bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypothermia/rewarming disrupts excitation-contraction coupling in cardiomyocytes
Authors: Schaible Niccole , Han Young Soo , Hoang Thuy , Arteaga Grace , Tveita Torkjel , Sieck Gary
Published: March 2016

Hypothermia/rewarming (H/R) is poorly tolerated by the myocardium; however, the underlying intracellular basis of H/R-induced cardiac dysfunction remains elusive. We hypothesized that in cardiomyocytes, H/R disrupts excitation-contraction coupling by reducing myofilament Ca2+sensitivity due to an increase in cardiac troponin I (cTnI) phosphorylation. To test this hypothesis, isolated rat cardiomyocytes (13–15 cells from 6 rats per group) were electrically stimulated to evoke both cytosolic Ca2+([Ca2+]cyto) and contractile (sarcomere shortening) responses that were simultaneously measured using an IonOptix system. Cardiomyocytes were divided into two groups: 1) those exposed to hypothermia (15°C for 2 h) followed by rewarming (35°C; H/R); or 2) time-matched normothermic (35°C) controls (CTL). Contractile dysfunction after H/R was indicated by reduced velocity and extent of sarcomere length (SL) shortening compared with time-matched controls. Throughout hypothermia, basal [Ca2+]cytoincreased and the duration of evoked [Ca2+]cytotransients was prolonged. Phase-loop plots of [Ca2+]cytovs. contraction were shifted rightward in cardiomyocytes during hypothermia compared with CTL, indicating a decrease in Ca2+sensitivity. Using Western blot, we found that H/R increases cTnI phosphorylation. These results support our overall hypothesis and suggest that H/R disrupts excitation-contraction coupling of cardiomyocytes due to increased cTnI phosphorylation and reduced Ca2+sensitivity.

Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/hypothermiarewarming-disrupts-e-c-coupling/ .
Sex differences in the impact of CYP2C19 polymorphisms and low-grade inflammation on coronary microvascular disorder
Authors: Akasaka Tomonori , Hokimoto Seiji , Sueta Daisuke , Tabata Noriaki , Sakamoto Kenji , Yamamoto Eiichiro , Yamamuro Megumi , Tsujita Kenichi , Kojima Sunao , Kaikita Koichi , Kajiwara Ayami , Morita Kazunori , Oniki Kentaro , Saruwatari Junji , Nakagawa Kazuko , Ogata Yasuhiro , Ogawa Hisao
Published: March 2016

Categorization as a cytochrome P-450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. It is correlated with an increase in the circulating levels of high-sense C-reactive protein (hs-CRP) in women only, although its role in coronary microcirculation is unclear. We examined sex differences in the impact of the CYP2C19 genotype and low-grade inflammation on coronary microvascular disorder (CMVD). We examined CYP2C19 genotypes in patients with CMVD ( n = 81) and in healthy subjects as control ( n = 81). CMVD was defined as the absence of coronary artery stenosis and epicardial spasms, the presence of inverted lactic acid levels between the intracoronary and coronary sinuses, or an adenosine triphosphate-induced coronary flow reserve ratio < 2.5. CYP2C19 PMs have two loss-of-function (LOF) alleles (*2, *3). Extensive metabolizers have no LOF alleles, and intermediate metabolizers have one LOF allele. The ratio of CYP2C19 PM and hs-CRP levels in CMVD was significantly higher than that of controls, especially in women (40.9 vs. 13.8%, P = 0.013; 0.11 ± 0.06 vs. 0.07 ± 0.04 mg/dl, P = 0.001). Moreover, in each CYP2C19 genotype, hs-CRP levels in CMVD in CYP2C19 PMs were significantly higher than those of the controls, especially in women (0.15 ± 0.06 vs. 0.07 ± 0.03, P = 0.004). Multivariate analysis for CMVD indicated that the female sex, current smoking, and hypertension were predictive factors, and that high levels of hs-CRP and CYP2C19 PM were predictive factors in women only (odds ratio 3.5, 95% confidence interval 1.26–9.93, P = 0.033; odds ratio 4.1, 95% confidence interval 1.15–14.1, P = 0.038). CYP2C19 PM genotype may be a new candidate risk factor for CMVD via inflammation exclusively in the female population.
Biosynthesis of the polymeric gel-forming mucin MUC5B
Authors: Ridley Caroline , Kirkham Sara , Williamson Sally J. , Davis C. William , Woodman Philip , Thornton David J.
Published: March 2016

MUC5B is a major polymeric mucin in the airway mucus gel and is an essential component of innate defense of the respiratory epithelium. Knowledge of the synthesis and intracellular processing of MUC5B is incomplete. We investigated the molecular details of MUC5B assembly in primary human bronchial epithelial cells (HBECs) grown at an air-liquid interface (ALI). Electrophoretic and centrifugal separations of intracellular forms of MUC5B probed with antibodies specific for non- O-glycosylated and O-glycosylated forms of the mucin identified three major intracellular populations of MUC5B (non- O-glycosylated monomer and dimer, and O-glycosylated polymers). Biophysical analysis of recombinant MUC5B COOH-terminus (CT5B; D4-B-C-CK) expressed in 293-EBNA cells showed that MUC5B dimerizes by disulfide linkage. Pulse-chase studies in the HBEC ALI cultures showed that non- O-glycosylated MUC5B was synthesized within 20 min of metabolic labeling and O-glycosylated, polymeric mucin within 2 h. Radiolabeled O-glycosylated mucin polymers were secreted within 2 h and the majority were released by 48 h. These data indicate that MUC5B follows a similar assembly to the related glycoprotein, von Willebrand factor (vWF); however, unlike vWF the MUC5B polypeptide shows no evidence of major proteolytic processing of D-domains during the production of the mature secreted polymeric mucin in normal and cystic fibrosis (CF) primary bronchial epithelial cells. In contrast, MUC5B D-domains were modified by neutrophil elastase, a protease commonly found in CF sputum, demonstrating that proteolytic degradation of MUC5B is an extracellular event in CF sputum. These results define the pathway for synthesis of MUC5B in primary human goblet cells.
Systematic phenotyping and correlation of biomarkers with lung function and histology in lung fibrosis
Authors: Fernandez Isis E. , Amarie Oana V. , Mutze Kathrin , Königshoff Melanie , Yildirim Ali Önder , Eickelberg Oliver
Published: March 2016

To date, phenotyping and disease course prediction in idiopathic pulmonary fibrosis (IPF) primarily relies on lung function measures. Blood biomarkers were recently proposed for diagnostic and outcome prediction in IPF, yet their correlation with lung function and histology remains unclear. Here, we comprehensively assessed biomarkers in liquid biopsies and correlated their abundance with lung function and histology during the onset, progression, and resolution of lung fibrosis, with the aim to more precisely evaluate disease progression in the preclinical model of bleomycin-induced pulmonary fibrosis in vivo. Importantly, the strongest correlation of lung function with histological extent of fibrosis was observed at day 14, whereas lung function was unchanged at days 28 and 56, even when histological assessment showed marked fibrotic lesions. Although matrix metalloproteinase-7 (MMP-7), MMP-9, and PAI-1 were significantly elevated in broncheoalveolar lavage of fibrotic mice, only soluble ICAM-1 (sICAM-1) was elevated in the peripheral blood of fibrotic mice and was strongly correlated with the extent of fibrosis. Importantly, tissue-bound ICAM-1 was also elevated in lung homogenates, with prominent staining in hyperplastic type II alveolar epithelial and endothelial cells. In summary, we show that lung function decline is not a prerequisite for histologically evident fibrosis, particularly during the onset or resolution thereof. Plasma levels of sICAM-1 strongly correlate with the extent of lung fibrosis, and may thus be considered for the assessment of intraindividual therapeutic studies in preclinical studies of pulmonary fibrosis.
Exosomes Derived from Hypoxic Oral Squamous Cell Carcinoma Cells Deliver miR-21 to Normoxic Cells to Elicit a Prometastatic Phenotype
Authors: Li Ling , Li Chao , Wang Shaoxin , Wang Zhaohui , Jiang Jian , Wang Wei , Li Xiaoxia , Chen Jin , Liu Kun , Li Chunhua , Zhu Guiquan
Published: March 2016

Hypoxia is a common feature of solid tumors and is associated with aggressiveness and poor patient outcomes. Exosomes, initially considered to be cellular “garbage dumpsters,” are now implicated in mediating interactions with the cellular environment. However, the mechanisms underlying the association between exosomes and hypoxia during cancer progression remain poorly understood. In this study, we found that exosomes derived from hypoxic oral squamous cell carcinoma (OSCC) cells increased the migration and invasion of OSCC cells in a HIF-1α and HIF-2α–dependent manner. Given that exosomes have been shown to transport miRNAs to alter cellular functions, we performed miRNA sequencing of normoxic and hypoxic OSCC-derived exosomes. Of the 108 miRNAs that were differentially expressed, miR-21 stood out as one of the most significantly upregulated miRNAs under hypoxic conditions. miR-21 depletion in hypoxic OSCC cells led to decreased miR-21 levels in exosomes and significantly reduced cell migration and invasion. Conversely, restoration of miR-21 expression in HIF-1α and HIF-2α–depleted exosomes rescued OSCC cell migration and invasion. Moreover, exosomal miR-21 markedly enhanced snail and vimentin expression, while significantly decreasing E-cadherin levels in OSCC cells, in vitro and in vivo. Finally, circulating exosomal miR-21 levels were closely associated with HIF-1α/HIF-2α expression, T stage, and lymph node metastasis in patients with OSCC. In conclusion, our findings suggest that the hypoxic microenvironment may stimulate tumor cells to generate miR-21–rich exosomes that are delivered to normoxic cells to promote prometastatic behaviors and prompt further investigation into the therapeutic value of exosome inhibition for cancer treatment. Cancer Res; 76(7); 1770–80. ©2016 AACR.
Endoscopic Improvement of the Adenoma Detection Rate during Colonoscopy - Where Do We Stand in 2015?
Authors: Floer Martin , Meister Tobias
Published: March 2016

Background: The presence of colorectal adenomas is considered a major risk factor for colorectal cancer development. The implementation of screening colonoscopy programs in the Western world has led to a substantial reduction of colorectal cancer death. Many efforts have been made to reduce the adenoma miss rates by the application of new endoscopic devices and techniques for better adenoma visualization. Summary: This special review gives the readership an overview of current endoscopic innovations that can aid in the increase of the adenoma detection rate (ADR) during colonoscopy. These innovations include the use of devices like EndoCuff® and EndoRings® as well as new technical equipment like third-eye endoscope® and full-spectrum endoscopy (FUSE®). Key Message: Technical improvements and newly developed accessories are able to improve the ADR. However, additional costs and a willingness to invest into potentially expensive equipment might be necessary. Investigator-dependent skills remain the backbone in the ADR detection.
Clinical Prediction Score for Successful Retrograde Procedure in Chronic Total Occlusion Percutaneous Coronary Intervention
Authors: Chai Wei-lu , Agyekum Francis , Zhang Bin , Liao Hong-tao , Ma Dun-liang , Zhong Zhi-an , Wang Pei-ning , Jin Li-jun
Published: March 2016

Objective: To develop and validate a prediction score for a successful retrograde procedure in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Methods: A total of 228 CTO lesions in 223 patients who underwent PCI by retrograde approach were analyzed. All subjects were randomly grouped to a derivation set and a validation set at a ratio of 2:1. A successful retrograde procedure was set as the end point. Each of the identified predictors for the end point by logistic regression was assigned 1 point and summed. Results: Independent predictors of a successful retrograde procedure were Werner's score [odds ratio (OR) 4.841, 95% confidence interval (CI) 1.952-12.005, p = 0.001], diameter of distal CTO segment (OR 5.263, 95% CI 2.067-13.398, p < 0.001) and tortuous collateral (type b; OR 0.119, 95% CI 0.032-0.444, p = 0.002). The predictive model developed in the derivation set stratified the difficulty of achieving a successful retrograde procedure into 4 grades - very difficult (10.5%), difficult (23.7%), intermediate (50.7%) and easy (15.1%) - and was demonstrated significantly in the validation set: very difficult (15.8%), difficult (18.4%), intermediate (47.4%) and easy (18.4%). The area under the receiver-operating characteristic curve was 0.832 ± 0.042 for the derivation set and 0.912 ± 0.041 for the validation set with an almost equal performance. Conclusions: According to the experience of our center, this model performed excellently in predicting the difficulty in achieving a successful retrograde procedure.
NaF Inhibits Matrix-Bound Cathepsin-Mediated Dentin Matrix Degradation
Authors: Altinci Pinar , Mutluay Murat , Seseogullari-Dirihan Roda , Pashley David , Tjäderhane Leo , Tezvergil-Mutluay Arzu
Published: March 2016

Matrix metalloproteinases (MMPs) and cysteine cathepsins (CCs) degrade the collagen fibrils of demineralized dentin. Sodium fluoride (NaF) has previously been shown to inhibit recombinant MMP-2 and MMP-9. This study aimed to evaluate the efficacy of NaF on the inhibition of dentin-bound MMPs and CCs. Dentin beams were completely demineralized in 10% phosphoric acid. The baseline total MMP activity and dry masses were measured. Beams were assigned to test groups based on similar MMP activity and dry mass (n = 10/group), and incubated in artificial saliva (control) or artificial saliva with NaF containing 6-238 mM fluoride for 1, 7 and 21 days. The dry mass loss and MMP activities were reassessed at each time point. The proteolytic activity was screened by gelatin zymography. ICTP and CTX released to the incubation medium were analyzed as indices of MMP and cathepsin K activity, respectively. The beams were examined under scanning electron microscopy. All NaF doses reduced the dry mass loss after 21 days (p < 0.05). NaF inhibition of the total MMP activity ranged between 5 and 80%. In gelatin zymography, the bands of MMP-2 and MMP-9 became less prominent with increasing NaF levels. NaF did not decrease the released ICTP (p > 0.05). Less CTX release was detected with F ≥179 mM (p < 0.05). CaF2-like minerals were observed on the beams. High levels of NaF may slow the degradation of the dentin matrix due to the inhibition of cathepsin K. Fluoride does not seem effective in the direct inhibition of proteolysis by dentin matrix-bound MMPs.
GABAA Receptor Modulation by Phenyl Ring Compounds Is Associated with a Water Solubility Cut-Off Value
Authors: Brosnan Robert J. , Pham Trung L.
Published: March 2016

Background: The modulation of N-methyl-D-aspartate receptors is associated with a molar water solubility cut-off effect of approximately 1.1 mmol/l and hence are unaffected by significantly less soluble compounds. However, compounds with this molar water solubility are still able to modulate γ-aminobutyric acid type A (GABAA) receptors. We hypothesized that GABAA receptor modulation by phenolic compounds would exhibit cut-off at a molar water solubility value less than 1.1 mmol/l. Methods: GABAA receptors consisting of human α1 and rat β2 and γ2s subunits were expressed in Xenopus laevis oocytes, and drug responses were measured using standard 2-electrode voltage clamp techniques. Twenty substituted phenols and benzenes of similar size and molecular volume were studied at saturated aqueous concentrations. Reversible and statistically significant change in GABAA receptor current that was 10% or greater in magnitude from the baseline response defined a positive drug effect. Results: All phenyl ring compounds with a molar water solubility value equal to or greater than 0.46 mmol/l positively modulated GABAA receptor currents. No compounds with a molar water solubility value equal to or less than 0.10 mmol/l had any effect on GABAA receptor currents. Saturated solutions of phenols with 2,6-dimethyl and 2,6-diisopropyl substituents also caused channel opening in the absence of GABA. Conclusions: The molar water solubility cut-off for GABAA receptor modulation by phenyl ring compounds lies between 0.10 and 0.46 mmol/l. Data suggest that hydrocarbons, perhaps including inhaled anesthetics, might modulate GABAA receptors by displacing water from one or more low-affinity amphipathic binding sites to induce conformational changes that increase ion conductance.
Diabetes Mellitus and Prevention of Late Myocardial Infarction After Coronary Stenting in the Randomized Dual Antiplatelet Therapy Study
Authors: Meredith Ian T. , Tanguay Jean-François , Kereiakes Dean J. , Cutlip Donald E. , Yeh Robert W. , Garratt Kirk N. , Lee David P. , Steg P. Gabriel , Weaver W. Douglas , Holmes David R. , Brindis Ralph G. , Trebacz Jaroslaw , Massaro Joseph M. , Hsieh Wen-Hua , Mauri Laura
Published: March 2016

Background—

Patients with diabetes mellitus (DM) are at high risk for recurrent ischemic events after coronary stenting. We assessed the effects of continued thienopyridine among patients with DM participating in the Dual Antiplatelet Therapy (DAPT) Study as a prespecified analysis.

Methods and Results—

After coronary stent placement and 12 months treatment with open-label thienopyridine plus aspirin, 11 648 patients free of ischemic or bleeding events and who were medication compliant were randomly assigned to continued thienopyridine or placebo, in addition to aspirin, for 18 more months. After randomization, patients with DM (n=3391), in comparison with patients without DM (n=8257), had increased composite outcome of death, myocardial infarction (MI), or stroke (6.8% versus 4.3%,
P
<0.001), increased death (2.5% versus 1.4%,
P
<0.001), and MI (4.2% versus 2.6%,
P
<0.001). Among patients with DM, in a comparison of continued thienopyridine versus placebo, rates of stent thrombosis were 0.5% versus 1.1%,
P
=0.06, and rates of MI were 3.5% versus 4.8%,
P
=0.058; and among patients without DM the rates were 0.4% versus 1.4%,
P
<0.001 (stent thrombosis,
P
interaction=0.21) and 1.6% versus 3.6%,
P
<0.001 (MI,
P
interaction=0.02). Bleeding risk with continued thienopyridine was similar among patients with or without DM (interaction
P
=0.61).

Conclusions—

In patients with DM, continued thienopyridine beyond 1 year after coronary stenting is associated with reduced risk of MI, although this benefit is attenuated in comparison with patients without DM.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00977938.
Carotid Atherosclerosis and Cerebral Microbleeds: The Framingham Heart Study
Authors: Romero José R. , Preis Sarah R. , Beiser Alexa , DeCarli Charles , D'Agostino Ralph B. , Wolf Philip A. , Vasan Ramachandran S. , Polak Joseph F. , Seshadri Sudha
Published: March 2016

Background

Carotid atherosclerosis is associated with subclinical ischemic cerebrovascular disease, but its role in hemorrhage‐prone small vessel disease—represented by cerebral microbleed (
CMB
)—is unclear, although vascular risk factors underlie both conditions. We hypothesized that persons with carotid atherosclerosis would have higher risk of
CMB
, particularly in deep regions.

Methods and Results

We studied 1243 participants in the Framingham Offspring Study (aged 56.9±8.8 years; 53% women) with carotid ultrasound available on 2 occasions (1995–1998 and 2005–2008) prior to brain magnetic resonance imaging. Using multivariable logistic regression, we related baseline carotid stenosis, baseline intima–media thickness, and site‐specific carotid intima–media thickness progression (at internal and common carotid locations) to the prevalence and location (lobar or deep plus mixed) of
CMB
. In addition, we assessed effect modification by lipid levels and use of statin and antithrombotic medications. Carotid stenosis ≥25% (a marker of cerebrovascular atherosclerosis) was associated with presence of
CMB
overall (Odds Ratio 2.20, 95%
CI
1.10–4.40) and at deep and mixed locations (odds ratio 3.60, 95%
CI
1.23–10.5). Baseline carotid intima–media thickness was not associated with
CMB
. Progression of common carotid artery intima–media thickness among persons on hypertension treatment was associated with lower risk of deep and mixed
CMB
(odds ratio per
SD
0.41, 95%
CI
0.18–0.96).

Conclusions

Cumulative vascular risk factor exposure may increase the risk of
CMB
, especially in deep regions. The apparent paradoxical association of carotid intima–media thickness progression with lower risk of
CMB
may reflect benefits of intensive vascular risk factor treatment among persons with higher cardiovascular risk and deserves further investigation. If replicated, the results may have potential implications for assessment of preventive and therapeutic interventions for subclinical cerebral hemorrhage.
Eliciting Patient Risk Willingness in Clinical Consultations as a Means of Improving Decision‐Making of Aortic Valve Replacement
Authors: Hussain Amjad I. , Garratt Andrew M. , Brunborg Cathrine , Aakhus Svend , Gullestad Lars , Pettersen Kjell I.
Published: March 2016

Background

Treatment decisions for aortic valve replacement (
AVR
) should be sensitive to patient preferences. However, we lack knowledge of patient preferences and how to obtain them.

Methods and Results

We assessed the mortality risk patients were willing to accept when undergoing
AVR
by using the Standard Gamble method and aimed to show how this risk willingness was affected by level of disease burden. We report findings from 439 patients, aged >18 years with severe aortic stenosis who were referred for evaluation of
AVR
to our institution. The vast majority of patients accepted a mortality risk regarded as high or prohibitive according to current guidelines. Of the 439 patients, 51% patients were willing to forego surgery with high mortality risk (8–50%) and 19% were willing accept a prohibitive mortality risk (>50%) as defined in current guidelines. However, the risk willingness varied considerably. Acceptance of prohibitive risk willingness (>50%) was associated with reporting of 3 to 5 different restricting symptoms, with an odds ratio of 4.07 (95%
CI
1.56–10.59) opposed by increasing score on
EuroQol
–Visual Analog Scale, with an odds ratio of 0.99 (95%
CI
0.97–1.00). The poor ability to predict risk willingness based on available clinical variables and health status suggests that other factors may be important advocating the need for tools for soliciting patient's preferences individually.

Conclusion

When undergoing
AVR
, patients were willing to accept considerably higher perioperative risk than what is considered acceptable in current guidelines and practice. Patient preferences varied considerably, and they should be directly assessed and taken into account in decision‐making and guidelines.

Clinical Trial Registration

URL
:
https://clinicaltrials.gov/
. Unique identifier:
NCT
01794832.
When Chinese Central Orders and Promotion Criteria Conflict
Authors: Solinger Dorothy J. , Jiang Ting
Published: March 2016

The 1999 relief plan for China’s Minimum Livelihood Guarantee (called, for short, the dibao)—originally designed to assist all of the urban poor—changed by the mid-2000s, emphasizing employment, not handouts, for the able-bodied impecunious. Also, the center ordered that cities should subsidize just the most ill and needy. We find that only some Chinese cities—the less well-endowed and politically less prominent—responded to this shift by cutting back their percentage of merely unemployed recipients and increasing the percentage of the truly needy among their dibao beneficiaries. We suggest that two factors could account for this disparity: politicians in wealthier cities have greater autonomy; and they are closer to fulfilling a momentous career goal—stepping up to a post in the central government, and are thus more ambitious. It could be that in prosperous cities—where politicians have control over their budgets and where their trajectories have already positioned them near the peak of the mobility channel—leaders choose to keep the unemployed from protesting by continuing their allowances. This suggests that when two central concerns (redirecting the dibao and social stability) collide, officials in richer cities make different choices than do those in poorer cities.
Daughters’ Generation: The Importance of Having Daughters Living Nearby for Older Korean Immigrants’ Mental Health
Authors: Oh Hunhui , Ardelt Monika , Koropeckyj-Cox Tanya
Published: March 2016

With declining adherence to filial piety in East Asian cultures, the closeness of adult daughters rather than sons may become more important for older Asian immigrants’ well-being. With a sample of 177 older Korean immigrants to the United States (age 60+, M = 72, SD = 7.7), we examined how and to what extent having daughters living nearby rather than sons (daughters-in-law) is related to older Asian immigrants’ mental health, moderating the direct relationship between stressful life events and depressive symptoms. The analyses showed physical proximity of daughters rather than sons (daughters-in-law) functioned as a stress buffer by reducing the direct relation between stressful life events and older immigrants’ depressive symptoms. The findings suggest that gendered cultural expectations of adult children’s caregiving roles for older Korean immigrants are changing, implying that companionship and the perceived quality of instrumental and emotional support might take priority over traditional gendered expectations of filial piety.
Sensory Processing Difficulties in Opsoclonus-Myoclonus Syndrome
Authors: Green Dido , Lim Ming , Lang Bethan , Pohl Keith , Turk Jeremy
Published: March 2016

Opsoclonus-myoclonus syndrome is a rare but serious neurological condition resulting in loss of control of eye movements, often accompanied by difficulties in posture and movement control with reports of sensory sensitivities potentially impacting on behavior. This pilot study characterizes the presence of atypical sensory behaviors in opsoclonus-myoclonus syndrome through questionnaire survey of a cohort of families. The Short Sensory Profile, Vineland Adaptive Behavior Scale, and Developmental Behaviour Checklist were distributed to 30 families; 16 were returned anonymously. Atypical sensory behaviors were identified in a large proportion (62.5%). Children reported as being more anxious showed greater sensitivity to auditory stimuli, U(14) 11, P = .026. This is consistent with recent recognition of more extensive disease neurocognitive effects in Opsoclonus-myoclonus syndrome. Further research is needed to increase understanding of the complex pathology of this disease and to provide indicators for sensory and behavioral as well as pharmacological interventions.
Children’s friendships in super-diverse localities: Encounters with social and ethnic difference
Authors: Iqbal Humera , Neal Sarah , Vincent Carol
Published: March 2016

This article explores how children make, manage, or avoid friendships in super-diverse primary school settings. We draw on interviews and pictorial data from 78 children, aged 8–9 years across three local London primary schools to identify particular friendship groupings and the extent to which they followed existing patterns of social division. Children in the study did recognise social and cultural differences, but their friendship perceptions, affections, conflicts and practices meant that the way in which difference impacted relationships was partial and unstable. Friendship practices in the routine settings of school involved interactions across difference, but also entrenchments around similarity.
The role of music in the lives of older adults with dementia ageing in place: A scoping review
Authors: Elliott Melanie , Gardner Paula
Published: March 2016

The number of people around the world living with dementia is predicted to rise from 44 million to 135 million by 2050. Traditional treatments for dementia have been largely unsuccessful and prompted the emergence of alternative strategies. Music is emerging as an effective therapeutic strategy for older adults with dementia however, most of the work to date has focused on institutions. The purpose of this scoping review was to summarize what is known about the role and impact that music plays in the lives of community-dwelling older adults with dementia. Using a five-stage framework for conducting a scoping review, analysis revealed three ways in which music influences the lives of community-dwelling older adults with dementia: (a) reduced agitation, (b) improved cognition, and (c) enhanced social well-being. The concept of personhood provided a lens with which to conceptualize the findings and highlights the need for continued research.
Original Research: Use of hydroxyurea and phlebotomy in pediatric patients with hemoglobin SC disease
Authors: Summarell Carly C Ginter , Sheehan Vivien A
Published: March 2016

Hydroxyurea is an excellent therapeutic agent for the pharmacological induction of HbF in patients with sickle cell disease (SCD). However, all completed clinical trials of hydroxyurea have excluded patients with hemoglobin SC (HbSC) disease. HbSC differs significantly in pathophysiology from HbSS, as HbC does not sickle, but instead causes cellular dehydration which potentiates sickling of HbS. Many severely affected HbSC patients have been placed on hydroxyurea on a case by case basis, but there are no large scale prospective data on safety or efficacy of hydroxyurea in this subset of patients with SCD. Here, we report a case series of 14 pediatric patients with HbSC treated to maximum tolerated dose (MTD) with hydroxyurea. Those who failed to show clinical improvement after at least six months at MTD were offered phlebotomy in addition to hydroxyurea. Five out of 11 patients with HbSC who achieved MTD failed to demonstrate clinical improvement on hydroxyurea. Of the four placed on dual hydroxyurea and phlebotomy therapy, all showed at least partial clinical improvement. Percent dense red blood cells (%DRBC) were measured via an ADVIA hematology analyzer. A marked rise in percent dense cells preceded clinical complications in three patients. Dual therapy with hydroxyurea and phlebotomy may be an effective approach to patients with HbSC that do not experience improvement with hydroxyurea alone. Monitoring of %DRBC may predict adverse events and aid in assessing hydroxyurea compliance. Large scale clinical trials are needed to evaluate the safety and efficacy of hydroxyurea and hydroxyurea with phlebotomy in patients with HbSC disease.
Pregnancy outcomes of antiphospholipid syndrome: In a low resource South Asian setting
Authors: Wijeyaratne CN , Galappaththi SLA , Palipane E , Jayawardane DBIA , Dodampahala SH , Tudawe MN , Gooneratne LV , Silva R de , Ratnayake D , Seneviratne SL
Published: March 2016

Problem

Antiphospholipid syndrome is associated with recurrent pregnancy loss, and specific treatment improves pregnancy outcome. Laboratory diagnosis is limited in South Asia. We assessed management outcomes of definite/probable antiphospholipid syndrome treated at a tertiary centre in Sri Lanka.

Method

Descriptive cross-sectional study of pregnancy outcomes with heparin and aspirin therapy. Outcome measures: miscarriage, intrauterine death and live birth when compared to previous untreated pregnancies.

Results

Of 646 gestations in 145 women, 146 (22.6%) received specific treatment. In the preceding pregnancies without specific treatment, the rates of miscarriage, late fetal loss, stillbirth and live birth were 60%, 26%, 8% and 7%, respectively. Following specific treatment with low-dose aspirin ± low-molecular weight heparin in 146 pregnancies (145 women), the rates of miscarriage, late fetal loss, stillbirth and live birth were 14%, 10%, 3% and 74%, respectively. Mean birth weight was 2.54 ± 0.62 kg, preterm births complicated 32 (29.6%) with a mean gestational age at delivery 33.7 ± 2.6 weeks, with three neonatal deaths. Maternal complications were: pre-eclampsia 16 (10.9%), gestational diabetes 28 (19.2%), antepartum haemorrhage in 1 patient. Only 73/145 (50.3%) women had laboratory confirmation of antiphospholipid syndrome, while others were treated empirically. Live births in diagnosed vs. empiric treatment – 80.8% vs. 67.1%.

Conclusion

Pregnant women with clinical antiphospholipid syndrome when treated with low-dose aspirin and heparin, the live birth rate of 7% in the previous pregnancy resulted in live births of 74% in a resource limited South Asian setting.
Psychosocial Impact of the Bionic Pancreas During Summer Camp
Authors: Weissberg-Benchell Jill , Hessler Danielle , Polonsky William H. , Fisher Lawrence
Published: March 2016

Background:

The psychosocial impact of the bionic pancreas (BP) was assessed among children attending diabetes camp.

Methods:

Nineteen children were randomly assigned for 5 days to the BP condition and 5 days to the control condition in a crossover design.

Results:

Significant reductions in hypoglycemic fear and regimen burden were found. Children felt less burdened or worried about diabetes and felt freer to do things they enjoyed while using the BP. Children wished the BP responded to out of range numbers faster and expressed annoyance about carrying around the necessary equipment.

Conclusions:

Children may experience improved psychosocial outcomes following use of BP while expressing key areas of user concern. Future studies in less controlled environments with larger sample sizes can determine if these findings are generalizable to other groups.
Engaging Young People: Deliberative Preferences in Discussions About News and Politics
Authors: Peacock Cynthia , Leavitt Peter
Published: March 2016

The Internet affords users a unique and low-cost way to engage with news, politics, and one another. Although young people are the most likely age cohort to go online, it is questionable whether young people take advantage of the Internet as a deliberative space. We examine the way college students perceive the online world as a venue for political discussion by analyzing responses from six focus groups conducted with college students across the United States. Using deliberative theory as a guide, we examine focus group participants’ thoughts about political discussion both online and offline. Our findings indicate that young people’s preferences for online discussions about politics and the news consistently link to the ideals of deliberation. Young people prefer engaging with others who are knowledgeable and remain flexible and calm during discussions. Goals for engaging in conversations about politics primarily revolved around sharing information and opinions. Participants preferred civil discourse that focuses on commonalities rather than differences between people. This study provides greater insight into how the rising generation currently engages with politics and the news and reasons why many people hesitate to participate in online discussions about public affairs.
An Empirical Investigation on Mobile Banking Service Adoption in Rural Karnataka
Authors: Kishore S. V. Krishna , Sequeira Aloysius Henry
Published: March 2016

Government of India (GOI) initialized financial inclusion campaign to quell exclusion. The campaign did not gain expected progress. Government employed technologies to speed up the process. Among banking technologies, mobile banking appeared as a possible solution for financial exclusion with wide mobile phone coverage. Inputs on rural people’s intention toward technologies for effective financial inclusion were essential. Technology adoption factors, performance expectancy, effort expectancy, social influence, attitude, perceived risk, and behavioral intention (BI), were short listed after literature review. Factors were subjected to reliability, exploratory factor analysis (EFA), multiple regression, and interaction analysis. Rural provinces in Karnataka state were surveyed. We used mixed sampling technique to reach 959 samples. Multiple regression–interaction analysis revealed age and gender moderated attitude’s path toward BI.
Acute Splenic Sequestration Crisis in a 70-Year-Old Patient With Hemoglobin SC Disease
Authors: Squiers John J. , Edwards Anthony G. , Parra Alberto , Hofmann Sandra L.
Published: March 2016

A 70-year-old African American female with a past medical history significant for chronic bilateral shoulder pain and reported sickle cell trait presented with acute-onset bilateral thoracolumbar pain radiating to her left arm. Two days after admission, Hematology was consulted for severely worsening microcytic anemia and thrombocytopenia. Examination of the patient’s peripheral blood smear from admission revealed no cell sickling, spherocytes, or schistocytes. Some targeting was noted. A Coombs test was negative. The patient was eventually transferred to the medical intensive care unit in respiratory distress. Hemoglobin electrophoresis confirmed a diagnosis of hemoglobin SC disease. A diagnosis of acute splenic sequestration crisis complicated by acute chest syndrome was crystallized, and red blood cell exchange transfusion was performed. Further research is necessary to fully elucidate the pathophysiology behind acute splenic sequestration crisis, and the role of splenectomy to treat hemoglobin SC disease patients should be better defined.
Modeling observed animal performance using the Weibull distribution
Authors: Hagey Travis J. , Puthoff Jonathan B. , Crandell Kristen E. , Autumn Kellar , Harmon Luke J.
Published: March 2016

Understanding how organisms adapt requires linking performance and microhabitat. However, measuring performance, especially maximum performance, can sometimes be difficult. Here we describe an improvement over previous techniques of only considering the largest observed values as maxima. Instead, we model expected performance observations via the Weibull distribution, a statistical approach that reduces the impact of rare observations. After calculating group-level weighted averages and variances by treating individuals separately to reduce pseudoreplication, our approach resulted in high statistical power despite small sample sizes. We fit lizard adhesive performance and bite force data to the Weibull distribution and found it to closely estimate maximum performance in both cases, illustrating the generality of our approach. Using the Weibull distribution to estimate observed performance greatly improves upon previous techniques by facilitating power analyses and error estimations around robustly estimated maximum values.
Effects of seasonal acclimatization on temperature-dependence of cardiac excitability in the roach, Rutilus rutilus
Authors: Badr A. , El-Sayed M.F. , Vornanen M.
Published: March 2016

Temperature-sensitivity of electrical excitability is a potential limiting factor for performance level and thermal tolerance of excitable tissues in ectothermic animals. In order to test whether rate and rhythm of the heart acclimatize to seasonal temperature changes, thermal sensitivity of cardiac excitation in a eurythermal teleost, the roach (Rutilus rutilus), was examined. Excitability of the heart was determined from in vivo electrocardiograms and in vitro microelectrode recordings of action potentials (APs) from winter (WiR) and summer (SuR) roach acclimated to 4°C and 18°C, respectively. Under heat ramps (3°C/h), starting from the acclimatization temperatures of the fish, heart rate (HR) increased to the maximum value of 78±5 beats/min (at 19.8±0.5°C) and 150±7 beats/min (at 28.1±0.5°C) for WiR and SuR, respectively, and then declined in both groups. Below 20°C HR was significantly higher in WiR than SuR (P<0.05) indicating positive thermal compensation. Cardiac arrhythmias appeared with rising temperature as missing QRS complexes, increase in variability of HR, episodes of atrial tachycardia, ventricular bradycardia and complete cessation of the heartbeat (asystole) in both WiR and SuR. Unlike WiR, atrial APs of SuR had a distinct early repolarization phase, which appeared as shorter duration of atrial AP at 10% and 20% repolarization levels in comparison to WiR (P<0.05). In contrast, seasonal acclimatization had only subtle effects on ventricular AP characteristics. Plasticity of cardiac excitation appears to be necessary for seasonal improvements in performance level and thermal resilience of the roach heart.
Ground States for a Nonlinear Schrödinger System with Sublinear Coupling Terms
Authors: Oliveira Filipe , Tavares Hugo
Published: March 2016

We study the existence of ground states for the coupled Schrödinger system

{

-

Δ
⁢

u
i

+

λ
i

⁢

u
i

=

μ
i

⁢

|

u
i

|

2
⁢
q

-
2

⁢

u
i

+

∑

j
≠
i

b

i
⁢
j

⁢

|

u
j

|

q

⁢

|

u
i

|

q
-
2

⁢

u
i

,

u
i

∈

H
1

⁢

(

ℝ
n

)

,

i
=

1
,
…
,
d

,

$\left\{\begin{aligned} &\displaystyle-\Delta u_{i}+\lambda_{i}u_{i}=\mu_{i}|u_% {i}|^{2q-2}u_{i}+\sum_{j\neq i}b_{ij}|u_{j}|^{q}|u_{i}|^{q-2}u_{i},\\ &\displaystyle u_{i}\in H^{1}(\mathbb{R}^{n}),\quad i=1,\ldots,d,\end{aligned}\right.$

n
≥
1

${n\geq 1}$

, for

λ
i

,

μ
i

>
0

${\lambda_{i},\mu_{i}>0}$

,

b

i
⁢
j

=

b

j
⁢
i

>
0

${b_{ij}=b_{ji}>0}$

(the so-called “symmetric attractive case”) and

1
<
q
<

n
/

(

n
-
2

)

+

${1<q<n/(n-2)^{+}}$

. We prove the existence of a nonnegative ground state

(

u
1
*

,
…
,

u
d
*

)

${(u_{1}^{*},\ldots,u_{d}^{*})}$

with

u
i
*

${u_{i}^{*}}$

radially decreasing. Moreover, we show that if in addition

q
<
2

${q<2}$

, such ground states are positive in all dimensions and for all values of the parameters.
Secretary General’s Column
Authors: Hartshorn Richard
Published: March 2016

As I sit down to write this column, IUPAC is about to tick off one biennium and begin another. Each time this happens the organisation renews itself as new people cycle into the positions and committees that plan, initiate, and undertake the work of the Union. It is a time when we look forward and consider our priorities—we seek to make our marks and to advance the discipline.
CFD Simulations of Copper-Ceria Based Microreactor for COPROX
Authors: Barbato Paola Sabrina , Landi Gianluca , Lisi Luciana , Di Benedetto Almerinda
Published: March 2016

A CFD model of a copper-ceria based micro-reactor for the CO preferential oxidation reaction is developed. Simulations are performed by changing the thermal conductivity of the support and the oxygen inlet concentration. It is found that the value of the wall thermal conductivity has a significant role on the temperature profiles, hot-spot and selectivity. On increasing the O2 content, the CO selectivity decreases. An increase of the oxygen content anticipates the activation of the H2 oxidation, thus competing with CO oxidation. Conversely, at low values of the O2 content, the H2 oxidation is activated only after an almost complete CO oxidation is obtained. From the results it appears that the temperature control and management in the reactor is a key for increasing the CO selectivity at high CO conversion.
Pragmalinguistic Categories in Discourse Analysis of Science Journalism
Authors: Molek-Kozakowska Katarzyna
Published: March 2016

Drawing on selected approaches from pragmatics, functional linguistics, discourse space theories and evaluation theories, this article proposes a methodological framework for the study of science journalism. It presents the institutional context of science journalism, which is considered a hybrid discourse, as it combines features of science communication and of market-driven journalism, particularly the need for the coverage to meet the criteria of newsworthiness. To enable the study of how science journalists tend to engage the readers linguistically without foregoing the appearances of credibility, the article demonstrates the analytic potential of such pragmalinguistic categories as illocutionary force, reference and positioning, agency and stance, proximization and alignment, as well as emotivity and evaluation. Finally, the article illustrates the applicability of the above categories in a qualitative analysis of a special corpus of “most-read” medicine and biotechnology reports published in the online version of the popular international science magazine New Scientist. The analysis shows how to combine these categories in a productive way in order to develop a methodologically viable and theoretically grounded approach to doing (critical) discourse analysis of science journalism.
The crystal structure of hexaqua(μ2-3-(3-(pyridin-4-yl)-1,2,4-oxadiazol-5-yl)propanoato-1κ2
O,O′;2κO′)(3-(3-(pyridin-4-yl)-1,2,4-oxadiazol-5-yl)propanoato-κO)(3-(3-(pyridin-4-yl)-1,2,4-oxadiazol-5-yl)propanoato-κ2
O,O′)digadolinium(III) octahydrate, C60H76Gd2N18O32
Authors: Chen Qifan , Huang Fang , Quan Wenjing , Lu Yanhua , Zhang Fang , Liu Fei
Published: March 2016

C60H76N18O32Gd2, monoclinic, P21/c (no. 14), a = 10.560(5) Å, b = 31.243(5) Å, c = 12.383(4) Å, β = 116.51(3)°, V = 3656(2) Å3, Z = 2, R
gt
(F) = 0.0470, wR
ref
(F
2
) = 0.1013, T = 293(2) K.
Crystal structure of ((1-((1-benzylpyrrolidin-2-yl)methyl)-3-ethyl-1H-imidazol-2(3H)-ylidene)-κ2
C,N)dichloridopalladium(II), C17H23Cl2N3Pd
Authors: Qian Peng-Cheng
Published: March 2016

C17H23Cl2N3Pd, orthorhombic, P212121 (no. 19), a = 9.6460(18) Å, b = 13.883(3) Å, c = 14.520(3) Å, V = 1944.4(6) Å3, Z = 4, R
gt
(F) = 0.0373, wR
ref
(F
2
) = 0.0917, T = 298(2) K.
R‐spondin 1 and noggin facilitate expansion of resident stem cells from non‐damaged gallbladders
Authors: Lugli Natalia , Kamileri Irene , Keogh Adrian , Malinka Thomas , Sarris Michalis E , Talianidis Iannis , Schaad Olivier , Candinas Daniel , Stroka Deborah , Halazonetis Thanos D
Published: March 2016

Pioneering studies within the last few years have allowed the in vitro expansion of tissue‐specific adult stem cells from a variety of endoderm‐derived organs, including the stomach, small intestine, and colon. Expansion of these cells requires activation of the receptor Lgr5 by its ligand R‐spondin 1 and is likely facilitated by the fact that in healthy adults the stem cells in these organs are highly proliferative. In many other adult organs, such as the liver, proliferating cells are normally not abundant in adulthood. However, upon injury, the liver has a strong regenerative potential that is accompanied by the emergence of Lgr5‐positive stem cells; these cells can be isolated and expanded in vitro as organoids. In an effort to isolate stem cells from non‐regenerating mouse livers, we discovered that healthy gallbladders are a rich source of stem/progenitor cells that can be propagated in culture as organoids for more than a year. Growth of these organoids was stimulated by R‐spondin 1 and noggin, whereas in the absence of these growth factors, the organoids differentiated partially toward the hepatocyte fate. When transplanted under the liver capsule, gallbladder‐derived organoids maintained their architecture for 2 weeks. Furthermore, single cells prepared from dissociated organoids and injected into the mesenteric vein populated the liver parenchyma of carbon tetrachloride‐treated mice. Human gallbladders were also a source of organoid‐forming stem cells. Thus, under specific growth conditions, stem cells can be isolated from healthy gallbladders, expanded almost indefinitely in vitro, and induced to differentiate toward the hepatocyte lineage.