bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of theory‐based knowledge translation interventions to facilitate the implementation of evidence‐based guidelines on the early management of adults with traumatic spinal cord injury
Authors: Bérubé Mélanie , Albert Martin , Chauny Jean‐Marc , Contandriopoulos Damien , DuSablon Anne , Lacroix Sébastien , Gagné Annick , Laflamme Élise , Boutin Nathalie , Delisle Stéphane , Pauzé Anne‐Marie , MacThiong Jean‐Marc
Published: April 2015

Rationale

Optimal, early management following a spinal cord injury (SCI) can limit individuals' disabilities and costs related to their care. Several knowledge syntheses were recently published to guide health care professionals with regard to early interventions in SCI patients. However, no knowledge translation (KT) intervention, selected according to a behaviour change theory, has been proposed to facilitate the use of SCI guidelines in an acute care setting.

Objectives

To develop theory‐informed KT interventions to promote the application of evidence‐based recommendations on the acute care management of SCI patients.

Methods

The first four phases of the knowledge‐to‐action model were used to establish the study design. Knowledge selection was based on the Grading of Recommendations Assessment, Development and Evaluation system. Knowledge adaptation to the local context was sourced from the ADAPTE process. The theoretical domains framework oriented the selection and development of the interventions based on an assessment of barriers and enablers to knowledge application.

Results

Twenty‐nine recommendations were chosen and operationalized in measurable clinical indicators. Barriers related to knowledge, skills, perceived capacities, beliefs about consequences, social influences, and the environmental context and resources theoretical domains were identified. The mapping of behaviour change techniques associated with those barriers led to the development of an online educational curriculum, interdisciplinary clinical pathways as well as policies and procedures.

Conclusions

This research project allowed us developing KT interventions according to a thorough behavioural change methodology. Exposure to the generated interventions will support health care professionals in providing the best care to SCI patients.
Epistemic injustice in assessment of delusions
Authors: Sanati Abdi , Kyratsous Michalis
Published: April 2015

Delusions are one of the most elusive concepts in psychiatry. There have been several theories on the nature and definition of delusions. Jaspers described them as entailing a total transformation of reality and considered primary delusions as un‐understandable. When it comes to clinical practice, psychiatrists resort to criteria of falsity, incorrigibility, conviction and being out of keeping with the person's culture. All these criteria have been subject to various criticisms, some of which will be discussed in the paper. We will use the concept of epistemic injustice to explore the role of stereotypes and prejudice in the identification of delusions. We will discuss cases where patients are suffering from testimonial injustice by virtue of having a mental disorder that is so often associated with attributions of irrationality, bizarreness and incomprehensibility. Two vignettes will be presented to show that this is often the case in clinical practice. We will discuss relevant issues around the epistemology of the delusions. We think that in order to challenge the testimonial injustice, there needs to be an awareness of its possibility and thus recognition of the role of certain stereotypes in assessing these mental states. Challenging the stigma against mentally ill and adopting a holistic view of delusions can help tackle the prejudice that pre‐empt the testimonial injustice.
Ethical persuasion: the rhetoric of communication in critical care
Authors: Dubov Alex
Published: April 2015

This article reviews the ethics of rhetoric in critical care. Rational appeals in critical care fail to move patients or surrogates to a better course of action. Appeals to their emotions are considered illegitimate because they may preclude autonomous choice. This article discusses whether it is always unethical to change someone's beliefs, whether persuasive communication is inherently harmful and whether it leaves no space for voluntariness. To answer these questions, the article engages with Aristotle's work, Rhetoric. In considering whether there is a place for emotionally charged messages in a patient–provider relationship, the article intends to delineate the nature of this relationship and describe the duties this relationship implies. The article presents examples of persuasive communication used in critical care and discusses whether providers may have a duty to persuade patients. This duty is supported by the fact that doctors often influence patients' and families' choices by framing presented options. Doctors should assume responsibility in recognizing these personal and contextual influences that may influence the medical choices of their patients. They should attempt to modify these contextual factors and biases in a way that would assist patients and families in reaching the desired outcomes. The opening sections surveyed a number of definitions found in relevant literature and outlined some of the concepts included in the proposed definition. This definition helps to distinguish instances of persuasion from cases of manipulation, coercion and deception. Considering the fact that patients and families often make irrational decisions and the fact that doctors inadvertently influence their choices, the article suggested that persuasion can be a positive tool in medical communication. When patients or families clearly do not understand the risks or make decisions that contradict their long‐term goals, persuasion can be used as a positive influence.
Development of an improved RT‐PCR for specific detection of spring viraemia of carp virus
Authors: Shimahara Y , Kurita J , Nishioka T , Kiryu I , Yuasa K , Sakai T , Oseko N , Sano M , Dixon P
Published: April 2015

Spring viraemia of carp (SVC) is a rhabdovirus infection, which has a significant economic impact in pond cultures of carp in Europe and western Independent States of the former Soviet Union. The causative agent of SVC, spring viraemia of carp virus (SVCV), has been divided into four subgroups, Ia, Ib, Ic and Id, on the basis of glycoprotein (G) protein gene sequences. In this study, a new primer set was designed from a G gene sequence of SVCV to identify the four subtypes of SVCV by reverse transcription polymerase chain reaction (RT‐PCR). The specific PCR products of 369 bp were amplified from 15 SVCV isolates of all four subtypes. However, pike fry rhabdovirus (PFRV), which is antigenically related to SVCV, and other viruses antigenically related to SVCV and PFRV were not amplified. The four subtypes of SVCV were specifically amplified by the RT‐PCR. Furthermore, the detection limit of the RT‐PCR was 7.1 × 102 copies/reaction, and it was not influenced by the addition of RNA extracted from fish tissues. The RT‐PCR will be applied not only to RNA extracted from viral suspensions, but also from fish tissue. It will contribute to rapid identification of SVCV in fish with clinical signs of SVC.
Identification of P‐glycoprotein co‐fractionating proteins and specific binding partners in rat brain microvessels
Authors: Tome Margaret E. , Schaefer Charles P. , Jacobs Leigh M. , Zhang Yifeng , Herndon Joseph M. , Matty Fabian O. , Davis Thomas P.
Published: April 2015

Drug delivery to the brain for the treatment of pathologies with a CNS component is a significant clinical challenge. P‐glycoprotein (PgP), a drug efflux pump in the endothelial cell membrane, is a major factor in preventing therapeutics from crossing the blood‐brain barrier (BBB). Identifying PgP regulatory mechanisms is key to developing agents to modulate PgP activity. Previously, we found that PgP trafficking was altered concomitant with increased PgP activity and disassembly of high molecular weight PgP‐containing complexes during acute peripheral inflammatory pain. These data suggest that PgP activity is post‐translationally regulated at the BBB. The goal of the current study was to identify proteins that co‐localize with PgP in rat brain microvessel endothelial cell membrane microdomains and use the data to suggest potential regulatory mechanisms. Using new density gradients of microvessel homogenates, we identified two unique pools (1,2) of PgP in membrane fractions. Caveolar constituents, caveolin1, cavin1, and cavin2, co‐localized with PgP in these fractions indicating the two pools contained caveolae. A chaperone (Hsc71), protein disulfide isomerase and endosomal/lysosomal sorting proteins (Rab5, Rab11a) also co‐fractionated with PgP in the gradients. These data suggest signaling pathways with a potential role in post‐translational regulation of PgP activity at the BBB.

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This model depicts two types of P‐glycoprotein (PgP)‐containing caveolae. Rat brain microvessels contain two unique pools of PgP that are of different densities. Each pool co‐fractionates with three caveolar proteins suggesting there are two populations of caveolae that contain PgP. The two caveolar populations differ in density indicating they have a different structure, lipoprotein content or intracellular location. Our model includes two newly identified PgP‐binding partners, Hsc71 and protein disulfide isomerase, in rat brain microvessels.
Effects of ketone bodies in Alzheimer's disease in relation to neural hypometabolism, β‐amyloid toxicity, and astrocyte function
Authors: Hertz Leif , Chen Ye , Waagepetersen Helle S.
Published: April 2015

Diet supplementation with ketone bodies (acetoacetate and β‐hydroxybuturate) or medium‐length fatty acids generating ketone bodies has consistently been found to cause modest improvement of mental function in Alzheimer's patients. It was suggested that the therapeutic effect might be more pronounced if treatment was begun at a pre‐clinical stage of the disease instead of well after its manifestation. The pre‐clinical stage is characterized by decade‐long glucose hypometabolism in brain, but ketone body metabolism is intact even initially after disease manifestation. One reason for the impaired glucose metabolism may be early destruction of the noradrenergic brain stem nucleus, locus coeruleus, which stimulates glucose metabolism, at least in astrocytes. These glial cells are essential in Alzheimer pathogenesis. The β‐amyloid peptide Aβ interferes with their cholinergic innervation, which impairs synaptic function because of diminished astrocytic glutamate release. Aβ also reduces glucose metabolism and causes hyperexcitability. Ketone bodies are similarly used against seizures, but the effectively used concentrations are so high that they must interfere with glucose metabolism and de novo synthesis of neurotransmitter glutamate, reducing neuronal glutamatergic signaling. The lower ketone body concentrations used in Alzheimer's disease may owe their effect to support of energy metabolism, but might also inhibit release of gliotransmitter glutamate.

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Alzheimer's disease is a panglial‐neuronal disorder with long‐standing brain hypometabolism, aberrations in both neuronal and astrocytic glucose metabolism, inflammation, hyperexcitability, and dementia. Relatively low doses of β‐hydroxybutyrate can have an ameliorating effect on cognitive function. This could be because of metabolic supplementation or inhibition of Aβ‐induced release of glutamate as gliotransmitter, which is likely to reduce hyperexcitability and inflammation. The therapeutic β‐hydroxybutyrate doses are too low to reduce neuronally released glutamate.
Vinexin‐β deficiency protects against cerebral ischaemia/reperfusion injury by inhibiting neuronal apoptosis
Authors: Li Mingchang , Guo Sen , Zhang Peng , Gong Jun , Zheng Ankang , Zhang Yan , Li Hongliang
Published: April 2015

Vinexin‐β is an adaptor protein that regulates cell adhesion, cytoskeletal organization and signal transduction. Our previous work showed that Vinexin‐β protects against cardiac hypertrophy. However, its function in stroke is largely unknown. In the present study, we observed a significant increase in Vinexin‐β expression in both human intracerebral haemorrhage and mouse cerebral ischaemia/reperfusion (I/R) injury model, indicating that Vinexin‐β is involved in stroke. Next, using Vinexin‐β knockout mice, we further demonstrated that Vinexin‐β deficiency significantly protected against cerebral I/R injury, as demonstrated by a dramatic decrease in the infarct volume and an improvement in neurological function. Additionally, immunofluorescence and western blotting showed that the deletion of Vinexin‐β attenuated neuronal apoptosis. Mechanically, we found that Akt signalling was up‐regulated in the brains of the Vinexin‐β knockout mice compared with those of the WT control mice after ischaemic injury. Taken together, our results demonstrate that the deletion of Vinexin‐β potently protects against ischaemic injury by inhibiting neuronal apoptosis, and this effect may occur via the up‐regulation of Akt signalling. Our findings revealed that Vinexin‐β acts as a novel modulator of ischaemic injury, suggesting that Vinexin‐β may represent an attractive therapeutic target for the prevention of stroke.

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Vinexin‐β is an adaptor protein that regulates cell adhesion and cytoskeletal organization. We revealed that Vinexin‐β‐deficient mice are potently protected against ischaemia/reperfusion (I/R) injury. The protective effect is mediated through inhibiting neuronal apoptosis, which may occur via the up‐regulation of Akt signalling. These findings suggest Vinexin‐β as a novel regulator of I/R injury and attractive therapeutic target for the prevention of stroke.
Morphology of the tympanic‐basicranial region in Mirounga leonina (Phocidae, Carnivora), postnatal ontogeny and sexual dimorphism
Authors: Loza C. M. , Scarano A. C. , Soibelzon L. H. , Negrete J. , Carlini A. A.
Published: April 2015

The auditory region of pinnipeds has seldom been described. Here we describe and analyze the ontogenetic trajectory of the tympanic bulla of the southern elephant seal, Mirounga leonina (Phocidae, Mammalia). This species is extremely sexually dimorphic and highly polygynous (organized in harems). We examined 118 specimens, arranged in three age classes (CI, CII, and CIII), ranging from newborn to adults (males and females). To analyze the overall size and shape of the tympanic bulla we performed a geometric morphometric analysis including 87 skulls. Females reach definitive shape and size of the bulla at earlier ontogenetic stages than males, in agreement with their earlier involvement in reproductive activities. The internal anatomy of the tympanic region (e.g. form and extension of the paries) does not show remarkable differences between sexes or age classes. The greatest differences between age classes are related to bone thickness, resulting from the apposition of new annual layers. An examination of possible sex‐related external differences among age classes shows significant shape differences between males and females in CIII. The morphology observed in neonates is conserved across all individuals from CI, which included specimens up to 1 year old. Clear morphological differences were observed between CI individuals, on one hand, and CII individuals plus CIII females on the other. During cranial development of both male and females, the glenoid cavity expands and compresses the bulla; this condition reaches its maximum expression in CIII males. CIII males showed the greatest morphological differences, with respect to both CI and CII individuals, and CIII females.
Placental melatonin system is present throughout pregnancy and regulates villous trophoblast differentiation
Authors: Soliman Ahmed , Lacasse Andrée‐Anne , Lanoix Dave , Sagrillo‐Fagundes Lucas , Boulard Véronique , Vaillancourt Cathy
Published: April 2015

Melatonin is highly produced in the placenta where it protects against molecular damage and cellular dysfunction arising from hypoxia/re‐oxygenation‐induced oxidative stress as observed in primary cultures of syncytiotrophoblast. However, little is known about melatonin and its receptors in the human placenta throughout pregnancy and their role in villous trophoblast development. The purpose of this study was to determine melatonin‐synthesizing enzymes, arylalkylamine N‐acetyltransferase (AANAT) and hydroxyindole O‐methyltransferase (HIOMT), and melatonin receptors (MT1 and MT2) expression throughout pregnancy as well as the role of melatonin and its receptors in villous trophoblast syncytialization. Our data show that the melatonin generating system is expressed throughout pregnancy (from week 7 to term) in placental tissues. AANAT and HIOMT show maximal expression at the 3rd trimester of pregnancy. MT1 receptor expression is maximal at the 1st trimester compared to the 2nd and 3rd trimesters, while MT2 receptor expression does not change significantly during pregnancy. Moreover, during primary villous cytotrophoblast syncytialization, MT1 receptor expression increases, while MT2 receptor expression decreases. Treatment of primary villous cytotrophoblast with an increasing concentration of melatonin (10 pm–1 mm) increases the fusion index (syncytium formation; 21% augmentation at 1 mm melatonin vs. vehicle) and β‐hCG secretion (121% augmentation at 1 mm melatonin vs. vehicle). This effect of melatonin appears to be mediated via its MT1 and MT2 receptors. In sum, melatonin machinery (synthetizing enzymes and receptors) is expressed in human placenta throughout pregnancy and promotes syncytium formation, suggesting an essential role of this indolamine in placental function and pregnancy well‐being.
Dehydration and drinking behavior in true sea snakes (Elapidae: Hydrophiinae: Hydrophiini)
Authors: Lillywhite H. B. , Heatwole H. , Sheehy C. M.
Published: April 2015

Water is an essential resource affecting behavior and the acquisition of energy, especially in environments where water is spatially or temporally restricted or unavailable. Recent investigations have shown that several species of marine snakes dehydrate at sea and are dependent on environmental sources of fresh water to maintain water balance. However, in this context, little is known concerning the majority of ‘true’ sea snakes (Hydrophiini). We investigated the dehydration and drinking responses of five species of hydrophiin sea snakes collected during the dry season in northern Australia. None of these snakes drank sea water, even when dehydrated. Dehydrated individuals of Hydrophis curtus, H. elegans and H. zweifeli drank fresh water, and the mean threshold levels of dehydration that first elicited drinking were deficits of −26, −29 and −27% of body mass, respectively. Individuals of Aipysurus mosaicus and H. peronii did not drink fresh water when similarly dehydrated. Few snakes that we collected following >4 months of drought drank fresh water immediately after capture. Hydrophiin species appear to have a high resistance to dehydration, which they evidently tolerate in marine habitats for extended periods during drought. Thirst in these species is significantly less sensitive than in other species, suggesting that marine snakes have variable requirements for drinking fresh water. These data illustrate that sea snakes are characterized by diverse responses to dehydration and likely have different osmoregulatory strategies for survival, with implications for better understanding the evolutionary success of secondarily marine vertebrates and their potential responses to future changes in tropical precipitation.
Spatial soil heterogeneity has a greater effect on symbiotic arbuscular mycorrhizal fungal communities and plant growth than genetic modification with Bacillus thuringiensis toxin genes
Authors: Cheeke Tanya E. , Schütte Ursel M. , Hemmerich Chris M. , Cruzan Mitchell B. , Rosenstiel Todd N. , Bever James D.
Published: April 2015

Maize, genetically modified with the insect toxin genes of Bacillus thuringiensis (Bt), is widely cultivated, yet its impacts on soil organisms are poorly understood. Arbuscular mycorrhizal fungi (AMF) form symbiotic associations with plant roots and may be uniquely sensitive to genetic changes within a plant host. In this field study, the effects of nine different lines of Bt maize and their corresponding non‐Bt parental isolines were evaluated on AMF colonization and community diversity in plant roots. Plants were harvested 60 days after sowing, and data were collected on plant growth and per cent AMF colonization of roots. AMF community composition in roots was assessed using 454 pyrosequencing of the 28S rRNA genes, and spatial variation in mycorrhizal communities within replicated experimental field plots was examined. Growth responses, per cent AMF colonization of roots and AMF community diversity in roots did not differ between Bt and non‐Bt maize, but root and shoot biomass and per cent colonization by arbuscules varied by maize cultivar. Plot identity had the most significant effect on plant growth, AMF colonization and AMF community composition in roots, indicating spatial heterogeneity in the field. Mycorrhizal fungal communities in maize roots were autocorrelated within approximately 1 m, but at greater distances, AMF community composition of roots differed between plants. Our findings indicate that spatial variation and heterogeneity in the field has a greater effect on the structure of AMF communities than host plant cultivar or modification by Bt toxin genes.
A critical care network pressure ulcer prevention quality improvement project
Authors: McBride Joanna , Richardson Annette
Published: April 2015

Background

Pressure ulcer prevention is an important safety issue, often underrated and an extremely painful event harming patients. Critically ill patients are one of the highest risk groups in hospital. The impact of pressure ulcers are wide ranging, and they can result in increased critical care and the hospital length of stay, significant interference with functional recovery and rehabilitation and increase cost.

Aims

This quality improvement project had four aims: (1) to establish a critical care network pressure ulcer prevention group; (2) to establish baseline pressure ulcer prevention practices; (3) to measure, compare and monitor pressure ulcers prevalence; (4) to develop network pressure ulcer prevention standards.

Methods

The approach used to improve quality included strong critical care nursing leadership to develop a cross‐organisational pressure ulcer prevention group and a benchmarking exercise of current practices across a well‐established critical care Network in the North of England. The National Safety Thermometer tool was used to measure pressure ulcer prevalence in 23 critical care units, and best available evidence, local consensus and another Critical Care Networks' bundle of interventions were used to develop a local pressure ulcer prevention standards document.

Results

The aims of the quality improvement project were achieved. This project was driven by successful leadership and had an agreed common goal. The National Safety Thermometer tool was an innovative approach to measure and compare pressure ulcer prevalence rates at a regional level. A limitation was the exclusion of moisture lesions.

Conclusion

The project showed excellent engagement and collaborate working in the quest to prevent pressure ulcers from many critical care nurses with the North of England Critical Care Network.

Relevance to clinical practice

A concise set of Network standards was developed for use in conjunction with local guidelines to enhance pressure ulcer prevention.
Accounting for the causal basis of collinearity when measuring the effects of habitat loss versus habitat fragmentation
Authors: Ruffell Jay , Banks‐Leite Cristina , Didham Raphael K.
Published: April 2015

Collinearity among metrics of habitat loss and habitat fragmentation is typically treated as a nuisance in landscape ecology, and it is the norm to use statistical approaches that remove collinear information prior to estimating model parameters. However, collinearity may arise from causal relationships among landscape metrics and may therefore signal the occurrence of indirect effects (where one model predictor influences the response variable by driving changes in another influential predictor). Here we suggest that, far from being merely a statistical nuisance, collinearity may be crucial for accurately quantifying the effects of habitat loss versus habitat fragmentation. We use simulation modelling to create datasets of collinear landscape metrics in which collinearity arose from causal relationships, then test the ability of two statistical approaches to estimate the effects of these metrics on a simulated response variable: 1) multiple regression, which statistically removes collinearity, and was identified in a recent study as the best approach for estimating the effects of collinear landscape metrics (although this study did not account for any indirect effects implied by collinearity among metrics); and 2) path analysis, which accounts for the causal basis of collinearity. In agreement with this previous study, we found that multiple regression gave unbiased estimates of direct effects (effects not mediated by other model predictors). However, it gave biased estimates of total (direct + indirect) effects when indirect effects occurred. In contrast, path analysis reliably identified the causal basis of collinearity and gave unbiased estimates of direct, indirect, and total effects. We suggest that effective research on the impacts of habitat loss versus fragmentation will often require tools that can empirically test whether collinear landscape metrics are causally related, and if so, account for the indirect effects that these causal relationships imply. Path analysis, but not multiple regression, provides such a tool.
Of niche differentiation, dispersal ability and historical legacies: what drives woody community assembly in recent Mediterranean forests?
Authors: Basnou Corina , Vicente Paloma , Espelta Josep Maria , Pino Joan
Published: April 2015

Community assembly rules have been extensively studied, but its association with regional environmental variation and land use history remains largely unexplored. Land use history might be especially important in Mediterranean forests, considering their historical deforestation and recent afforestation. Using forest inventories and historical (1956) and recent (2000) land cover maps, we explored the following hypotheses: 1) woody species assembly is driven by environmental factors, but also by historical landscape attributes; 2) recent forests exhibit lower woody species richness than pre‐existing due to the existence of colonization credits; 3) these credits are modulated by species’ life‐forms and dispersal mechanisms. We examined the association of forest historical type (pre‐existing versus recent) with total species richness and that of diverse life‐forms and dispersal groups, also considering the effects of current environment and past landscape factors. When accounting for these effects, no significant differences in woody species richness were found between forest historical types except for vertebrate‐dispersed species. Species richness of this group was affected by the interaction of forest historical type with distance to coast and rainfall: vertebrate‐dispersed species richness increased with rainfall and distance to the coast in recent forests, while it was higher in dryer sites in pre‐existing forests. In addition, forest historical types showed differences in woody species composition associated to diverse environmental and past landscape factors. In view of these results we can conclude that: 1) community assembly in terms of species richness is fast enough to exhaust most colonization credit in recent Mediterranean forests except for vertebrate‐dispersed species; 2) for these species, colonization credit is affected by the interplay of forest history and a set of proxies of niche and landscape constraints of species dispersal and establishment; 3) woody species assemblage is mostly shaped by the species’ ecological niches in these forests.
Rare sialoliths of the minor salivary glands: a case series and review of the literature
Authors: Tanna N. , Koshal S.
Published: April 2015

Sialolithiasis is a common disease of the salivary glands. However, sialolith formation in the minor salivary glands is considered very rare. Clinical features can be unusual, and this can cause difficulties with diagnosis. In this case series, we report three rare cases of sialoliths found in the minor salivary glands; two cases presenting in the lower lip and one in the substance of the tongue. In all three cases, the diagnosis was not immediately clear. The literature suggests that sialoliths in the minor salivary glands may occur more frequently than previously thought, and they should therefore be included in the clinical differential diagnoses of submucosal swellings in the oral cavity.
Time trends in the incidence, prevalence and age at diagnosis of asthma in children
Authors: Engelkes Marjolein , Janssens Hettie M. , de Ridder Maria A. J. , de Jongste Johan C. , Sturkenboom Miriam C. J. M. , Verhamme Katia M. C.
Published: April 2015

Background

Current knowledge on the prevalence of asthma is mainly based on cross‐sectional questionnaire data. Current population‐based data on the incidence of asthma in children are scarce.

Objective

To study the incidence, prevalence, and age at diagnosis of asthma in children in the Netherlands over the study period 2000–2012.

Methods

A population‐based cohort study was conducted in the Integrated Primary Care Information database. The cohort consisted of 176,516 children (379,536 personyears (PY) of follow‐up), aged 5–18 years between 2000 and 2012. All medical records of children with physician diagnosed asthma were validated. Incidence rates, annual percent change (APC), and prevalence for asthma were calculated. Influence of age and gender on incidence rates and change in age at diagnosis were studied.

Results

We identified an asthma cohort of 14,303 children with 35,118PY. The overall incidence rate was 6.7/1000PY(95%CI, 6.45–6.97). Until 2008, the incidence rate was significantly increasing (APC5.79 (95%CI1.43–10.34); from 2008 onwards, a non‐significant decrease was observed (APC−12.16 (95%CI−23.07 to 0.28). Incidence for girls was lower than for boys, this difference decreased with increasing age. (p < 0.001) Overall, the age at diagnosis increased over calendar time and was lower for boys. (linear trend p < 0.001).

Conclusion

Our population‐based cohort study observed an incidence rate of 6.7 per 1000PYof physician‐diagnosed asthma in children in the Netherlands over 2000–2012. The asthma incidence rate was increasing until 2008. Further studies are needed to confirm the decrease in asthma incidence rate from 2008 onwards.
Contributions of photosynthetic and non‐photosynthetic cell types to leaf respiration in Vicia faba L. and their responses to growth temperature
Authors: Long Benedict M. , Bahar Nur H. A. , Atkin Owen K.
Published: April 2015

In intact leaves, mitochondrial populations are highly heterogeneous among contrasting cell types; how such contrasting populations respond to sustained changes in the environment remains, however, unclear. Here, we examined respiratory rates, mitochondrial protein composition and response to growth temperature in photosynthetic (mesophyll) and non‐photosynthetic (epidermal) cells from fully expanded leaves of warm‐developed (WD) and cold‐developed (CD) broad bean (Vicia faba L.). Rates of respiration were significantly higher in mesophyll cell protoplasts (MCPs) than epidermal cell protoplasts (ECPs), with both protoplast types exhibiting capacity for cytochrome and alternative oxidase activity. Compared with ECPs, MCPs contained greater relative quantities of porin, suggesting higher mitochondrial surface area in mesophyll cells. Nevertheless, the relative quantities of respiratory proteins (normalized to porin) were similar in MCPs and ECPs, suggesting that ECPs have lower numbers of mitochondria yet similar protein complement to MCP mitochondria (albeit with lower abundance serine hydroxymethyltransferase). Several mitochondrial proteins (both non‐photorespiratory and photorespiratory) exhibited an increased abundance in response to cold in both protoplast types. Based on estimates of individual protoplast respiration rates, combined with leaf cell abundance data, epidermal cells make a small but significant (2%) contribution to overall leaf respiration which increases twofold in the cold. Taken together, our data highlight the heterogeneous nature of mitochondrial populations in leaves, both among contrasting cell types and in how those populations respond to growth temperature.
Urinary screening and urinary abnormalities in 3‐year‐old children in Japan
Authors: Yanagihara Takeshi , Hamada Riku , Ishikura Kenji , Uemura Osamu , Matsuyama Takeshi , Takahashi Shori , Honda Masataka
Published: April 2015

Abstract

In Japan, urinary screening for preschool children has been obligatory since 1961. The system was reconsidered and has been under review since 2012, because many problems in the system had been identified, and its usefulness was uncertain. In the process, the following were analyzed: (i) frequency of urinary abnormalities identified on screening; (ii) diseases identified from urinary abnormalities; (iii) clinical course of children found to have urinary abnormalities; and (iv) screening for asymptomatic urinary tract infection (UTI) as a way of screening for congenital anomalies of the kidney and urinary tract. A computerized literature search was conducted, and study reports issued by the Ministry of Health, Labour and Welfare study group, and data of Akita City and Chiba City were reviewed. The prevalence of abnormal results at the first urinalysis was high, but at the second urinalysis the prevalence decreased in the range 1/6–1/20. The prevalence of tentative diagnosis at the third urinalysis was similar to the school urinary screening results. Serious illness was not found in children who had hematuria alone. In contrast, diseases requiring immediate attention were found in children with proteinuria, although the prevalence of proteinuria was not high. The dipstick method for leukocyturia was inefficient. The importance of two consecutive urinalyses before detailed examination, the lack of usefulness of screening for hematuria in 3‐year‐old children, and the importance of proteinuria were confirmed. Screening for asymptomatic UTI using urinary leukocytes was very inefficient.
Early pulmonary inflammation and lung damage in children with cystic fibrosis
Authors: Schultz André , Stick Stephen
Published: April 2015

Individuals with cystic fibrosis (CF) suffer progressive airway inflammation, infection and lung damage. Airway inflammation and infection are present from early in life, often before children are symptomatic. CF gene mutations cause changes in the CF transmembrane regulator protein that result in an aberrant airway microenvironment including airway surface liquid (ASL) dehydration, reduced ASL acidity, altered airway mucin and a dysregulated inflammatory response. This review discusses how an altered microenvironment drives CF lung disease before overt airway infection, the response of the CF airway to early infection, and methods to prevent inflammation and early lung disease.
Role of imaging in COPD phenotyping
Authors: Milne Stephen , King Gregory G.
Published: April 2015

See article, page 594
Emphysema and airway disease affect within‐breath changes in respiratory resistance in COPD patients
Authors: Hasegawa Koichi , Sato Susumu , Tanimura Kazuya , Fuseya Yoshinori , Uemasu Kiyoshi , Sato Atsuyasu , Hirai Toyohiro , Mishima Michiaki , Muro Shigeo
Published: April 2015

Background and objective

Chronic obstructive pulmonary disease (COPD) is characterized by a mixture of emphysema and airway disease. The forced oscillation technique (FOT) has been applied to COPD patients to clarify changes in respiratory mechanics; dynamic changes in respiratory resistance (Rrs) during breathing (within‐breath changes in Rrs, ΔRrs) are characteristic of COPD. However, the pathophysiological significance of these changes is unknown. The aim of this study was to assess how emphysema and airway disease influence ΔRrs in COPD patients.

Methods

In this cross‐sectional study, stable COPD patients were recruited and underwent respiratory impedance measurements with a commercially available FOT device. Rrs was recorded during tidal breathing and then analyzed as whole‐breath Rrs (Rrs at 5 Hz, R5; Rrs at 20 Hz, R20; and their difference, R5−R20) or as ΔRrs, the difference between the expiratory and inspiratory Rrs (ΔR5, ΔR20 and ΔR5–R20). The percentage of the low attenuation area (LAA%) and airway wall area (WA%) was quantified by computed tomography analysis, and their contributions to ΔRrs were examined.

Results

Seventy‐five COPD patients were recruited. LAA% was negatively correlated with ΔR5 and ΔR5−R20 (P = 0.0002 and P = 0.0033, respectively); meanwhile, WA% in B10 was positively correlated with ΔR5 and ΔR5−R20 (P = 0.0057 and P < 0.0001, respectively). Multivariate analysis revealed that the contribution of both LAA% and WA% in B10 to ΔRrs was independent of the severity of airflow limitations.

Conclusion

This study shows that emphysema suppresses ΔRrs in COPD patients, while airway disease increases ΔRrs in these patients.
Possible role of anaerobes in the pathogenesis of nontuberculous mycobacterial infection
Authors: Yamasaki Kei , Mukae Hiroshi , Kawanami Toshinori , Fukuda Kazumasa , Noguchi Shingo , Akata Kentarou , Naito Keisuke , Oda Keishi , Ogoshi Takaaki , Nishida Chinatsu , Orihashi Takeshi , Kawanami Yukiko , Ishimoto Hiroshi , Taniguchi Hatsumi , Yatera Kazuhiro
Published: April 2015

Background and objective

Recent advances in cultivation‐independent molecular biological modalities for detecting bacterial species have indicated that several bacterial species may play a role in the pathogenesis of certain infectious diseases. The aim of this study was to evaluate the role of bacterial flora in the pathogenesis of nontuberculous mycobacteriosis (NTM) using a bacterial floral analysis of bronchoalveolar lavage fluid (BALF) with 16S rRNA gene sequencing in patients with bronchiectasis.

Methods

Fifty‐eight patients with bronchiectasis evaluated using chest computed tomography were enrolled. BALF obtained from the most affected lung lesions was evaluated using culture and culture‐independent methodologies. Approximately 600 bp of the bacterial 16S rRNA gene (E341F‐E907R) was amplified via polymerase chain reaction using universal primers, and clone libraries were constructed. Nucleotide sequences of 96 randomly chosen clones for each specimen were determined, and the homology was searched using a basic local alignment search tool to determine the bacterial phylotypes and their proportions (bacterial floral analysis) in each specimen.

Results

Twenty‐nine patients with bronchiectasis were diagnosed with NTM based on culture‐based methods using Ogawa medium. The molecular method showed a significantly high rate of anaerobes among the patients with NTM compared with that observed in the bronchiectasis patients without NTM. In addition, findings of collapse/consolidation were significantly related to the proportion of Prevotella species in the BALF samples determined using the molecular method (P < 0.001).

Conclusion

Given the results of the present study, anaerobes may play an important role in the pathogenesis of bronchiectasis in patients with NTM.
Chlamydia pneumoniae and Chlamydia Trachomatis Infection Differentially Modulates Human Dendritic Cell Line (MUTZ) Differentiation and Activation
Authors: Armitage C. W. , O'Meara C. P. , Beagley K. W.
Published: April 2015

Chlamydia trachomatis and Chlamydia pneumoniae are important human pathogens that infect the urogenital/anorectal and respiratory tracts, respectively. Whilst the ability of these bacteria to infect epithelia is well defined, there is also considerable evidence of infection of leucocytes, including dendritic cells (DCs). Using a human dendritic cell line (MUTZ), we demonstrate that the infection and replication of chlamydiae inside DCs is species and serovar specific and that live infection with C. pneumoniae is required to upregulate costimulatory markers CD80, CD83 and human leucocyte antigen (HLA)‐DR on MUTZ cells, as well as induce secretion of interleukin (IL)‐2, IL‐6, IL‐8, IL‐12 (p70), interferon‐gamma and tumour necrosis factor‐alpha Conversely, C. trachomatis serovar D failed to upregulate DC costimulatory markers, but did induce secretion of high concentrations of IL‐8. Interestingly, we also observed that infection of MUTZ cells with C. pneumoniae or C. trachomatis serovar L2, whilst not replicative, remained infectious and upregulated lymph node migratory marker CCR7 mRNA. Taken together, these data confirm the findings of other groups using primary DCs and demonstrate the utility of MUTZ cells for further studies of chlamydial infection.
Efficacy of Cell Wall‐Deficient Spheroplasts Against Experimental Murine Listeriosis
Authors: Ansari M. A. , Zia Q. , Kazmi S. , Ahmad E. , Azhar A. , Johnson K. E. , Zubair S. , Owais M.
Published: April 2015

Various strategies adapted to develop an efficient vaccine against foodborne pathogen, Listeria monocytogenes, have met with little success. Spheroplasts (bacterial cell devoid of cell wall) are likely to undergo membrane–membrane fusion, leading to the delivery of their content to the cytosol of antigen‐presenting cells, thus facilitating MHC class I antigen processing and presentation. In this study, we evaluated the prophylactic potential of Listeria spheroplast‐based vaccine against experimental murine listeriosis in comparison with heat‐killed Listeria (HKL) and archaeosome‐entrapped Listeria whole‐cell protein (LWCP). Compared with HKL, the spheroplast‐based vaccine was found to evoke better Th1 response as exhibited by the presence of type 1 cytokines in the host (interferon‐γ and IL‐12) and a high IgG2a/IgG1 ratio. Robust lympho‐proliferative efficacy was apparent in both spheroplast‐immunized and archaeosome‐entrapped LWCP‐immunized groups. The upregulation of costimulatory and effector memory markers upon immunization with spheroplasts was found to be at par with that evoked by archaeosome‐entrapped LWCP‐immunized group. Central memory response in gated CD8+ T cell was much higher in spheroplast‐immunized animals when compared with archaeosome‐entrapped LWCP group. The data presented here clearly demonstrate that spheroplasts evoked a robust immune response and offer better prophylactic potential against L. monocytogenes.
Immunopathogenesis of Myocarditis: The Interplay Between Cardiac Fibroblast Cells, Dendritic Cells, Macrophages and CD4+T Cells
Authors: Amoah B. Prince , Yang H. , Zhang P. , Su Z. , Xu H.
Published: April 2015

The myocardium responds to aetiologically different pathological injuries through a common multistep process involving highly co‐ordinated interactions between cardiac and immune cells. Cardiac fibroblast cells which constitute the prevalent cell type in the heart to have their functional effects that express contractile proteins and exhibit increased migratory, proliferative and secretory properties. During the pathogenesis of myocarditis, cardiac fibroblast, dendritic cells, macrophages, CD4+ T cells and other immune cells are known to play variable roles. It is becoming increasingly clear that cardiac fibroblasts are not passive players in immune responses, and several evidences show this through the release of soluble signals and/or direct interactions with these immune cells. Typically, fibroblasts are involved in synthesizing factors such as cytokines, chemokines, prostanoids, matrix components and matrix‐degrading enzymes to influence dendritic cells, CD4+ T cells and macrophage functions and vice versa in the pathogenesis of myocarditis. Again, evidence proves a crosstalk between cardiac fibroblasts and immune cells recruited into the myocardium during myocarditis in the microenvironments. This piece reviews the properties and roles of cardiac fibroblast cells, dendritic cells, macrophages and CD4+ T cells in the pathogenesis of myocarditis, and how these cells interplay on each other in the microenvironment.
Vitamin D status in Well‐Controlled Caucasian HIV Patients in Relation to Inflammatory and Metabolic Markers – A Cross‐Sectional Cohort Study in Sweden
Authors: Missailidis C. , Höijer J. , Johansson M. , Ekström L. , Bratt G. , Hejdeman B. , Bergman P.
Published: April 2015

To study vitamin D (25OH D3) in relation to (i) microbial translocation (ii) systemic inflammation and (iii) blood lipid markers, in Caucasian, well‐controlled HIV patients and healthy controls, plasma and serum samples from n = 97 male, HIV patients on HAART with immeasurable viral load (<20 copies/ml) since median 6.5 years and no concurrent inflammatory or infectious disease and n = 30 healthy controls were analysed for (i) LPS; (ii) sCD14, hsCRP, IL‐4, IL‐6, IL‐10, IL‐17, MCP‐1 and IFN‐γ; as well as (iii) blood lipids. Vitamin D levels were similarly distributed and equally low in both HIV patients and controls. There was no association between vitamin D levels and markers of microbial translocation, systemic inflammation or dyslipidemia. LPS levels were similar in both groups but HIV patients expressed higher levels of sCD14 and hsCRP, with HIV as an independent risk factor. HIV patients had higher cholesterol and Apo B levels. Notably, more HIV patients smoked and smoking was associated with lower vitamin D levels. In conclusion; these well‐treated Caucasian HIV patients had similar vitamin D levels as healthy controls. However, despite perfect virological control, they exhibited slightly increased inflammatory markers and disturbed blood lipids. However, neither of these parameters were associated with low vitamin D levels but appeared to be linked to the HIV‐disease per se. Thus, the rationale for vitamin D substitution as a way to improve microbial translocation and systemic inflammation is not fully supported in this HIV population.
The chromatin‐remodeling factor AtINO80 plays crucial roles in genome stability maintenance and in plant development
Authors: Zhang Chi , Cao Lin , Rong Liang , An Zengxuan , Zhou Wangbin , Ma Jinbiao , Shen Wen‐Hui , Zhu Yan , Dong Aiwu
Published: April 2015

INO80 is a conserved chromatin‐remodeling factor in eukaryotes. While a previous study reported that the Arabidopsis thaliana INO80 (AtINO80) is required for somatic homologous recombination (HR), the role of AtINO80 in plant growth and development remains obscure. Here, we identified and characterized two independent atino80 mutant alleles, atino80‐5 and atino80‐6, which display similar and pleiotropic phenotypes, including smaller plant and organ size, and late flowering. Under standard growth conditions, atino80‐5 showed decreased HR; however, after genotoxic treatment, HR in the mutant increased, accompanied by more DNA double‐strand breaks and stronger cellular responses. Transcription analysis showed that many developmental and environmental responsive genes are overrepresented in the perturbed genes in atino80‐5. These genes significantly overlapped with the category of H2A.Z body‐enriched genes. AtINO80 also interacts with H2A.Z, and facilitates the enrichment of H2A.Z at the ends of the key flowering repressor genes FLC and MAF4/5. Our characterization of the atino80‐5 and atino80‐6 mutants confirms and extends the previous AtINO80 study, and provides perspectives for linking studies of epigenetic mechanisms involved in plant chromatin stability with plant response to developmental and environmental cues.