bluuebunny/crossref_metadata_2025 huggingface dataset:
A Practical Israeli Strategy for Appealing for Organ Donation
Authors: Ashkenazi Tamar , Klein Moti
Published: June 2013

Context

Most reports on organ donation have been related to the importance of support for families, explanations of brain death, and the appeal for organ donation. In contrast, no reports have addressed organ donation from the perspective of intervention in cases of “sudden mourning” and the practical aspects of how to facilitate donation in such cases.

Objective

To develop a specific strategy for professional intervention in cases of imminent death to bring the family to a state of cognitive and emotional preparedness that will enable them to accept the tragic news, donate organs, and then take leave of the deceased.

Method

The strategy presented here was developed on the basis of the records of donor coordinators who documented their interaction with families; consultations with professionals in the fields of marketing, persuasion, and negotiating; research conducted on families who did or did not donate organs; and statements made by family members of donors in focus and support groups in more than 10 years.

Results

The strategic approach includes early-stage rules such as staff self-awareness, and then later, critical stages of the process that take place before and at the time of determination of brain death: preparation for and the notification of death itself and the request for organ donation, including persuasion skills, coping with resistance and expressions of anger, and physical leave-taking from the decease.

Conclusions

The flexible, strategic approach set out here is designed to maximize the chances of procuring organ donation while protecting the family's rights and welfare.
Safety Considerations: Breastfeeding after Transplant
Authors: Thiagarajan Kristina (Muñoz-Flores) , Arakali Schweta R. , Mealey Kathleen J. , Cardonick Elyce H. , Gaughan William J. , Davison John M. , Moritz Michael J. , Armenti Vincent T.
Published: June 2013

Organ transplant is an effective treatment for end-stage organ failure. For women, restoration of organ function can restore fertility and the ability to successfully carry a pregnancy. Posttransplant pregnancies have been reported among recipients of all types of solid organ transplants via case and center reports plus registry data. Stable graft function is dependent on prevention of rejection, currently accomplished by using maintenance immunosuppressant medications, to which the fetus is exposed in utero. Common among neonatal outcomes in transplant recipients are preterm and low-birth-weight infants. Emotional, nutritional, and immunologic benefits of breastfeeding have been well-documented and could be valuable for these newborns. Concern must be directed at the effects of the child's exposure to immunosuppressive agents excreted into the breast milk. Breastfeeding could be considered in transplant recipients if it can be shown that the level of exposure does not result in risks to the newborn, immediately and throughout childhood. Despite concerns of health care professionals, some recipients have chosen to breastfeed. Breastfeeding after transplant must be approached with consideration of many issues, and the potential risks require further study. This review focuses on benefits of breastfeeding, common immunosuppressive agents used in organ transplant recipients, a summary of the reports of women who have breastfed their infants while on immunosuppressive therapy and the published studies on breastfeeding and immunosuppressive agents. Recommendations are provided to guide health care professionals to help mothers receiving immunosuppressive agents to make informed choices about breastfeeding their infants.
Making Meaning in the Legacy of Tissue Donation for Donor Families
Authors: Hogan Nancy S. , Coolican Maggie , Schmidt Lee A.
Published: June 2013

Context

Individuals needing lifesaving (heart valves, skin grafts for repair of critical burn injuries) and life-enhancing (corneas, bone and tendon grafts, skin, and veins) tissue donations outnumber the tissues available for transplant.

Objective

To describe the grief family members experienced 6 months after donation and to learn how family decision makers gained meaning from the decision to donate a loved one's tissues. This is phase 1 of a longitudinal study in which family decision makers will be surveyed again at 13 and 25 months after donation.

Design

Qualitative descriptive.

Participants

One hundred seven family decision makers whose family member died a traumatic sudden death and who authorized donating tissues for transplant.

Data Collection and Analysis

Data were written responses to the questions, “If you could ask or tell your dead family member something, what would it be” and “What meaning does donating tissue to others have for you” Data were analyzed by using content analysis procedures.

Results

Concepts derived from the first question represent the context of family members grieving the sudden death of a loved one. Concepts were (1) feeling empty, (2) missing and loving, (3) being grateful, and (4) having regrets. The concepts derived from the second question were (1) fulfilling their family member's wish, (2) doing the right thing, (3) believing something good came from the death, (4) helping others, and (5) living on. Reasons for donating were based, in part, on honoring the legacy of their loved ones who had given of themselves to others in life and now continued to give to others after death.

Conclusion

The results of this study provide a basis for health professionals and donation staffs to better understand the context within which families grieve and give meaning to tissue donation.
Cohort mortality study of garment industry workers exposed to formaldehyde: Update and internal comparisons
Authors: Meyers Alysha R. , Pinkerton Lynne E. , Hein Misty J.
Published: June 2013

Background

To further evaluate the association between formaldehyde and leukemia, we extended follow‐up through 2008 for a cohort mortality study of 11,043 US formaldehyde‐exposed garment workers.

Methods

We computed standardized mortality ratios and standardized rate ratios stratified by year of first exposure, exposure duration, and time since first exposure. Associations between exposure duration and rates of leukemia and myeloid leukemia were further examined using Poisson regression models.

Results

Compared to the US population, myeloid leukemia mortality was elevated but overall leukemia mortality was not. In internal analyses, overall leukemia mortality increased with increasing exposure duration and this trend was statistically significant.

Conclusions

We continue to see limited evidence of an association between formaldehyde and leukemia. However, the extended follow‐up did not strengthen previously observed associations. In addition to continued epidemiologic research, we recommend further research to evaluate the biological plausibility of a causal relation between formaldehyde and leukemia. Am. J. Ind. Med. 56:1027–1039, 2013. © 2013 Wiley Periodicals, Inc.
Nanostructuring of Ionic Bridged Silsesquioxanes
Authors: Monge‐Marcet Amàlia , Cattoën Xavier , Dieudonné Philippe , Pleixats Roser , Wong Chi Man Michel
Published: June 2013

The transformation by hydrolysis/condensation of four new mesityl‐(bis or tris)imidazolium‐based alkoxysilane precursors into their corresponding bridged silsesquioxanes has been investigated. These precursors feature urea groups and either short or long alkylene chains, which are known to favor self‐assembly. The most regular nanostructures were obtained by a combination of the tripodal precursors with C10H20 alkylene chains, as shown by powder X‐ray diffraction (PXRD) analysis, independent of the reaction conditions.
Can marine cloud brightening reduce coral bleaching?
Authors: Latham John , Kleypas Joan , Hauser Rachel , Parkes Ben , Gadian Alan
Published: June 2013

Increases in coral bleaching events over the last few decades have been largely caused by rising sea surface temperatures (SST), and continued warming is expected to cause even greater increases through this century. We use a Global Climate Model to examine the potential of marine cloud brightening (MCB) to cool oceanic surface waters in three coral reef provinces. Our simulations indicate that under doubled CO2 conditions, the substantial increases in coral bleaching conditions from current values in three reef regions (Caribbean, French Polynesia, and the Great Barrier Reef) were eliminated when MCB was applied, which reduced the SSTs at these sites roughly to their original values.
Multiple Compression of Moist Spherical Elastic‐Plastic Zeolite 4A Granules
Authors: Russell A. , Müller P. , Tomas J.
Published: June 2013

The compression, deformation and material behavior of moist spherical elastic‐plastic zeolite 4A granules under multiple stressing conditions at unique and random contacts were experimentally studied with the help of uniaxial diametrical compression tests. The force‐displacement curves were approximated and the coefficient of restitution was determined using appropriate mechanical models from literature. The phenomenon of cyclic hardening was studied and the critical number of cycles required to reach fracture was determined. Furthermore, the influence of particle size and moisture content on the material behavior at cyclic loading, the coefficient of restitution, and the critical number of cycles required to reach fracture were investigated.
Disentangling the effect of exploratory learning and exploitative learning in product innovation process
Authors: Li Ci‐Rong
Published: June 2013

Although studies have highlighted the importance of exploratory and exploitative learning in new product development, little is understood about the distinctiveness of team‐level exploratory and exploitative learning in the distinct phases of the product development process. This study uses a two‐phase product innovation process model to examine the differences in the effects of the two distinct learning strategies in the initiation and implementation phases. The findings from 126 teams show that (a) the effect of exploratory learning on innovativeness in the initiation phase is greater than that of exploitative learning and (b) exploitative learning can strengthen the link between the initiation phase's innovativeness and new product success more than exploratory learning. Copyright © 2013 ASAC. Published by John Wiley & Sons, Ltd.
What Do We Currently Know About Metabolic Syndrome and Atrial Fibrillation?
Authors: Tadic Marijana , Ivanovic Branislava , Cuspidi Cesare
Published: June 2013

Metabolic syndrome represents a cluster of atherogenic risk factors including hypertension, insulin resistance, obesity, and dyslipidemia. Considering that all of these risk factors could influence the development of atrial fibrillation, an association between atrial fibrillation and the metabolic syndrome has been suggested. Additionally, oxidative stress and inflammation have been involved in the pathogenesis of both metabolic syndrome and atrial fibrillation. The mechanisms that relate metabolic syndrome to the increased risk of atrial fibrillation occurrence are not completely understood. Metabolic syndrome and atrial fibrillation are associated with increased cardiovascular morbidity and mortality. Because atrial fibrillation is the most common arrhythmia, and along with the prevalence of metabolic syndrome constantly increasing, it would be very important to determine the relationship between these 2 entities, especially due to the fact that the risk factors of metabolic syndrome are mainly correctable. This review focused on the available evidence supporting the association between metabolic syndrome components and metabolic syndrome as a clinical entity with atrial fibrillation.
DNA purification from crude samples for human identification using gradient elution isotachophoresis
Authors: Strychalski Elizabeth A. , Konek Christopher , Butts Erica L. R. , Vallone Peter M. , Henry Alyssa C. , Ross David
Published: June 2013

Gradient elution isotachophoresis (GEITP) was demonstrated for DNA purification, concentration, and quantification from crude samples, represented here by soiled buccal swabs, with minimal sample preparation prior to human identification using STR analysis. During GEITP, an electric field applied across leading and trailing electrolyte solutions resulted in isotachophoretic focusing of DNA at the interface between these solutions, while a pressure‐driven counterflow controlled the movement of the interface from the sample reservoir into a microfluidic capillary. This counterflow also prevented particulates from fouling or clogging the capillary and reduced or eliminated contamination of the delivered DNA by PCR inhibitors. On‐line DNA quantification using laser‐induced fluorescence compared favorably with quantitative PCR measurements and potentially eliminates the need for quantitative PCR prior to STR analysis. GEITP promises to address the need for a rapid and robust method to deliver DNA from crude samples to aid the forensic community in human identification.
A Melamine‐Modified β‐Zeolite with Enhanced CO2 Capture Properties
Authors: Ahmad Khalil , Mowla Omid , Kennedy Eric M. , Dlugogorski Bogdan Z. , Mackie John C. , Stockenhuber Michael
Published: June 2013

A novel adsorbent for CO2 capture from gas streams was prepared by functionalization of Na‐β zeolite with melamine using post‐synthesis impregnation. The new material was characterized using X‐ray diffraction, scanning electron microscopy, temperature gravimetric analysis, and BET surface area analysis. The dynamic CO2 adsorption capacity of the modified adsorbent at 298 K and 101 kPa was found to be 3.7 mmol g−1. The adsorbent can be regenerated at 373 K with nitrogen flowing at 40 cm3 min−1. The adsorbent has shown excellent performance for CO2 adsorption–desorption in comparison to conventional adsorption systems.
Metallothionein multigene family expression is differentially affected by Chromium (III) and (VI) in Solanum nigrum L. plants
Authors: Teixeira Jorge , Ferraz Pedro , Almeida Agostinho , Verde Nuno , Fidalgo Fernanda
Published: June 2013

Solanum nigrum L. plants were grown in hydroponic systems exposed to Cr (III) or Cr (VI) under two different exposure regimes (a 4‐week prolonged treatment with lower concentrations and a 1‐week shock treatment with higher concentrations), to determinate the effects of Cr exposure on plant metabolism and growth and to define the Cr phytoremediation potential of this plant species. The data obtained shows that only Cr (VI) induced the appearance of visible symptoms of metal toxicity (reduction of root and shoot growth and fresh mass), while none of the Cr oxidation states caused induction of lipid peroxidation, in terms of malondialdehyde content, neither affected total chlorophyll and carotenoids content. An increase of free proline content in shoots from plants exposed to both Cr (VI) treatments and to a prolonged 375 μmol L−1 Cr (III) exposure was found, as well as in roots from shock treatments with both metals. The levels of Cr (III) and Cr (VI) quantified in these plants' tissues do not allow this plant species to be considered as a hyperaccumulator for Cr, but these plants can be used to phytostabilize this pollutant. The metallothioneins (MT) mRNA accumulation analysis showed that Cr (III) induced an increased accumulation of MT2a‐related transcripts in both roots and shoots, and of MT1‐ and MT2d‐related transcripts only in roots, whereas Cr (VI) induced the accumulation of MT2a‐ and MT2d‐related transcripts only in roots from the shock treatment, and the de novo accumulation of the MT2c‐related transcripts only in shoots, suggesting that these MTs are related to the Cr homeostasis in S. nigrum.
Recommended Joint and Meta‐Analysis Strategies for Case‐Control Association Testing of Single Low‐Count Variants
Authors: Ma Clement , Blackwell Tom , Boehnke Michael , Scott Laura J.
Published: June 2013

In genome‐wide association studies of binary traits, investigators typically use logistic regression to test common variants for disease association within studies, and combine association results across studies using meta‐analysis. For common variants, logistic regression tests are well calibrated, and meta‐analysis of study‐specific association results is only slightly less powerful than joint analysis of the combined individual‐level data. In recent sequencing and dense chip based association studies, investigators increasingly test low‐frequency variants for disease association. In this paper, we seek to (1) identify the association test with maximal power among tests with well controlled type I error rate and (2) compare the relative power of joint and meta‐analysis tests. We use analytic calculation and simulation to compare the empirical type I error rate and power of four logistic regression based tests: Wald, score, likelihood ratio, and Firth bias‐corrected. We demonstrate for low‐count variants (roughly minor allele count [MAC] < 400) that: (1) for joint analysis, the Firth test has the best combination of type I error and power; (2) for meta‐analysis of balanced studies (equal numbers of cases and controls), the score test is best, but is less powerful than Firth test based joint analysis; and (3) for meta‐analysis of sufficiently unbalanced studies, all four tests can be anti‐conservative, particularly the score test. We also establish MAC as the key parameter determining test calibration for joint and meta‐analysis.
The sensitivity of hurricane frequency to ITCZ changes and radiatively forced warming in aquaplanet simulations
Authors: Merlis Timothy M. , Zhao Ming , Held Isaac M.
Published: June 2013

The response of hurricane frequency to climate changes in an aquaplanet configuration of a 50‐km resolution atmospheric general circulation model is examined. The lower boundary condition is an energetically consistent slab ocean with a prescribed cross‐equatorial ocean heat flux, which breaks the hemispheric symmetry and moves the Intertropical Convergence Zone (ITCZ) off the equator. In this idealized configuration, hurricane frequency increases in response to radiatively forced warming. The ITCZ shifts poleward when the model is warmed with fixed cross‐equatorial ocean heat flux, and it is argued that the increase in hurricane frequency results from this poleward shift. Varying the imposed cross‐equatorial ocean heat flux amplitude with fixed radiative forcing can isolate the effect of ITCZ shifts. If an increase in radiative forcing is accompanied by a reduction in the ocean heat flux amplitude such that the position of the ITCZ is unchanged, the simulated hurricane frequency decreases under warmed conditions.
Cancer cells acquire a drug resistant, highly tumorigenic, cancer stem‐like phenotype through modulation of the PI3K/Akt/β‐catenin/CBP pathway
Authors: He Kaijie , Xu Tong , Xu Yucheng , Ring Alexander , Kahn Michael , Goldkorn Amir
Published: June 2013

Cancer initiation and progression have been attributed to newly discovered subpopulations of self‐renewing, highly tumorigenic, drug‐resistant tumor cells termed cancer stem cells. Recently, we and others reported a new phenotypic plasticity wherein highly tumorigenic, drug‐resistant cell populations could arise not only from pre‐existing cancer stem‐like populations but also from cancer cells lacking these properties. In the current study, we hypothesized that this newfound phenotypic plasticity may be mediated by PI3K/Akt and Wnt/β‐catenin signaling, pathways previously implicated in carcinogenesis, pluripotency and drug resistance. Using GFP expression, Hoechst dye exclusion and fluorescence activated cell sorting (FACS) of cancer cell lines, we identified and tracked cancer stem‐like side populations (SP) of cancer cells characterized by high tumorigenicity and drug resistance. We found that pharmacological inhibition or genetic depletion of PI3K and AKT markedly reduced the spontaneous conversion of nonside population (NSP) cells into cancer stem‐like SP cells, whereas PI3K/Akt activation conversely enhanced NSP to SP conversion. PI3K/AKT signaling was mediated through downstream phosphorylation of GSK3β, which led to activation and accumulation of β‐catenin. Accordingly, pharmacological or genetic perturbation of GSK3β or β‐catenin dramatically impacted conversion of NSP to SP. Further downstream, β‐catenin's effects on NSP‐SP equilibrium were dependent upon its interaction with CBP, a KAT3 family coactivator. These studies provide a mechanistic model wherein PI3K/Akt/β‐catenin/CBP signaling mediates phenotypic plasticity in and out of a drug‐resistant, highly tumorigenic state. Therefore, targeting this pathway has unique potential for overcoming the therapy resistance and disease progression attributed to the cancer stem‐like phenotype.
Adiponectin Is a Candidate Biomarker of Lower Extremity Bone Density in Men With Chronic Spinal Cord Injury
Authors: Doherty Ashley L , Battaglino Ricardo A , Donovan Jayne , Gagnon David , Lazzari Antonio A , Garshick Eric , Zafonte Ross , Morse Leslie R
Published: June 2013

Adipose tissue is a major regulator of bone metabolism and in the general population obesity is associated with greater bone mineral density (BMD). However, bone-fat interactions are multifactorial, and may involve pathways that influence both bone formation and resorption with competing effects on the skeleton. One such pathway involves adipocyte production of adipokines that regulate bone metabolism. In this study we determined the association between BMD, walking status, and circulating adipokines (adiponectin and leptin) in 149 men with chronic spinal cord injury (SCI). Although adipokine levels did not vary significantly based on walking status, there was a significant inverse association between adiponectin and BMD in wheelchair users independent of body composition. We found no association between adiponectin and BMD in the walkers and no association between leptin and BMD in either group. These findings suggest that for subjects with chronic SCI, walking may mitigate the effect of adiponectin mediated bone loss. For wheelchair users, adipose-derived adiponectin may contribute to SCI-induced osteoporosis because the osteoprotective benefits of obesity appear to require mechanical loading during ambulation. © 2014 American Society for Bone and Mineral Research.
Magnesium Metabolism in 4-Year-Old to 8-Year-Old Children
Authors: Abrams Steven A , Chen Zhensheng , Hawthorne Keli M
Published: June 2013

Magnesium (Mg) is a key factor in bone health, but few studies have evaluated Mg intake or absorption and their relationship with bone mineral content (BMC) or bone mineral density (BMD) in children. We measured Mg intake, absorption, and urinary excretion in a group of children 4 to 8 years of age. Mg absorption was determined using a dual-tracer stable isotope technique, with 25Mg given intravenously and 26Mg given orally. We found a small, but significantly greater Mg absorption efficiency (percentage absorption) in males than females (67% ± 12% versus 60% ± 8%, p = 0.02) but no difference in estimated net Mg retention (average of 37 mg/d in both males and females). Relating dietary Mg intake to estimated Mg retention showed that an intake of 133 mg/d, slightly above the current estimated average requirement (EAR) of 110 mg/d, led to a net average retention of 10 mg/d, the likely minimum growth-related need for this age group. Covariate analysis showed that Mg intake and total Mg absorption, but not calcium intake or total absorption were significantly associated with both total body BMC and BMD. These results suggest that usual Mg intakes in small children in the United States meet dietary requirements in most but not all children. Within the usual range of children's diets in the United States, dietary Mg intake and absorption may be important, relatively unrecognized factors in bone health. © 2014 American Society for Bone and Mineral Research.
Modeling subglacial water routing at Paakitsoq, W Greenland
Authors: Banwell Alison F. , Willis Ian C. , Arnold Neil S.
Published: June 2013

The functioning of the Greenland Ice Sheet's subglacial drainage system and its effect on ice dynamics have been inferred largely from hypothetical hydrology dynamics models and from analysis of satellite data and in situ GPS measurements. Despite this, there is still uncertainty about how the surface hydrology interacts with the subglacial drainage system and affects basal water pressures and ice flow, especially over annual time scales. To address this, we developed a high spatial (100 m) and temporal (1 h) resolution, distributed, physically based, subglacial hydrological model, and applied it to the Paakitsoq region, western Greenland. The model is driven with moulin input hydrographs calculated by a surface routing and lake filling/draining model, forced ultimately with distributed hourly runoff calculated by a surface mass balance model. Key outputs from the model are spatially and temporally varying subglacial water pressures and proglacial stream hydrographs. Early in the melt season, short spikes in water pressure lasting less than a day occur as a result of lake drainage events. During midsummer, there are sustained periods of high water pressure lasting days to weeks, even at times when the subglacial system is inferred to be predominantly efficient. Later in the summer, large diurnal fluctuations in water pressure occur with peaks regularly exceeding ice overburden pressure superimposed on a gradually declining trend. These phenomena support the results of previous hypothetical modeling efforts and inferences drawn from GPS measurements.
K‐Pg extinction patterns in marine and freshwater environments: The impact winter model
Authors: Robertson Douglas S. , Lewis William M. , Sheehan Peter M. , Toon Owen B.
Published: June 2013

The Chicxulub asteroid impact produced massive extinction in terrestrial environments most likely through an intense heat pulse and subsequent widespread fires. Aquatic environments were shielded from this heat and fire but nevertheless showed massive extinction in marine environments and, for reasons unexplained, far less extinction in freshwater environments. Extinction in marine environments resulted from the effects of an “impact winter” caused by dust and smoke in the atmosphere that extinguished sunlight at the Earth's surface for a period of months to years. The resulting cessation of photosynthesis caused a globally extensive extinction of phytoplankton taxa. Because aquatic ecosystems, unlike terrestrial environments, are strongly dependent on daily photosynthetic output by autotrophs, loss of phytoplankton likely caused catastrophic mortality and extinction in aquatic ecosystems. Other potential causes of mortality in aquatic ecosystems include lower ambient temperatures and anoxia due to the lack of photosynthetic oxygen. Inland waters, although probably subject to high mortality, showed lower proportionate extinction than marine environments probably because of the greater potential among the freshwater taxa for dormancy, the greater efficiency of reaeration by rapid flow to offset oxygen demand, abundant thermal refugia fed by groundwater at moderate temperatures, and preadaptation of freshwater taxa to a great degree of environmental variability. In addition, detrital feeders appear to have had low extinction rates in either marine or freshwater environments, but again freshwater taxa would have been favored by higher renewal rates of detrital organic matter as a result of their direct hydrologic contact with soil.
Severity and prognostic assessment of the endotoxin activity assay in biliary tract infection
Authors: Sato Mari , Matsuyama Ryusei , Kadokura Toshiaki , Mori Ryutaro , Kumamoto Takafumi , Nojiri Kazunori , Taniguchi Koichi , Takeda Kazuhisa , Kubota Kensuke , Tanaka Kuniya , Endo Itaru
Published: June 2013

Background

Acute cholangitis and cholecystitis (AC) often progress to severe septic conditions. We evaluated the endotoxin activity assay (EAA) for assessment and prediction of the severity of AC.

Methods

We retrospectively reviewed 98 patients diagnosed with AC. We divided them into low (<0.4) and high (≥0.4) groups based on EAA values.

Results

Endotoxin levels showed no correlation with EAA values. Serum C‐reactive protein (8.57 vs. 5.23 mg/dl, P = 0.02), procalcitonin (2.45 vs. 0.48 ng/ml, P = 0.004), and the positive culture rate of blood (50% vs. 15%, P < 0.001) were significantly higher in the high group than in the low group. Platelet counts were significantly lower in the high group than in the low group (23.9 vs. 13.5 104/ml, P = 0.004). The ratio of patients with a Japanese Association for Acute Medicine disseminated intravascular coagulation score ≥4 (32% vs. 14%, P = 0.032) was significantly higher in the high group than in the low group. There was a significantly higher percentage of patients with a severe grade of AC in the high group than patients with a mild or moderate grade (32% vs. 15%, P = 0.05).

Conclusions

Endotoxin activity assay is useful for assessment and early prediction of septic conditions due to AC.
The differences in binding 12‐carbon aliphatic ligands by bovine β‐lactoglobulin isoform A and B studied by isothermal titration calorimetry and X‐ray crystallography
Authors: Loch Joanna I. , Bonarek Piotr , Polit Agnieszka , Świątek Sylwia , Dziedzicka‐Wasylewska Marta , Lewiński Krzysztof
Published: June 2013

Isoforms A (LGB‐A) and B (LGB‐B) of bovine lactoglobulin, the milk protein, differ in positions 64 (D↔G) and 118 (V↔A). Interactions of LGB‐A and LGB‐B with sodium dodecyl sulfate (SDS), dodecyltrimethylammonium chloride (DTAC) and lauric acid (LA), 12‐carbon ligands possessing differently charged polar groups, were investigated using isothermal titration calorimetry and X‐ray crystallography, to study the proton linkage phenomenon and to distinguish between effects related to different isoforms and different ligand properties. The determined values of ΔS and ΔH revealed that for all ligands, binding is entropically driven. The contribution from enthalpy change is lower and shows strong dependence on type of buffer that indicates proton release from the protein varying with protein isoform and ligand type and involvement of LA and Asp64 (in isoform A) in this process. The ligand affinities for both isoforms were arranged in the same order, DTAC < LA < SDS, and were systematically lower for variant B. The entropy change of the complexation process was always higher for isoform A, but these values were compensated by changes in enthalpy, resulting in almost identical ΔG for complexes of both isoforms. The determined crystal structures showed that substitution in positions 64 and 118 did not influence the overall structure of LGB complexes. The chemical character of the ligand polar group did not affect the position of its aliphatic chain in protein β‐barrel, indicating a major role of hydrophobic interactions in ligand binding that prevailed even with the repulsion between positively charged DTAC and lysine residues located at binding site entrance. Copyright © 2013 John Wiley & Sons, Ltd.
A simple approach to prepare molecularly imprinted polymers from nylon‐6
Authors: Dmitrienko E. V. , Bulushev R. D. , Haupt K. , Kosolobov S. S. , Latyshev A. V. , Pyshnaya I. A. , Pyshnyi D. V.
Published: June 2013

A convenient and simple approach for the preparation of molecularly imprinted polymers (MIPs) based on polyamide (nylon‐6) was developed. The polymer matrix formation occurred during the transition of nylon from dissolved to solid state in the presence of template molecules in the initial solution. 2,2,2‐Trifluoroethanol (TFE) was chosen as a main solvent for the polyamide. It provides a high solubility of nylon and does not significantly change the structure of biopolymers. The alteration of the polymer matrix structure after the addition of different types of porogens in the nylon/TFE solution was investigated. The structured polymers in the form of films and microparticles were prepared in the chosen optimal conditions. Different model biomolecular templates (of low‐ and high‐molecular weight) were used for the preparation of MIPs, which were shown to specifically recognize these molecules upon binding experiments. The binding of the template molecules to MIPs was monitored using spectrophotometric, radioisotopic, or fluorometric detection. The selectivity coefficients of the MIPs were estimated to be 1.4–4.6 depending on the type of templates and conditions of the polymer matrix formation. Copyright © 2013 John Wiley & Sons, Ltd.
The sub‐nanomolar binding of DNA–RNA hybrids by the single‐chain Fv fragment of antibody S9.6
Authors: Phillips Damilola D. , Garboczi David N. , Singh Kavita , Hu Zonglin , Leppla Stephen H. , Leysath Clinton E.
Published: June 2013

The monoclonal antibody S9.6 binds DNA–RNA hybrids with high affinity, making it useful in research and diagnostic applications, such as in microarrays and in the detection of R‐loops. A single‐chain variable fragment (scFv) of S9.6 was produced, and its affinities for various synthetic nucleic acid hybrids were measured by surface plasmon resonance (SPR). S9.6 exhibits dissociation constants of approximately 0.6 nM for DNA–RNA and, surprisingly, 2.7 nM for RNA–RNA hybrids that are AU‐rich. The affinity of the S9.6 scFv did not appear to be strongly influenced by various buffer conditions or by ionic strength below 500 mM NaCl. The smallest epitope that was strongly bound by the S9.6 scFv contained six base pairs of DNA–RNA hybrid. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
Spontaneous cerebrospinal fluid leak repair: A five‐year prospective evaluation
Authors: Chaaban Mohamad R. , Illing Elisa , Riley Kristen O. , Woodworth Bradford A.
Published: June 2013

Objectives/Hypothesis

Mounting evidence indicates the majority of spontaneous cerebrospinal fluid (CSF) leaks are associated with intracranial hypertension. The objectives of the current study were to assess outcomes regarding spontaneous CSF leaks focusing on premorbid factors, surgical technique, and management of intracranial pressure.

Study Design

Prospective cohort.

Methods

Prospective evaluation of patients with spontaneous CSF leaks was performed. Data regarding demographics, nature of presentation, body mass index (BMI), location and size of defect, intracranial pressure, clinical follow‐up, and complications were collected.

Results

Over 5 years, 46 patients (average age, 51 years) with 56 spontaneous CSF leaks were treated by a single otolaryngologist. Twenty‐one subjects presented with recurrence of their CSF leak following previous endoscopic and/or open approaches by other physicians. Obesity was present in 78% of individuals (average BMI, 35.6). Fifty‐two CSF leaks (93%) were successfully repaired at first attempt. With secondary repair, all CSF leaks were closed at last clinical follow‐up (average, 93 weeks). Three patients developed late failures (>2 months), with one recurrence at a distinct location from the primary site at 8 months postprocedure (associated with ventriculoperitoneal shunt failure). Opening pressures via lumbar puncture averaged 24.3 ± 8.3 cm H20, which increased significantly to 32.3 ± 9.0 cm H20 (P < .0001) following closure of the skull base defect(s). Management of intracranial hypertension included acetazolamide (n = 23) or permanent CSF diversion (n = 19, including five revisions of failed preexisting shunts).

Conclusions

Although spontaneous CSF leaks have the highest recurrence rate of any etiology, prospective evaluation demonstrates high success rates with control of intracranial hypertension.

Level of Evidence

4. Laryngoscope, 124:70–75, 2014
Compliance, Detection, and Mergers and Acquisitions
Authors: Ghosal Vivek , Sokol D. Daniel
Published: June 2013

Firms operate under a wide range of rules and regulations. These include, for example, environmental regulations (in which some industries have increased regulatory exposure) and finance and accounting (where all industries have reporting requirements). In other areas, such as antitrust cartels, enforcement is unregulated, and antitrust leaves the market as the default tool to police against anticompetitive behavior. In all of these areas, detection of noncompliance by a firm can result in significant penalties. This issue of noncompliance has implications in the merger and acquisitions (M&A) context. In a transaction between an acquiring firm (buyer) and a target firm (seller), there is asymmetric information about the target's quality. In our framework, we link a target's quality directly to the strength of its regulatory compliance. In an M&A transaction, an acquirer seeks information about the target's compliance, as a compliance failure may result in substantial penalties and sanctions, post‐acquisition. In the presence of quality (compliance) uncertainty about target firms, low‐quality targets can masquerade as high quality. This would tend to give rise to an M&A market with Lemons‐like characteristics, resulting in low transaction prices and dampening of M&A activity. We examine how M&A transactions in such regulatory areas – environmental, finance and accounting, and antitrust compliance problems – might function to alleviate quality uncertainty. Copyright © 2013 John Wiley & Sons, Ltd.
Exploring the Molecular Basis of Qobc1 Complex Inhibitors Activity to Find Novel Antimalarials Hits
Authors: Carrasco Marta P. , Gut Jiri , Rodrigues Tiago , Ribeiro Maria H. L. , Lopes Francisca , Rosenthal Philip J. , Moreira Rui , dos Santos Daniel J. V. A.
Published: June 2013

Cytochrome bc1 complex is a crucial element in the mitochondrial respiratory chain, being indispensable for the survival of several species of Plasmodia that cause malaria and, therefore, it is a promising target for antimalarial drug development. We report a molecular docking study building on the most recently obtained X‐ray structure of the Saccharomyces cerevisiae bc1 complex (PDB code: 3CX5) using several reported inhibitors with experimentally determined IC50 values against the Plasmodium falciparum bc1 complex. We produced a molecular docking model that correlated the calculated binding free energy with the experimental inhibitory activity of each compound. This Qo model was used to search the drug‐like database included in the MOE package for novel potential bc1 complex inhibitors. Twenty three compounds were chosen to be tested for their antimalarial activity and four of these compounds demonstrated activity against the chloroquine‐resistant W2 strain of P. falciparum. The most active compounds were also active against the atovaquone‐resistant P. falciparum FCR3 strain and S. cerevisiae. Our study suggests the validity of the yeast bc1 complex structure as a model for the discovery of new antimalarial hits.
Nonlinear simulations of vesicle wrinkling
Authors: Liu Kai , Li Shuwang
Published: June 2013

In this paper, we study nonlinear wrinkling dynamics of a vesicle in an extensional flow. Motivated by the recent experiments and linear theory on wrinkles of a quasi‐spherical membrane, we are interested in examining the linear theory and exploring wrinkling dynamics in a nonlinear regime. We focus on a quasi‐circular vesicle in two dimensions and show that the linear analytical results are qualitatively independent of the number of dimensions. Hence, the two‐dimensional studies can provide insights into the full three‐dimensional problem. We develop a spectral accurate boundary integral method to simulate the nonlinear evolution of surface tension and the nonlinear interactions between flow and membrane morphology. We demonstrate that for a quasi‐circular vesicle, the linear theory well predicts the characteristic wavenumber during the wrinkling dynamics. Nonlinear results of an elongated vesicle show that there exist dumbbell‐like stationary shapes in weak flows. For strong flows, wrinkles with pronounced amplitudes will form during the evolution. As far as the shape transition is concerned, our simulations are able to capture the main features of wrinkles observed in the experiments. Interestingly, numerical results reveal that, in addition to wrinkling, asymmetric rotation can occur for slightly tilted vesicles. The mathematical theory and numerical results are expected to lead to a better understanding of related problems in biology such as cell wrinkling. Copyright © 2013 John Wiley & Sons, Ltd.
A continuous dependence result for a nonstandard system of phase field equations
Authors: Colli Pierluigi , Gilardi Gianni , Krejčí Pavel , Sprekels Jürgen
Published: June 2013

The present note deals with a nonstandard system of differential equations describing a two‐species phase segregation. This system naturally arises in the asymptotic analysis carried out recently by the same authors, as the diffusion coefficient in the equation governing the evolution of the order parameter tends to zero. In particular, an existence result has been proved for the limit system in a very general framework. On the contrary, uniqueness was shown by assuming a constant mobility coefficient. Here, we generalize this result and prove a continuous dependence property in the case that the mobility coefficient suitably depends on the chemical potential. Copyright © 2013 John Wiley & Sons, Ltd.
The evolution of MRI probes: from the initial development to state‐of‐the‐art applications
Authors: Mulder Willem J. M. , McMahon Michael T. , Nicolay Klaas
Published: June 2013

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Cardiometabolic risks during anabolic hormone supplementation in older men
Authors: He J. , Bhasin S. , Binder E.F. , Yarasheski K.E. , Castaneda‐Sceppa C. , Schroeder E.T. , Roubenoff R. , Chou C.‐P. , Azen S.P. , Sattler F.R.
Published: June 2013

Objective:

To determine the cardiometabolic risks of testosterone and growth hormone (GH) replacement therapy to youthful levels during aging.

Design and Methods:

A double‐masked, partially placebo controlled study in 112 men 65‐90 years‐old was conducted. Transdermal testosterone (5 g vs. 10 g/day) using a Leydig Cell Clamp and subcutaneous recombinant GH (rhGH) (0 vs. 3 vs. 5 μg/kg/day) were administered for 16‐weeks. Measurements included testosterone and IGF‐1 levels, body composition by DEXA, and cardiometabolic risk factors (upper body fat, blood pressure, insulin sensitivity, fasting triglycerides, HDL‐cholesterol, and serum adiponectin) at baseline and after 16 weeks of treatment.

Results:

Some cardiometabolic factors improved (total and trunk fat, triglycerides, HDL‐cholesterol) and others worsened (systolic blood pressure, insulin sensitivity index [QUICKI], adiponectin). Cardiometabolic risk composite scores (CRCSs) improved (−0.69 ± 1.55, P < 0.001). In multivariate analyses, QUICKI, triglycerides, and HDL‐cholesterol contributed 33%, 16%, and 14% of the variance in CRCS, respectively. Pathway analyses indicated that changes in fat and lean mass were related to individual cardiometabolic variables and CRCS in a complex manner. Changes in BMI, reflecting composite effects of changes in fat and lean mass, were more robustly associated with cardiometabolic risks than changes in fat mass or LBM individually.

Conclusions:

Testosterone and rhGH administration was associated with diverse changes in individual cardiometabolic risk factors, but in aggregate appeared not to worsen cardiometabolic risk in healthy older men after 4‐months. The long‐term effects of these and similar anabolic therapies on cardiovascular events should be investigated in populations with greater functional limitations along with important health disabilities including upper body obesity and other cardiometabolic risks.
Serum amyloid A is found on ApoB‐containing lipoproteins in obese humans with diabetes
Authors: Jahangiri Anisa , Wilson Patricia G. , Hou Tianfei , Brown Aparna , King Victoria L. , Tannock Lisa R.
Published: June 2013

Objective:

In murine models of obesity/diabetes, there is an increase in plasma serum amyloid A (SAA) levels along with redistribution of SAA from high‐density lipoprotein (HDL) to apolipoprotein B (apoB)‐containing lipoprotein particles, namely, low‐density lipoprotein and very low‐density lipoprotein. The goal of this study was to determine if obesity is associated with similar SAA lipoprotein redistribution in humans.

Design and Methods:

Three groups of obese individuals were recruited from a weight loss clinic: healthy obese (n = 14), metabolic syndrome (MetS) obese (n = 8), and obese with type 2 diabetes (n = 6). Plasma was separated into lipoprotein fractions by fast protein liquid chromatography, and SAA was measured in lipid fractions using enzyme‐linked immunosorbent assay and Western blotting.

Results:

Only the obese diabetic group had SAA detectable in apoB‐containing lipoproteins, and SAA reverted back to HDL with active weight loss.

Conclusions:

In human subjects, SAA is found in apoB‐containing lipoprotein particles only in obese subjects with type 2 diabetes, but not in healthy obese or obese subjects with MetS.
Maternal serum leptin during pregnancy and infant birth weight: The influence of maternal overweight and obesity
Authors: Misra Vinod K. , Straughen Jennifer K. , Trudeau Sheri
Published: June 2013

Objective:

Few studies have examined whether the distinct metabolic patterns found in obese and nonobese pregnant women have different effects on the growing fetus. Our objective was to estimate the influence of longitudinal variation in maternal serum leptin levels on variation in infant birth weight in overweight/obese versus normal‐weight women.

Design and Methods:

In a prospective cohort of 286 gravidas, maternal weight and serum leptin levels at 6–10, 10–14, 16–20, 22–26, and 32–36 weeks gestation were measured. Effects of leptin levels on infant birth weight adjusted for gestational age at delivery (aBW) were analyzed using a linear regression model that accounted for the relationship of time‐varying predictors to the log‐transformed leptin concentrations.

Results:

Different relationships of aBW to maternal serum leptin and its rate of change across pregnancy were exhibited by overweight/obese and normal‐weight gravidas. For normal‐weight women, aBW is not associated with either the magnitude of the logarithm of the leptin concentration or with its rate of change in either the first or second half of pregnancy. Conversely, for overweight/obese women, an increase in the rate of change in maternal serum leptin in the second half of pregnancy is significantly associated with a decrease in aBW. This effect is distinct from that of maternal weight.

Conclusion:

Differences in the effect of maternal serum leptin on fetal growth between overweight/ obese and normal‐weight women suggest metabolic and physiologic heterogeneity between these groups. Such differences may be involved in the long‐term physiologic effects of the obese intrauterine environment on the health of the offspring.