bluuebunny/crossref_metadata_2025 huggingface dataset:
An Integrated Array of Microfluidic Oxygenators as a Neonatal Lung Assist Device: In Vitro Characterization and In Vivo Demonstration
Authors: Rochow Niels , Manan Asmaa , Wu Wen‐I , Fusch Gerhard , Monkman Shelley , Leung Jennifer , Chan Emily , Nagpal Dipen , Predescu Dragos , Brash John , Selvaganapathy Ponnambalam Ravi , Fusch Christoph
Published: April 2014

A miniaturized oxygenator device that is perfused like an artificial placenta via the umbilical vessels may have significant potential to save the lives of newborns with respiratory insufficiency. Recently we presented the concept of an integrated modular lung assist device (LAD) that consists of stacked microfluidic single oxygenator units (SOUs) and demonstrated the technical details and operation of SOU prototypes. In this article, we present a LAD prototype that is designed to accommodate the different needs of term and preterm infants by permitting changing of the number of parallel‐stacked microfluidic SOUs according to the actual body weight. The SOUs are made of polydimethylsiloxane, arranged in parallel, and connected though 3D‐printed polymeric interconnects to form the LAD. The flow characteristics and the gas exchange properties were tested in vitro using human blood. We found that the pressure drop of the LAD increased linearly with flow rate. Gas exchange rates of 2.4–3.8 μL/min/cm2 (0.3–0.5 mL/kg/min) and 6.4–10.1 μL/min/cm2 (0.8–1.3 mL/kg/min) for O2 and CO2, respectively, were achieved. We also investigated protein adsorption to provide preliminary information on the need for application of anticoagulant coating of LAD materials. Albumin adsorption, as measured by gold staining, showed that surface uptake was evenly distributed and occurred at the monolayer level (>0.2 μg/cm2). Finally, we also tested the LAD under in vivo conditions using a newborn piglet model (body weight 1.65–2.0 kg). First, the effect of an arteriovenous bypass via a carotid artery‐to‐jugular vein shortcut on heart rate and blood pressure was investigated. Heart rate and mean arterial blood pressure remained stable for extracorporeal flow rates of up to 61 mL/kg/min (101 mL/min). Next, the LAD was connected to umbilical vessels (maximum flow rate of 24 mL/min [10.4 mL/kg/min]), and O2 gas exchange was measured under hypoxic conditions (FiO2 = 0.15) and was found to be 3.0 μL/min/cm2. These results are encouraging and support the feasibility of an artificial placental design for an LAD.
Severe Lactic Acidosis in a Diabetic Patient after Ethanol Abuse and Floor Cleaner Intake
Authors: Hendrikx Jeroen J. M. A. , Lagas Jurjen S. , Daling Ratana , Hooijberg Jan Hendrik , Schellens Jan H. M. , Beijnen Jos H. , Brandjes Desiderius P. M. , Huitema Alwin D. R.
Published: April 2014

An intoxication with drugs, ethanol or cleaning solvents may cause a complex clinical scenario if multiple agents have been ingested simultaneously. The situation can become even more complex in patients with (multiple) co‐morbidities. A 59‐year‐old man with type 2 diabetes mellitus (without treatment two weeks before the intoxication) intentionally ingested a substantial amount of ethanol along with ~750 mL of laminate floor cleaner containing citric acid. The patient was admitted with severe metabolic acidosis (both ketoacidosis and lactic acidosis, with serum lactate levels of 22 mM). He was treated with sodium bicarbonate, insulin and thiamine after which he recovered within two days. Diabetic ketoacidosis and lactic acidosis aggravated due to ethanol intoxication, thiamine deficiency and citrate. The high lactate levels were explained by excessive lactate formation caused by the combination of untreated diabetes mellitus, thiamine deficiency and ethanol abuse. Metabolic acidosis in diabetes is multi‐factorial, and the clinical situation may be further complicated, when ingestion of ethanol and toxic agents are involved. Here, we reported a patient in whom diabetic ketoacidosis was accompanied by severe lactic acidosis as a result of citric acid and mainly ethanol ingestion and a possible thiamine deficiency. In the presence of lactic acidosis in diabetic ketoacidosis, physicians need to consider thiamine deficiency and ingestion of ethanol or other toxins.
Neuroprogressive effects of lifetime illness duration in older adults with bipolar disorder
Authors: Gildengers Ariel G , Chung Kuo‐Hsuan , Huang Shou‐Hung , Begley Amy , Aizenstein Howard J , Tsai Shang‐Ying
Published: April 2014

Objective

The aim of the present study was to examine the long‐term effects of bipolar disorder (BD) on brain structure (gray matter volumes).

Methods

Fifty‐four adults with BD [mean (standard deviation) age = 64.4 (5.4) years] underwent brain MR imaging along with comprehensive clinical assessment. Total gray matter, hippocampal, and amygdala volumes were extracted using methods developed through the Geriatric Neuroimaging Laboratory at the University of Pittsburgh (Pittsburgh, PA, USA).

Results

Lower total gray matter volumes were related to longer duration of BD, even when controlling for current age and cerebrovascular accident (CVA) risk/burden. Additionally, longer exposure to antipsychotic medication was related to lower gray matter volumes. Lower hippocampal volumes were related to total years of antipsychotic agent exposure and CVA risk/burden scores. Older age was related to lower total gray matter, hippocampal, and amgydala volumes.

Conclusions

Our study of older adults with BD supports the understanding that BD is a neuroprogressive disorder with a longer duration of illness and more antipsychotic agent exposure related to lower gray matter volume.
Clinical applications of SPECT/CT after first I‐131 ablation in patients with differentiated thyroid cancer
Authors: Jeong Shin Young , Lee Sang‐Woo , Kim Hae Won , Song Bong‐Il , Ahn Byeong‐Cheol , Lee Jaetae
Published: April 2014

Objective

This study aimed to determine which thyroid cancer patients would benefit from SPECT/CT in addition to whole‐body planar scintigraphy (RxWBS) for the detection and characterization of I‐131 focal uptake after first ablation.

Design and Patients

Neck and thoracic SPECT/CT was performed in 187 patients with I‐131 focal uptake suggestive of remnant thyroid tissue (Rem group, n = 152) or presumed lymph node (LN) metastases (mLN group, n = 35) on RxWBS. Clinical and pathologic parameters were analysed and compared in patients with and without additional SPECT/CT findings.

Results

wIn the Rem group, SPECT/CT revealed additional occult findings on RxWBS in 13 patients (8·6%). The serum thyroglobulin levels at the time of ablation were significantly higher in patients with additional SPECT/CT findings than in patients without additional findings (4·3 ± 3·4 ng/ml vs 1·6 ± 2·7 ng/ml, P = 0·001). In the mLN group, SPECT/CT demonstrated only remnant thyroid tissues without evidence of lymph node metastasis in 14 (40·0%) patients, whereas in the remaining 21 (60·0%) patients, I‐131 uptake was confirmed in the corresponding neck and mediastinal lymph nodes on SPECT/CT.

Conclusions

Even in the Rem group, additional SPECT/CT could provide useful information for detecting hidden metastasis, especially in patients with high serum thyroglobulin levels. SPECT/CT should be recommended for patients with focal uptake lymph node metastasis on RxWBS.
Altered expression of noncanonical Wnt pathway genes in paediatric and adult adrenocortical tumours
Authors: Mermejo Livia M. , Leal Leticia F. , Colli Leandro M. , Fragoso Maria C.B.V. , Latronico Ana C. , Tone Luiz G. , Scrideli Carlos A. , Tucci Silvio , Martinelli Carlos E. , Yunes Jose A. , Mastellaro Maria J. , Seidinger Ana L. , Brandalise Silvia R. , Moreira Ayrton C. , Ramalho Leandra N. , Antonini Sonir R. , Castro Margaret
Published: April 2014

Context

The role of planar cell polarity (Wnt/PCP) and calcium‐dependent (Wnt/Ca) noncanonical Wnt pathways in adrenocortical tumours (ACTs) is unknown.

Objectives

To investigate the gene expression of Wnt/PCP and Wnt/Ca pathways and its association with TP53 p.R337H and CTNNB1 mutations in paediatric and adult ACTs and to correlate these findings with clinical outcome.

Patients

Expression of noncanonical Wnt‐related genes was evaluated in 91 ACTs (66 children and 25 adults) by qPCR and the expression of beta‐catenin, P53 and protein effectors of Wnt/Ca (NFAT) and Wnt/PCP (JNK) by immunohistochemistry. TP53 and CTNNB1 genes were sequenced.

Results

TP53 p.R337H mutation frequency was higher in children (86% vs 28%), while CTNNB1 mutation was higher in adults (32% vs 6%). Mortality was higher in adults harbouring TP53 p.R337H and in children with CTNNB1 mutations. Overexpression of WNT5A, Wnt/Ca ligand, was observed in children and adults. Overexpression of MAPK8 and underexpression of PRICKLE, Wnt/PCP mediators, were observed in paediatric but not in adult cases. Cytoplasmic/nuclear beta‐catenin and P53 accumulation was observed in the majority of paediatric and adult ACTs as well as NFAT and JNK. Overexpression of MAPK8 and underexpression of PRICKLE were associated with mortality in children, while overexpression of WNT5A and underexpression of PRICKLE were associated with mortality in adults.

Conclusions

In our study, TP53 p.R337H and CTNNB1 mutations correlated with poor prognosis in adults and children, respectively. We demonstrate, for the first time, the activation of Wnt/PCP and Wnt/Ca noncanonical pathway genes, and their association with poor outcome in children and adults, suggesting their putative involvement in ACTs aggressiveness.
An exploratory study of family‐centred help‐giving practices in early intervention: families of young children with autism spectrum disorder
Authors: Coogle Christan Grygas , Hanline Mary Frances
Published: April 2014

The purpose of this exploratory qualitative study was to investigate the early intervention (EI) experiences of mothers who have a young child at risk for autism spectrum disorder. Data were collected through observations, interviews and document analyses. Results of the study suggest (i) interpersonal skills of practitioners and provisions for family choice and collaboration lead to positive experiences for mothers; (ii) asset‐based attitudes lead to family progress and competence; (iii) effective partnerships are developed through supportive provider communication techniques; and (iv) satisfaction with EI services results from practitioner responsiveness to help families access resources and facilitate child development.
Demanding to Be Seen and Heard: Latino Immigrant Organizing and the Defense of Human Rights in Houston
Authors: KOVIC CHRISTINE
Published: April 2014

Latino migrants in Houston mobilize in myriad ways to defend their rights in the current context of increased enforcement and restrictive laws. Through an exploration of the mobilization strategies of Living Hope Wheelchair Association, an organization of Latino migrants with spinal cord injuries, this article considers the ways this organization reframes migration as an issue of human rights and social justice rather than one of criminalization. It explores Living Hope's demands for rights as its members are excluded from the nation and the city based on immigration status, ethnicity, and physical disability as well as the ways the association's claims for rights addresses the profoundly unequal relationships between the United States and Latin American nations.
Patients with osteoporosis have higher incidence of sensorineural hearing loss
Authors: Kahveci O.K. , Demirdal U.S. , Yücedag F. , Cerci U.
Published: April 2014

Objective

Osteoporosis is a common metabolic disorder that causes progressive changes in bone structure. Metabolic changes and possible degeneration of middle ear ossicles or the cochlear capsule may cause hearing loss in patients with osteoporosis. The aim of this study was to evaluate the hearing function and otolaryngologic symptoms of patients with osteoporosis.

Methods

One hundred patients with osteoporosis, 50 osteopenic patients and 25 healthy controls were evaluated prospectively. Bone mineral density (BMD) of patients was measured by dual‐energy X‐ray absorptiometry (DEXA). Otorhinolaryngologic examinations were performed on all patients together with an otologic symptoms survey, pure tone audiometry, word recognition test and distortion product otoacoustic emission (DPOAE).

Results

Patients with osteoporosis showed higher incidence of sensorineural type of hearing loss (SNHL). Mean pure tone audiometry findings of the patients and controls were significantly different in 500–8000 Hz frequencies (P < 0.01 for 500–2000 Hz, P < 0.05 for 4000–8000 Hz). Distortion product otoacoustic emission results of patients with osteoporosis at 6 kHz were significantly lower than controls and osteopenic patients (P < 0.05). Tinnitus complaints were remarkably higher in patients with osteoporosis (P < 0.01). No correlation was found between BMD scores and hearing levels.

Conclusion

The data show that osteoporosis may be associated with SNHL. Cochlear dysfunction may play role in this hearing loss.
Piloting a Nationally Disseminated, Interactive Human Subjects Protection Program for Community Partners: Unexpected Lessons Learned from the Field
Authors: Solomon Stephanie , Bullock Sherita , Calhoun Karen , Crosby Lori , Eakin Brenda , Franco Zeno , Hardwick Emily , Leinberger‐Jabari Andrea , Newton Gail , Odell Jere , Paberzs Adam , Spellecy Ryan
Published: April 2014

Funders, institutions, and research organizations are increasingly recognizing the need for human subjects protections training programs for those engaged in academic research. Current programs tend to be online and directed toward an audience of academic researchers. Research teams now include many nonacademic members, such as community partners, who are less likely to respond to either the method or the content of current online trainings. A team at the CTSA‐supported Michigan Institute for Clinical and Health Research at the University of Michigan developed a pilot human subjects protection training program for community partners that is both locally implemented and adaptable to local contexts, yet nationally consistent and deliverable from a central administrative source. Here, the developers of the program and the collaborators who participated in the pilot across the United States describe 10 important lessons learned that align with four major themes: The distribution of the program, the implementation of the program, the involvement of community engagement in the program, and finally lessons regarding the content of the program. These lessons are relevant to anyone who anticipates developing or improving a training program that is developed in a central location and intended for local implementation.
Ivermectin sensitivity is an ancient trait affecting all ecdysozoa but shows phylogenetic clustering among sepsid flies
Authors: Puniamoorthy Nalini , Schäfer Martin A. , Römbke Jörg , Meier Rudolf , Blanckenhorn Wolf U.
Published: April 2014

Avermectins are potent and popular veterinary pharmaceuticals used globally to fight parasites of livestock and humans. By disturbing ion channel transport through the membrane, avermectins are effective against endo‐ and ectoparasitic round and horsehair worms (Nematoida), insects, or ticks (Arthropoda), but not against Plathelminthes, including flatworms (Trematoda) and tapeworms (Cestoda), or segmented worms (Annelida). Unfortunately, excreted avermectins have strong nontarget effects on beneficial arthropods such as the insect community decomposing livestock dung, ultimately impeding this important ecosystem function to the extent that regulators mandate standardized eco‐toxicological tests of dung organisms worldwide. We show that the ancient phylogenetic pattern and qualitative mechanism of avermectin sensitivity is conserved and compatible with most recent phylogenomic hypotheses grouping the Nematoida with the Arthropoda as Ecdysozoa (molting animals). At the species level, we demonstrate phylogenetic clustering in ivermectin sensitivities of 23 species of sepsid dung flies (Diptera: Sepsidae). This clustered 500‐fold quantitative variation in sensitivity may indicate recent lineage‐specific responses to selection, but more likely reflects pre‐existing genetic variation with pleiotropic effects on eco‐toxicological responses to pollutants. Regardless, our results question the common practice in eco‐toxicology of choosing single test species to infer detrimental effects on entire species communities, which should ideally assess a representative taxonomic sample.
The coexistence of an equal amount of Alzheimer's amyloid‐β 40 and 42 forms structurally stable and toxic oligomers through a distinct pathway
Authors: Chang Yu‐Jen , Chen Yun‐Ru
Published: April 2014

Fibrillar amyloid‐β (Aβ) is the major constituent of senile plaques in the brain of patients with Alzheimer's disease (AD). Aβ is a short peptide generated from amyloid precursor protein with two main isoforms, Aβ40 and Aβ42, with the latter having two additional hydrophobic residues at the C‐terminus. The two isoforms have distinct characteristics, in which Aβ42 plays a more pathogenic role. Some early‐onset familial AD cases possess an elevated Aβ42/Aβ40 level, and biochemical studies show the two species interact with each other. Therefore, understanding structural conversion in the aggregation of mixed Aβ isoforms is essential for elucidating AD pathogenesis. Here, we systematically examined the differences between Aβ42, Aβ40 and various Aβ42/Aβ40 mixtures by monitoring the fibrillization kinetics, epitope changes, assembly, morphology and induced cytotoxicity. We found that the minor Aβ species in different mixing ratios modulated the major aggregation pathway. Size exclusion chromatography, circular dichroism spectroscopy and photo‐crosslinking assay showed that soluble Aβ42 oligomers were stabilized after Aβ40 addition, and the equimolar Aβ42/Aβ40 mixture rapidly formed spherical oligomers. These oligomers were the most toxic among those examined as evidenced by neurite degeneration and neuronal toxicity. However, the oligomers were not responsible for intracellular calcium elevation. Overall, our results demonstrated that differently mixed Aβ species repartitioned oligomer intermediates on the major aggregation pathway. Furthermore, the equimolar mixture rapidly formed structurally stable and the most toxic oligomers. These results provided information on the potential pathological mechanisms underlying the elevated Aβ42/Aβ40 ratio in familial AD patients and in the local environment of sporadic AD brains.

Structured digital abstract

Abeta40 and Abeta42 bind by fluorescence technology (View interaction); by filter binding (View interaction); by electron microscopy (View interaction); by molecular sieving (View interaction) and by cross-linking study (View interaction)

Abeta42 and Abeta42 bind by fluorescence technology (View interaction); by filter binding (View interaction); by electron microscopy (View interaction); by molecular sieving (View interaction) and by cross-linking study (View interaction)

Abeta40 and Abeta40 bind by fluorescence technology (View interaction); by filter binding (View interaction); by electron microscopy (View interaction); by molecular sieving (View interaction) and by cross-linking study (View interaction)
A novel role for the proteasomal chaperone PSMD9 and hnRNPA1 in enhancing IκBα degradation and NF‐κB activation – functional relevance of predicted PDZ domain–motif interaction
Authors: Sahu Indrajit , Sangith Nikhil , Ramteke Manoj , Gadre Rucha , Venkatraman Prasanna
Published: April 2014

PSMD9 is a PDZ domain containing chaperone of proteasome assembly. Based on the ability of PDZ‐like domains to recognize C‐terminal residues in their interactors, we recently predicted and identified heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) as one of the novel interacting partners of PSMD9. Contingent on the reported role of hnRNPA1 in nuclear factor κB (NF‐κB) activation, we tested the role of human PSMD9 and hnRNPA1 in NF‐κB signaling. We demonstrated in human embryonic kidney 293 cells that PSMD9 influences both basal and tumor necrosis factor α (TNF‐α) mediated NF‐κB activation through inhibitor of nuclear factor κB α (IκBα) proteasomal degradation. PSMD9 mediates IκBα degradation through a specific domain–motif interaction involving its PDZ domain and a short linear sequence motif in the C‐terminus of hnRNPA1. Point mutations in the PDZ domain or deletion of C‐terminal residues in hnRNPA1 disrupt interaction between the two proteins which has a direct influence on NF‐κB activity. hnRNPA1 interacts with IκBα directly, whereas PSMD9 interacts only through hnRNPA1. Furthermore, hnRNPA1 shows increased association with the proteasome upon TNF‐α treatment which has no such effect in the absence of PSMD9. On the other hand endogenous and trans‐expressed PSMD9 are found associated with the proteasome complex. This association is unaffected by PDZ mutations or TNF‐α treatment. Collectively, these interactions between IκBα, hnRNPA1 and proteasome bound PSMD9 illustrate a potential mechanism by which ubiquitinated IκBα is recruited on the proteasome for degradation. In this process, hnRNPA1 may act as a shuttle receptor and PSMD9 as a subunit acceptor. The interaction sites of PSMD9 and hnRNPA1 may emerge as a vulnerable drug target in cancer cells which require consistent NF‐κB activity for survival.
Gender differences in commute time and accessibility in Sofia, Bulgaria: a study using 3D geovisualisation
Authors: Kwan Mei‐Po , Kotsev Alexander
Published: April 2014

Much research on human mobility patterns and accessibility to date has been conducted largely in Western European and North American countries, where the private vehicle is the main means for commuting. As a result, most studies focused largely on car‐based mobility (automobility) and accessibility, and relatively little is known about countries in other regions of the world. Based on an activity‐travel dataset collected in Sofia, Bulgaria and using 3D geovisualisation, this study attempts to fill this gap through examining gender differences in commute time and potential access to urban opportunities. The results reveal important gender differences in commute time and individual accessibility. Among the surveyed participants, women tend to spend more time on their commute trips and have more restrictive spatial reach to urban opportunities compared with men, largely as a result of their reliance on public transit as their primary mode of transport. Further, women have lower accessibility compared with men who used the same travel mode. This case study adds important new knowledge about a geographical area that has been under‐studied by Anglophone geographers. It also shows that GIS‐based geovisualisation and analysis are powerful tools for uncovering gender differences in the geographical distribution of commute time, which conventional quantitative methods cannot reveal.
Safe switching from a pdFIX (Immunine®) to a rFIX (Bax326)
Authors: Solano Trujillo M. H. , Stasyshyn O. , Rusen L. , Serban M. , Lamas J. L. , Perina F. G. , Urasinski T. , Oh M. , Knowlton W. B. , Valenta‐Singer B. , Pavlova B. G. , Abbuehl B.
Published: April 2014

The ability to switch between coagulation factors safely is of common interest to haemophilia patients and treating physicians. This is the first formal prospective comparative evaluation of safety, efficacy and incremental recovery of a plasma‐derived FIX (pdFIX) and a recombinant FIX (rFIX) in the same haemophilia B patients following a switch from pdFIX Immunine® to a recently developed rFIX Bax326 product. Patients (aged <65 years) who completed a pretreatment study which prospectively documented the exposure to Immunine® and monitored FIX inhibitors while receiving prophylactic treatment were transitioned into pivotal (patients aged 12–65 years) and paediatric (patients aged <12 years) clinical studies investigating prophylaxis and treatment of bleeding episodes with Bax326. None of the 44 patients developed inhibitory or specific binding anti‐FIX antibodies during the course of the studies. A total of 38 unrelated adverse events (AEs) were occurred in 20/44 (45.5%) subjects during the Immunine® study. Following a switch to Bax326, 51 AEs were reported in 25/44 (56.8%) subjects. The incidence of AEs related to Bax326 treatment (two episodes of dysgeusia in one patient) was low (2.3%); there were no serious adverse reactions. The comparison between Immunine® and Bax326 demonstrated analogous haemostatic characteristics and annualized bleeding rates. Overall, there is direct evidence indicating a safe and clinically effective transition from a pdFIX (Immunine®) to a newly developed rFIX (Bax3261) for prophylaxis and treatment of bleeding in previously treated patients of all age cohorts with severe or moderately severe haemophilia B.
Hepatitis B virus surface antigen and anti‐hepatitis C virus rapid tests underestimate hepatitis prevalence among HIV‐infected patients
Authors: Hønge BL , Jespersen S , Medina C , Té DS , da Silva ZJ , Østergaard L , Laursen AL , Wejse C , Krarup H , Erikstrup C ,   Bissau HIV cohort study group
Published: April 2014

Objectives

In the case of coinfection with HIV and hepatitis B virus (HBV) and/or hepatitis C virus (HCV), hepatic disease progression is often accelerated, with higher rates of liver cirrhosis and liver‐related mortality. We aimed to evaluate the performance of the rapid tests used routinely to detect HBV surface antigen (HBsAg) and anti‐HCV among HIV‐infected patients in Guinea‐Bissau.

Methods

Blood samples from HIV‐infected patients in Guinea‐Bissau were stored after testing for HBsAg and anti‐HCV with rapid tests. Samples were subsequently re‐tested for HBsAg and anti‐HCV in Denmark.

Results

Two rapid tests were used in Guinea‐Bissau: HBsAg Strip Ref 2034 (VEDA.LAB, Alençon, France; sensitivity 62.3%; specificity 99.2%) and HEPA‐SCAN (Bhat Bio‐Tech, Bangalore, India; sensitivity 57.1%; specificity 99.7%). In the two tests the ability to obtain the correct outcome depended on the antigen and antibody concentrations, respectively. Sex, age, CD4 cell count and antiretroviral therapy status did not differ between false negative and true positive samples in either of the tests. The study is limited by a low number of anti‐HCV positive samples.

Conclusions

New diagnostic rapid tests should always be evaluated in the setting in which they will be used before implementation.
Ectoparasite density is associated with mouth colour and size in nestling House Sparrows Passer domesticus
Authors: Dugas Matthew B. , Doumas L. Tess
Published: April 2014

Dependent offspring influence allocation of parental investment using specialized traits thought to contain information about offspring condition. To test this hypothesis, we examined the relationship between one component of avian begging, the phenotype of the nestling mouth, and the density of a haematophagous mite, Pellonyssus reedi, in nestling House Sparrows Passer domesticus. Ectoparasite density in broods was negatively associated with average nestling mass and flange colour intensity and positively associated with mouth width, but was not related to the intensity of blood‐based gape coloration or flange width. These results support the hypothesis that components of offspring solicitations signal high quality, and highlight the diverse selective pressures shaping offspring–parent communication.
Film and Video
Authors: Pedersen Lene
Published: April 2014

Film reviewed in this issue.

The Act of Killing (2012/2014). 115 & 159 minute versions. Director: Joshua Oppenheimer. Co‐directors: Anonymous and Christine Cynn. Cinematographers: Carlos Arango de Montis and Lars Skree.
Enhanced Piezoelectric and Dielectric Responses in 92.5%(Bi0.5Na0.5) TiO3 ‐7.5%BaTiO3 Ceramics
Authors: Anthoniappen J. , Lin C.‐H. , Tu C. S. , Chen P.‐Y. , Chen C.‐S. , Chiu S.‐J. , Lee H.‐Y. , Wang S.‐F. , Hung C.‐M.
Published: April 2014

Structure and piezoelectric coefficient (d33) of lead‐free 7.5% mole BaTiO3‐doped (Bi0.5Na0.5) TiO3 (BNT‐7.5%BT) polycrystalline piezoceramics have been characterized systematically as a function of poling electric (E) field. Dielectric permittivity and loss were also measured as functions of frequency and temperature. The piezoelectric coefficient d33 after poling at E = 35 kV/cm can reach d33~186 pC/N, which is the highest value reported among (1−x) BNT–xBT compositions. A prior poling E field can reduce rhomobherdal lattice distortion, and enhance tetragonal phase and polarization ordering, that contribute significantly to the rapid raise of d33 and lower depolarizing temperature (Td). The reduced dielectric permittivity for the poled sample is attributed to ordered state and the pinning of field‐induced nanodomain walls by the presence of oxygen vacancies.
Synthesis of Single‐Phase Gd‐Doped Ceria Nanopowders by Radio Frequency Thermal Plasma Treatment
Authors: Lee Mi‐Yeon , Song Min‐Kyung , Kim Jeong‐Soo , Seo Jun‐Ho , Kim Min‐Ho
Published: April 2014

Gd‐doped ceria nanopowders were synthesized using Radio Frequency (RF) thermal plasma. The powders were prepared by ball‐milling Gd2O3 and CeO2 powders of several tens of μm in size at the cation ratio of 8:2 and 9:1. The prepared precursors were treated by RF thermal plasma at a plate power level of ~140 kVA, and then, small‐sized powders (~50 nm) were retrieved by filtration. Transmission Electron Microscopy, Electron Energy Loss Spectroscopy, and Selected‐Area Electron‐Diffraction images of the as‐synthesized powders showed that Gd atoms were incorporated into the CeO2 particles. In addition, no crystalline peak for Gd2O3 appeared in the X‐ray diffraction patterns of the as‐synthesized powders, which is attributed to the solid solution of Gd3+ into the CeO2 lattices. Finally, Inductively Coupled Plasma‐Optical Emission Spectrometry analysis data revealed relatively small changes within 3 at.% in the cation composition between the ball milled powder mixtures and the nanoscale powders prepared from these mixtures.
Phase Structure and Property Evaluation of (Ba,Ca)(Ti,Sn)O3 Sintered with Li2CO3 Addition at Low Temperature
Authors: Zhao Lei , Zhang Bo‐Ping , Zhou Peng‐Fei , Zhao Xiao‐Kun , Zhu Li‐Feng
Published: April 2014

A series of Li2CO3‐added (Ba0.95Ca0.05)(Ti0.90Sn0.10)O3 (BCTS) ceramics were prepared by normal sintering at a low temperature of 1300°C; Their microstructure and electrical property evaluation were investigated with special emphases on the effect of Li2CO3 addition. Adding Li2CO3 significantly improves the sinterability of BCTS ceramics, resulting in a reduced sintering temperature by more than 150°C. The coexistence of R and T phases is confirmed by the Raman spectrum at room temperature for all samples and at a temperature range from −80°C to 40°C for sample with 3% mol Li2CO3 addition. The specific ratio of R to T phase decreases with increasing temperature or Li2CO3 addition. A higher εr is observed in T phase compared to R phase in the studied BCTS system. Better properties with d33 = 485 pC/N, kp = 39%, and Qm = 191 were obtained for BCTS sample with 3% mol Li2CO3 addition, which is attributed to the increased grain size and density along with the variation in the specific ratio of R to T phase.
The origin of feather holes: a word of caution
Authors: Vágási Csongor I.
Published: April 2014

Antagonistic processes between parasites and their hosts are hallmarks of evolutionary ecology. A group of parasites is adapted to feed on feather keratin. In doing so, they inflict a variety of costs on avian hosts by causing feathers to degrade faster. Feather holes represent a class of feather damage that is attributed to the chewing bites of Phthirapteran lice. Consequently, hole counts were used as an approximation of lice infestation intensity when studying bird–lice interaction. Here, I express some reservations regarding this practice. I survey the literature concerning feather holes and the state of the hole–lice concept, highlight some uncertainties regarding its reliability, offer possible alternative explanations for the origin of holes, and suggest directions for future investigations. I conclude that the origin of holes is still unknown, and so a prudent approach is desirable when interpreting the relationship between avian phenotype or fitness and lice infestation inferred from hole counts.
Initial Persistence With Antihypertensive Therapies Is Associated With Depression Treatment Persistence, But Not Depression
Authors: Schmittdiel Julie A. , Dyer Wendy , Uratsu Connie , Magid David J. , O'Connor Patrick J. , Beck Arne , Butler Melissa , Ho Michael P. , Vazquez‐Benitez Gabriela , Adams Alyce S.
Published: April 2014

The purpose of this study was to examine the relationship between the presence of clinical depression and persistence to drug therapy treatment for depression with early nonpersistence to antihypertensive therapies in a large, diverse cohort of newly treated hypertension patients. Using a hypertension registry atKaiserPermanenteNorthernCalifornia, the authors conducted a retrospective cohort study of 44,167 adults (18 years and older) with hypertension who were new users of antihypertensive therapy in 2008. We used multivariate logistic regression analysis to model the relationships between the presence of clinical depression and early nonpersistence (defined as failing to refill the first prescription within 90 days after the end of the first fill days' supply) to antihypertensive therapies, controlling for sociodemographic and clinical risk factors. Within the group of 1484 patients who had evidence of clinical depression in the 12 months prior to the initiation of antihypertensive therapy, the authors examined the relationship between drug therapy treatment for depression and 6‐month persistence with antidepressant therapy with early nonpersistence with antihypertensive therapies. No association was found between the presence of clinical depression and early nonpersistence to antihypertensive therapies after adjustment for individual demographic and clinical characteristics and neighborhood‐level socioeconomic status. However, among the subset of 1484 patients with documented evidence of clinical depression in the 12 months prior to the initiation of antihypertensive therapy, being prescribed and persistence with antidepressant therapy was strongly associated with lower odds of early nonpersistence to antihypertensive medications (odds ratio,0.64;confidence interval, 0.42–0.96). In an integrated delivery system, the authors found that treatment for depression was associated with higher levels of antihypertensive persistence. Improving quality of depression care in patients with comorbid hypertension may be an important strategy in decreasingcardiovascular diseaserisk in these patients.
Retinoic acid reduces migration of human breast cancer cells: role of retinoic acid receptor beta
Authors: Flamini Marina Inés , Gauna Gisel Valeria , Sottile Mayra Lis , Nadin Beatriz Silvina , Sanchez Angel Matias , Vargas‐Roig Laura María
Published: April 2014

Breast cancer is the most common malignancy in women and the appearance of distant metastases produces the death in 98% of cases. The retinoic acid receptor β (RARβ) is not expressed in 50% of invasive breast carcinoma compared with normal tissue and it has been associated with lymph node metastasis. Our hypothesis is that RARβ protein participates in the metastatic process. T47D and MCF7 breast cancer cell lines were used to perform viability assay, immunobloting, migration assays, RNA interference and immunofluorescence. Administration of retinoic acid (RA) in breast cancer cells induced RARβ gene expression that was greatest after 72 hrs with a concentration 1 μM. High concentrations of RA increased the expression of RARβ causing an inhibition of the 60% in cell migration and significantly decreased the expression of migration‐related proteins [moesin, c‐Src and focal adhesion kinase (FAK)]. The treatment with RARα and RARγ agonists did not affect the cell migration. On the contrary, the addition of the selective retinoid RARβ‐agonist (BMS453) significantly reduced cell migration comparable to RA inhibition. When RARβ gene silencing was performed, the RA failed to significantly inhibit migration and resulted ineffective to reduce moesin, c‐Src and FAK expressions. RARβ is necessary to inhibit migration induced by RA in breast cancer cells modulating the expression of proteins involved in cell migration.
Inhibition of JNK by compound C66 prevents pathological changes of the aorta in STZ‐induced diabetes
Authors: Liu Yucheng , Wang Yonggang , Miao Xiao , Zhou Shanshan , Tan Yi , Liang Guang , Zheng Yang , Liu Quan , Sun Jian , Cai Lu
Published: April 2014

Cardiovascular diseases as leading causes of the mortality world‐wide are related to diabetes. The present study was to explore the protective effect of curcumin analogue C66 on diabetes‐induced pathogenic changes of aortas. Diabetes was induced in male C57BL/6 mice with a single intraperitoneal injection of streptozotocin. Diabetic mice and age‐matched non‐diabetic mice were randomly treated with either vehicle (Control and Diabetes), C66 (C66 and Diabetes/C66) or c‐Jun N‐terminal kinase (JNK) inhibitor (sp600125, JNKi and Diabetes/JNKi). All three treatments were given by gavage at 5 mg/kg every other day for 3 months. Aortic inflammation, oxidative stress, fibrosis, cell apoptosis and proliferation, Nrf2 expression and transcription were assessed by immunohistochemical staining for the protein level and real‐time PCR method for mRNA level. Diabetes increased aortic wall thickness and structural derangement as well as JNK phosphorylation, all of which were attenuated by C66 treatment as JNKi did. Inhibition of JNK phosphorylation by C66 and JNKi also significantly prevented diabetes‐induced increases in inflammation, oxidative and nitrative stress, apoptosis, cell proliferation and fibrosis. Furthermore, inhibition of JNK phosphorylation by C66 and JNKi significantly increased aortic Nrf2 expression and transcription function (e.g. increased expression of Nrf2‐downstream genes) in normal and diabetic conditions. These results suggest that diabetes‐induced pathological changes in the aorta can be protected by C66 via inhibition of JNK function, accompanied by the up‐regulation of Nrf2 expression and function.
Isolation and characterization of a ranavirus from koi, Cyprinus carpio L., experiencing mass mortalities in India
Authors: George M R , John K R , Mansoor M M , Saravanakumar R , Sundar P , Pradeep V
Published: April 2014

We investigated mass mortalities of koi, Cyprinus carpio Linnaeus, 1758, experienced in South Indian fish farms by virus isolation, electron microscopy, PCR detection, sequencing of capsid protein gene and transmission studies. Samples of moribund koi brought to the laboratory suffered continuous mortality exhibiting swimming abnormalities, intermittent surfacing and skin darkening. Irido‐like virus was isolated from the infected fish in the indigenous snakehead kidney cell line (SNKD2a). Icosahedral virus particles of 100 to 120 nm were observed in the infected cell cultures, budding from the cell membrane. Virus transmission and pathogenicity studies revealed that horizontal transmission occurred associated with mortality. PCR analysis of infected fish and cell cultures confirmed the presence of Ranavirus capsid protein sequences. Sequence analysis of the major capsid protein gene showed an identity of 99.9% to that of largemouth bass virus isolated from North America. Detection and successful isolation of this viral agent becomes the first record of isolation of a virus resembling Santee–Cooper Ranavirus from a koi and from India. We propose the name koi ranavirus to this agent.
Rufy3, a protein specifically expressed in neurons, interacts with actin‐bundling protein Fascin to control the growth of axons
Authors: Wei Zhe , Sun Ming , Liu Xinyi , Zhang Jian , Jin Ying
Published: April 2014

For our nervous system to function properly, each neuron must generate a single axon and elongate the axon to reach its target. It is known that actin filaments and their dynamic interaction with microtubules within growth cones play important roles in inducing axon extension. However, it remains unclear how cytoskeletal dynamics is controlled in growth cones. In this study, we report that Rufy3, a RUN domain‐containing protein, is a neuron‐specific and actin filament‐relevant protein. We find that the appropriate expression of Rufy3 in mouse hippocampal neurons is required for the development of a single axon and axon growth. Our results show that Rufy3 specifically interacts with actin filament‐binding proteins, such as Fascin, and colocalizes with Fascin in growth cones. Knockdown of Rufy3 impairs the distribution of Fascin and actin filaments, accompanied by an increased proportion of neurons with multiple axons and a decrease in the axon length. Therefore, Rufy3 may be particularly important for neuronal axon elongation by interacting with Fascin to control actin filament organization in axonal growth cones.

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We propose that Rufy3 may control mouse neuron axon development through its specific interaction with Fascin and Drebrin. Over‐expression of Rufy3 (Rufy3 OE) leads to longer axons and expands the distribution of Drebrin to almost the entire growth cone. In contrast, knockdown of Rufy3 (Rufy3 RNAi) results in shortened axons and enhanced the percentage of mutipolar neurons. Moreover, silencing of Rufy3 reduces and restricts the expression of Fascin and F‐actin to the edge of the growth cone. These findings provide new insights into the molecular regulation of axonal outgrowth and cell polarization in neurons.
Inflammation and tuberculosis: host‐directed therapies
Authors: Zumla A. , Rao M. , Parida S. K. , Keshavjee S. , Cassell G. , Wallis R. , Axelsson‐Robertsson R. , Doherty M. , Andersson J. , Maeurer M.
Published: April 2014

Tuberculosis (TB) is an airborne infectious disease that kills almost two million individuals every year. Multidrug‐resistant (MDR) TB is caused by strains of Mycobacterium tuberculosis (M. tb) resistant to isoniazid and rifampin, the backbone of first‐line antitubercular treatment. MDR TB affects an estimated 500 000 new patients annually. Genetic analysis of drug‐resistant MDR‐TB showed that airborne transmission of undetected and untreated strains played a major role in disease outbreaks. The need for new TB vaccines and faster diagnostics, as well as the development of new drugs, has recently been highlighted. The major problem in terms of current TB research and clinical demands is the increasing number of cases of extensively drug‐resistant and ‘treatment‐refractory’ TB. An emerging scenario of adjunct host‐directed therapies is intended to target pulmonary TB where inflammatory processes can be deleterious and lead to immune exhaustion. ‘Target‐organ‐saving’ strategies may be warranted to prevent damage to infected tissues and achieve focused, clinically relevant and long‐lasting anti‐M. tb cellular immune responses. Candidates for such interventions may be biological agents or already approved drugs that can be ‘re‐purposed’ to interfere with biologically relevant cellular checkpoints. Here, we review current concepts of inflammation in TB disease and discuss candidate pathways for host‐directed therapies to achieve better clinical outcomes.
Urine soluble urokinase‐type plasminogen activator receptor levels correlate with proteinuria in Puumala hantavirus infection
Authors: Outinen T. K. , Mäkelä S. , Huttunen R. , Mäenpää N. , Libraty D. , Vaheri A. , Mustonen J. , Aittoniemi J.
Published: April 2014

Objectives

Urokinase‐type plasminogen activator receptor (uPAR) is upregulated during inflammation and known to bind to β3‐integrins, receptors used by pathogenic hantaviruses to enter endothelial cells. It has been proposed that soluble uPAR (suPAR) is a circulating factor that causes focal segmental glomerulosclerosis and proteinuria by activating β3‐integrin in kidney podocytes. Proteinuria is also a characteristic feature of hantavirus infections. The aim of this study was to evaluate the relation between urine suPAR levels and disease severity in acute Puumala hantavirus (PUUV) infection.

Design

A single‐centre, prospective cohort study.

Subjects and methods

Urinary suPAR levels were measured twice during the acute phase and once during convalescence in 36 patients with serologically confirmed PUUV infection. Fractional excretion of suPAR (FE suPAR) and of albumin (FE alb) was calculated.

Results

The FE suPAR was significantly elevated during the acute phase of PUUV infection compared to the convalescent phase (median 3.2%, range 0.8–52.0%, vs. median 1.9%, range 1.0–5.8%, P = 0.005). Maximum FE suPAR was correlated markedly with maximum FE alb (r = 0.812, P < 0.001) and with several other variables that reflect disease severity. There was a positive correlation with the length of hospitalization (r = 0.455, P = 0.009) and maximum plasma creatinine level (r = 0.780, P < 0.001) and an inverse correlation with minimum urinary output (r = −0.411, P = 0.030). There was no correlation between FE suPAR and plasma suPAR (r = 0.180, P = 0.324).

Conclusion

Urinary suPAR is markedly increased during acute PUUV infection and is correlated with proteinuria. High urine suPAR level may reflect local production of suPAR in the kidney during the acute infection.
Association analysis between MTHFR genetic polymorphisms and the risk of congenital heart diseases in Chinese Han population
Authors: Zhang Quan , Zha Daogang , Dong Peikang , Zhang Ye , Zhang Wenjing , Liu Yili
Published: April 2014

Objectives

Congenital heart diseases (CHD) are common birth defects in the world. The methylenetetrahydrofolate reductase (MTHFR) gene is one of the most important candidate genes for the development of CHD. This case–control study aimed to evaluate the effect of MTHFR c.382A>G and c.1129C>T genetic polymorphisms as risk factors for the development of CHD.

Methods

A total of 230 CHD patients and 237 non-CHD controls were included in the present study. The genotyping of MTHFR c.382A>G and c.1129C>T genetic polymorphisms were detected by the polymerase chain reaction-restriction fragment length polymorphism and created restriction site-polymerase chain reaction methods, respectively.

Key findings

The alleles/genotypes distribution from these two genetic polymorphisms were statistically associated with the increased risk of CHD (for c.382A>G, GG versus AA: odds ratio (OR) = 2.39, 95% confidence interval (CI), 1.27 to 4.52, P = 0.006; for c.1129C>T, TT versus CC: OR = 2.73, 95% CI, 1.33 to 5.62, P = 0.005). The allele G and genotype GG of c.382A>G and allele T and genotype TT of c.1129C>T genetic polymorphisms might contribute to CHD susceptibility.

Conclusion

These preliminary findings indicate that these two MTHFR genetic polymorphisms are related with the risk of CHD in Chinese Han population, and might be potentially utilized as molecular markers.