bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive genetic changes related to haemoglobin concentration in native high‐altitude Tibetans
Authors: Simonson T. S. , Huff C. D. , Witherspoon D. J. , Prchal J. T. , Jorde L. B.
Published: October 2015

New Findings

What is the topic of this review?

Tibetans have genetic adaptations that are hypothesized to underlie the distinct set of traits they exhibit at altitude.

What advances does it highlight?

Several adaptive signatures in the same genomic regions have been identified among Tibetan populations resident throughout the Qinghai‐Tibetan Plateau. Many highland Tibetans exhibit a haemoglobin concentration within the range expected at sea level, and this trait is associated with putatively adaptive regions harbouring the hypoxia‐inducible factor pathway genes EGLN1, EPAS1 and PPARA. Precise functional variants at adaptive loci and relationships to physiological traits, beyond haemoglobin concentration, are currently being examined in this population.

Some native Tibetan, Andean and Ethiopian populations have lived at altitudes ranging from 3000 to >4000 m above sea level for hundreds of generations and exhibit distinct combinations of traits at altitude. It was long hypothesized that genetic factors contribute to adaptive differences in these populations, and recent advances in genomics provide evidence that some of the strongest signatures of positive selection in humans are those identified in Tibetans. Many of the top adaptive genomic regions highlighted thus far harbour genes related to hypoxia sensing and response. Putatively adaptive copies of three hypoxia‐inducible factor pathway genes, EPAS1, EGLN1 and PPARA, are associated with sea‐level range, rather than elevated, haemoglobin concentration observed in many Tibetans at high altitude, and recent studies provide insight into some of the precise adaptive variants, timing of adaptive events and functional roles. While several studies in highland Tibetans have converged on a few hypoxia‐inducible factor pathway genes, additional candidates have been reported in independent studies of Tibetans located throughout the Qinghai‐Tibetan Plateau. Various aspects of adaptive significance have yet to be identified, integrated, and fully explored. Given the rapid technological advances and interdisciplinary efforts in genomics, physiology and molecular biology, careful examination of Tibetans and comparisons with other distinctively adapted highland populations will provide valuable insight into evolutionary processes and models for both basic and clinical research.
Sea‐level haemoglobin concentration is associated with greater exercise capacity in Tibetan males at 4200 m
Authors: Wagner P. D. , Simonson T. S. , Wei G. , Wagner H. E. , Wuren T. , Qin G. , Yan M. , Ge R. L.
Published: October 2015

New Findings

What is the topic of this review?

Recent developments link relatively lower hemoglobin concentration in Tibetans at high altitude to exercise capacity and components of oxygen transport.

What advances does it highlight?

Haemoglobin concentration (ranging from 15.2 to 22.9 g dl−1) in Tibetan males was negatively associated with peak oxygen (O2) uptake per kilogram, cardiac output and muscle O2 diffusion conductance. Most variance in the peak O2 uptake per kilogram of Tibetan males was attributed to cardiac output, muscle diffusional conductance and arterial partial pressure of CO2. The mechanisms underlying these differences in oxygen transport in Tibetans require additional analyses.

Despite residence at >4000 m above sea level, many Tibetan highlanders, unlike Andean counterparts and lowlanders at altitude, exhibit haemoglobin concentration ([Hb]) within the typical sea‐level range. Genetic adaptations in Tibetans are associated with this relatively low [Hb], yet the functional relevance of the lower [Hb] remains unknown. To address this, we examined each major step of the oxygen transport cascade [ventilation (VE), cardiac output (QT) and diffusional conductance in lung (DL) and muscle (DM)] in Tibetan males at maximal exercise on a cycle ergometer. Ranging from 15.2 to 22.9 g dl−1, [Hb] was negatively associated with peak O2 uptake per kilogram (r = −0.45, P < 0.05) and both cardiac output (QT/kg: r = −0.54, P < 0.02) and muscle O2 diffusion conductance (DM/kg: r = −0.44, P < 0.05) but not ventilation, arterial partial pressure of O2 or pulmonary diffusing capacity. Most variance in peak O2 uptake per kilogram was attributed to QT, DM and arterial partial pressure of CO2 (r2 = 0.90). In summary, lack of polycythaemia in Tibetans is associated with increased exercise capacity, which is explained by elevated cardiac, muscle and, to a small extent, ventilatory responses rather than pulmonary gas exchange. Whether lower [Hb] is the cause or result of these changes in O2 transport or is causally unrelated will require additional study.
Impact of extreme exercise at high altitude on oxidative stress in humans
Authors: Quindry John , Dumke Charles , Slivka Dustin , Ruby Brent
Published: October 2015

Exercise and oxidative stress research continues to grow as a physiological subdiscipline. The influence of high altitude on exercise and oxidative stress is among the recent topics of intense study in this area. Early findings indicate that exercise at high altitude has an independent influence on free radical generation and the resultant oxidative stress. This review provides a detailed summary of oxidative stress biochemistry as gleaned mainly from studies of humans exercising at high altitude. Understanding of the human response to exercise at altitude is largely derived from field‐based research at altitudes above 3000 m in addition to laboratory studies which employ normobaric hypoxia. The implications of oxidative stress incurred during high altitude exercise appear to be a transient increase in oxidative damage followed by redox‐sensitive adaptations in multiple tissues. These outcomes are consistent for lowland natives, high altitude acclimated sojourners and highland natives, although the latter group exhibits a more robust adaptive response. To date there is no evidence that altitude‐induced oxidative stress is deleterious to normal training or recovery scenarios. Limited evidence suggests that deleterious outcomes related to oxidative stress are limited to instances where individuals are exposed to extreme elevations for extended durations. However, confirmation of this tentative conclusion requires further investigation. More applicably, altitude‐induced hypoxia may have an independent influence on redox‐sensitive adaptive responses to exercise and exercise recovery. If correct, these findings may hold important implications for athletes, mountaineers, and soldiers working at high altitude. These points are raised within the confines of published research on the topic of oxidative stress during exercise at altitude.

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Gold tetrahedra coil up: Kekulé-like and double helical superstructures
Authors: Zeng Chenjie , Chen Yuxiang , Liu Chong , Nobusada Katsuyuki , Rosi Nathaniel L. , Jin Rongchao
Published: October 2015

Structures of gold clusters resemble the benzene and DNA molecules and reveal a “supermolecule” origin of the magic-sized clusters.
MED12 methylation by CARM1 sensitizes human breast cancer cells to chemotherapy drugs
Authors: Wang Lu , Zeng Hao , Wang Qiang , Zhao Zibo , Boyer Thomas G. , Bian Xiuwu , Xu Wei
Published: October 2015

MED12 is methylated by CARM1, and methylated MED12 serves as a sensor for anticancer drug response in human breast cancer.
Contractility parameters of human β-cardiac myosin with the hypertrophic cardiomyopathy mutation R403Q show loss of motor function
Authors: Nag Suman , Sommese Ruth F. , Ujfalusi Zoltan , Combs Ariana , Langer Stephen , Sutton Shirley , Leinwand Leslie A. , Geeves Michael A. , Ruppel Kathleen M. , Spudich James A.
Published: October 2015

Force parameters of human β-cardiac myosin with the hypertrophic cardiomyopathy mutation R403Q show loss of molecular motor function.
Optogenetic pacing in
Drosophila melanogaster
Authors: Alex Aneesh , Li Airong , Tanzi Rudolph E. , Zhou Chao
Published: October 2015

Heart rhythm of fruit flies at different developmental stages can be noninvasively controlled by light using optogenetics.
Persistent optical gating of a topological insulator
Authors: Yeats Andrew L. , Pan Yu , Richardella Anthony , Mintun Peter J. , Samarth Nitin , Awschalom David D.
Published: October 2015

A flexible, bidirectional optical effect in SrTiO
3
allows us to write and erase tiny p-n junctions in a topological insulator.
On the decadal scale correlation between African dust and Sahel rainfall: The role of Saharan heat low–forced winds
Authors: Wang Weijie , Evan Amato T. , Flamant Cyrille , Lavaysse Christophe
Published: October 2015

Interannual variability in rainfall and surface wind speeds over the Sahara are the result of changes in tropospheric air temperature.
Copper-catalyzed aerobic oxidative coupling: From ketone and diamine to pyrazine
Authors: Wu Kun , Huang Zhiliang , Qi Xiaotian , Li Yingzi , Zhang Guanghui , Liu Chao , Yi Hong , Meng Lingkui , Bunel Emilio E. , Miller Jeffrey T. , Pao Chih-Wen , Lee Jyh-Fu , Lan Yu , Lei Aiwen
Published: October 2015

A new copper-catalyzed reaction toward the synthesis of pyrazine compounds is demonstrated.
Mixing unmixables: Unexpected formation of Li-Cs alloys at low pressure
Authors: Desgreniers Serge , Tse John S. , Matsuoka Takahiro , Ohishi Yasuo , Tse Justin J.
Published: October 2015

Unexpected Li-Cs alloy with unusual Cs to Li charge transfer characterized from valence charge topology has been synthesized under 10 GPa.
Global prevalence and distribution of genes and microorganisms involved in mercury methylation
Authors: Podar Mircea , Gilmour Cynthia C. , Brandt Craig C. , Soren Allyson , Brown Steven D. , Crable Bryan R. , Palumbo Anthony V. , Somenahally Anil C. , Elias Dwayne A.
Published: October 2015

A global metagenome assessment reveals a low risk of methylmercury production in humans and a high potential in Arctic permafrost.
Accretion-induced variability links young stellar objects, white dwarfs, and black holes
Authors: Scaringi Simone , Maccarone Thomas J. , Körding Elmar , Knigge Christian , Vaughan Simon , Marsh Thomas R. , Aranzana Ester , Dhillon Vikram S. , Barros Susana C. C.
Published: October 2015

Astrophysical accretion is a universal process in objects from proto-stars to supermassive black holes.
Dehalogenimonas sp. Strain WBC-2 Genome and Identification of Its
trans
-Dichloroethene Reductive Dehalogenase, TdrA
Authors: Molenda Olivia , Quaile Andrew T. , Edwards Elizabeth A.
Published: October 2015

The
Dehalogenimonas
population in a dechlorinating enrichment culture referred to as WBC-2 was previously shown to be responsible for
trans
-dichloroethene (tDCE) hydrogenolysis to vinyl chloride (VC). In this study, blue native polyacrylamide gel electrophoresis (BN-PAGE) followed by enzymatic assays and protein identification using liquid chromatography coupled with mass spectrometry (LC-MS/MS) led to the functional characterization of a novel dehalogenase, TdrA. This new reductive dehalogenase (RDase) catalyzes the dechlorination of tDCE to VC. A metagenome of the WBC-2 culture was sequenced, and a complete
Dehalogenimonas
genome, only the second
Dehalogenimonas
genome to become publicly available, was closed. The
tdrA
dehalogenase found within the
Dehalogenimonas
genome appears to be on a genomic island similar to genomic islands found in
Dehalococcoides
. TdrA itself is most similar to TceA from
Dehalococcoides
sp. strain FL2 with 76.4% amino acid pairwise identity. It is likely that the horizontal transfer of
rdhA
genes is not only a feature of
Dehalococcoides
but also a feature of other
Dehalococcoidia
, including
Dehalogenimonas.
A set of primers was developed to track
tdrA
in WBC-2 subcultures maintained on different electron acceptors. This newest dehalogenase is an addition to the short list of functionally defined RDases sharing the usual characteristic motifs (including an AB operon, a TAT export sequence, two iron-sulfur clusters, and a corrinoid binding domain), substrate flexibility, and evidence for horizontal gene transfer within the
Dehalococcoidia
.
The Antisense RNA Approach: a New Application for
In Vivo
Investigation of the Stress Response of Oenococcus oeni, a Wine-Associated Lactic Acid Bacterium
Authors: Darsonval Maud , Msadek Tarek , Alexandre Hervé , Grandvalet Cosette
Published: October 2015

Oenococcus oeni
is a wine-associated lactic acid bacterium mostly responsible for malolactic fermentation in wine. In wine,
O. oeni
grows in an environment hostile to bacterial growth (low pH, low temperature, and ethanol) that induces stress response mechanisms. To survive,
O. oeni
is known to set up transitional stress response mechanisms through the synthesis of heat stress proteins (HSPs) encoded by the
hsp
genes, notably a unique small HSP named Lo18. Despite the availability of the genome sequence, characterization of
O. oeni
genes is limited, and little is known about the
in vivo
role of Lo18. Due to the lack of genetic tools for
O. oeni
, an efficient expression vector in
O. oeni
is still lacking, and deletion or inactivation of the
hsp18
gene is not presently practicable. As an alternative approach, with the goal of understanding the biological function of the
O. oeni
hsp18
gene
in vivo
, we have developed an expression vector to produce antisense RNA targeting of
hsp18
mRNA. Recombinant strains were exposed to multiple stresses inducing
hsp18
gene expression: heat shock and acid shock. We showed that antisense attenuation of
hsp18
affects
O. oeni
survival under stress conditions. These results confirm the involvement of Lo18 in heat and acid tolerance of
O. oeni
. Results of anisotropy experiments also confirm a membrane-protective role for Lo18, as previous observations had already suggested. This study describes a new, efficient tool to demonstrate the use of antisense technology for modulating gene expression in
O. oeni
.
Determining Roles of Accessory Genes in Denitrification by Mutant Fitness Analyses
Authors: Vaccaro Brian J. , Thorgersen Michael P. , Lancaster W. Andrew , Price Morgan N. , Wetmore Kelly M. , Poole Farris L. , Deutschbauer Adam , Arkin Adam P. , Adams Michael W. W.
Published: October 2015

Enzymes of the denitrification pathway play an important role in the global nitrogen cycle, including release of nitrous oxide, an ozone-depleting greenhouse gas. In addition, nitric oxide reductase, maturation factors, and proteins associated with nitric oxide detoxification are used by pathogens to combat nitric oxide release by host immune systems. While the core reductases that catalyze the conversion of nitrate to dinitrogen are well understood at a mechanistic level, there are many peripheral proteins required for denitrification whose basic function is unclear. A bar-coded transposon DNA library from
Pseudomonas stutzeri
strain RCH2 was grown under denitrifying conditions, using nitrate or nitrite as an electron acceptor, and also under molybdenum limitation conditions, with nitrate as the electron acceptor. Analysis of sequencing results from these growths yielded gene fitness data for 3,307 of the 4,265 protein-encoding genes present in strain RCH2. The insights presented here contribute to our understanding of how peripheral proteins contribute to a fully functioning denitrification pathway. We propose a new low-affinity molybdate transporter, OatABC, and show that differential regulation is observed for two MoaA homologs involved in molybdenum cofactor biosynthesis. We also propose that NnrS may function as a membrane-bound NO sensor. The dominant HemN paralog involved in heme biosynthesis is identified, and a CheR homolog is proposed to function in nitrate chemotaxis. In addition, new insights are provided into nitrite reductase redundancy, nitric oxide reductase maturation, nitrous oxide reductase maturation, and regulation.
The Siderophore Metabolome of Azotobacter vinelandii
Authors: Baars Oliver , Zhang Xinning , Morel François M. M. , Seyedsayamdost Mohammad R.
Published: October 2015

In this study, we performed a detailed characterization of the siderophore metabolome, or “chelome,” of the agriculturally important and widely studied model organism
Azotobacter vinelandii
. Using a new high-resolution liquid chromatography-mass spectrometry (LC-MS) approach, we found over 35 metal-binding secondary metabolites, indicative of a vast chelome in
A. vinelandii
. These include vibrioferrin, a siderophore previously observed only in marine bacteria. Quantitative analyses of siderophore production during diazotrophic growth with different sources and availabilities of Fe showed that, under all tested conditions, vibrioferrin was present at the highest concentration of all siderophores and suggested new roles for vibrioferrin in the soil environment. Bioinformatic searches confirmed the capacity for vibrioferrin production in
Azotobacter
spp. and other bacteria spanning multiple phyla, habitats, and lifestyles. Moreover, our studies revealed a large number of previously unreported derivatives of all known
A. vinelandii
siderophores and rationalized their origins based on genomic analyses, with implications for siderophore diversity and evolution. Together, these insights provide clues as to why
A. vinelandii
harbors multiple siderophore biosynthesis gene clusters. Coupled with the growing evidence for alternative functions of siderophores, the vast chelome in
A. vinelandii
may be explained by multiple, disparate evolutionary pressures that act on siderophore production.
Depletion of
UBC9
Causes Nuclear Defects during the Vegetative and Sexual Life Cycles in Tetrahymena thermophila
Authors: Yang Qianyi , Nasir Amjad M. , Coyne Robert S. , Forney James D.
Published: October 2015

Ubc9p is the sole E2-conjugating enzyme for SUMOylation, and its proper function is required for regulating key nuclear events such as transcription, DNA repair, and mitosis. In
Tetrahymena thermophila
, the genome is separated into a diploid germ line micronucleus (MIC) that divides by mitosis and a polyploid somatic macronucleus (MAC) that divides amitotically. This unusual nuclear organization provides novel opportunities for the study of SUMOylation and Ubc9p function. We identified the
UBC9
gene and demonstrated that its complete deletion from both MIC and MAC genomes is lethal. Rescue of the lethal phenotype with a
GFP-UBC9
fusion gene driven by a metallothionein promoter generated a cell line with CdCl
2
-dependent expression of green fluorescent protein (GFP)-Ubc9p. Depletion of Ubc9p in vegetative cells resulted in the loss of MICs, but MACs continued to divide. In contrast, expression of catalytically inactive Ubc9p resulted in the accumulation of multiple MICs. Critical roles for Ubc9p were also identified during the sexual life cycle of
Tetrahymena
. Cell lines that were depleted for Ubc9p did not form mating pairs and therefore could not complete any of the subsequent stages of conjugation, including meiosis and macronuclear development. Mating between cells expressing catalytically inactive Ubc9p resulted in arrest during macronuclear development, consistent with our observation that Ubc9p accumulates in the developing macronucleus.
Characterization of a Novel Prevacuolar Compartment in Neurospora crassa
Authors: Bowman Barry J. , Draskovic Marija , Schnittker Robert R. , El-Mellouki Tarik , Plamann Michael D. , Sánchez-León Eddy , Riquelme Meritxell , Bowman Emma Jean
Published: October 2015

Using confocal microscopy, we observed ring-like organelles, similar in size to nuclei, in the hyphal tip of the filamentous fungus
Neurospora crassa
. These organelles contained a subset of vacuolar proteins. We hypothesize that they are novel prevacuolar compartments (PVCs). We examined the locations of several vacuolar enzymes and of fluorescent compounds that target the vacuole. Vacuolar membrane proteins, such as the vacuolar ATPase (VMA-1) and the polyphosphate polymerase (VTC-4), were observed in the PVCs. A pigment produced by adenine auxotrophs, used to visualize vacuoles, also accumulated in PVCs. Soluble enzymes of the vacuolar lumen, alkaline phosphatase and carboxypeptidase Y, were not observed in PVCs. The fluorescent molecule Oregon Green 488 carboxylic acid diacetate, succinimidyl ester (carboxy-DFFDA) accumulated in vacuoles and in a subset of PVCs, suggesting maturation of PVCs from the tip to distal regions. Three of the nine Rab GTPases in
N. crassa
, RAB-2, RAB-4, and RAB-7, localized to the PVCs. RAB-2 and RAB-4, which have similar amino acid sequences, are present in filamentous fungi but not in yeasts, and no function has previously been reported for these Rab GTPases in fungi. PVCs are highly pleomorphic, producing tubular projections that subsequently become detached. Dynein and dynactin formed globular clusters enclosed inside the lumen of PVCs. The size, structure, dynamic behavior, and protein composition of the PVCs appear to be significantly different from those of the well-studied prevacuolar compartment of yeasts.
Adaptations of the Secretome of Candida albicans in Response to Host-Related Environmental Conditions
Authors: Klis Frans M. , Brul Stanley
Published: October 2015

The wall proteome and the secretome of the fungal pathogenCandida albicanshelp it to thrive in multiple niches of the human body. Mass spectrometry has allowed researchers to study the dynamics of both subproteomes. Here, we discuss some major responses of the secretome to host-related environmental conditions. Three β-1,3-glucan-modifying enzymes, Mp65, Sun41, and Tos1, are consistently found in large amounts in culture supernatants, suggesting that they are needed for construction and expansion of the cell wall β-1,3-glucan layer and thus correlate with growth and might serve as diagnostic biomarkers. The genesENG1,CHT3, andSCW11, which encode an endoglucanase, the major chitinase, and a β-1,3-glucan-modifying enzyme, respectively, are periodically expressed and peak in M/G1. The corresponding protein abundances in the medium correlate with the degree of cell separation during single-yeast-cell, pseudohyphal, and hyphal growth. We also discuss the observation that cells treated with fluconazole, or other agents causing cell surface stress, form pseudohyphal aggregates. Fluconazole-treated cells secrete abundant amounts of the transglucosylase Phr1, which is involved in the accumulation of β-1,3-glucan in biofilms, raising the question whether this is a general response to cell surface stress. Other abundant secretome proteins also contribute to biofilm formation, emphasizing the important role of secretome proteins in this mode of growth. Finally, we discuss the relevance of these observations to therapeutic intervention. Together, these data illustrate thatC. albicansactively adapts its secretome to environmental conditions, thus promoting its survival in widely divergent niches of the human body.
What matters to children with CFS/ME? A conceptual model as the first stage in developing a PROM
Authors: Parslow Roxanne , Patel Aarti , Beasant Lucy , Haywood Kirstie , Johnson Debbie , Crawley Esther
Published: October 2015

Background

Paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) is relatively common and disabling. Research is hampered because current patient-reported outcome measures (PROMs) do not capture outcomes that are important to children with CFS/ME.

Aim

The aim of this study was to explore the aspects of life and health outcomes that matter to children with CFS/ME.

Methods

Twenty-five children with CFS/ME were interviewed (11 males, 14 females; mean age 12.9 years (SD 2.2), range 8–17). Twelve were trial participants interviewed during the trial and 13 were recruited as part of a follow-up qualitative study. Parents were present in 19 interviews with their children. Three mothers participated in a focus group. All the interviews and the focus group were audio-recorded and transcribed. Data were analysed thematically using techniques of constant comparison. NVivo was used to structure and categorise data in a systematic way.

Results

Children identified four key themes (health outcome domains): ‘symptoms’ that fluctuated, which caused an unpredictable reduction in both ‘physical activity’ and ‘social participation’ all of which impacted on ‘emotional well-being’. These domains were influenced by both ‘management’ and ‘contextual factors’, which could be positive and negative. The relationship between healthcare and school was considered pivotal.

Conclusions

Children's descriptions helped to inform a conceptual model that is necessary to develop a new paediatric CFS/ME PROM. Doctors need to be aware of how children conceptualise CFS/ME; the relationship between healthcare and school is fundamental to ameliorate the impact of CFS/ME.

Trial registration number

ISRCTN81456207.
Diabetes and glucose disturbances in patients with psychosis in Sweden
Authors: Olsson Eric , Westman Jeanette , Sudic Hukic Dzana , Eriksson Sven V , Edman Gunnar , Bodén Robert , Jedenius Erik , Reutfors Johan , Berntsson Anders , Hilding Agneta , Schalling Martin , Östenson Claes-Göran , Ösby Urban
Published: October 2015

Objective

The objectives of this study were to (1) analyze the prevalence of diabetes, prediabetes, and antidiabetic medication in patients with psychosis compared with control subjects and (2) determine what factors in patients with psychosis were associated with antidiabetic medication.

Method

We studied 977 patients with psychosis recruited from outpatient clinics in Stockholm County, Sweden, and they were compared with 3908 non-psychotic control subjects for fasting plasma glucose levels; prevalence of diabetes, prediabetes, antidiabetic treatment, and tobacco use; and blood pressure, weight, height, and waist circumference. Group differences were evaluated with analysis of variance and χ2test, and factors associated with antidiabetic treatment were evaluated with logistic regression.

Results

Diabetes was observed in 94 (10%) patients with psychosis, 2.7 times the prevalence observed in control subjects. Among patients with psychosis, 87 (10%) had prediabetes (fasting glucose, 6.1–6.9 mmol/L) compared with 149 (3.8%) control subjects. Most patients with psychosis (77%) who had prediabetes fulfilled criteria for metabolic syndrome. In patients with psychosis, both lipid-lowering medication and fasting glucose were significantly associated with antidiabetic treatment. There was no significant relation between antidiabetic treatment and lifestyle factors such as smoking or degree of psychiatric illness.

Conclusions

The high prevalence of impaired fasting glucose and metabolic syndrome in patients with psychosis warrants further clinical research in preventing or delaying the onset of diabetes in these patients by pharmacotherapy and/or lifestyle intervention.
Evaluating the validity of self-reported smoking in Mexican adolescents
Authors: Valladolid-López María del Carmen , Barrientos-Gutiérrez Tonatiuh , Reynales-Shigematsu Luz Myriam , Thrasher James F , Peláez-Ballestas Ingris , Lazcano-Ponce Eduardo , Hernández-Ávila Mauricio
Published: October 2015

Objectives

We aimed to evaluate the validity of the self-reported smoking indicator used in the Global Youth Tobacco Survey (GYTS).

Setting

43 middle and high-school classrooms from 26 schools were selected from Mexico City and Cuernavaca, Morelos.

Participants

A total of 1257 students provided both a questionnaire and a urine sample.

Primary and secondary outcome

Sensitivity and specificity of self-reported smoking compared to urinary cotinine. Validity indices were evaluated by subgroups of gender, social acceptability of smoking (ie, smoking parents or friends) and smoking frequency.

Results

Sensitivity and specificity for current smoking were 93.2% and 81.7%, respectively. Validity indices remained stable across gender. Parental smoking status moderated the validity of self-report, which had lower sensitivity in adolescents with non-smoking parents (86.7%) than in adolescents with smoking parents (96.6%). Sensitivity and specificity increased with smoking frequency.

Conclusions

This first validation study of self-reported current smoking used in the GYTS among Mexican adolescents suggests that self-reported smoking in the past 30 days is a valid and stable indicator of current smoking behaviour. This measure appears suitable for public health research and surveillance.
Women's weight and disordered eating in a large Norwegian community sample: the Nord-Trøndelag Health Study (HUNT)
Authors: Eik-Nes Trine , Romild Ulla , Guzey Ismail , Holmen Turid , Micali Nadia , Bjørnelv Sigrid
Published: October 2015

Objectives

An increasing part of the population is affected by disordered eating (DE) even though they do not meet the full eating disorder (ED) criteria. To improve treatment in the range of weight-related disorders, there is a need to improve our knowledge about DE and relevant correlates of weight problems such as underweight, overweight and obesity. However, studies investigating DE and weight problems in a wide range of ages in the general population have been lacking. This paper explores DE, weight problems, dieting and weight dissatisfaction among women in a general population sample.

Design

Cross-sectional study.

Setting

The third survey of the Nord-Trøndelag Health Study (HUNT3).

Participants

The population included 27 252 women, aged 19–99 years, with information on DE outcomes and covariates.

Outcomes

DE was assessed with an 8-item version of the Eating Attitude Test and the Eating Disorder Scale-5. Body mass index (BMI) was objectively measured. Data on dieting and weight dissatisfaction were collected from self-reported questionnaires and analysed across weight categories. Crude and adjusted logistic and multinomial logistic regression models were used.

Results

High rates of overweight (38%) and obesity (23%) were found. DE was associated with weight problems. In women aged <30 years, 11.8% (95% CI 10.3 to 13.1) reported DE, and 12% (95% CI 11.5 to 12.6) reported DE in women aged >30 years. In those of younger ages (19–29 years), lower weight predicted DE, while increasing weight predicted DE in older aged women (30–99 years). The majority of women were dissatisfied with their weight (58.8%), and 54.1% of the women reported dieting. Neither BMI status nor age was associated with dieting or weight dissatisfaction.

Conclusions

A high prevalence of DE was observed, and findings suggest that weight problems and DE are not distinct from one another. Dieting was associated with women's weight dissatisfaction, rather than with actual weight. This requires further investigations about directionality of effects.
Symptom appraisal and healthcare-seeking for symptoms suggestive of colorectal cancer: a qualitative study
Authors: Hall N , Birt L , Banks J , Emery J , Mills K , Johnson M , Rubin G P , Hamilton W , Walter F M
Published: October 2015

Objectives

Timely diagnosis of colorectal cancer is important to improve survival. This study explored symptom appraisal and help-seeking among patients referred to specialist services with symptoms of colorectal cancer.

Design

Qualitative in-depth interview study.

Setting and participants

Participants were recruited on referral to gastroenterology clinics (North East and East of England); interviews were conducted soon after referral. We purposively sampled participants to ensure a range of accounts in terms of age, sex, diagnosis and geographical location.

Methods

Data collection and analysis were underpinned by the Model of Pathways to Treatment. Framework analysis was used to explore the data within and across cases, focusing on patient beliefs and experiences, disease factors and healthcare influences.

Results

40 participants were interviewed (aged 43–87 years, 17 women, 18 diagnosed with colorectal cancer). Patients diagnosed with and without colorectal cancer had similar symptom pathways. We found a range of interacting and often competing biopsychosocial, contextual and cultural influences on the way in which people recognised, interpreted and acted on their symptoms. People attempted to ‘maintain normality’ through finding benign explanations for their symptoms. Bodily changes were appraised within the context of usual bowel patterns, comorbidities and life events, and decisions to seek help were made in relation to expectations about the course of symptoms. The ‘private nature’ of colorectal cancer symptoms could affect both their identification and discussions with others including healthcare professionals. Within the context of the National Health Service, people needed to legitimise appropriate use of healthcare services and avoid being thought of as wasting doctors’ time.

Conclusions

Findings provide guidance for awareness campaigns on reducing stigma around appraising and discussing bowel movements, and the importance of intermittent and non-specific symptoms. Altering perceptions about the appropriate use of health services could have a beneficial effect on time to presentation.
Potentially inappropriate prescribing (PIP) in long-term care (LTC) patients: validation of the 2014 STOPP-START and 2012 Beers criteria in a LTC population—a protocol for a cross-sectional comparison of clinical and health administrative data
Authors: Bjerre Lise M , Halil Roland , Catley Christina , Farrell Barbara , Hogel Matthew , Black Cody D , Williams Margo , Ryan Cristín , Manuel Douglas G
Published: October 2015

Introduction

Potentially inappropriate prescribing (PIP) is frequent and problematic in older patients. Identifying PIP is necessary to improve prescribing quality; ideally, this should be performed at the population level. Screening Tool of Older Persons’ potentially inappropriate Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START) and Beers criteria were developed to identify PIP in clinical settings and are useful at the individual patient level; however, they are time-consuming and costly to apply. Only a subset of these criteria is applicable to routinely collected population-level health administrative data (HAD) because the clinical information necessary to implement these tools is often missing from databases. The performance of subsets of STOPP/START and Beers criteria in HAD compared with clinical data from the same patients is unknown; furthermore, the performance of the updated 2014 STOPP-START and 2012 Beers criteria compared with one another is also unknown.

Methods and analysis

A cross-sectional study of linked HAD and clinical data will be conducted to validate the subsets of STOPP/START and Beers criteria applicable to HAD by comparing their performance when applied to clinical and HAD for the same patients. Eligible patients will be 66 years and over and recently admitted to 1 of 6 long-term care facilities in Ottawa, Ontario. The target sample size is 275, but may be less if statistical significance can be achieved sooner. Medication, diagnostic and clinical data will be collected by a consultant pharmacist. The main outcome measure is the proportion of PIP missed by the subset of STOPP/START and Beers criteria applied to HAD when compared with clinical data.

Ethics and dissemination

The study was approved by the Ottawa Health Services Network Research Ethics Board, the Bruyère Continuing Care Research Ethics Board and the ethics board of the City of Ottawa Long Term Care Homes. Dissemination will occur via publication, national and international conference presentations, and exchanges with regional, provincial and national stakeholders.

Trial registration number

NCT02523482.
A mixed-methods investigation of health professionals’ perceptions of a physiological track and trigger system
Authors: Lydon Sinéad , Byrne Dara , Offiah Gozie , Gleeson Louise , O'Connor Paul
Published: October 2015

Background

Physiological track and trigger systems (PTTSs) regulate the monitoring of patients’ vital signs and facilitate the detection and treatment of deteriorating patients. These systems are widely used, although compliance with protocol is often poor.

Objective

This study aimed to examine the perceptions of a national PTTS among nurses and doctors and to identify the variables that impact on intention to comply with protocol.

Methods

A mixed-methods research design was employed. During the initial qualitative phase, 30 hospital-based nurses and doctors participated in a series of semistructured interviews. During the subsequent quantitative phase, 215 nurses and doctors (24.1% response rate) responded to a questionnaire designed to assess attitudes towards the PTTS and factors that influence adherence to protocol.

Results

Interview data revealed largely positive attitudes towards the PTTS but highlighted a number of barriers to its implementation and indicated that it is sometimes a source of tension between doctors and nurses. Quantitative data confirmed the validity of these findings, although nurses appeared to have more positive attitudes towards, and to perceive fewer barriers to, the usage of PTTS than were reported by the participating doctors.

Conclusions

These findings reveal that non-compliance with PTTS protocol is unlikely to be attributable to negative perceptions of PTTSs. Instead, there are a number of barriers to the implementation of the system. These findings suggest that interprofessional training in PTTSs is essential while increased support for PTTS implementation among senior doctors would also yield improved adherence to protocol.
The financial impact of a nurse-led telemedicine service for inflammatory bowel disease in a large district general hospital
Authors: Squires Seth Ian , Boal Allan John , Naismith Graham Douglas
Published: October 2015

Introduction

It has become increasingly recognised that outpatient management is more cost-effective in inflammatory bowel disease (IBD). IBD Standards (Revised 2013) recommend telephone advice for patients with regard to symptoms and medication management. This report attempts to quantify the net financial impact of this service at our hospital since it was introduced in August 2013.

Method

The Royal Alexandra Hospital in Paisley (National Health Service, Greater Glasgow and Clyde) is a district general hospital with a catchment population of 200 000 with approximately 2500 patients with IBD. Data relating to the use of the IBD telemedicine service were prospectively recorded on a daily basis for a period of 5 months. We documented reasons for calling and the likely action taken by the patient had the telephone advice line not been available. Cost savings based on alternative outcomes were made in accordance with the Department of Health figures (Department of Health reference costs 2011–2012).

Results

The mean number of calls per month was 88 (IQR 24)—(the mean number of calls which were deemed non-IBD issues was 30 calls per month (IQR 8.0)) The mean cost of staffing the IBD advice line with an IBD clinical nurse specialist was £482.00 per month (IQR 195.5). The mean time spent on calls per month was 28.5 h (IQR 11.5). Cost savings over 5 months for avoidance of general practitioner (GP) consultation was £3408.00. Savings for avoidance of a consultant appointment made over the 5-month period was £27 454.00. Savings made from patients avoiding either an accident and emergency (A&E) or a hospital admission were £540.00 and £11 488.00, respectively, over the 5-month period. The net saving was £42 890.00.

Conclusions

A nurse-led telephone advice line appears to be a cost-effective intervention. It may prevent patients from unnecessary hospital attendance. Savings can be made to both primary care and secondary care. Overall, it appears that the advice line is providing a highly valuable service not just in terms of accessible treatment decisions and guidance for patients, but cost savings when IBD clinic nurse specialist time is compared with that of GPs, consultants or hospital facilities.
National survey of B1 and B2 reporting of breast needle core biopsies
Authors: Deb Rahul , Jenkins Jacquie A , Rowlands David , Ellis Ian O , Lee Andrew HS
Published: October 2015

Aim

This survey investigated the variation in the use of the breast core biopsy categories B1 normal and B2 benign.

Method

A survey with case scenarios was circulated to 701 breast pathologists in the UK.

Results

The response rate was 40%. If there was concordance between the radiological and histological findings, then there was a clear consensus on the appropriate B category. However, if there was discordance between the radiological and histological findings, then frequently there was poor agreement on the appropriate category. Analysis of these cases and supplementary questions on the criteria used to make a pathological categorisation showed that some pathologists are influenced by the radiological features or by the multidisciplinary discussion, rather than just using the histological features.

Conclusions

This survey shows that pathologists frequently do not follow the National Health Service breast screening guideline that B categories should be based solely on the histological changes.
Compaction of flow diverters improves occlusion of experimental wide-necked aneurysms
Authors: Gentric Jean-Christophe , Salazkin Igor , Gevry Guylaine , Raymond Jean , Darsaut Tim
Published: October 2015

Introduction

Flow diverters (FDs) are increasingly used in the treatment of wide-necked aneurysms.

Objective

To examine the hypothesis that intentional FD compaction might improve aneurysm occlusion rates.

Methods

Bilateral wide-necked carotid aneurysms were created in 12 dogs. Endovascular treatment was performed 1 month later, using Pipeline embolization devices deployed with compaction across the aneurysm neck (n=12). Group 1a consisted of aneurysms treated with a single compacted FD (n=8), while group 1b aneurysms required two compacted FDs (n=4). Control aneurysms were treated with a single non-compacted FD (group 3; n=6), or not treated (group 4; n=4). Angiographic results were compared at 3 months. Pathology specimens were photographed and the neointimal coverage of devices scored using an ordinal grading system.

Results

Twenty-two of 24 aneurysms were patent at 1 month. Deployment with compaction was successful in eight cases (group 1a aneurysms). The compaction maneuver led to immediate FD prolapse into the aneurysm in four cases, rescued by deploying a second, telescoping FD (forming group 1b aneurysms). One compacted device later migrated distally, leaving the aneurysm untreated. Angiographic results differed significantly between groups (p=0.0002). At 3 months, aneurysms successfully treated with a single compacted FD were more often occluded at 3 months (7/7) than aneurysms flow-diverted without compaction (2/6; p=0.021). All aneurysms treated with two compacted FDs were occluded, while all untreated aneurysms remained patent. There were no parent vessel stenoses.

Conclusions

Compaction of FDs can improve angiographic occlusion of experimental wide-necked aneurysms.
Carotid artery stenting for vulnerable plaques on MR angiography and ultrasonography: utility of dual protection and blood aspiration method
Authors: Sakamoto Shigeyuki , Kiura Yoshihiro , Okazaki Takahito , Shinagawa Katsuhiro , Ishii Daizo , Ichinose Nobuhiko , Kurisu Kaoru
Published: October 2015

Background

Carotid artery stenting (CAS) for internal carotid artery (ICA) stenosis with vulnerable plaques is controversial. We analyzed the effect of a dual protection and blood aspiration method during CAS in patients with vulnerable plaques.

Methods

A total of 111 patients with ICA stenosis underwent CAS using the dual protection (simultaneous flow reversal and distal filter) and blood aspiration method. In 103 of 111 patients, preoperative carotid plaque was estimated by both 3 T MRI and ultrasonography (US). ICA plaques with a high intensity signal on time-of-flight-MR angiography (TOF-MRA) and/or mobile component on US were defined as vulnerable plaques. We assessed major adverse events (MAE) (ie, major stroke, myocardial infarction, and death) and hyperintense spots on diffusion-weighted images (DWI) after CAS. We then evaluated the visible debris captured by dual protection and blood aspiration during CAS.

Results

The preoperative ICA plaque on TOF-MRA and US was judged to be vulnerable in 48.5% (50/103 patients). The success rate of the CAS procedure was 100% with no MAE within 30 days. DWI showed small hyperintense spots in 18% (9/50 patients) and 18.9% (10/53 patients) in the vulnerable and non-vulnerable plaque groups, respectively. Visible debris was captured in 68% (34/50 patients) and 45.3% (24/53 patients) in the vulnerable and non-vulnerable plaque groups, respectively (p=0.0286).

Conclusions

The combination of dual protection and blood aspiration could provide effective distal embolic protection although vulnerable plaques on TOF-MRA and US had a high incidence of debris during CAS. Thus, CAS using dual protection and blood aspiration is safe in patients with vulnerable plaques.
Results of comprehensive diagnostic work-up in ‘idiopathic’ dilated cardiomyopathy
Authors: Broch Kaspar , Andreassen Arne K , Hopp Einar , Leren Trond P , Scott Helge , Müller Fredrik , Aakhus Svend , Gullestad Lars
Published: October 2015

Objective

Dilated cardiomyopathy (DCM) is characterised by left ventricular dilation and dysfunction not caused by coronary disease, valvular disease or hypertension. Owing to the considerable aetiological and prognostic heterogeneity in DCM, an extensive diagnostic work-up is recommended. We aimed to assess the value of diagnostic testing beyond careful physical examination, blood tests, echocardiography and coronary angiography.

Methods

From October 2008 to November 2012, we prospectively recruited 102 patients referred to our tertiary care hospital with a diagnosis of ‘idiopathic’ DCM based on patient history, physical examination, routine blood tests, echocardiography and coronary angiography. Extended work-up included cardiac MRI, exercise testing, right-sided catheterisation with biopsies, 24 h ECG and genetic testing.

Results

In 15 patients (15%), a diagnosis other than ‘idiopathic’ DCM was made based on additional tests. In 10 patients (10%), a possibly disease-causing mutation was detected. 2 patients were found to have non-compaction cardiomyopathy based on MRI findings; 2 patients had systemic inflammatory disease with cardiac involvement; and in 1 patient, cardiac amyloidosis was diagnosed by endomyocardial biopsy. Only in 5 cases did the results of the extended work-up have direct therapeutic consequences.

Conclusions

In patients with DCM, in whom patient history and routine work-up carry no clues to the aetiology, the diagnostic and therapeutic yield of extensive additional testing is modest.