1 to the appearance of mesoderm.
MiR‐29‐mediated elastin down‐regulation contributes to inorganic phosphorus‐induced osteoblastic differentiation in vascular smooth muscle cells
Authors: Sudo Ryo , Sato Fumiaki , Azechi Takuya , Wachi Hiroshi
Published: November 2015

Vascular calcification increases the risk of cardiovascular mortality. We previously reported that expression of elastin decreases with progression of inorganic phosphorus (Pi)‐induced vascular smooth muscle cell (VSMC) calcification. However, the regulatory mechanisms of elastin mRNA expression during vascular calcification remain unclear. MicroRNA‐29 family members (miR‐29a, b and c) are reported to mediate elastin mRNA expression. Therefore, we aimed to determine the effect of miR‐29 on elastin expression and Pi‐induced vascular calcification. Calcification of human VSMCs was induced by Pi and evaluated measuring calcium deposition. Pi stimulation promoted Ca deposition and suppressed elastin expression in VSMCs. Knockdown of elastin expression by shRNA also promoted Pi‐induced VSMC calcification. Elastin pre‐mRNA measurements indicated that Pi stimulation suppressed elastin expression without changing transcriptional activity. Conversely, Pi stimulation increased miR‐29a and miR‐29b expression. Inhibition of miR‐29 recovered elastin expression and suppressed calcification in Pi‐treated VSMCs. Furthermore, over‐expression of miR‐29b promoted Pi‐induced VSMC calcification. RT‐qPCR analysis showed knockdown of elastin expression in VSMCs induced expression of osteoblast‐related genes, similar to Pi stimulation, and recovery of elastin expression by miR‐29 inhibition reduced their expression. Our study shows that miR‐29‐mediated suppression of elastin expression in VSMCs plays a pivotal role in osteoblastic differentiation leading to vascular calcification.
The Second Crusade, 1145–49: Damascus, Lisbon and the Wendish Campaigns
Authors: Roche Jason T.
Published: November 2015

The Second Crusade (1145–49) is thought to have encompassed near simultaneous Christian attacks on Muslim towns and cities in Syria and Iberia and pagan Wend strongholds around the southern shore of the Baltic Sea. The motivations underpinning the attacks on Damascus, Lisbon and – taken collectively – the Wendish strongholds have come in for particular attention. The doomed decision to assault Damascus in 1148 rather than recover Edessa, the capital of the first so‐called crusader state, was once thought to be ill‐conceived. Historians now believe the city was attacked because Damascus posed a significant threat to the Latin kingdom of Jerusalem when the Second Crusaders arrived in the East. The assault on Lisbon and the Wendish strongholds fell into a long‐established pattern of regional, worldly aggression and expansion; therefore, historians tend not to ascribe any spiritual impulses behind the native Christians' decisions to attack their enemies. Indeed, the siege of Lisbon by an allied force of international crusaders and those of the Portuguese ruler, Afonso Henriques, is perceived primarily as a politico‐strategic episode in the on‐going Christian–Muslim conflict in Iberia – commonly referred to as thereconquista. The native warrior and commercial elite undoubtedly had various temporal reasons for engaging in warfare in Iberia and the Baltic region between 1147 and 1149, although the article concludes with some notes of caution before clinically construing motivation from behaviour in such instances.
HIV, highly active antiretroviral therapy and the heart: a cellular to epidemiological review
Authors: Lambert CT , Sandesara PB , Hirsh B , Shaw LJ , Lewis W , Quyyumi AA , Schinazi RF , Post WS , Sperling L
Published: November 2015

The advent of potent highly active antiretroviral therapy (HAART) for persons infected with HIV‐1 has led to a “new” chronic disease with complications including cardiovascular disease (CVD). CVD is a significant cause of morbidity and mortality in persons with HIV infection. In addition to traditional risk factors such as smoking, hypertension, insulin resistance and dyslipidaemia, infection with HIV is an independent risk factor for CVD. This review summarizes: (1) the vascular and nonvascular cardiac manifestations of HIV infection; (2) cardiometabolic effects of HAART; (3) atherosclerotic cardiovascular disease (ASCVD) risk assessment, prevention and treatment in persons with HIV‐1 infection.
Fine‐scale climatic variation drives altitudinal niche partitioning of tabanid flies in a tropical montane cloud forest, Ecuadorian Chocó
Authors: Cárdenas Rafael E.
Published: November 2015

In montane systems, global warming may lead communities to disassemble by forcing organisms to shift their distributions to higher elevations or by causing the extinction of those that are unable to adapt. To predict which species are most at risk from environmental change, physiological responses to multiple factors must be measured in natural conditions at fine spatial and temporal scales.

To examine the potential drivers of elevational distributions in tabanid flies, specimens were exhaustively sampled at three altitudes within a tropical montane cloud forest in Western Ecuador. Observed abundances were then correlated with seven environmental variables measured in situ. It was hypothesised that (1) tabanid distributions were significantly associated with particular environmental conditions measured in each altitudinal habitat, and (2) a greater proportion of lowland species were limited to a specific elevation than highland species.

Most species occupied well‐defined altitudinal niches corresponding to optimal climatic conditions. Colder weather, higher daily temperature variability, and higher levels of moisture seemed to limit most species from establishing in high elevation sites of this mountainous ecosystem.

Despite the high dispersal potential of tabanids within the study area, results suggest that most tabanid flies are limited to the subset of altitudes where their climatic requirements are satisfied.
Effect of preoperative chemotherapy on survival of patients with upper urinary tract urothelial carcinoma clinically involving regional lymph nodes
Authors: Kobayashi Kazuhiro , Saito Toshihiro , Kitamura Yasuo , Bilim Vladimir , Toba Tomotaka , Kawasaki Takashi , Hara Noboru , Tanikawa Toshiki , Tomita Yoshihiko
Published: November 2015

Objectives

To determine the effect of preoperative chemotherapy on survival in patients with upper urinary tract urothelial carcinoma clinically involving regional lymph nodes.

Methods

We retrospectively analyzed 55 consecutive patients who received radical nephroureterectomy with or without preoperative chemotherapy for upper urinary tract urothelial carcinoma clinically involving regional lymph nodes at a single institution between January 1991 and December 2013.

Results

Median follow up was 18 months (range 2–193). Of 55 patients, 24 (43.6%) received preoperative chemotherapy (study group) and 31 (56.4%) underwent primary surgery (control group). Preoperative chemotherapy consisted of two to four cycles (median 3) of cisplatin‐containing regimens. The fraction of patients with lower pathological T stage and N stage than clinical T stage and N stage was higher in the study group (29.2% and 54.2%) compared with the control group (3.2% and 16.1%; P = 0.013 and 0.010, respectively). The 5‐year overall survival rate was significantly higher in the study group than in the control group (44.0% vs 12.9%, log–rank, P = 0.003). In multivariate analysis incorporating age at diagnosis, Eastern Cooperative Oncology Group Performance Status, clinical N stage and the number of removed lymph nodes, preoperative chemotherapy was a predictor of better overall survival (P = 0.047, HR 0.47, 95% CI 0.22–0.99).

Conclusions

Preoperative chemotherapy might provide better survival outcomes in patients with upper urinary tract urothelial carcinoma clinically involving regional lymph nodes.
The Federal Reserve: The Weakest Lender of Last Resort Among Its Peers
Authors: Scott Hal S.
Published: November 2015

This article for the first time compares the Federal Reserve's powers as lender of last resort (‘LLR’) and its ability to fight contagion, with its three major peers, the Bank of England (the ‘BOE’), the European Central Bank (the ‘ECB’) and the Bank of Japan (the ‘BOJ’). It concludes that the Federal Reserve (the ‘Fed’) is currently the weakest of the four, largely due to a hostile political environment for LLR powers, which are equated with bailouts, and restrictions placed by the 2010 Dodd–Frank Act on the Fed's ability to loan to non‐banks, whose role in the financial system is ever‐increasing. This is a concern for the global as well as the US financial system, given the economic importance of the United States and the use of the dollar as a reserve currency.
Increased risk of A(H1N1)pdm09 influenza infection in UK pig industry workers compared to a general population cohort
Authors: Fragaszy Ellen , Ishola David A. , Brown Ian H. , Enstone Joanne , Nguyen‐Van‐Tam Jonathan S. , Simons Robin , Tucker Alexander W. , Wieland Barbara , Williamson Susanna M. , Hayward Andrew C. ,   the Flu Watch Group, Wood James L. N. ,   the Combating Swine Influenza (COSI) Consortium
Published: November 2015

Background

Pigs are mixing vessels for influenza viral reassortment, but the extent of influenza transmission between swine and humans is not well understood.

Objectives

To assess whether occupational exposure to pigs is a risk factor for human infection with human and swine‐adapted influenza viruses.

Methods

UK pig industry workers were frequency‐matched on age, region, sampling month, and gender with a community‐based comparison group from the Flu Watch study. HI assays quantified antibodies for swine and human A(H1) and A(H3) influenza viruses (titres ≥ 40 considered seropositive and indicative of infection). Virus‐specific associations between seropositivity and occupational pig exposure were examined using multivariable regression models adjusted for vaccination. Pigs on the same farms were also tested for seropositivity.

Results

Forty‐two percent of pigs were seropositive to A(H1N1)pdm09. Pig industry workers showed evidence of increased odds of A(H1N1)pdm09 seropositivity compared to the comparison group, albeit with wide confidence intervals (CIs), adjusted odds ratio after accounting for possible cross‐reactivity with other swine A(H1) viruses (aOR) 25·3, 95% CI (1·4–536·3), P = 0·028.

Conclusion

The results indicate that A(H1N1)pdm09 virus was common in UK pigs during the pandemic and subsequent period of human A(H1N1)pdm09 circulation, and occupational exposure to pigs was a risk factor for human infection. Influenza immunisation of pig industry workers may reduce transmission and the potential for virus reassortment.
Playing with political fire: Cameron, the Conservatives and the EU referendum
Authors: Curtice John
Published: November 2015

John Curtice sketches out the polling data on the EU referendum question, and finds a nation divided. With the prime minister's negotiation demands now in the open, he asks, has Cameron set the bar too low to secure the support of his own party and his voters?
Are we ‘post‐democratic’ – or have we not (yet) been democratic at all?
Authors: Martel James
Published: November 2015

James Martel frames a view of ‘post‐democracy’ that eschews a chronological interpretation – ‘democracy is dead; long live democracy’ – and replaces it with a philosophical interpretation that acknowledges the essential failures of democracy and seeks instead to achieve what democracy never has and never will.
Post‐democracy, democratic renewal and the recent history of British politics
Authors: Stears Marc
Published: November 2015

Informed partly by his experiences inside the Miliband HQ prior to the 2015 general election, Marc Stears asks why Labour's impulse to democratic reform seems to have petered out, and whether the problems of post‐democratic disengagement in fact lie beyond issues of professionalisation, party structures and modern political stylings.
The Impact of Dividend Covenants on Investment and Operating Performance
Authors: Jung Boochun , Lee Woo‐Jong , Yang Yanhua Sunny
Published: November 2015

This paper examines the influence of dividend covenants in corporate bonds on investment and operating performance. Prior literature analytically demonstrates that by limiting dividend distribution to shareholders, dividend restrictions effectively place a minimum on investment expenditures. This suggests a positive relation between dividend covenants and investment. The literature also conjectures that the influence of dividend covenants on investment (1) mitigates the under‐investment problem associated with debt financing; or (2) exacerbates over‐investment. We empirically document that the presence of dividend covenants is associated with a higher level of investment and poorer future performance. Further analyses confirm that the higher level of investment is consistent with dividend covenants exacerbating over‐investment, not mitigating under‐investment. Our results shed light on the cost aspect of dividend covenants proposed in prior literature.
Supply Chain Citizenship: Investigating the Antecedents of Customer Interorganizational Citizenship Behaviors
Authors: Esper Terry L. , Bradley Randy V. , Thomas Rodney , Thornton LaDonna M.
Published: November 2015

Research has consistently established the strategic importance of supply chain collaboration. As a result, interfirm behavioral dynamics and relationships have emerged as key topics for both the academic and practitioner communities. This paper explores an interpersonal exchange tactic that is inherent to many collaborative initiatives—interorganizational citizenship behaviors (ICBs). The study specifically investigates why retail customers in business‐to‐business exchange relationships would exhibit ICBs, and explores how they assess and respond to the ICBs of suppliers. Findings of the study suggest that customers generally interpret and value the various types of ICBs differently, resulting in differential effects regarding the supply chain performance and relational implications of the behavior. These results not only inform managerial practice but also provide future research opportunities in the area of ICBs and the broader realm of interpersonal supply chain dynamics.
Exosomes from hypoxic endothelial cells have increased collagen crosslinking activity through up‐regulation of lysyl oxidase‐like 2
Authors: de Jong Olivier G. , van Balkom Bas W. M. , Gremmels Hendrik , Verhaar Marianne C.
Published: November 2015

Exosomes are important mediators of intercellular communication. Additionally, they contain a variety of components capable of interacting with the extracellular matrix (ECM), including integrins, matrix metalloproteinases and members of the immunoglobin superfamily. Despite these observations, research on exosome‐ECM interactions is limited. Here, we investigate whether the exosome‐associated lysyl oxidase family member lysyl oxidase‐like 2 (LOXL2) is involved in ECM remodelling. We found that LOXL2 is present on the exterior of endothelial cell (EC)‐derived exosomes, placing it in direct vicinity of the ECM. It is up‐regulated twofold in EC‐derived exosomes cultured under hypoxic conditions. Intact exosomes from hypoxic EC and LOXL2 overexpressing EC show increased activity in a fluorometric lysyl oxidase enzymatic activity assay as well as in a collagen gel contraction assay. Concordantly, knockdown of LOXL2 in exosome‐producing EC in both normal and hypoxic conditions reduces activity of exosomes in both assays. Our findings show for the first time that ECM crosslinking by EC‐derived exosomes is mediated by LOXL2 under the regulation of hypoxia, and implicate a role for exosomes in hypoxia‐regulated focal ECM remodelling, a key process in both fibrosis and wound healing.
Price-Level Changes and the Redistribution of Nominal Wealth across the Euro Area
Authors: Adam Klaus , Zhu Junyi
Published: November 2015

We show that unexpected price-level movements generate sizable wealth redistribution in the Euro Area (EA), using sectoral accounts and newly available data from the Household Finance and Consumption Survey. The EA as a whole is a net loser of unexpected price-level decreases, with Italy, Greece, Portugal, and Spain losing most in per capita terms, and Belgium and Malta being net winners. Governments are net losers of deflation, while the household (HH) sector is a net winner in the EA as a whole. HHs in Belgium, Ireland, Malta, and Germany experience the biggest per capita gains, while HHs in Finland and Spain turn out to be net losers. Considerable heterogeneity exists also within the HH sector: relatively young middle class HHs are net losers of deflation, while older and richer HHs are winners. As a result, wealth inequality in the EA increases with unexpected deflation, although in some countries (Austria, Germany, and Malta) inequality decreases due to the presence of relatively few young borrowing HHs. We document that HHs’ inflation exposure varies systematically across countries, with HHs in high-inflation EA countries holding systematically lower nominal exposures.
Quantitative immunoenzymatic detection of viral encephalopathy and retinopathy virus (betanodavirus) in sea bass Dicentrarchus labrax
Authors: Nuñez‐Ortiz N , Stocchi V , Toffan A , Pascoli F , Sood N , Buonocore F , Picchietti S , Papeschi C , Taddei A R , Thompson K D , Scapigliati G
Published: November 2015

Viral encephalopathy and retinopathy disease caused by betanodavirus, genus of the family Nodaviridae, affects marine, wild and farmed species including sea bass, one of the most important farmed species in Europe. This work describes a reliable and sensitive indirect ELISA assay to detect betanodavirus in biological samples using a polyclonal antiserum (pAb 283) against the 283/I09 virus strain, the most common red‐spotted grouper nervous necrosis virus (RGNNV) genotype in the Mediterranean area, and a capture‐based ELISA using a monoclonal antibody (mAb 4C3) specific to a common epitope present on the capsid protein. Using adsorbed, purified VERv preparation, the detection limit of indirect ELISA was 2 μg mL−1 (3 × 105 TCID50 per mL), whereas for capture‐based ELISA, the sensitivity for the antigen in solution was 17 μg mL−1 (35 × 105 TCID50 per mL). The capture‐based ELISA was employed to detect VERv in brain homogenates of in vivo infected sea bass and resulted positive in 22 of 32 samples, some of these with a high viral load estimates (about 1.1 × 108 TCID50 per mL). The ELISA system we propose may be helpful in investigations where coupling of viral content in fish tissues with the presence of circulating VERv‐specific IgM is required, or for use in samples where PCR is difficult to perform.
Incorporating Nurse‐Midwifery Students into Graduate Medical Education: Lessons Learned in Interprofessional Education
Authors: Kaplan Rebekah , Shaw‐Battista Jenna , Stotland Naomi Ellen
Published: November 2015

There is a current emphasis on interprofessional education in health care with the aim to improve teamwork and ultimately the quality and safety of care. As part of a Health Resources and Services Administration Advanced Nursing Education project, an interprofessional faculty and student team planned and implemented the first didactic coursework for nurse‐midwifery and medical students at the University of California, San Francisco and responded to formative feedback in order to create a more meaningful educational experience for future combined cohorts. This article describes the process of including advanced nurse‐midwifery students into 2 classes previously offered solely to medical students: 1) an elective in which students are matched with a pregnant woman to observe care that she receives before, during, and after giving birth; and 2) a required course on basic clinical care across the human lifespan. The development of these interprofessional courses, obstacles to success, feedback from students, and responses to course evaluations are reviewed. Themes identified in student course evaluations included uncertainty about interprofessional roles, disparity in clinical knowledge among learners, scheduling difficulties, and desire for more interprofessional education opportunities and additional time for facilitated interprofessional discussion. As a result of this feedback, more class time was designated for interprofessional exchange; less experienced rather than advanced midwifery students were included in both classes; and more interdisciplinary panel presentations were provided, along with clearer communication about student and clinician roles. Early project activities indicated nurse‐midwifery students can be effectively included in existing medical student courses with revised curriculum and highlighted challenges that should be considered in the planning phase of similar projects in the future. This article is part of a special series of articles that address midwifery innovations in clinical practice, education, interprofessional collaboration, health policy, and global health.