bluuebunny/crossref_metadata_2025 huggingface dataset:
The mitochondrial permeability transition: the brain's point of view
Authors: Dubinsky Janet M. , Brustovetsky Nickolay , Pinelis Vsevolod , Kristal Bruce S. , Herman Carter , Li Xinren
Published: August 2015

The mitochondrial permeability transition (mPT) has been implicated in both central nervous system ischaemia/reperfusion injury and excitotoxic neuronal death. To characterize the mPT of brain mitochondria, fluorescent mitochondrial dyes were applied to cultured neurons and astrocytes and isolated brain mitochondria were prepared. In astrocytes, mPT induction was observed as calcium-induced mitochondrial swelling following permeabilization by digitonin or introduction of a calcium ionophore. In hippocampal neurons, mPT induction was observed upon introduction of calcium and ionophore or application of toxic doses of glutamate. In isolated brain mitochondria, calcium dose-dependently produced calcium accumulation and mitochondrial swelling that was prevented by pretreatment with ADP or cyclosporin A. Additionally, when mitochondrial substrates were limited, calcium dose-dependently produced mitochondrial depolarization without swelling or calcium accumulation that was reversed by ADP, cyclosporin A or Ruthenium Red. The degree of mitochondrial depolarization was modulated by free fatty acids, magnesium, calcium concentration and protonophore Repolarization of mitochondria and closure of this low-conductance manifestation of the mPT pore by cyclosporin A was modulated by the degree of depolarization.
Secondary abnormalities of mitochondrial DNA associated with neurodegeneration
Authors: Tabrizi S.J. , Schapira A.H.V.
Published: August 2015

The central nervous system has a particularly high energy requirement, thus making it very susceptible to defects in mitochondrial function. A number of neurodegenerative diseases, in particular Parkinson's disease (PD), Huntington's disease (HD) and Friedreich's ataxia (FRDA), are associated with mitochondrial dysfunction. The identification of a mitochondrial complex-I defect in PD provides a link between toxin models of the disease, and clues to the pathogenesis of idiopathic PD. We have undertaken genomic transplantation studies involving the transfer of mitochondrial DNA (mtDNA) from PD patients with a complex-I defect to a novel nuclear background. Histochemical, immunohistochemical and functional analysis of the resulting cybrids all showed a pattern in the PD clones indicative of a mtDNA mutation. There is good evidence for the involvement of defective energy metabolism and excitotoxicity in the aetiology of HD. We, and others, have shown a severe deficiency of complex II/III confined to the striatum that mimics the toxin-induced animal models of HD. There is also a milder defect in complex IV in the caudate. The tricarboxylic acid cycle enzyme aconitase is particularly sensitive to inhibition by peroxynitrite and superoxide radicals. We have found this enzyme to be severely decreased in HD caudate, putamen and cortex in a pattern that parallels the severity of neuronal loss seen. We propose a scheme for the role of nitric oxide, free radicals and excitotoxicity in the pathogenesis of HD. FRDA is caused by an expanded GAA repeat in intron 1 of the X25 gene encoding a protein called frataxin. Frataxin is widely expressed and is a mitochondrial protein, although its function is unknown. We have found abnormal magnetic resonance spectroscopy in the skeletal muscle of FRDA patients, which parallels our biochemical findings of reduced complexes I-III in patients' heart and skeletal muscle. There is also reduced aconitase activity in these areas. Increased iron deposition was seen in patients' tissues in a pattern consistent with a mitochondrial location. The mitochondrial iron accumulation, defective respiratory chain activity and aconitase dysfunction suggest that frataxin may be involved in mitochondrial iron regulation. There is also evidence that oxidative stress contributes to cellular toxicity.
Tau gene mutations and neurodegeneration
Authors: Goedert Michel , Spillantini Maria Grazia
Published: August 2015

Abundant neurofibrillary lesions made of the microtubule-associated protein tau constitute a defining neuropathological characteristic of Alzheimer's disease. Filamentous tau protein deposits are also the defining neuropathological characteristic of other neurodegenerative diseases, many of which are frontotemporal dementias or movement disorders, such as Pick's disease, progressive supranuclear palsy and corticobasal degeneration. It is well established that the distribution of tau pathology correlates with the presence of symptoms of disease. However, until recently, there was no genetic evidence linking dysfunction of tau protein to neurodegeneration and dementia. This has now changed with the discovery of close to 20 mutations in the tau gene in frontotemporal dementia with Parkinsonism linked to chromosome 17. All cases with tau mutations examined to date have shown an abundant filamentous tau pathology in brain cells. Pathological heterogeneity is determined to a large extent by the location of mutations in tau. Known mutations are either coding region or intronic mutations located close to the splice-donor site of the intron downstream of exon 10. Most coding region mutations produce a reduced ability of tau to interact with microtubules. Several of these mutations also promote sulphated glycosaminoglycan-induced assembly of tau into filaments. Intronic mutations and some coding region mutations produce increased splicing in of exon 10, resulting in an overexpression of four-repeat tau isoforms. Thus a normal ratio of three-repeat to four-repeat tau isoforms is essential for preventing the development of tau pathology. The new work has shown that dysfunction of tau protein can cause neurodegeneration and dementia.
Control of the expression of inflammatory response genes
Authors: Saklatvala Jeremy , Dean Jonathan , Clark Andrew
Published: August 2015

The expression of genes involved in the inflammatory response is controlled both transcriptionally and post-transcriptionally. Primary inflammatory stimuli, such as microbial products and the cytokines interleukin-1 (IL-1) and tumour necrosis factor α (TNFα), act through receptors of either the Toll and IL-1 receptor (TIR) family or the TNF receptor family. These cause changes in gene expression by activating four major intracellular signalling pathways that are cascades of protein kinases: namely the three mitogen-activated protein kinase (MAPK) pathways, and the pathway leading to activation of the transcription factor nuclear factor ϰB (NFϰB). The pathways directly activate and induce the expression of a limited set of transcription factors which promote the transcription of inflammatory response genes. Many of the mRNAs are unstable, and are stabilized by the p38 MAPK pathway. Instability is mediated by clusters of the AUUUA motif in the 3″ untranslated regions of the mRNAs. Control of mRNA stability provides a means of increasing the amplitude of a response and allows rapid adjustment of mRNA levels. Not all mRNAs stabilized by p38 contain AUUUA clusters; for example, matrix metalloproteinase-1 and -3 mRNAs lack these clusters, but are stabilized. Inflammatory gene expression is inhibited by glucocorticoids. These suppress MAPK signalling by inducing a MAPK phosphatase. This may be a significant mechanism additional to that by which the glucocorticoid receptor interferes with transcription factors.
Designing TIMP (tissue inhibitor of metalloproteinases) variants that are selective metalloproteinase inhibitors
Authors: Nagase Hideaki , Brew Keith
Published: August 2015

The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs), enzymes that play central roles in the degradation of extracellular matrix components. The balance between MMPs and TIMPs is important in the maintenance of tissues, and its disruption affects tissue homoeostasis. Four related TIMPs (TIMP-1 to TIMP-4) can each form a complex with MMPs in a 1:1 stoichiometry with high affinity, but their inhibitory activities towards different MMPs are not particularly selective. The three-dimensional structures of TIMP-MMP complexes reveal that TIMPs have an extended ridge structure that slots into the active site of MMPs. Mutation of three separate residues in the ridge, at positions 2, 4 and 68 in the amino acid sequence of the N-terminal inhibitory domain of TIMP-1 (N-TIMP-1), separately and in combination has produced N-TIMP-1 variants with higher binding affinity and specificity for individual MMPs. TIMP-3 is unique in that it inhibits not only MMPs, but also several ADAM (a disintegrin and metalloproteinase) and ADAMTS (ADAM with thrombospondin motifs) metalloproteinases. Inhibition of the latter groups of metalloproteinases, as exemplified with ADAMTS-4 (aggrecanase 1), requires additional structural elements in TIMP-3 that have not yet been identified. Knowledge of the structural basis of the inhibitory action of TIMPs will facilitate the design of selective TIMP variants for investigating the biological roles of specific MMPs and for developing therapeutic interventions for MMP-associated diseases.
Dynamin I phosphorylation and the control of synaptic vesicle endocytosis.
Authors: Smillie Karen J. , Cousin Michael A.
Published: August 2015

The GTPase dynamin I is essential for synaptic vesicle endocytosis in nerve terminals. It is a nerve terminal phosphoprotein that is dephosphorylated on nerve terminal stimulation by the calcium-dependent protein phosphatase calcineurin and then rephosphorylated by cyclin-dependent kinase 5 on termination of the stimulus. Because of its unusual phosphorylation profile, the phosphorylation status of dynamin I was assumed to be inexorably linked to synaptic vesicle endocytosis; however, direct proof of this link has been elusive until very recently. This review will describe current knowledge regarding dynamin I phosphorylation in nerve terminals and how this regulates its biological function with respect to synaptic vesicle endocytosis.
Endocytosis and retrograde axonal traffic in motor neurons.
Authors: Deinhardt Katrin , Schiavo Giampietro
Published: August 2015

Spinal cord motor neurons control voluntary movement by relaying messages that arrive from upper brain centres to the innervated muscles. Despite the importance of motor neurons in human health and disease, the precise control of their membrane dynamics and its effect on motor neuron homoeostasis and survival are poorly understood. In particular, the molecular basis of the co-ordination of specific endocytic events with the axonal retrograde transport pathway is largely unknown. To study these important vesicular trafficking events, we pioneered the use of atoxic fragments of tetanus and botulinum neurotoxins to follow endocytosis and retrograde axonal transport in motor neurons. These neurotoxins bind specifically to pre-synaptic nerve terminals, where they are internalized. Whereas botulinum neurotoxins remain at the neuromuscular junction, tetanus toxin is retrogradely transported along the axon to the cell body, where it is released into the intersynaptic space and is internalized by adjacent inhibitory interneurons. The high neurospecificity and the differential intracellular sorting make tetanus and botulinum neurotoxins ideal tools to study neuronal physiology. In the present review, we discuss recent developments in our understanding of the internalization and trafficking of these molecules in spinal cord motor neurons. Furthermore, we describe the development of a reliable transfection method for motor neurons based on microinjection, which will be extremely useful for dissecting further the molecular basis of membrane dynamics and axonal transport in these cells.
Consequences of lipid raft association on G-protein-coupled receptor function.
Authors: Becher Anja , McIlhinney R. A. Jeffrey
Published: August 2015

GPCRs (G-protein-coupled receptors) play key roles in many cellular processes, and malfunction may lead to a range of pathologies, including psychiatric and neurological disorders. It is therefore not surprising that this group of receptors supplies a majority of the targets for pharmaceutical drug development. Despite their importance, the mechanisms that regulate their function and signalling still remain only partially understood. Recently, it has become evident that a subset of GPCRs is not homogeneously distributed in the plasma membrane, but localizes instead to specific membrane microdomains known as lipid rafts. Lipid rafts are characterized by their enrichment in cholesterol and sphingolipids, and have been suggested to serve as platforms for a range of cellular signalling complexes. In the present review, we will be discussing the effects of the lipid raft environment on trafficking, signalling and internalization of raft-associated GPCRs.
Mechanistic studies of the mRNA transcription cycle
Authors: Cramer Patrick
Published: August 2015

We have now completed an atomic crystallographic model of the 12-subunit yeast RNA polymerase II in elongation mode, with DNA and RNA in the active-centre cleft, and the NTP substrate at the growing end of the RNA. From these studies has emerged a detailed three-dimensional view of mRNA elongation. We have extended this structural analysis to a polymerase elongation complex bound by the transcript cleavage factor TFIIS (transcription factor IIS), which is required for polymerase escape from DNA arrest sites. A detailed model of this complex reveals a single tuneable active site for RNA polymerization and cleavage, and changes in the position of the RNA and polymerase domains, reflecting the dynamic nature of the elongation complex. An additional structure of a polymerase CTD (C-terminal domain) phosphopeptide bound by the 3′-RNA processing factor Pcf11 provides insights into the coupling of transcription elongation to mRNA processing. The structure of the CTD phosphatase Scp1 trapped in an intermediary enzymatic state explains CTD dephosphorylation during recycling of the polymerase. We also recently reported the first crystal structure of a Mediator subcomplex, which reveals an extended helical fold with a conserved hinge.
The modulation of WTI transcription function by cofactors
Authors: Roberts Stefan G.E.
Published: August 2015

Wilms' tumour is a paediatric malignancy of the kidneys that affects one in every 10 000 live births, making it the most common solid tumour in the young. This cancer arises due to a failure of the metanephric mesenchyme to differentiate and form the kidney filtration units and tubules, which instead undergo uncontrolled proliferation. WT1 (Wilms' tumour 1) was identified as a factor that is frequently mutated in Wilms' tumours. WT1 plays a central role in the development of the genito-urinary organs and also other regions of the embryo. A major function of WT1 is to act as a regulator of transcription, controlling the expression of genes that are involved in proliferation and differentiation. WT1 can either activate or repress transcription of its target genes. Thus the transcription function of WT1 is highly context-specific, and can be modulated by a number of cofactors. Here, the known interaction partners of WT1 and the mechanisms by which they modulate WT1 transcription function will be discussed.
PLCζ, a sperm-specific PLC and its potential role in fertilization
Authors: Saunders Christopher M. , Swann Karl , Lai F. Anthony
Published: August 2015

A dramatic rise in intracellular calcium plays a vital role at the moment of fertilization, eliciting the resumption of meiosis and the initiation of embryo development. In mammals, the rise takes the form of oscillations in calcium concentration within the egg, driven by an elevation in inositol trisphosphate. The causative agent of these oscillations is proposed to be a recently described phosphoinositide-specific phospholipase C, PLCζ, a soluble sperm protein that is delivered into the egg following membrane fusion. In the present review, we examine some of the distinctive structural and functional characteristics of this crucial enzyme that sets it apart from the other known forms of mammalian PLC.
Evolutionarily conserved structural and functional roles of the FYVE domain
Authors: Hayakawa Akira , Hayes Susan , Leonard Deborah , Lambright David , Corvera Silvia
Published: August 2015

The FYVE domain is an approx. 80 amino acid motif that binds to the phosphoinositide PtdIns3P with high specificity and affinity. It is present in 38 predicted gene products within the human genome, but only in 12–13 in Caenorhabditis elegans and Drosophila melanogaster. Eight of these are highly conserved in all three organisms, and they include proteins that have not been characterized in any species. One of these, WDFY2, appears to play an important role in early endocytosis and was revealed in a RNAi (RNA interference) screen in C. elegans. Interestingly, some proteins contain FYVE-like domains in C. elegans and D. melanogaster, but have lost this domain during evolution. One of these is the homologue of Rabatin-5, a protein that, in mammalian cells, binds both Rab5 and Rabex-5, a guanine-nucleotide exchange factor for Rab5. Thus the Rabatin-5 homologue suggests that mechanisms to link PtdIns3P and Rab5 activation developed in evolution. In mammalian cells, these mechanisms are apparent in the existence of proteins that bind PtdIns3P and Rab GTPases, such as EEA1, Rabenosyn-5 and Rabip4′. Despite the comparable ability to bind to PtdIns3P in vitro, FYVE domains display widely variable abilities to interact with endosomes in intact cells. This variation is due to three distinct properties of FYVE domains conferred by residues that are not involved in PtdIns3P head group recognition: These properties are: (i) the propensity to oligomerize, (ii) the ability to insert into the membrane bilayer, and (iii) differing electrostatic interactions with the bilayer surface. The different binding properties are likely to regulate the extent and duration of the interaction of specific FYVE domain-containing proteins with early endosomes, and thereby their biological function.
Regulation of phospholipase D activity, membrane targeting and intracellular trafficking by phosphoinositides
Authors: Morris Andrew J.
Published: August 2015

Generation of PA (phosphatidic acid) by PLD (phospholipase D)-catalysed hydrolysis of phosphatidylcholine plays a pivotal role in cellular signalling pathways that regulate organization of the actin cytoskeleton, vesicular transport and exocytosis and stimulation of cell growth and survival. PLD regulation and function are intimately linked with phosphoinositide metabolism. Phosphatidyl 4-phosphate 5-kinase is stimulated by PA in vitro and this enzyme is the downstream effector of a significant subset of PLD signalling pathways. Yeast and mammalian PLDs are potently and specifically activated by the product of this kinase, PtdIns(4,5)P2, through interactions mediated by a polybasic motif within the catalytic core of the enzyme. Integrity of this motif is critical for agonist activation of mammalian PLD and for PLD function in secretion, sporulation and exocytosis in vivo. Although dispensable for catalysis in vitro, these PLD enzymes also contain N-terminal PH (pleckstrin) and PX (phox) homology domains. Binding studies using recombinantly expressed PLD fragments indicate that the PH and PX domains also interact specifically with distinct phosphoinositide ligands. Both the PX and PH domains are important for PLD function by controlling the dynamic association of the enzyme with the plasma membrane and its intracellular trafficking by the endocytic pathway. These results identify two distinct modes of regulation of PLD by phosphoinositides: stimulation of catalysis mediated by the polybasic domain and dynamic regulation of membrane targeting mediated primarily by the PH and PX domains.
A Facile Preparation of α-Aryl Carboxylic Acid via One-Flow Arndt–Eistert Synthesis
Authors: Fuse Shinichiro , Otake Yuma , Mifune Yuto , Tanaka Hiroshi
Published: August 2015

An efficient, one-flow Arndt–Eistert synthesis was demonstrated. A sequence of acid chloride formation–nucleophilic acyl substitution–Wolff rearrangement–nucleophilic addition was performed in a microflow system without isolating any intermediates, which included a potentially explosive compound. The microflow system was made from simple, inexpensive, and readily available instruments and tubes. α-Aryl esters 2a and 2b were prepared in yields of 33 and 23 % (three steps) respectively.
US Supreme Court Law Clerks as Information Sources
Authors: Kromphardt Christopher D.
Published: August 2015

Justices use information from attorneys, amici, and the solicitor general to learn about cases. One source that has gone with little empirical scrutiny is their law clerks. I validate a measure of clerk preferences and analyze the role of information conveyed by clerks in shaping the justices’ votes on the merits. I report asymmetric support for the theory that clerks get what they want when they craft credible signals: the results support the conclusion that conservative clerks can influence vote direction. These findings bolster understanding of the role of information in hierarchical relationships and shine light on clerks’ roles.
Writing the Book of Judges
Authors: Slotnick Elliot , Goldman Sheldon , Schiavoni Sara
Published: August 2015

This is part 1 of a two-part series detailing the selection and confirmation processes of lower federal court judges during President Obama’s first 6 years. Our attention in part 1 is on Obama’s lower federal court appointments during the 113th Congress, specifically on the selection processes. We then examine the backgrounds and attributes of those confirmed during the 113th, looking at the appointees to the district and appeals courts separately. Confirmation processes are the main focus of part 2 of our study, where we discuss the lead-up to the nuclear option, the “fallout” from its invocation, and the renewed emphasis on the Blue Slip system as a tool of the minority party in the Senate. We conclude by taking a deeper look at the administration’s historic contribution to enhancing diversity on the federal bench across the district and circuit courts and, as well, make a similar assessment of the impact of the Obama appointments on the partisan makeup of the federal bench on the district courts and across the appellate circuits.
The complexities of assessments in professional hospitality education
Authors: Brinkman-Staneva Marina
Published: August 2015

Purpose

– The purpose of this paper is to highlight some inadequacies of the position of lecturers’ qualifications to design assessments within hospitality curricula while meeting the requirements of international and national quality frameworks.The Framework for Qualifications of the European Higher Education Area leaves the responsibility for designing appropriate teaching and assessment strategies in the hands of educators without fully recognizing the complexity of formulating the desired learning outcomes. Additionally, the subject-oriented background of the majority of educators within universities of applied sciences seems to be ignored in respect of its influence on assessment design.

Design/methodology/approach

– This paper reflects on the author’s experience in designing courses, teaching and assessment strategies at the NHTV University of Applied Sciences in The Netherlands, as well as observations of processes at other universities of applied sciences.

Findings

– The author argues for a uniform delineation of hospitality professional qualifications which integrates learning outcomes from international, national and industry profiles. It is proposed that course design should start with assessment design to achieve alignment with learning outcomes and instructional strategies. Universities of applied sciences will have to train course designers in advanced assessment methods and encourage all faculty to acquire appropriate didactical training in assessing students.

Practical implications

– This paper offers a view on the strategy necessary to ensuring adequate preparation of lecturers in the areas of writing–learning outcomes and preparing assessment.

Originality/value

– The value of the paper lies in the fact that it is a unique critique of pedagogy in Dutch universities of applied sciences.
Retracted: Formin‐like2 regulates Rho/ROCK pathway to promote actin assembly and cell invasion of colorectal cancer
Authors: Zeng Yuanfeng , Xie Huijun , Qiao Yudan , Wang Jianmei , Zhu Xiling , He Guoyang , Li Yuling , Ren Xiaoli , Wang Feifei , Liang Li , Ding Yanqing
Published: August 2015

Formin‐like2 (FMNL2) is a member of the diaphanous‐related formins family, which act as effectors and upstream modulators of Rho GTPases signaling and control the actin‐dependent processes, such as cell motility or invasion. FMNL2 has been identified as promoting the motility and metastasis in colorectal carcinoma (CRC). However, whether FMNL2 regulates Rho signaling to promote cancer cell invasion remains unclear. In this study, we demonstrated an essential role for FMNL2 in the activations of Rho/ROCK pathway, SRF transcription or actin assembly, and subsequent CRC cell invasion. FMNL2 could activate Rho/ROCK pathway, and required ROCK to promote CRC cell invasion. Moreover, FMNL2 promoted the formation of filopodia and stress fiber, and activated the SRF transcription in a Rho‐dependent manner. We also demonstrated that FMNL2 was necessary for LPA‐induced invasion, RhoA/ROCK activation, actin assembly and SRF activation. FMNL2 was an essential component of LPA signal transduction toward RhoA by directly interacting with LARG. LARG silence inhibited RhoA/ROCK pathway and CRC cell invasion. Collectively, these data indicate that FMNL2, acting as upstream of RhoA by interacting with LARG, can promote actin assembly and CRC cell invasion through a Rho/ROCK‐dependent mechanism.
Urinothorax: a rare finding after urinary intervention
Authors: Abdel‐Rahman Ahmed M.
Published: August 2015

Introduction

We report a case in our center of unilateral urinothorax that occurred post percutaneous nephrolithotomy as a rare cause of pleural effusion and acute dyspnea.

Methods

Report of a case.

Results

Initial chest CT showed massive left sided pleural effusion from which biochemical investigations revealed exudative effusion and urinothorax. The effusion was drained by central venous pressure catheter and urologic problem was resolved.

Conclusions

urinothorax should be suspected as a cause of pleural effusion in obstructive uropathy and post renal and ureteric maneuvers.
A comparative study on free and bound phenolic acid content and their antioxidant activity in bran of rice (Oryza sativa L.) cultivars of Eastern Himalayan range
Authors: Begum Ashma , Goswami Aradhana , Chowdhury Pritish
Published: August 2015

In our study, seven most prevailing but unexplored indigenous rice cultivars of northeast India, situated in the Eastern Himalayan Range, were investigated for their phenolic acid profile, total phenolic content (TPC) and antioxidant capacities in free and bound phenolic extracts of their bran. HPLC studies showed the presence of ferulic, p‐coumaric, sinapic, caffeic, chlorogenic and vanillic acids, with ferulic and p‐coumaric acids being the dominant phenolic acids in the bound form. The lower EC50 values of the bound extracts than the free extracts suggested the better radical scavenging activity of the bound extracts. Significant correlations were observed between TPC and phenolic acid content (HPLC‐DAD) of bound extracts, and between Trolox equivalents antioxidant capacity (TEAC) and phenolic acid content (HPLC‐DAD) of both free and bound extracts. The findings suggest that phenolic acids in the rice cultivars investigated were exclusively present in bound form and contribute significantly towards their antioxidant capacity.
‘Am I Free Now?’ Overseas Domestic Workers in Slavery
Authors: Mantouvalou Virginia
Published: August 2015

This article examines United Kingdom overseas domestic worker and diplomatic domestic worker visas in place since 2012. These visas tie workers to an employer by making it unlawful for them to change employer, even when seriously exploited or abused. The article presents the findings of a qualitative study of overseas domestic workers, exploring how this vulnerable and difficult (for researchers) to reach group experience these visas in practice. Workers reported instances of exploitation and abuse by the employers with whom they arrived in the United Kingdom. Having escaped, they have become undocumented, and are trapped in ongoing cycles of exploitation. The article assesses what light this empirical exploration sheds on the question of whether the visa is contrary to the prohibition of slavery, servitude, forced and compulsory labour in article 4 of the European Convention on Human Rights and the UK Modern Slavery Act 2015.
Inequality in Political Philosophy and in Epidemiology: A Remarriage
Authors: Eyal Nir
Published: August 2015

In political philosophy and in economics, unfair inequality is usually assessed between individuals, nowadays often on luck‐egalitarian grounds. You have more than I do (through no fault of my own) and that's unfair. By contrast, in epidemiology and sociology, unfair inequality is traditionally assessed between groups. More is concentrated among people of your class or race than among people of mine, and that's unfair. I shall call this difference the egalitarian ‘divorce’.

Epidemiologists, and their ‘divorce lawyers’ Paula Braveman, Norman Daniels, and Iris Marion Young, explain that not every inequality between individuals is an inequity. Only inequality between social status groups is unfair. Only such inequality stems from problems like partiality, discrimination, oppression, inequality‐related population health problems, and unfair distribution of prospects. And it alone is actionable. By contrast, inequality between individuals, e.g. in longevity, is natural, inevitable, less important, or otherwise less informative — not unjust.

In ‘divorce trial’ mode, I respond to epidemiologists that group inequalities lack the intrinsic disvalue that they ascribe them. They may be instrumentally or contingently bad or wrong, not essentially so. I then shift to ‘remarriage’: although group inequalities lack intrinsic badness or wrongness, for multiple reasons they remain useful to measure.
Performance of a Culturally Tailored Cognitive‐Behavioral Intervention Integrated in a Public Health Setting to Reduce Risk of Antepartum Depression: A Randomized Controlled Trial
Authors: Jesse D. Elizabeth , Gaynes Bradley N. , Feldhousen Elizabeth B. , Newton Edward R. , Bunch Shelia , Hollon Steven D.
Published: August 2015

Introduction

Cognitive‐behavioral group interventions have been shown to improve depressive symptoms in adult populations. This article details the feasibility and efficacy of a 6‐week, culturally tailored, cognitive‐behavioral intervention offered to rural, minority, low‐income women at risk for antepartum depression.

Methods

A total of 146 pregnant women were stratified by high risk for antepartum depression (Edinburgh Postnatal Depression Scale [EPDS] score of 10 or higher) or by low‐moderate risk (EPDS score of 4‐9) and randomized to a cognitive‐behavioral intervention or treatment as usual. Differences in mean change of EPDS and Beck Depression Inventory (BDI)‐II scores for low‐moderate and high‐risk women in the cognitive‐behavioral intervention and treatment as usual for the full sample were assessed from baseline (T1), posttreatment (T2), and one‐month follow‐up (T3), and for African American women in the subsample.

Results

Both the cognitive‐behavioral intervention and treatment‐as‐usual groups had significant reductions in the EPDS scores from T1 to T2 and T1 to T3. In women at high risk for depression (n = 62), there was no significant treatment effect from T1 to T2 or T3 for the EPDS. However, in low‐moderate risk women, there was a significantly greater mean change in the BDI‐II scores from significant decrease in the BDI‐II scores from T1 to T2 (4.92 vs 0.59, P = .018) and T1 to T3 (5.67 vs 1.51, P = .04). Also, the cognitive‐behavioral intervention significantly reduced EPDS scores for African American women at high risk (n = 43) from T1 to T2 (5.59 vs 2.18, P = .02) and from T1 to T3 (6.32 vs 3.14, P = .04).

Discussion

A cognitive‐behavioral intervention integrated within prenatal clinics is feasible in this sample, although attrition rates were high. Compared to treatment as usual, the cognitive‐behavioral intervention reduced depressive symptoms for African American women at high risk for antepartum depression and for the full sample of women at low‐moderate risk for antepartum depression. These promising findings need to be replicated in a larger controlled clinical trial that incorporates methods to maintain greater participant engagement.
Medication errors in hospitals: a literature review of disruptions to nursing practice during medication administration
Authors: Hayes Carolyn , Jackson Debra , Davidson Patricia M , Power Tamara
Published: August 2015

Aims and objectives

The purpose of this review was to explore what is known about interruptions and distractions on medication administration in the context of undergraduate nurse education.

Background

Incidents and errors during the process of medication administration continue to be a substantial patient safety issue in health care settings internationally. Interruptions to the medication administration process have been identified as a leading cause of medication error. Literature recognises that some interruptions are unavoidable; therefore in an effort to reduce errors, it is essential understand how undergraduate nurses learn to manage interruptions to the medication administration process.

Design

Systematic, critical literature review.

Methods

Utilising the electronic databases, of Medline, Scopus, PubMed and CINAHL, and recognised quality assessment guidelines, 19 articles met the inclusion criteria. Search terms included: nurses, medication incidents or errors, interruptions, disruption, distractions and multitasking.

Results

Researchers have responded to the impact of interruptions and distractions on the medication administration by attempting to eliminate them. Despite the introduction of quality improvements, little is known about how nurses manage interruptions and distractions during medication administration or how they learn to do so. A significant gap in the literature exists in relation to innovative sustainable strategies that assist undergraduate nurses to learn how to safely and confidently manage interruptions in the clinical environment.

Conclusions

Study findings highlight the need for further exploration into the way nurses learn to manage interruptions and distractions during medication administration. This is essential given the critical relationship between interruptions and medication error rates.

Relevance to clinical practice

Better preparing nurses to safely fulfil the task of medication administration in the clinical environment, with increased confidence in the face of interruptions, could lead to a reduction in errors and concomitant improvements to patient safety.
Body fat distribution and its associated factors in Korean women with polycystic ovary syndrome
Authors: Jin Chan Hee , Yuk Jin Sung , Choi Kyung Mook , Yi Kyung Wook , Kim Tak , Hur Jun Young , Shin Jung‐Ho
Published: August 2015

Aim

To investigate the body fat distribution in Korean women with polycystic ovary syndrome (PCOS) and the association of those distribution with metabolic parameters and hormone profiles.

Methods

A total 90 patients with PCOS and 97 women without PCOS (control group) were included in this study. Total body fat, abdominal visceral fat, and subcutaneous fat were determined on abdominal fat computed tomography. Lipid profiles and sex‐hormone binding globulin (SHBG), testosterone, free androgen index (FAI), and cortisol were measured in PCOS group.

Results

Total body fat and body fat distribution in the PCOS group were not significantly different from the control group in Korean women (P = 0.054, P = 0.761, P = 0.104), but abdominal visceral to subcutaneous fat ratio was larger in the PCOS group than the control group (P = 0.047). Not only total body fat and visceral fat, but also subcutaneous fat in the PCOS group had a positive correlation with homeostatic model assessment–insulin resistance, fasting blood sugar, low‐density lipoprotein cholesterol, triglyceride, systolic blood pressure, diastolic blood pressure, fasting insulin, free testosterone, FAI, body mass index, but negative correlation with SHBG and high‐density lipoprotein cholesterol.

Conclusions

Korean PCOS women had the same body fat distribution as the control group. Subcutaneous fat was also correlated with metabolic parameters and hormone profiles in the Korean PCOS group.
The effect of antimicrobial agents on bond strength of orthodontic adhesives: a meta‐analysis of in vitro studies
Authors: Altmann A. S. P. , Collares F. M. , Leitune V. C. B. , Samuel S. M. W.
Published: August 2015

Antimicrobial orthodontic adhesives aim to reduce white spot lesions' incidence in orthodontic patients, but they should not jeopardizing its properties. Systematic review and meta‐analysis were performed to answer the question whether the association of antimicrobial agents with orthodontic adhesives compromises its mechanical properties and whether there is a superior antimicrobial agent. PubMed and Scopus databases. In vitro studies comparing shear bond strength of conventional photo‐activated orthodontic adhesives to antimicrobial photo‐activated orthodontic adhesives were considered eligible. Search terms included the following: orthodontics, orthodontic, antimicrobial, antibacterial, bactericidal, adhesive, resin, resin composite, bonding agent, bonding system, and bond strength. The searches yielded 494 citations, which turned into 467 after duplicates were discarded. Titles and abstracts were read and 13 publications were selected for full‐text reading. Twelve studies were included in the meta‐analysis. The global analysis showed no statistically significant difference between control and experimental groups. In the subgroup analysis, only the chlorhexidine subgroup showed a statistically significant difference, where the control groups had higher bond strength than the experimental groups. Many studies on in vitro orthodontic bond strength fail to report test conditions that could affect their outcomes. The pooled in vitro data suggest that adding an antimicrobial agent to an orthodontic adhesive system does not influence bond strength to enamel. It is not possible to state which antimicrobial agent is better to be associated.
Complement activation product C4d in oral and oropharyngeal squamous cell carcinoma
Authors: Ajona D , Pajares MJ , Chiara MD , Rodrigo JP , Jantus‐Lewintre E , Camps C , Suarez C , Bagán JV , Montuenga LM , Pio R
Published: August 2015

Objective

Complement C4d‐containing fragments have been proposed as diagnostic markers for lung cancer. The purpose of this study was to evaluate the presence of C4d in oropharyngeal (OPSCC) and oral (OSCC) squamous cell carcinomas.

Subjects and Methods

C4d staining was analyzed by immunohistochemistry in 244 OPSCC surgical specimens. C4d levels were quantified by ELISA in resting saliva samples from 48 patients with oral leukoplakia and 62 with OSCC. Plasma samples from 21 patients with leukoplakia and 30 with oral carcinoma were also studied.

Results

C4d staining in OPSCC specimens was associated with nodal invasion (P = 0.001), histopathologic grade (P = 0.014), disease stage (P = 0.040), and focal‐adhesion kinase expression (P < 0.001). No association was found between C4d and prognosis. Saliva C4d levels were higher in patients with oral cancer than in subjects with leukoplakia (0.07 ± 0.07 vs 0.04 ± 0.03 μg ml−1, P = 0.003). The area under the ROC curve was 0.63 (95%CI: 0.55–0.71). Salivary C4d levels in stage IV patients were higher than in patients with earlier stages (P = 0.028) and correlated with tumor size (P = 0.045). Plasma C4d levels also correlated with salivary C4d levels (P = 0.041), but differences between patients with oral cancer and subjects with leukoplakia were not significant (1.26 ± 0.59 vs 1.09 ± 0.39 μg ml−1, P = 0.232).

Conclusion

C4d‐containing fragments are detected in oral primary tumors and are increased in saliva from patients with OSCC.
Oral bacteria in placental tissues: increased molecular detection in pregnant periodontitis patients
Authors: Blanc V , O'Valle F , Pozo E , Puertas A , León R , Mesa F
Published: August 2015

Objectives

The objective of this study was to identify the DNA of oral bacteria in placental samples from women with and without periodontitis who had or had not had preterm births and/or low birthweight (PB/LBW) neonates.

Methods

Data were gathered from 57 puerperal women in relation to socio‐demographic, gynaecological, and periodontal variables and to placental histomorphology. Fifty‐seven biopsies, 28 from mothers with periodontitis, were taken aseptically from preterm placentas (n = 36) and from full‐term placentas (n = 21). Total DNA was extracted, and the presence of 15 oral bacteria was assessed using Nested‐PCR.

Results

The placentas from women with periodontitis showed a higher prevalence of periodontopathogens compared to those from women without periodontitis (P = 0.009). Samples showed low prevalences of Actinomyces israelii, Parvimonas micra and Tannerella forsythia. An association was found between Eikenella corrodens in placenta and periodontitis (P = 0.002). The most ubiquitous bacterium, Fusobacterium nucleatum, was more prevalent in mothers with periodontitis and PB/LBW (P = 0.033). Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia and Aggregatibacter actinomycetemcomitans were not detected.

Conclusions

These results, along with previous findings, show that oral bacteria may be normally present in the placenta, however, the levels of certain oral pathogens in the placenta would highly depend on the mother's periodontal state.
Assessing Systematic Effects of Stroke on Motor Control by Using Hierarchical Function-On-Scalar Regression
Authors: Goldsmith Jeff , Kitago Tomoko
Published: August 2015

This work is concerned with understanding common population level effects of stroke on motor control while accounting for possible subject level idiosyncratic effects. Upper extremity motor control for each subject is assessed through repeated planar reaching motions from a central point to eight prespecified targets arranged on a circle. We observe the kinematic data for hand position as a bivariate function of time for each reach. Our goal is to estimate the bivariate function-on-scalar regression with subject level random functional effects while accounting for potential correlation in residual curves; covariates of interest are severity of motor impairment and target number. We express fixed effects and random effects by using penalized splines, and we allow for residual correlation by using a Wishart prior distribution. Parameters are jointly estimated in a Bayesian framework, and we implement a computationally efficient approximation algorithm using variational Bayes methods. Simulations indicate that the method proposed yields accurate estimation and inference, and application results suggest that the effect of stroke on motor control has a systematic component observed across subjects.
An Investigation of Nonlinear Flow Oscillations in a High-Pressure Centrifugal Pump
Authors: Lettieri Claudio , Defoe Jeff , Spakovszky Zoltán S.
Published: August 2015

High-pressure multistage pumps and their coupled piping systems, typically used in the process and power generation industry, can experience dangerous system-level instabilities. This can occur at flow coefficients well away from the surge limit and in the absence of cavitation. Such a pumping system and a related new kind of instability are the focus of this paper. A system-wide instability was observed at 0.05 times rotor frequency for flow coefficients near maximum head rise but at negative slope, thus on the stable side of the head rise characteristic. A previous study based on system-level experiments concluded that this instability differs from classical surge, cavitation surge, rotating stall, and rotating cavitation, but the underlying mechanism and necessary flow conditions remain unknown. This paper investigates the root cause of the system-wide pump instability, employing a systematic analysis of the impact of geometry changes on pump stability and performance. It is found that the upstream influence of the unsteady flow separation in the return channel leads to a time-varying incidence angle change on the volute tongue which causes periodic ingestion of low-stagnation pressure fluid into the diffuser passages. This sets up a limit cycle, promoting the system-wide instability. With the instability mechanism determined, the pump is redesigned to remove the flow separation while maintaining performance at design conditions. Unsteady numerical simulations demonstrate improved efficiency and pressure recovery at low flow coefficients. A time accurate calculation also indicates stable operation at all relevant flow conditions. The paper resolves a long-standing pump stability problem and provides design guidelines for reliable and improved performance, important to the chemical processing and power generation industry.
Iterative Learning Active Flow Control Applied to a Compressor Stator Cascade With Periodic Disturbances
Authors: Steinberg Simon J. , Staats Marcel , Nitsche Wolfgang , King Rudibert
Published: August 2015

This paper presents the capability of iterative learning active flow control to decrease the impact of periodic disturbances in an experimental compressor stator cascade with sidewall actuation. The periodic disturbances of the individual passage flows are generated by a damper flap device that is located downstream of the trailing edges of the blades. The device mimics the throttling effect of periodically closed combustion tubes in a pulsed detonation engine (PDE). For the purpose of rejecting this disturbance, the passage flow is manipulated by fluidic actuators that introduce an adjustable amount of pressurized air through slots in the sidewalls of the cascade. Pressure sensors that are mounted flush to the suction surface of the middle blade provide information on the current flow situation. These data are fed back in real-time to an optimization-based iterative learning controller (ILC). By learning from period to period, the controller modifies the actuation amplitude such that, eventually, a control command trajectory is calculated that reduces the impact of the periodic disturbance on the flow in an optimal manner.
Investigation of Flow Separation in a Diffuser of a Bulb Turbine
Authors: Duquesne Pierre , Maciel Yvan , Deschênes Claire
Published: August 2015

A three-dimensional unsteady flow separation in the straight diffuser of a model bulb turbine is investigated using tuft visualizations, unsteady wall pressure sensors, and particle image velocimetry (PIV). Experimental results reveal a link between the flow separation zone extension and the sudden drop in turbine performances. The flow separation zone grows as the flow rate increases past the best efficiency operating point (OP). It starts on the bottom wall and expands azimuthally and upstream. It deviates and perturbs the flow far upstream. Despite high unsteadiness, a global separation streamline pattern composed of a saddle point and a convergence line emerges.