bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin‐4 single nucleotide polymorphisms in juvenile systemic lupus erythematosus
Authors: Mahmoudi M. , Tahghighi F. , Ziaee V. , Harsini S. , Rezaei A. , Soltani S. , Sadr M. , Moradinejad M. H. , Aghighi Y. , Rezaei N.
Published: October 2014

Juvenile systemic lupus erythematosus (JSLE) is a chronic, recurrent multisystem inflammatory disease, caused by a combination of environmental events and genetic risk factors. As cytokines, including interleukin‐4 (IL‐4), seem to have a role in the pathogenesis of JSLE, the investigation was performed to evaluate the associations of specific single nucleotide polymorphisms (SNPs) of IL‐4 and IL‐4RA genes in a case–control study. Fifty‐nine patients with JSLE were recruited in this study as patients' group and compared with 140 healthy volunteers. Genotyping was performed for IL‐4 gene at positions −1098, −590 and −33, as well as IL‐4 receptor α (IL‐4RA) gene at position +1902, using polymerase chain reaction with sequence‐specific primers method. Following alleles were found to be more common among patients with JSLE: C at −590 and −33 and T at −1098 of IL‐4 gene (P value < 0.001; OR = 4.6, P value < 0.001; OR = 2.7 and P value < 0.001; OR = 2.1, respectively). Additionally, significant positive associations for the following genotypes were recognized in JSLE cases, compared with controls: C/C at −33, C/C at −590 and T/T at −1098 of IL‐4 gene (P value < 0.001; OR = 5.3, P value < 0.001; OR = 29.5 and P value < 0.001; OR = 3.3, respectively), while following genotypes were less frequent among patients with JSLE: T/C at −33 and −590 and T/G at −1098 of IL‐4 gene (P value < 0.001; OR = 0.1, P value < 0.001; OR = 0.03 and P value < 0.001; OR = 0.3, respectively). Furthermore, we noticed an astonishing negative haplotypic association for JSLE for IL‐4 (positions −1098, −509 and −33) TTC, GCC and TTT haplotypes (P value < 0.001). There was also a significant relationship between TCC haplotype (IL‐4 gene at positions −1098, −590 and −33) and having JSLE (P value < 0.001). On the other hand, we found no significant associations between IL‐4R polymorphisms and the susceptibility to JSLE. Cytokine gene polymorphisms may influence susceptibility to JSLE. Particular IL‐4 gene variants are associated with JSLE and might have a role in the pathophysiology of disease.
Evaluation of the Sebia Minicap Flex Piercing capillary electrophoresis for hemoglobinopathy testing
Authors: Oyaert M. , Van Laer C. , Claerhout H. , Vermeersch P. , Desmet K. , Pauwels S. , Kieffer D.
Published: October 2014

Introduction

Capillary zone electrophoresis (CZE) at alkaline pH is one of the techniques used for hemoglobinopathy screening. In this study, an evaluation of the performance of a lower throughput CZE instrument, the Sebia Minicap Flex Piercing system, for this purpose is reported for the first time.

Methods

The analytical performance of the Sebia Minicap Flex Piercing system was evaluated. Furthermore, a method comparison between the Sebia Minicap Flex Piercing and two HPLC methods, that is, the Bio‐Rad Variant Classic™ and the Bio‐Rad D‐10™ systems was performed by measuring samples with and without clinically relevant hemoglobin disorders.

Results

The analytical performance was acceptable for the determination of HbA, HbA2, HbS, and HbF, with an imprecision ≤2.0%. Method comparison showed a linear correlation for HbA2, HbF, and HbS measurements. Clinical concordance was acceptable when comparing CZE and HPLC.

Conclusions

Lower throughput CZE using the Sebia Minicap Flex Piercing can be used for precise and accurate first line screening and follow‐up of hemoglobinopathies.
Advantages of Susceptibility-Weighted Magnetic Resonance Sequences in the Visualization of Intravascular Thrombi in Acute Ischemic Stroke
Authors: Allibert R. , Grand C. Billon , Vuillier F. , Cattin F. , Muzard E. , Biondi A. , Moulin T. , Medeiros E.
Published: October 2014

Background

In gradient echo magnetic resonance imaging (MRI), intravascular thrombi (IT) can appear as vascular susceptibility artifacts, linked to local presence of intra-arterial deoxyhaemoglobin, and called susceptibility vessel signs (SVS).

Aims

Our objectives were to evaluate the sensitivity of susceptibility-weighted sequences, such as T2* weighted angiography (SWAN) in the visualization of SVS compared with T2*, to consider whether it enabled a better understanding of the importance of SVS, and to compare cerebral circulation regulation profiles according to the localization of the SVS (i.e. proximal or distal).

Methods

We prospectively studied the clinical and imaging data of 78 consecutive patients admitted for acute cerebral ischemia to the stroke unit of Besançon University Hospital between 1 April 2009 and 31 January 2010.

Results

An SVS was visualized in 44/78 (56%) patients using SWAN and in 13/78 (16%) patients using T2*. All the SVS visible using T2* were also visible on the SWAN. The interobserver kappa score was 0·72 [CI (0·53–0·91)] for T2*, 0·72 [CI (0·57–0·87)] for SWAN, and weighted kappa was 0·77 [CI (0·61–0·92)] for both T2* and SWAN. When an MCA occlusion was visible on MRA imaging (22/78 patients), a SVS was visualized in 7/22 cases (31·8%) using T2* and in 20/22 cases (91%) using SWAN. When the occlusion was visible in the M1 or M2 segments (17/78 patients), an SVS was visualized in 6/17 cases (35·3%) using T2* and in 15/17 cases (88·2%) using SWAN. When the occlusion was visible in the M3 segment (5/78 patients), an SVS was visualized in 1/5 cases (20%) using T2* and in 5/5 cases (100%) using SWAN. Presence of SVS was not associated with cardioembolic etiology of the stroke.

Conclusions

SWAN was more sensitive than T2* in the visualization of SVS in the intracranial arteries during the acute phase of ischemic stroke. Our study shows that the low number of SVS visualized using T2* in previous studies is probably related to a lack of sensitivity of the sequence, rather than to the nature or age of the thrombus. The greater sensitivity of SWAN seems to be linked to the visualization of SVS in cases of small thrombi.
Imaging Selection in Ischemic Stroke: Feasibility of Automated CT-Perfusion Analysis
Authors: Campbell Bruce C.V. , Yassi Nawaf , Ma Henry , Sharma Gagan , Salinas Simon , Churilov Leonid , Meretoja Atte , Parsons Mark W. , Desmond Patricia M. , Lansberg Maarten G. , Donnan Geoffrey A. , Davis Stephen M.
Published: October 2014

Background

Advanced imaging may refine patient selection for ischemic stroke treatment but delays to acquire and process the imaging have limited implementation.

Aims

We examined the feasibility of imaging selection in clinical practice using fully automated software in the EXTEND trial program.

Methods

CTP and perfusion-diffusion MRI data were processed using fully-automated software to generate a yes/no ‘mismatch’ classification that determined eligibility for trial therapies. The technical failure/mismatch classification error rate and time to image and treat with CT vs. MR-based selection were examined.

Results

In a consecutive series of 776 patients from five sites over six-months the technical failure rate of CTP acquisition/processing (uninterpretable maps) was 3·4% (26/776, 95%CI 2·2–4·9%). Mismatch classification was overruled by expert review in an additional 9·0% (70/776, 95%CI 7·1–11·3%) due to artifactual ‘perfusion lesion’. In 154 consecutive patients at one site, median additional time to acquire CTP after noncontrast CT was 6·5 min. Subsequent RAPID processing time varied from 3–10 min across 20 trial centers (median 5 min 20 s). In the EXTEND trial, door-to-needle times in patients randomized on the basis of CTP ( n = 47) were median 78 min shorter than MRI-selected ( n = 16) patients ( P < 0·001).

Conclusions

Automated CTP-based mismatch selection is rapid, robust in clinical practice, and associated with faster treatment decisions than MRI. This technological advance has the potential to improve the standardization and reproducibility of interpretation of advanced imaging and extend use to practice settings beyond highly specialized academic centers.
Validation of the Korean language version of the incontinence‐quality of life scale
Authors: Kang Youngmi
Published: October 2014

The purpose of this study is to determine the reliability and validity of the translated Korean version of the incontinence‐quality of life (I‐QOL) in a sample of community‐dwelling Korean American women with urinary incontinence in the USA. A survey design was used and a convenience sampling method of 176 Korean American women who reported having urinary incontinence symptoms was used. Translation–back translation procedures were used to translate the English version of the I‐QOL into Korean version. Reliability of the Korean I‐QOL questionnaire was demonstrated by Cronbach's α coefficients. Pearson's correlations of an item with its own scale and other scales were calculated to evaluate item‐convergent and item‐discriminant validity. Confirmatory factor analysis was performed to examine the underlying factor structure of the Korean version of the I‐QOL. Cronbach's α coefficient for all three subscales was greater than 0·70. The results of item‐convergent validity indicated that each item was strongly correlated with the originally belonged subscale. Item‐discriminant validity was evidenced by all lower correlations of an item to the other subscales than that of own subscale. Three factors were extracted from I‐QOL, accounting for 67·37% of the variance. The findings supported the reliability and validity of Korean version of I‐QOL questionnaire. It would be considered as a valuable instrument to assess the different aspects of health‐related quality of life in incontinence patients and recommended for use in clinical research.
A decade of progress in adipose tissue macrophage biology
Authors: Hill Andrea A. , Reid Bolus W. , Hasty Alyssa H.
Published: October 2014

One decade has passed since seminal publications described macrophage infiltration into adipose tissue (AT) as a key contributor to inflammation and obesity‐related insulin resistance. Currently, a PubMed search for ‘adipose tissue inflammation’ reveals over 3500 entries since these original reports. We now know that resident macrophages in lean AT are alternatively activated, M2‐like, and play a role in AT homeostasis. In contrast, the macrophages in obese AT are dramatically increased in number and are predominantly classically activated, M1‐like, and promote inflammation and insulin resistance. Mediators of AT macrophage (ATM) phenotype include adipokines and fatty acids secreted from adipocytes as well as cytokines secreted from other immune cells in AT. There are several mechanisms that could explain the large increase in ATMs in obesity. These include recruitment‐dependent mechanisms such as adipocyte death, chemokine release, and lipolysis of fatty acids. Newer evidence also points to recruitment‐independent mechanisms such as impaired apoptosis, increased proliferation, and decreased egress. Although less is known about the homeostatic function of M2‐like resident ATMs, recent evidence suggests roles in AT expansion, thermoregulation, antigen presentation, and iron homeostasis. The field of immunometabolism has come a long way in the past decade, and many exciting new discoveries are bound to be made in the coming years that will expand our understanding of how AT stands at the junction of immune and metabolic co‐regulation.
Macrophage proliferation, provenance, and plasticity in macroparasite infection
Authors: Rückerl Dominik , Allen Judith E.
Published: October 2014

Macrophages have long been center stage in the host response to microbial infection, but only in the past 10–15 years has there been a growing appreciation for their role in helminth infection and the associated type 2 response. Through the actions of the IL‐4 receptor α (IL‐4Rα), type 2 cytokines result in the accumulation of macrophages with a distinctive activation phenotype. Although our knowledge of IL‐4Rα‐induced genes is growing rapidly, the specific functions of these macrophages have yet to be established in most disease settings. Understanding the interplay between IL‐4Rα‐activated macrophages and the other cellular players is confounded by the enormous transcriptional heterogeneity within the macrophage population and by their highly plastic nature. Another level of complexity is added by the new knowledge that tissue macrophages can be derived either from a resident prenatal population or from blood monocyte recruitment and that IL‐4 can increase macrophage numbers through proliferative expansion. Here, we review current knowledge on the contribution of macrophages to helminth killing and wound repair, with specific attention paid to distinct cellular origins and plasticity potential.
Macrophage heterogeneity in tissues: phenotypic diversity and functions
Authors: Gordon Siamon , Plüddemann Annette , Martinez Estrada Fernando
Published: October 2014

During development and throughout adult life, macrophages derived from hematopoietic progenitors are seeded throughout the body, initially in the absence of inflammatory and infectious stimuli as tissue‐resident cells, with enhanced recruitment, activation, and local proliferation following injury and pathologic insults. We have learned a great deal about macrophage properties ex vivo and in cell culture, but their phenotypic heterogeneity within different tissue microenvironments remains poorly characterized, although it contributes significantly to maintaining local and systemic homeostasis, pathogenesis, and possible treatment. In this review, we summarize the nature, functions, and interactions of tissue macrophage populations within their microenvironment and suggest questions for further investigation.
Tissue macrophage identity and self‐renewal
Authors: Gentek Rebecca , Molawi Kaaweh , Sieweke Michael H.
Published: October 2014

Macrophages are cellular components of the innate immune system that reside in virtually all tissues and contribute to immunity, repair, and homeostasis. The traditional view that all tissue‐resident macrophages derive from the bone marrow through circulating monocyte intermediates has dramatically shifted recently with the observation that macrophages from embryonic progenitors can persist into adulthood and self‐maintain by local proliferation. In several tissues, however, monocytes also contribute to the resident macrophage population, on which the local environment can impose tissue‐specific macrophage functions. These observations have raised important questions: What determines resident macrophage identity and function, ontogeny or environment? How is macrophage proliferation regulated? In this review, we summarize the current knowledge about the identity, proliferation, and turnover of tissue‐resident macrophages and how they differ from freshly recruited short‐lived monocyte‐derived cells. We examine whether macrophage proliferation can be qualified as self‐renewal of mature differentiated cells and whether the concepts and molecular pathways are comparable to self‐renewal mechanisms in stem cells. Finally, we discuss how improved understanding of macrophage identity and self‐renewal could be exploited for therapeutic intervention of macrophage‐mediated pathologies by selectively targeting freshly recruited or resident macrophages.
Platelet thromboembolism
Authors: KESSLER C. M. , HANSON S. R.
Published: October 2014

Abstract. Platelet‐dependent thrombosis and subsequent embolization are major causes of cerebral ischaemia. Beside aspirin which irreversibly blocks platelet cyclo‐oxygenase, several other substances interfere in different platelet metabolic pathways and block platelet adhesion and aggregation. We found in an experimental model using non‐human primates that a specific peptide inhibitor blocking GP IIb/IIIa platelet receptor which binds fibrinogen completely, prevents the retention of embolized platelet aggregates in the cerebral circulation. As thrombin may play a key role for platelet activation in vivo leech‐derived hirudin, a direct thrombin inhibitor as well as activated protein C which limits thrombin production and also prevents platelet dependent thrombus formation very effective.

We demonstrated in the same non‐human primate model of platelet embolization that the amount of retention of platelet emboli in the vascular bed depends on the nature of the vasculature. For example, platelet emboli were cleared very quickly from brain microcirculation, whereas platelet embolization into the lower limb via the femoral artery caused a significantly longer retention of the embolized material. Such specific mechanisms may be caused by different levels of local vasodilators as PGI2 or EDRF.
Model‐Based Nitrogen and Phosphorus (Nutrient) Criteria for Large Temperate Rivers: 2. Criteria Derivation
Authors: Suplee Michael W. , Flynn Kyle F. , Chapra Steven C.
Published: October 2014

Nitrogen and phosphorus criteria were developed for 233 km of the Yellowstone River, one of the first cases where a mechanistic model has been used to derive large river numeric nutrient criteria. A water quality model and a companion model which simulates lateral algal biomass across transects were used to simulate effects of increasing nutrients on five variables (dissolved oxygen, total organic carbon, total dissolved gas,pH, and benthic algal biomass in depths ≤1 m). Incremental increases in nutrients were evaluated relative to their impact on predefined thresholds for each variable; the first variable to exceed a threshold set the nutrient criteria. Simulations were made at a low flow, the 14Q5 (lowest average 14 consecutive day flow, July‐September, recurring one in five years), which was derived using benthic algae growth curves and EPA guidance on excursion frequency. An extant climate dataset with an annual recurrence was used, and tributary water quality and flows were coincident with the river's 10 lowest flow years. The river had different sensitivities to nutrients longitudinally,pHbeing the most sensitive variable in the upstream reach and algal biomass in the lower. Model‐based criteria for the Yellowstone River are as follows: between the Bighorn and Powder river confluences, 55 μg TP/l and 655 μg TN/l; from the Powder River confluence to Montana state line, 95 μg TP/l and 815 μg TN/l. Pros and cons of using steady‐state models to derive river nutrient criteria are discussed.
Rapid onset of syndrome of inappropriate antidiuretic hormone secretion induced by duloxetine in an elderly type 2 diabetic patient with painful diabetic neuropathy
Authors: Kamei Shinji , Kaneto Hideaki , Tanabe Akihito , Irie Shintaro , Hirata Yurie , Shimoda Masashi , Kohara Kenji , Mune Tomoatsu , Kaku Kohei
Published: October 2014

Diabetic neuropathy is the most common diabetic complication. Duloxetine, a serotonin noradrenaline reuptake inhibitor (SNRI), is widely used for the treatment of diabetic painful neuropathy (DPN) because of the efficacy and safety profile. Syndrome of inappropriate antidiuretic hormone secretion, which is strongly associated duloxetine, is a rare but occasionally life‐threatening adverse effect. Here, we report a case of syndrome of inappropriate antidiuretic hormone secretion that rapidly developed after starting duloxetine in an elderly Japanese female type 2 diabetes mellitus patient. Furthermore, we discuss the possible relationship between the onset of syndrome of inappropriate antidiuretic hormone secretion and the gene polymorphism of cytochrome P450 isoform 1A2 and 2D6, both of which are responsible for duloxetine metabolism.
More explicit communication after classroom‐based crew resource management training: results of a pragmatic trial
Authors: Verbeek‐van Noord Inge , de Bruijne Martine C. , Twisk Jos W. R. , van Dyck Cathy , Wagner Cordula
Published: October 2014

Rationale, aims and objectives

Aviation‐based crew resource management trainings to optimize non‐technical skills among professionals are often suggested for health care as a way to increase patient safety. Our aim was to evaluate the effect of a 2‐day classroom‐based crew resource management (CRM) training at emergency departments (EDs) on explicit professional oral communication (EPOC; non‐technical skills).

Method

A pragmatic controlled before‐after trial was conducted. Four EDs of general teaching hospitals were recruited (two intervention and two control departments). ED nurses and ED doctors were observed on their non‐technical skills by means of a validated observation tool (EPOC). Our main outcome measure was the amount of EPOC observed per interaction in 30 minutes direct observations. Three outcome measures from EPOC were analysed: human interaction, anticipation on environment and an overall EPOC score. Linear and logistic mixed model analyses were performed. Models were corrected for the outcome measurement at baseline, days between training and observation, patient safety culture and error management culture at baseline.

Results

A statistically significant increase after the training was found on human interaction (β = 0.27, 95% CI 0.08–0.49) and the overall EPOC score (β = 0.25, 95% CI 0.06–0.43), but not for anticipation on environment (OR = 1.19, 95% CI .45–3.15). This means that approximately 25% more explicit communication was shown after CRM training.

Conclusions

We found an increase in the use of CRM skills after classroom‐based crew resource management training. This study adds to the body of evidence that CRM trainings have the potential to increase patient safety by reducing communication flaws, which play an important role in health care‐related adverse events.
Effect of medication adherence on blood pressure control and risk factors for antihypertensive medication adherence
Authors: Yue Zhao , Bin Wang , Weilin Qi , Aifang Yang
Published: October 2014

Rationale, aims and objectives

We aim to investigate a range of risk factors associated with medication adherence among Chinese hypertensive patients. We also aim to investigate the association between medication adherence and blood pressure control.

Methods

A cross‐sectional study was conducted among Chinese hypertensive patients in a comprehensive teaching hospital in Shanghai, China, using a validated scale, a self‐designed questionnaire and patients' medical records.

Results

Of the 232 eligible participants, 61 (26.3%), 51 (22.0%) and 120 (51.7%) showed low, medium and high adherence, respectively. Adjusted for socio‐demographic, clinical and patient‐related factors, antihypertensive medication adherence was significantly associated with better systolic blood pressure control (P = 0.001), whereas the association with diastolic blood pressure control was relatively weak (P = 0.334). In the multivariate analysis, patients with longer duration of drug use [P = 0.012, odds ratio (OR) = 0.46, 95% confidence interval (CI) 0.25–0.84], combination of antiplatelet agents (0.002, 0.38, 0.20–0.71), less concerns of medical cost (0.001, 0.18, 0.02–0.51), more availability of professional guidance (0.002, 0.34, 0.17–0.66) and more availability of family support (0.036, 0.51, 0.27–0.96) were more likely to adhere to their drug regimens.

Conclusions

The rate of suboptimal medication adherence among Chinese hypertensive patients is quite high. Interventions could focus upon the risk factors to improve antihypertensive medication adherence in clinical practice.
P301L tau expression affects glutamate release and clearance in the hippocampal trisynaptic pathway
Authors: Hunsberger Holly C. , Rudy Carolyn C. , Batten Seth R. , Gerhardt Greg A. , Reed Miranda N.
Published: October 2014

Individuals at risk of developing Alzheimer's disease (AD) often exhibit hippocampal hyperexcitability. A growing body of evidence suggests that perturbations in the glutamatergic tripartite synapse may underlie this hyperexcitability. Here, we used a tau mouse model of AD (rTg(TauP301L)4510) to examine the effects of tau pathology on hippocampal glutamate regulation. We found a 40% increase in hippocampal vesicular glutamate transporter, which packages glutamate into vesicles, and has previously been shown to influence glutamate release, and a 40% decrease in hippocampal glutamate transporter 1, the major glutamate transporter responsible for removing glutamate from the extracellular space. To determine whether these alterations affected glutamate regulation in vivo, we measured tonic glutamate levels, potassium‐evoked glutamate release, and glutamate uptake/clearance in the dentate gyrus, cornu ammonis 3(CA3), and cornu ammonis 1(CA1) regions of the hippocampus. P301L tau expression resulted in a 4‐ and 7‐fold increase in potassium‐evoked glutamate release in the dentate gyrus and CA3, respectively, and significantly decreased glutamate clearance in all three regions. Both release and clearance correlated with memory performance in the hippocampal‐dependent Barnes maze task. Alterations in mice expressing P301L were observed at a time when tau pathology was subtle and before readily detectable neuron loss. These data suggest novel mechanisms by which tau may mediate hyperexcitability.

image

Pre‐synaptic vesicular glutamate transporters (vGLUTs) package glutamate into vesicles before exocytosis into the synaptic cleft. Once in the extracellular space, glutamate acts on glutamate receptors. Glutamate is removed from the extracellular space by excitatory amino acid transporters, including GLT‐1, predominantly localized to glia. P301L tau expression increases vGLUT expression and glutamate release, while also decreasing GLT‐1 expression and glutamate clearance.
Zinc transporter‐1: a novel NMDA receptor‐binding protein at the postsynaptic density
Authors: Mellone Manuela , Pelucchi Silvia , Alberti Lorenzo , Genazzani Armando A. , Di Luca Monica , Gardoni Fabrizio
Published: October 2014

Zinc (Zn2+) is believed to play a relevant role in the physiology and pathophysiology of the brain. Hence, Zn2+ homeostasis is critical and involves different classes of molecules, including Zn2+ transporters. The ubiquitous Zn2+ transporter‐1 (ZNT‐1) is a transmembrane protein that pumps cytosolic Zn2+ to the extracellular space, but its function in the central nervous system is not fully understood. Here, we show that ZNT‐1 interacts with GluN2A‐containing NMDA receptors, suggesting a role for this transporter at the excitatory glutamatergic synapse. First, we found that ZNT‐1 is highly expressed at the hippocampal postsynaptic density (PSD) where NMDA receptors are enriched. Two‐hybrid screening, coimmunoprecipitation experiments and clustering assay in COS‐7 cells demonstrated that ZNT‐1 specifically binds the GluN2A subunit of the NMDA receptor. GluN2A deletion mutants and pull‐down assays indicated GluN2A(1390–1464) domain as necessary for the binding to ZNT‐1. Most importantly, ZNT‐1/GluN2A complex was proved to be dynamic, since it was regulated by induction of synaptic plasticity. Finally, modulation of ZNT‐1 expression in hippocampal neurons determined a significant change in dendritic spine morphology, PSD‐95 clusters and GluN2A surface levels, supporting the involvement of ZNT‐1 in the dynamics of excitatory PSD.

image

Zn2+ transporter‐1 (ZNT‐1) pumps cytosolic Zn2+ to the extracellular space, but its function in the central nervous system is not fully understood. We show that ZNT‐1 interacts with GluN2A‐containing NMDA receptors at the glutamatergic synapse. Most importantly, ZNT‐1/GluN2A complex is regulated by induction of synaptic plasticity. Modulation of ZNT‐1 expression in hippocampal neurons determined a shrinkage of dendritic spines and a reduction of GluN2A surface levels supporting the involvement of ZNT‐1 in the dynamics of the excitatory synapse.
Localization of heat shock protein HSPA6 (HSP70B') to sites of transcription in cultured differentiated human neuronal cells following thermal stress
Authors: Khalouei Sam , Chow Ari M. , Brown Ian R.
Published: October 2014

Heat shock proteins (Hsps) are a set of highly conserved proteins that are involved in cellular repair and protective mechanisms. In order to identify potential stress‐sensitive sites in differentiated SH‐SY5Y human neuronal cells, localization of two inducible members of the HSPA (HSP70) family was investigated, namely HSPA6 (HSP70B') and HSPA1A (HSP70‐1). Following heat shock, yellow fluorescent protein (YFP)‐tagged HSPA6 and HSPA1A proteins localized to nuclear speckles that are enriched in RNA splicing factors (identified by SC35 and SON marker proteins) and then to the granular component of the nucleolus (identified by nucleophosmin). Subsequently, YFP‐HSPA6 protein, but not YFP‐HSPA1A, localized to the periphery of nuclear speckles that are sites of RNA transcription. The HSPA6 gene is present in the human genome but not in genomes of rat and mouse. Hence, current animal models of neurodegenerative diseases are lacking a potentially protective member of the HSPA family.

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Potential stress‐sensitive sites were identified in differentiated human SH‐SY5Y cells by the localization of HSPA6 (HSP70B') and HSPA1A (HSP70‐1) to nuclear components following heat shock. HSPA6 and HSPA1A rapidly moved to nuclear speckles, enriched in RNA splicing factors, then to the granular layer of the nucleolus. Subsequently, HSPA6 exhibited a novel localization not observed for the more widely studied HSPA1A, namely association with the periphery of nuclear speckles that are sites of transcription. HS = heat shock; HSPA6 = HSP70B' protein; HSPA1A = HSP70‐1 protein.
High Cortisol Response to Adrenocorticotrophic Hormone Identifies Ewes with Reduced Melanocortin Signalling and Increased Propensity to Obesity
Authors: Hewagalamulage S. D. , Clarke I. J. , Young I. R. , Rao A. , Henry B. A.
Published: October 2014

We have identified female sheep that have either high (HR) or low (LR) cortisol responses to adrenocorticotrophin. On a high‐energy diet, HR have greater propensity to weight gain and obesity, although the underlying mechanisms remain to be determined. Hypothalamic appetite‐regulating peptides (ARP) exert reciprocal effects on food intake and energy expenditure. We aimed to quantify the expression and function of ARP in LR and HR ewes (n = 4 per group). Gene expression for neuropeptide Y (NPY), agouti‐related peptide (AgRP) pro‐opiomelanocortin (POMC), melanin‐concentrating hormone (MCH), orexin and the melanocortin receptors (MC3R and MC4R) was measured by in situ hybridisation. Expression of NPY, AgRP and POMC was similar in HR and LR, although expression of orexin, MCH, MC3R and MC4R was higher (P < 0.05) in LR. Intracerebroventricular infusions of a low dose (50 μg/h) of NPY, α‐melanocyte‐stimulating hormone (αMSH), orexin and MCH were performed between 10.00 h and 16.00 h in meal‐fed ewes (n = 6–7 per group). Skeletal muscle and retroperitoneal (RP) fat temperatures were recorded using dataloggers. Post‐prandial thermogenesis in muscle was higher (P < 0.05) in LR. There was little effect of ARP infusion on muscle or fat temperature in either group. Infusion of these doses of NPY, MCH or orexin did not stimulate food intake in meal‐fed ewes, although αMSH reduced (P < 0.01) food intake in LR only. Using 24‐h ARP infusions with ad lib. feeding, NPY increased (P < 0.001) food intake in both groups but αMSH was only effective in LR (P < 0.05). In summary, we show that HR are resistant to the satiety effects of αMSH and this coincides with a reduced expression of both the MC3R and MC4R in the paraventricular nucleus of the hypothalamus. We conclude that an increased propensity to obesity in HR female sheep is associated with reduced melanocortin signalling.
The impact of obesity on skeletal muscle architecture in untrained young vs. old women
Authors: Tomlinson D. J. , Erskine R. M. , Winwood K. , Morse C. I. , Onambélé G. L.
Published: October 2014

It is unknown whether loading of the lower limbs through additional storage of fat mass as evident in obesity would promote muscular adaptations similar to those seen with resistance exercise. It is also unclear whether ageing modulates any such adjustments. This study aimed to examine the relationships between adiposity, ageing and skeletal muscle size and architecture. A total of 100 untrained healthy women were categorised by age into young (Y) (mean ± SD: 26.7 ± 9.4 years) vs. old (O) (65.1 ± 7.2 years) and body mass index (BMI) classification (underweight, normal weight, overweight and obese). Participants were assessed for body fat using dual energy x‐ray absorptiometry, and for gastrocnemius medialis (GM) muscle architecture (skeletal muscle fascicle pennation angle and length) and size [GM muscle volume and physiological cross‐sectional area (PCSA)] using B‐mode ultrasonography. GM fascicle pennation angle (FPA) in the obese Y females was 25% greater than underweight (P = 0.001) and 25% greater than normal weight (P = 0.001) individuals, while O females had 32 and 22% greater FPA than their underweight (P = 0.008) and normal weight (P = 0.003) counterparts. Furthermore, FPA correlated with body mass in both Y and O females (Y r = 0.303; P < 0.001; O r = 0.223; P = 0.001), yet no age‐related differences in the slope or r‐values were observed (P > 0.05). Both GM muscle volume (P = 0.003) and PCSA (P = 0.004) exhibited significant age × BMI interactions. In addition, muscle volume and PCSA correlated with BMI, body mass and fat mass. Interestingly, ageing reduced both the degree of association in these correlations (P < 0.05) and the slope of the regressions (P < 0.05). Our findings partly support our hypotheses in that obesity‐associated changes in GM PCSA and volume differed between the young and old. The younger GM muscle adapted to the loading induced by high levels of body mass, adiposity and BMI by increasing its volume and increasing its pennation angle, ultimately enabling it to produce higher maximum torque. Such an adaptation to increased loading did not occur in the older GM muscle. Nonetheless, the older GM muscle FPA increased to a similar extent to that seen in young GM muscle, an effect which partly explains the relatively enhanced absolute maximum torque observed in obese older females.
Durability and Weibull Characteristics of Lithium Disilicate Crowns Bonded on Abutments with Knife‐Edge and Large Chamfer Finish Lines after Cyclic Loading
Authors: Cortellini Davide , Canale Angelo , Souza Rodrigo O.A. , Campos Fernanda , Lima Julia C. , Özcan Mutlu
Published: October 2014

Purpose

The aim of this study was to evaluate the durability of lithium disilicate crowns bonded on abutments prepared with two types of finish lines after long‐term cyclic loading.

Materials and Methods

Pressed lithium disilicate all‐ceramic molar crowns were bonded (Variolink II) to epoxy abutments (height: 5.5 mm, Ø: 7.5 mm, conicity: 6°) (N = 20) with either knife‐edge (KE) or large chamfer (LC) finish lines. Each assembly was submitted to cyclic loading (1,200,000×; 200 N; 1 Hz) in water and then tested until fracture in a universal testing machine (1 mm/min). Failure types were classified and further evaluated under stereomicroscope and SEM. The data (N) were analyzed using one‐way ANOVA. Weibull distribution values including the Weibull modulus (m), characteristic strength (0), probability of failure at 5% (0.05), 1% (0.01), and correlation coefficient were calculated.

Results

Type of finish line did not significantly influence the mean fracture strength of pressed ceramic crowns (KE: 1655 ± 353 N; LC: 1618 ± 263 N) (p = 0.7898). Weibull distribution presented lower shape value (m) of KE (m = 5.48; CI: 3.5 to 8.6) compared to LC (m = 7.68; CI: 5.2 to 11.3). Characteristic strengths (0) (KE: 1784.9 N; LC: 1712.1 N) were higher than probability of failure at 5% (0.05) (KE: 1038.1 N; LC: 1163.4 N) followed by 1% (0.01) (KE: 771 N; LC: 941.1 N), with a correlation coefficient of 0.966 for KE and 0.924 for LC. Type V failures (severe fracture of the crown and/or tooth) were more common in both groups. SEM findings showed that fractures occurred mainly from the cement/ceramic interface at the occlusal side of the crowns.

Conclusion

Lithium disilicate ceramic crowns bonded onto abutment teeth with KE preparation resulted in similar fracture strength to those bonded on abutments with LC finish line.

Clinical Significance

Pressed lithium disilicate ceramic crowns may not require invasive finish line preparations since finish line type did not impair the strength after aging conditions.
Paediatric bacteraemias in tropical Australia
Authors: Er Jeremy , Wallis Peter , Maloney Samuel , Norton Robert
Published: October 2014

Aim

Bacteraemias in children are an important cause of morbidity and mortality. Knowledge of local epidemiology and trends is important to inform practitioners of likely pathogens in the sick child. This study aimed to determine trends over time in pathogenic organisms causing paediatric bacteraemia in North Queensland and to audit a hospital's blood culture results with respect to contamination rate.

Methods

This was a retrospective review of 8385 blood cultures collected from children attending a tertiary centre in North Queensland over a 10‐year period (2001–2010).

Results

There were 696 positive blood cultures (8.3%) with 70 different bacterial species detected. Gram‐positive and Gram‐negative bacteria accounted for 48.6% and 51.4% of isolates, respectively. Overall, bacteraemia accounted for 4.7 per 1000 admissions. The rate of contamination was 60.6% among positive blood cultures and 5.0% for all blood cultures sampled. These results were compared with previous published reports. Notable differences were seen in the frequencies of Salmonella and group A Streptococcus bacteraemias in North Queensland when compared with other reports. There was also a decline in vaccine‐preventable infections such as S. pneumoniae and an increasing trend of community‐acquired MRSA bacteraemia.

Conclusion

This study has demonstrated the unique profile of causative pathogens of paediatric bacteraemias in tropical Australia. In light of the increasing prevalence of MRSA, empiric treatment for sepsis for children in this region needs to be reconsidered.
Effect of dietary supplementation with resveratrol on nutrient digestibility, methanogenesis and ruminal microbial flora in sheep
Authors: Ma T. , Chen D.‐D. , Tu Y. , Zhang N.‐F. , Si B.‐W. , Deng K.‐D. , Diao Q.‐Y.
Published: October 2014

Two experiments were conducted to evaluate the effect of resveratrol on methanogenesis and microbial flora in Dorper × thin‐tailed Han cross‐bred ewes. In experiment 1, ten ewes (67.2 ± 2.24 kg BW) were assigned to two dietary treatments, a basal diet and a basal diet supplemented with resveratrol (0.25 g/head·day), to investigate the effect of resveratrol on nutrient digestibility and nitrogen balance. In experiment 2, six ewes (64.0 ± 1.85 kg BW) with ruminal cannulae were assigned to the identical dietary treatments used in experiment 1 to investigate supplementary resveratrol on ruminal fermentation and microbial flora using qPCR. The results showed that supplementary resveratrol improved the digestibility of organic matter (OM; p < 0.001), nitrogen (N; p = 0.007), neutral detergent fibre (NDF; p < 0.001) and acid detergent fibre (ADF; p < 0.001). The excretion of faecal N was reduced (p = 0.007), whereas that of urinary N increased (p = 0.002), which led to an unchanged N retention (p = 0.157). Both CO2 and CH4 output scaled to digestible dry matter (DM) intake decreased from 602.5 to 518.7 (p = 0.039) and 68.2 to 56.6 (p < 0.001) respectively. Ruminal pH (p = 0.341), ammonia (p = 0.512) and total volatile fatty acid (VFA) (p = 0.249) were unaffected by resveratrol. The molar proportion of propionate increased from 13.1 to 17.5% (p < 0.001) while that of butyrate decreased from 11.0 to 9.55% (p < 0.001). The ratio of acetate to propionate (A/P) decreased from 5.44 to 3.96 (p < 0.001). Supplementary resveratrol increased ruminal population of Fibrobacter succinogenes, Ruminococcus albus and Butyrivibrio fibrisolvens (p < 0.001) while decreased protozoa and methanogens. In conclusion, dietary resveratrol inhibited methanogenesis without adversely affecting ruminal fermentation.
Size and Depth of Vocabulary Knowledge: What the Research Shows
Authors: Schmitt Norbert
Published: October 2014

When discussing vocabulary, a distinction is often made between size of vocabulary (number of known words) and depth of knowledge (how well those words are known). However, the relationship between the two constructs is still unclear. Some scholars argue that there is little real difference between the two, while regression analyses show that depth typically adds unique explanatory power compared to size alone. Ultimately, the relationship between size and depth of vocabulary knowledge depends on how each is conceptualized and measured. In an attempt to provide an empirical basis for exploring the size–depth relationship, this critical synthesis identifies studies that contain measures of both size and depth. Based on a number of different conceptualizations of depth, various patterns emerged. For higher frequency words and for learners with smaller vocabulary sizes, there is often little difference between size and a variety of depth measures. However, for lower frequency words and for larger vocabulary sizes, there is often a gap between size and depth, as depth measures lag behind the measures of size. Furthermore, some types of word knowledge (e.g., derivative knowledge) seem to have generally lower correlations with size than other types.
Origin and flatness of ponds on asteroid 433 Eros
Authors: Roberts James H. , Kahn Eliezer G. , Barnouin Olivier S. , Ernst Carolyn M. , Prockter Louise M. , Gaskell Robert W.
Published: October 2014

NEAR‐Shoemaker Multi‐Spectral Imager data reveal several hundred “ponds” on 433 Eros: smooth deposits that sharply embay the bounding depressions in which they lie, and whose spectra appear blue relative to that of the surrounding terrain. We investigate the topography of these ponds on Eros using a new shape model derived from stereophotoclinometric analysis, and validated against altimetry from the NEAR Laser Rangefinder, to constrain the mode of pond formation from three existing models. We update the locations of 55 pond candidates identified in images registered to the new shape model. We classify the flatness of these features according to the behavior of the first and second derivatives of the topography. We find that less than half of pond candidates have clearly flat floors. Based on the pond topography, we favor an external origin for the ponds' deposits. We suggest that fine dust may be transported into bounding depressions by electrostatic levitation, but may adhere to slopes, and that seismic shaking may not be sufficient to bring the deposits to an equipotential surface. Disaggregation of a central boulder should result in an obvious break in slope, such a variation is only observed in roughly half the pond candidates.
Two‐stage polybaric formation of the new enriched, pyroxene‐oikocrystic, lherzolitic shergottite, NWA 7397
Authors: Howarth Geoffrey H. , Pernet‐Fisher John F. , Balta J. Brian , Barry Peter H. , Bodnar Robert J. , Taylor Lawrence A.
Published: October 2014

Northwest Africa (NWA) 7397 is a newly discovered, enriched, lherzolitic shergottite, the third described example of this group. This meteorite consists of two distinct textural lithologies (1) poikilitic—comprised of zoned pyroxene oikocrysts, with chadacrysts of chromite and olivine, and (2) nonpoikilitic—comprised of olivine, low‐Ca and high‐Ca pyroxene, maskelynite, and minor abundances of merrillite, spinel, ilmenite, and pyrrhotite. The constant Ti/Al ratios of pyroxene oikocrysts suggests initial crystallization of the poikilitic lithology at depth (equivalent to pressures of approximately 10 kbar), followed by crystallization of the nonpoikilitic lithology at shallower levels. Oxygen fugacity conditions become more oxidizing during crystallization ranging from fO2 conditions of approximately QFM‐2 to QFM‐0.7. Magma calculated to be in equilibrium with the major rock‐forming minerals is LREE‐enriched relative to depleted or intermediate shergottites and has flat overall profiles. Therefore, we suggest that the parental magma for NWA 7397 had sampled an enriched, oxidized, Martian geochemical source, similar to that of other enriched basaltic and olivine‐phyric shergottites. We present a polybaric formation model for the lherzolitic shergottite NWA 7397, to account for the petrologic constraints. Three successive stages in the development of NWA 7397 are discussed (1) formation of a REE‐enriched parental magma from a distinct Martian mantle reservoir; (2) magma ponding and development of a staging chamber concomitant with initial crystallization of the poikilitic lithology; and (3) magma ascent to the near surface, with entrainment of cumulates from the staging chamber and subsequent crystallization of the nonpoikilitic lithology en route to the surface.
Mineral and chemical composition of theJezersko meteorite—A new chondrite fromSlovenia
Authors: Miler Miloš , Ambrožič Bojan , Mirtič Breda , Gosar Mateja , Šturm Sašo , Dolenec Matej , Jeršek Miha
Published: October 2014

The Jezersko meteorite is a newly confirmed stony meteorite found in 1992 in the Karavanke mountains, Slovenia. The meteorite is moderately weathered (W2), indicating short terrestrial residence time. Chondrules in partially recrystallized matrix are clearly discernible but often fragmented and have mean diameter of 0.73 mm. The meteorite consists of homogeneous olivine (Fa19.4) and low‐Ca pyroxenes (Fs16.7Wo1.2), of which 34% are monoclinic, and minor plagioclase (Ab83An11Or6) and Ca‐pyroxene (Fs6Wo45.8). Troilite, kamacite, zoned taenite, tetrataenite, chromite, and metallic copper comprise about 16.5 vol% of the meteorite. Phosphates are represented by merrillite and minor chlorapatite. Undulatory extinction in some olivine grains and other shock indicators suggests weak shock metamorphism between stages S2 and S3. The bulk chemical composition generally corresponds to the mean H chondrite composition. Low siderophile element contents indicate the oxidized character of the Jezersko parent body. The temperatures recorded by two‐pyroxene, olivine‐chromite, and olivine‐orthopyroxene geothermometers are 854 °C, 737–787 °C, and 750 °C, respectively. Mg concentration profiles across orthopyroxenes and clinopyroxenes indicate relatively fast cooling at temperatures above 700 °C. A low cooling rate of 10 °C Myr−1was obtained from metallographic data. Considering physical, chemical, and mineralogical properties, meteorite Jezersko was classified as an H4 S2(3) ordinary chondrite.