bluuebunny/crossref_metadata_2025 huggingface dataset:
Provision of Public Goods with the Presence of Inter-Class Conflicts
Authors: Thampanishvong Kannika
Published: April 2012

In the countries that experience the problem of inter-class conflict, the self-interested elite tend to pursue allocation policies that maximize their own welfare. In the absence of the binding revolutionary constraint, under some conditions, the amount of public goods provided is too low, relative to the optimal level of public good from the perspective of general welfare. With the revolutionary constraint, there exists a set of parameter values whereby the elite provide strictly positive amount of public goods. With unconditional foreign aid, there is no guarantee that the elite will use these additional resources to finance public good provision. For conditional foreign aid, the conditionality requirements depend on the degree of transparency of the recipient country.
Using the Boiling Point of Water to Learn about Hydrogen Bonds
Authors: Offner Susan
Published: April 2012

The boiling point of water is 300°C higher than expected because of hydrogen bonds.
Applying the Scientific Method & Phylogenetics to Understand the Transition from Kingdoms to Domains: Does One Plus One Equal Five, Six, or Three?
Authors: Davis Sandra L.
Published: April 2012

The progression of the taxonomic organization of life from Linnaeus’s original two kingdoms to the traditional five-kingdom system to today’s widely accepted three-domain system is explored in a group-learning activity. Working with a set of organisms, students organize them into each system. Discussion after each step focuses on viewing classification schemes as hypotheses about the relatedness of organisms and how hypotheses are altered with accumulation of new data. Finally, the connection between phylogenetic trees and the hierarchal system of biological classification is emphasized by using tree-thinking to analyze the universal phylogenetic tree as the basis of the three-domain system.
Evaluation of a Clinical Dehydration Scale in Children Requiring Intravenous Rehydration
Authors: Kinlin Laura M. , Freedman Stephen B.
Published: April 2012

OBJECTIVES:

To evaluate the reliability and validity of a previously derived clinical dehydration scale (CDS) in a cohort of children with gastroenteritis and evidence of dehydration.

METHODS:

Participants were 226 children older than 3 months who presented to a tertiary care emergency department and required intravenous rehydration. Reliability was assessed at treatment initiation, by comparing the scores assigned independently by a trained research nurse and a physician. Validity was assessed by using parameters reflective of disease severity: weight gain, baseline laboratory results, willingness of the physician to discharge the patient, hospitalization, and length of stay.

RESULTS:

Interobserver reliability was moderate, with a weighted κ of 0.52 (95% confidence interval [CI] 0.41, 0.63). There was no correlation between CDS score and percent weight gain, a proxy measure of fluid deficit (Spearman correlation coefficient = −0.03; 95% CI −0.18, 0.12). There were, however, modest and statistically significant correlations between CDS score and several other parameters, including serum bicarbonate (Pearson correlation coefficient = −0.35; 95% CI −0.46, −0.22) and length of stay (Pearson correlation coefficient = 0.24; 95% CI 0.11, 0.36). The scale’s discriminative ability was assessed for the outcome of hospitalization, yielding an area under the receiver operating characteristic curve of 0.65 (95% CI 0.57, 0.73).

CONCLUSIONS:

In children administered intravenous rehydration, the CDS was characterized by moderate interobserver reliability and weak associations with objective measures of disease severity. These data do not support its use as a tool to dictate the need for intravenous rehydration or to predict clinical course.
2011 Joseph W. St Geme Jr Lecture: Five Things I'd Like to See Changed in American Pediatrics, Five Lessons I've Learned
Authors: Lister George
Published: April 2012

OBJECTIVE:

In response to limitations in access to subspecialty care, I present personal observations and suggestions related to education of future pediatricians regarding development of critical thinking skills, care of complex and chronically ill patients, development of empathy, and restoration of responsibility that may help ameliorate this serious problem. Toward this end, I also offer 1 approach, a 24/7 telephone consultation network, for enriching interaction of primary care providers (PCPs) and subspecialists who can potentially provide rapid access to needed advice, reduce demand for subspecialty appointments, bolster decision-making and expertise, and realign resources with need.

METHODS:

Data were obtained from 579 requests by PCPs for telephone consultation by subspecialists in 8 areas (including child psychiatry).

RESULTS:

Of calls, 27% took <5 minutes and 79% took 5 to 15 minutes. Of calls, 28% resulted in a clinic visit; 8% prompted hospital transfer, hospital admission, or referral to an emergency department; and the remaining 64% resulted in continued management by PCP with reinforcement of the plan. Assuming most inquiries would have resulted in referral to a subspecialist were there no telephone consultation, we estimated that 70% (8+64%) of consultations realigned resources with need, resulting in large saving of unnecessary clinic visits, travel, expense to families, lost days at work, or missed school.

CONCLUSIONS:

Development of rapid telephone consultation networks could provide increased access to care for those children in greatest need, use limited resources more efficiently, foster collegial and productive relationships between medical providers, and increase expertise of PCPs and subspecialists.
Functional Reconstruction of Epignathus with Cleft Palate Using Part of a Mature Teratoma
Authors: Kobayashi Shinji , Tanaka Mari , Ohashi Yukie , Tanaka Yukichi , Maegawa Jiro
Published: April 2012

Epignathus is an extremely rare, benign, congenital teratoma that arises from the oral cavity. When treating epignathus with cleft palate, it is particularly important to consider velopharyngeal function and maxillary growth after surgical repair. The case of an infant with a complete cleft palate and a large mass, histologically diagnosed as a mature teratoma, that protruded from the right soft palate is described. At 8 months of age, a double-opposing Z-plasty was performed using a part of the tumor over the right soft palate that had been left at the time of primary excision at 3 months of age for an epignathus protruding from the mouth. Though all that could be done was suture tumor tissue on the right side and the left hypoplastic levator veli palatine muscle using the double-opposing Z-plasty, velopharyngeal function and maxillary growth were good at 10 years of age.
Optical-televiewer-based identification and characterization of material facies associated with an Antarctic ice-shelf rift
Authors: Hubbard Bryn , Tison Jean-Louis , Pattyn Frank , Dierckx Marie , Boereboom Thierry , Samyn Denis
Published: April 2012

We have drilled 13 boreholes within and around a through-cutting rift on the (unofficially named) Roi Baudouin Ice Shelf, East Antarctica. Logging by optical televiewer (OPTV) combined with core inspection has resulted in the identification and characterization of several material facies. Outside the rift, OPTV-imaged annual layering indicates ~150 years of accumulation over the 66 m length of one of the boreholes. Luminosity analysis of this image also reveals the presence of numerous dark melt layers as well as a systematic decrease in background luminosity, interpreted in terms of a progressive increase in light transmission during firnification. We identify four material facies within the rift: snow, granular ice, marine ice and unconsolidated platelets. We interpret the granular ice facies as snow that has been saturated by percolating sea water, and the underlying marine ice as compacted buoyant platelets that have adhered to the rift base. Core sections reveal the presence of tubular channels within the marine ice, indicating that it is macroporous and permeable to sea water. The lower boundary of this facies merges into a mushy layer of unconsolidated platelets that were successfully imaged by OPTV, revealing irregular sub-horizontal layering similar to that reported previously on the basis of (directional) borehole video.
Phage Displayed Peptides/Antibodies Recognizing Growth Factors and Their Tyrosine Kinase Receptors as Tools for Anti-Cancer Therapeutics
Authors: Ronca Roberto , Benzoni Patrizia , De Luca Angela , Crescini Elisabetta , Dell’Era Patrizia
Published: April 2012

The basic idea of displaying peptides on a phage, introduced by George P. Smith in 1985, was greatly developed and improved by McCafferty and colleagues at the MRC Laboratory of Molecular Biology and, later, by Barbas and colleagues at the Scripps Research Institute. Their approach was dedicated to building a system for the production of antibodies, similar to a naïve B cell repertoire, in order to by-pass the standard hybridoma technology that requires animal immunization. Both groups merged the phage display technology with an antibody library to obtain a huge number of phage variants, each of them carrying a specific antibody ready to bind its target molecule, allowing, later on, rare phage (one in a million) to be isolated by affinity chromatography. Here, we will briefly review the basis of the technology and the therapeutic application of phage-derived bioactive molecules when addressed against key players in tumor development and progression: growth factors and their tyrosine kinase receptors.
Studies on the Synthesis of Derivatives of Marine-Derived Bostrycin and Their Structure-Activity Relationship against Tumor Cells
Authors: Chen Hong , Zhong Lili , Long Yuhua , Li Jia , Wu Jueheng , Liu Lan , Chen Shengping , Lin Yongcheng , Li Mengfeng , Zhu Xun , She Zhigang
Published: April 2012

A series of new derivatives (5–29) of marine-derived bostrycin (1) were synthesized. The in vitro cytotoxic activities of all compounds were evaluated against MCF-7, MDA-MB-435, A549, HepG2, HCT-116 and MCF-10A cells using the MTT method. The compounds 7, 8, 22, 23, 25, 28 and 29 of the total showed comparable activity to epirubicin, the positive control, against the tested cancer cell lines. However, these compounds also exhibited cytotoxicity towards MCF-10A cells. The structure-activity relationship (SAR) of bostrycin derivatives was also discussed based on the obtained experimental data.
123I-FP-CIT SPECT imaging of the dopaminergic state
Authors: Eggers C. , Holstein A. , Schneider C. , Pedrosa D. J. , Dietlein M. , Kobe C. , Timmermann L. , Schmidt M. , Kahraman D.
Published: April 2012

123I-N-ω-fluoropropyl-2β-carbomethoxy-3β- (4-iodophenyl)nortropan (123I-FP-CIT) single photon emission computed tomography (SPECT) can be evaluated by both visual assessment and quantitative analysis to assess the striatal dopamine state in vivo. The aim of our study was to investigate if visual assessment according to a predefined image grading scale reflects the results of quantitative assessment techniques. Patients, methods: 195 patients with a clinical diagnosis of idiopathic Parkinson's disease (n = 134), atypical parkinsonian syndrome (n = 47) or essential tremor (n = 14) were examined with 123I-FP-CIT SPECT and included in this retrospective study. Results were analysed according to predefined visual patterns of dopaminergic degeneration and graded as normal (grade 5) or abnormal (grade 1–4) independently by three raters. Quantitative two-dimensional (2D) operator-dependent, manual and three-dimensional (3D) operator- independent, automated approaches were used for quantitative analysis of the specific 123I-FP-CIT tracer binding ratio (SBR) for caudate and putamen. Results: Sensitivity, specificity, PPV, NPV and diagnostic accuracy of visual assessment of 123I-FP-CIT SPECT for the diagnosis of a neuro degenerative Parkinson's syndrome were 99%, 86%, 99%, 86% and 98%, respectively. Visual assessment and quantitative analysis agreed well in evaluating the degree of dopaminergic degeneration. Significant differences (p < 0.001) were found between degeneration patterns. Only between the so-called eagle wing degeneration and the normal pattern no significant differences in SBR caudate and putamen were found, neither by the quantitative manual (p = 1.00; p = 0.196) nor by the quantitative automated method (p = 1.0; p = 0.785). Inter-rater agreement for visual assessment was substantial for all possible pairs of the three raters (κ = 0.70 to 0.74). Strong correlations were observed between the quantitative manual and quantitative automated methods for quantification of SBR caudatum (r = 0.920, r2 = 0.846, p < 0.001) and SBR putamen (r = 0.908, r2 = 0.824, p < 0.001). Conclusion: Visual assessment was highly consistent with the results obtained by quantitative analysis and showed a substantial inter-rater agreement between experienced and inexperienced raters. Our findings indicate that visual assessment might be a reliable analysis approach for clinical routine.
Evaluation of Intracellular Labeling with Micron-Sized Particles of Iron Oxide (MPIOs) as a General Tool for In Vitro and in Vivo Tracking of Human Stem and Progenitor Cells
Authors: Boulland Jean-Luc , Leung Doreen S. Y. , Thuen Marte , Vik-Mo Einar , Joel Mrinal , Perreault Marie-Claude , Langmoen Iver A. , Haraldseth Olav , Glover Joel C.
Published: April 2012

Magnetic resonance imaging (MRI)-based tracking is increasingly attracting attention as a means of better understanding stem cell dynamics in vivo. Intracellular labeling with micrometer-sized particles of iron oxide (MPIOs) provides a practical MRI-based approach due to superior detectability relative to smaller iron oxide particles. However, insufficient information is available about the general utility across cell types and the effects on cell vitality of MPIO labeling of human stem cells. We labeled six human cell types from different sources: mesenchymal stem cells derived from bone marrow (MSCs), mesenchymal stem cells derived from adipose tissue (ASCs), presumptive adult neural stem cells (ad-NSCs), fetal neural progenitor cells (f-NPCs), a glioma cell line (U87), and glioblastoma tumor stem cells (GSCs), with two different sizes of MPIOs (0.9 and 2.84 μm). Labeling and uptake efficiencies were highly variable among cell types. Several parameters of general cell function were tested in vitro. Only minor differences were found between labeled and unlabeled cells with respect to proliferation rate, mitotic duration, random motility, and capacity for differentiation to specific phenotypes. In vivo behavior was tested in chicken embryos and severe combined immunodeficient (SCID) mice. Postmortem histology showed that labeled cells survived and could integrate into various tissues. MRI-based tracking over several weeks in the SCID mice showed that labeled GSCs and f-NPCs injected into the brain exhibited translocations similar to those seen for unlabeled cells and as expected from migratory behavior described in previous studies. The results support MPIO-based cell tracking as a generally useful tool for studies of human stem cell dynamics in vivo.
Losartan Improves Adipose Tissue-Derived Stem Cell Niche by Inhibiting Transforming Growth Factor-β and Fibrosis in Skeletal Muscle Injury
Authors: Park Jin-Kyu , Ki Mi-Ran , Lee Eun-Mi , Kim Ah-Young , You Sang-Young , Han Seon-Young , Lee Eun-Joo , Hong Il-Hwa , Kwon Soon-Hak , Kim Seong-Jin , Rando Thomas A. , Jeong Kyu-Shik
Published: April 2012

Recently, adipose tissue-derived stem cells (ASCs) were emerged as an alternative, abundant, and easily accessible source of stem cell therapy. Previous studies revealed losartan (an angiotensin II type I receptor blocker) treatment promoted the healing of skeletal muscle by attenuation of the TGF-β signaling pathway, which inhibits muscle differentiation. Therefore, we hypothesized that a combined therapy using ASCs and losartan might dramatically improve the muscle remodeling after muscle injury. To determine the combined effect of losartan with ASC transplantation, we created a muscle laceration mouse model. EGFP-labeled ASCs were locally transplanted to the injured gastrocnemius muscle after muscle laceration. The dramatic muscle regeneration and the remarkably inhibited muscular fibrosis were observed by combined treatment. Transplanted ASCs fused with the injured or differentiating myofibers. Myotube formation was also enhanced by ASC+ satellite coculture and losartan treatment. Thus, the present study indicated that ASC transplantation effect for skeletal muscle injury can be dramatically improved by losartan treatment inducing better niche.
Human Neural Stem Cells Genetically Modified to Express Human Nerve Growth Factor (NGF) Gene Restore Cognition in the Mouse with Ibotenic Acid-Induced Cognitive Dysfunction
Authors: Lee Hong J. , Lim In J. , Park Seung W. , Kim Yun B. , Ko Yong , Kim Seung U.
Published: April 2012

Alzheimer's disease (AD) is characterized by degeneration and loss of neurons and synapses throughout the brain, causing the progressive decline in cognitive function leading to dementia. No effective treatment is currently available. Nerve growth factor (NGF) therapy has been proposed as a potential treatment of preventing degeneration of basal forebrain cholinergic neurons in AD. In a previous study, AD patient's own fibroblasts genetically modified to produce NGF were transplanted directly into the brain and protected cholinergic neurons from degeneration and improved cognitive function in AD patients. In the present study, human neural stem cells (NSCs) are used in place of fibroblasts to deliver NGF in ibotenic acid-induced learning-deficit rats. Intrahippocampal injection of ibotenic acid caused severe neuronal loss, resulting in learning and memory deficit. NGF protein released by F3.NGF human NSCs in culture medium is 10-fold over the control F3 naive NSCs at 1.2 μg/106 cells/day. Overexpression of NGF in F3.NGF cells induced improved survival of NSCs from cytotoxic agents H2O2, Aβ, or ibotenic acid in vitro. Intrahippocampal transplantation of F3.NGF cells was found to express NGF and fully improved the learning and memory function of ibotenic acid-challenged animals. Transplanted F3.NGF cells were found all over the brain and differentiated into neurons and astrocytes. The present study demonstrates that human NSCs overexpressing NGF improve cognitive function of learning-deficit model mice.
Adipose-Derived Stem Cells Improve Renal Function in a Mouse Model of IgA Nephropathy
Authors: Hyun Young Youl , Kim In Ok , Kim Mi Hyung , Nam Deok Hwa , Lee Mi Hwa , Kim Jung Eun , Song Hye Kyoung , Cha Jin Joo , Kang Young Sun , Lee Ji Eun , Kim Hyun Wook , Han Jee Young , Cha Dae Ryong
Published: April 2012

T-cell dysregulation plays an important role in the pathogenesis of immunoglobulin A nephropathy (IgAN). Adipose-derived stem cells (ASCs) have been reported to be able to prevent tissue damage through immune-modulating effects. To evaluate the effects of ASCs in high IgA ddY (HIGA) mice, ASCs were isolated from HIGA mice with different stages of IgAN before and after disease onset. ASCs were injected at a dose of 5 × 106cells/kg body weight through the tail vein every 2 weeks for 3 months. Although the administered ASCs were rarely detected in the glomeruli, 24-h proteinuria was markedly decreased in all ASC-treated groups. Although glomerular deposition of IgA was not significantly different among groups, mesangial proliferation and glomerulosclerosis were dramatically decreased in most ASC treatment groups. In addition, levels of fibrotic and inflammatory molecules were markedly decreased by ASC treatment. Interestingly, ASC therapy significantly decreased Th1 cytokine activity in the kidney and caused a shift to Th2 responses in spleen T-cells as determined by FACS analysis. Furthermore, conditioned media from ASCs abrogated aggregated IgA-induced Th1 cytokine production in cultured HIGA mesangial cells. These results suggest that the beneficial effects of ASC treatment in IgAN occur via paracrine mechanisms that modulate the Th1/Th2 cytokine balance. ASCs are therefore a promising new therapeutic agent for the treatment of IgAN.
Human Adipose-Derived Stromal Cells for Cell-Based Therapies in the Treatment of Systemic Sclerosis
Authors: Scuderi Nicolò , Ceccarelli Simona , Onesti Maria Giuseppina , Fioramonti Paolo , Guidi Chiara , Romano Ferdinando , Frati Luigi , Angeloni Antonio , Marchese Cinzia
Published: April 2012

The present study was designed to evaluate the clinical outcome of cell-based therapy with cultured adipose-derived stromal cells (ASCs) for the treatment of cutaneous manifestations in patients affected by systemic sclerosis (SSc). ASCs have an extraordinary developmental plasticity, including the ability to undergo multilineage differentiation and self-renewal. Moreover, ASCs can be easily harvested from small volumes of liposuction aspirate, showing great in vitro viability and proliferation rate. Here we isolated, characterized, and expanded ASCs, assessing both their mesenchymal origin and their capability to differentiate towards the adipogenic, osteogenic, and chondrogenic lineage. We developed an effective method for ASCs transplantation into sclerodermic patients by means of a hyaluronic acid (HA) solution, which allowed us to achieve precise structural modifications. ASCs were isolated from subcutaneous adipose tissue of six sclerodermic patients and cultured in a chemical-defined medium before autologous transplantation to restore skin sequelae. The results indicated that transplantation of a combination of ASCs in HA solution determined a significant improvement in tightening of the skin without complications such as anechoic areas, fat necrosis, or infections, thus suggesting that ASCs are a potentially valuable source of cells for skin therapy in rare diseases such as SSc and generally in skin disorders.
Pure-Tone Hearing Asymmetry: A Logistic Approach Modeling Age, Sex, and Noise Exposure History
Authors: Zapala David A. , Criter Robin E. , Bogle Jamie M. , Lundy Larry B. , Cevette Michael J. , Bauch Christopher D.
Published: April 2012

Background:Asymmetric hearing loss (AHL) can be an early sign of vestibular schwannoma (VS). However, recognizing VS-induced AHL is challenging. There is no universally accepted definition of a “medically significant pure-tone hearing asymmetry,” in part because AHL
is a common feature of medically benign forms of hearing loss (e.g., age- or firearm-related hearing loss). In most cases, the determination that an observed AHL does not come from a benign cause involves subjective clinical judgment.Purpose:Our purpose was threefold: (1) to quantify
hearing asymmetry distributions in a large group of patients with medically benign forms of hearing loss, stratifying for age, sex, and noise exposure history; (2) to assess how previously proposed hearing asymmetry calculations segregate tumor from nontumor cases; and (3) to present the results
of a logistic regression method for defining hearing asymmetry that incorporates age, sex, and noise information.Research Design:Retrospective chart review.Study Sample:Five thousand six hundred and sixty-one patients with idiopathic, age- or noise exposure-related hearing loss
and 85 untreated VS patients.Data Collection and Analysis:Audiometric, patient history, and clinical impression data were collected from 22,785 consecutive patient visits to the audiology section at Mayo Clinic in Florida from 2006 to 2009 to screen for eligibility. Those eligible were
then stratified by VS presence, age, sex, and self-reported noise exposure history. Pure-tone asymmetry distributions were analyzed. Audiometric data from VS diagnoses were used to create four additional audiograms per patient to model the hypothetical development of AHL prior to the actual
hearing test. The ability of 11 previously defined hearing asymmetry calculations to distinguish between VS and non-VS cases was described. A logistic regression model was developed that integrated age, sex, and noise exposure history with pure-tone asymmetry data. Regression model performance
was then compared to existing asymmetry calculation methods.Results:The 11 existing pure-tone asymmetry calculations varied in tumor detection performance. Age, sex, and noise exposure history helped to predict benign forms of hearing asymmetry. The logistic regression model outperformed
existing asymmetry calculations and better accounted for normal age-, sex-, and noise exposure-related asymmetry variability.Conclusions:Our logistic regression asymmetry method improves the clinician's ability to estimate risk of VS, in part by integrating categorical patient history
and numeric test data. This form of modeling can enhance clinical decision making in audiology and otology.
Efavirenz in an Obese HIV-Infected Patient – a Report and An In Vitro–In Vivo Extrapolation Model Indicate Risk of Underdosing
Authors: De Roche Mirjam , Siccardi Marco , Stoeckle Marcel , Livio Françoise , Back David , Battegay Manuel , Marzolini Catia
Published: April 2012

Here, we report suboptimal efavirenz exposure in an obese patient treated with the standard 600 mg dose. Tripling the dose allowed attainment of therapeutic efavirenz concentrations. We developed an in vitro–in vivo extrapolation model to quantify dose requirements in obese individuals. Obesity represents a risk factor for antiretroviral therapy underdosing.
Stem Cell Factor Programs the Mast Cell Activation Phenotype
Authors: Ito Tomonobu , Smrž Daniel , Jung Mi-Yeon , Bandara Geethani , Desai Avanti , Smržová Šárka , Kuehn Hye Sun , Beaven Michael A. , Metcalfe Dean D. , Gilfillan Alasdair M.
Published: April 2012

Mast cells, activated by Ag via FcεRI, release an array of proinflammatory mediators that contribute to allergic disorders, such as asthma and anaphylaxis. The KIT ligand, stem cell factor (SCF), is critical for mast cell expansion, differentiation, and survival, and under acute conditions, it enhances mast cell activation. However, extended SCF exposure in vivo conversely protects against fatal Ag-mediated anaphylaxis. In investigating this dichotomy, we identified a novel mode of regulation of the mast cell activation phenotype through SCF-mediated programming. We found that mouse bone marrow-derived mast cells chronically exposed to SCF displayed a marked attenuation of FcεRI-mediated degranulation and cytokine production. The hyporesponsive phenotype was not a consequence of altered signals regulating calcium flux or protein kinase C, but of ineffective cytoskeletal reorganization with evidence implicating a downregulation of expression of the Src kinase Hck. Collectively, these findings demonstrate a major role for SCF in the homeostatic control of mast cell activation with potential relevance to mast cell-driven disease and the development of novel approaches for the treatment of allergic disorders.
Tumor-Expressed Inducible Nitric Oxide Synthase Controls Induction of Functional Myeloid-Derived Suppressor Cells through Modulation of Vascular Endothelial Growth Factor Release
Authors: Jayaraman Padmini , Parikh Falguni , Lopez-Rivera Esther , Hailemichael Yared , Clark Amelia , Ma Ge , Cannan David , Ramacher Marcel , Kato Masashi , Overwijk Willem W. , Chen Shu-Hsia , Umansky Viktor Y. , Sikora Andrew G.
Published: April 2012

Inducible NO synthase (iNOS) is a hallmark of chronic inflammation that is also overexpressed in melanoma and other cancers. Whereas iNOS is a known effector of myeloid-derived suppressor cell (MDSC)-mediated immunosuppression, its pivotal position at the interface of inflammation and cancer also makes it an attractive candidate regulator of MDSC recruitment. We hypothesized that tumor-expressed iNOS controls MDSC accumulation and acquisition of suppressive activity in melanoma. CD11b+GR1+ MDSC derived from mouse bone marrow cells cultured in the presence of MT-RET-1 mouse melanoma cells or conditioned supernatants expressed STAT3 and reactive oxygen species (ROS) and efficiently suppressed T cell proliferation. Inhibition of tumor-expressed iNOS with the small molecule inhibitor L-NIL blocked accumulation of STAT3/ROS-expressing MDSC, and abolished their suppressive function. Experiments with vascular endothelial growth factor (VEGF)-depleting Ab and recombinant VEGF identified a key role for VEGF in the iNOS-dependent induction of MDSC. These findings were further validated in mice bearing transplantable MT-RET-1 melanoma, in which L-NIL normalized elevated serum VEGF levels; downregulated activated STAT3 and ROS production in MDSC; and reversed tumor-mediated immunosuppression. These beneficial effects were not observed in iNOS knockout mice, suggesting L-NIL acts primarily on tumor- rather than host-expressed iNOS to regulate MDSC function. A significant decrease in tumor growth and a trend toward increased tumor-infiltrating CD8+ T cells were also observed in MT-RET transgenic mice bearing spontaneous tumors. These data suggest a critical role for tumor-expressed iNOS in the recruitment and induction of functional MDSC by modulation of tumor VEGF secretion and upregulation of STAT3 and ROS in MDSC.
Mast Cell TLR2 Signaling Is Crucial for Effective Killing of Francisella tularensis
Authors: Rodriguez Annette R. , Yu Jieh-Juen , Guentzel M. Neal , Navara Christopher S. , Klose Karl E. , Forsthuber Thomas G. , Chambers James P. , Berton Michael T. , Arulanandam Bernard P.
Published: April 2012

TLR signaling is critical for early host defense against pathogens, but the contributions of mast cell TLR-mediated mechanisms and subsequent effector functions during pulmonary infection are largely unknown. We have previously demonstrated that mast cells, through the production of IL-4, effectively control Francisella tularensis replication. In this study, the highly human virulent strain of F. tularensis SCHU S4 and the live vaccine strain were used to investigate the contribution of mast cell/TLR regulation of Francisella. Mast cells required TLR2 for effective bacterial killing, regulation of the hydrolytic enzyme cathepsin L, and for coordination and trafficking of MHC class II and lysosomal-associated membrane protein 2. Infected TLR2−/− mast cells, in contrast to wild-type and TLR4−/− cells, lacked detectable IL-4 and displayed increased cell death with a 2–3 log increase of F. tularensis replication, but could be rescued with rIL-4 treatment. Importantly, MHC class II and lysosomal-associated membrane protein 2 localization with labeled F. tularensis in the lungs was greater in wild-type than in TLR2−/− mice. These results provide evidence for the important effector contribution of mast cells and TLR2-mediated signaling on early innate processes in the lung following pulmonary F. tularensis infection and provide additional insight into possible mechanisms by which intracellular pathogens modulate respiratory immune defenses.
A2A Adenosine Receptor Signaling in Lymphocytes and the Central Nervous System Regulates Inflammation during Experimental Autoimmune Encephalomyelitis
Authors: Mills Jeffrey H. , Kim Do-Geun , Krenz Antje , Chen Jiang-Fan , Bynoe Margaret S.
Published: April 2012

Extracellular adenosine has an important role in regulating the severity of inflammation during an immune response. Although there are four adenosine receptor (AR) subtypes, the A2AAR is both highly expressed on lymphocytes and known as a prime mediator of adenosine’s anti-inflammatory effects. To define the importance of A2AAR signaling during neuroinflammatory disease progression, we used the experimental autoimmune encephalomyelitis (EAE) animal model for multiple sclerosis. In EAE induction experiments, A2AAR antagonist treatment protected mice from disease development and its associated CNS lymphocyte infiltration. However, A2AAR−/− mice developed a more severe acute EAE phenotype characterized by more proinflammatory lymphocytes and activated microglia/macrophages. Interestingly, very high levels of A2AAR were expressed on the choroid plexus, a well-established CNS lymphocyte entry point. To determine the contribution of A2AAR signaling in lymphocytes and the CNS during EAE, we used bone marrow chimeric mice. Remarkably, A2AAR−/− donor hematopoietic cells potentiated severe EAE, whereas lack of A2AAR expression on nonhematopoietic cells protected against disease development. Although no defect in the suppressive ability of A2AAR−/− regulatory T cells was observed, A2AAR−/− lymphocytes were shown to proliferate more and produced more IFN-γ following stimulation. Despite this more proinflammatory phenotype, A2AAR antagonist treatment still protected against EAE when A2AAR−/− lymphocytes were adoptively transferred to T cell-deficient A2AAR+/+ mice. These results indicate that A2AAR expression on nonimmune cells (likely in the CNS) is required for efficient EAE development, while A2AAR lymphocyte expression is essential for limiting the severity of the inflammatory response.
A Novel Th Cell Epitope of Candida albicans Mediates Protection from Fungal Infection
Authors: Bär Eva , Gladiator André , Bastidas Sonia , Roschitzki Bernd , Acha-Orbea Hans , Oxenius Annette , LeibundGut-Landmann Salomé
Published: April 2012

Fungal pathogens are a frequent cause of opportunistic infections. They live as commensals in healthy individuals but can cause disease when the immune status of the host is altered. T lymphocytes play a critical role in pathogen control. However, specific Ags determining the activation and function of antifungal T cells remain largely unknown. By using an immunoproteomic approach, we have identified for the first time, to our knowledge, a natural T cell epitope from Candida albicans. Isolation and sequencing of MHC class II-bound ligands from infected dendritic cells revealed a peptide that was recognized by a major population of all Candida-specific Th cells isolated from infected mice. Importantly, human Th cells also responded to stimulation with the peptide in an HLA-dependent manner but without restriction to any particular HLA class II allele. Immunization of mice with the peptide resulted in a population of epitope-specific Th cells that reacted not only with C. albicans but also with other clinically highly relevant species of Candida including the distantly related Candida glabrata. The extent of the reaction to different Candida species correlated with their degree of phylogenetic relationship to C. albicans. Finally, we show that the newly identified peptide acts as an efficient vaccine when used in combination with an adjuvant inducing IL-17A secretion from peptide-specific T cells. Immunized mice were protected from fatal candidiasis. Together, these results uncover a new immune determinant of the host response against Candida ssp. that could be exploited for the development of antifungal vaccines and immunotherapies.
Topical Azithromycin 1% in acute management of inflammatory pterygium
Authors: Hua Len V , Halvorson Ami , Lonsberry Blair , Horn Fraser
Published: April 2012

The purpose of the article is to investigate the effects of topical azithromycin 1% (Azasite) in treating acute ocular inflammation related to long standing pterygium. A prospective interventional study of 8 consecutive cases with pterygium presenting to our University Eye Clinics over the period of one month with acute symptoms of red eye(s) and irritation. After patient education and receipt of consent to the study, patients were treated with topical azithromycin 1% (Azasite) twice a day for the first two days and once a day for the next 12 days. Anterior segment photo was taken before treatment and 3-day and/or 7-day after treatment in addition to eye examination. Six out of the eight cases reported of significant improvement or resolution of signs and symptoms on the follow up visits. One severe case did not respond as well after a week of treatment and was successfully managed by topical prednisolone. Another case did not comply with the study protocol. In this small pilot study, Azasite was effective in management of acute mild to moderate ocular inflammation triggered by ocular surface disease, including pterygium. Severe ocular inflammation may require more potent anti-inflammatory therapy like topical steroids.
Usefulness of anterior chamber optical coherence tomography in glaucoma
Authors: Bogado Marco , Navero Jose
Published: April 2012

The aim of the study is to describe and assess whether anterior chamber optical coherence tomography (OCT) has the capacity to produce high quality images of patients with different angle configurations and to follow bleb’s morphology after glaucoma surgery. The eyes of two patients were evaluated with Visante OCT (Carl Zeiss Meditec, Inc., Dublin, CA, USA) in emergency pupillary block and in follow-up after nonpenetrating deep sclerectomy. Visante OCT provided high-resolution information regarding iris configuration and was useful to explore bleb’s morphology in patients after glaucoma surgery. Visante OCT offers a quick non-contact method of assessing the configuration of the anterior chamber angle. Despite its limitations, it may be of help during routine clinical evaluation of patients with glaucoma.
Battling with Rising Prevalence of Gestational Diabetes Mellitus: Screening and Diagnosis
Authors: Divakar Hema , Manyonda Issac
Published: April 2012

Introduction

Gestational diabetes affects 2 to 4% of all pregnancies, with an increased risk of developing diabetes for both the mother and the child. The prevalence of gestational diabetes mellitus (GDM) in India varied from 3.8 to 21% with the geographical locations and diagnostic methods used.

Objective

To study the differences in the type of tests and timing of tests; failure to screen and diagnose; this could explain the varying prevalence reported from different centers indicating that there could be an underestimation due to missed diagnosis.

Materials and methods

A 15-question online survey (www.abcofobg.com) was developed to assess providers’ knowledge; practices and attitudes related to the screening and management of GDM. All data were entered into an electronic database without personal identifiers, to maintain confidentiality. The data was analyzed by using SPSS version 16.0.

Results

A total of 584 respondents were participated in the survey. Overall, 82.14% of doctors screened all their antenatal patients for GDM. A total of 65.48% of them ordered for a blood glucose test during first antenatal visit even in first trimester. During screening, 39.29% of doctors preferred 50 gm glucose challenge test and 26.19% of doctors preferred 75 gm glucose and 2-hour reading. When the test was positive, 47.62% of doctors ordered for 100 gm oral glucose tolerance test (OGTT) and 38.1% for 75 gm OGTT. A total of 40.48% of doctors used C and C criteria, 26.4 % used National Diabetes Data Group (NDDG) criteria and 32.14% took 140 at 2 hours for 75 gm OGTT criteria of cutoff to diagnose the GDM.

Conclusion

Preventive measures against type 2 diabetes (T2DM) should start with proper screening and diagnosis during pregnancy. Many tests with varied criteria are in use. There is an urgent need to institute uniform standards for the timing and type of tests done for identifying the cases of GDM. This is crucial to reduce the burden of T2DM in India for now and for generations to come.
Is Advanced Paternal Age associated with Fetal Growth and Adverse Neonatal Outcomes? A Case-Control Study
Authors: Surapaneni Tarakeswari , Dudlani Manisha
Published: April 2012

Aim

To determine associations of advanced paternal age with fetal growth and adverse neonatal outcomes.

Methods

A hospital-based unmatched case-control study with random selection of controls. Fetal growth was determined by serial ultrasound measurements and growth was classified at birth by a neonatalogist based on the Lubchenco charts. Advanced paternal age was explored using two cutoffs (35 and 40 years). Likelihood ratios, unadjusted and adjusted odds ratios and the 95% confidence intervals around point estimates are presented.

Results

The study covered 218 pregnant women that included 137 (63.72%) pregnant women who delivered a live AGA/LGA baby and 78 (36.28%) pregnant women who delivered a live small for gestational age baby and 45 (20.64%) fathers with advanced paternal age based on a cutoff of ≥ 40 years and 73 (33.49%) fathers with advanced paternal age based on a age cutoff ≥ 35 years. Although advanced paternal age (both ≥ 35 and ≥ 40 years) was protective for small for gestational age babies in a bivariate analysis, the association was not significant in a multivariate regression model that adjusted for maternal age, parity, diabetes and gestational age at delivery. Advanced paternal age (both ≥ 35 and ≥ 40 years) did not show a clinically meaningful positive or negative likelihood ratio with other adverse neonatal outcomes.

Conclusion

Paternal age does not seem to be associated with fetal growth or adverse neonatal outcomes; however, a prospective cohort study is necessary to provide further evidence after controlling for potential confounders.
Nudging technique for scale bridging in air quality/climate atmospheric composition modelling
Authors: Maurizi A. , Russo F. , D'Isidoro M. , Tampieri F.
Published: April 2012

Abstract. The interaction between air quality and climate involves dynamical scales that cover a very wide range. Bridging these scales in numerical simulations is fundamental in studies devoted to megacity/hot-spot impacts on larger scales. A technique based on nudging is proposed as a bridging method that can couple different models at different scales. Here, nudging is used to force low resolution chemical composition models with a run of a high resolution model on a critical area. A one-year numerical experiment focused on the Po Valley hot spot is performed using the BOLCHEM model to asses the method. The results show that the model response is stable to perturbation induced by the nudging and that, taking the high resolution run as a reference, performances of the nudged run increase with respect to the non-forced run. The effect outside the forcing area depends on transport and is significant in a relevant number of events although it becomes weak on seasonal or yearly basis.
Regional radiative impact of volcanic aerosol from the 2009 eruption of Mt. Redoubt
Authors: Young C. L. , Sokolik I. N. , Dufek J.
Published: April 2012

Abstract. High northern latitude eruptions have the potential to release volcanic aerosol into the Arctic environment, perturbing the Arctic's climate system. We present assessments of shortwave (SW), longwave (LW) and net direct aerosol radiative forcing efficiencies and atmospheric heating/cooling rates caused by volcanic aerosol from the 2009 eruption of Mt. Redoubt by performing radiative transfer modeling constrained by NASA A-Train satellite data. The optical properties of volcanic aerosol were calculated by introducing a compositionally resolved microphysical model developed for both ash and sulfates. Two compositions of volcanic aerosol were considered in order to examine a fresh, ash rich plume and an older, ash poor plume. Optical models were incorporated into a modified version of the SBDART radiative transfer model. Our results indicate that environmental conditions, such as surface albedo and solar zenith angle (SZA), can influence the sign and the magnitude of the radiative forcing at the top of the atmosphere (TOA) and at the surface and the magnitude of the forcing in the aerosol layer. We find that a fresh, thin plume (~2.5–7 km) at an AOD (550 nm) range of 0.18–0.58 and SZA = 55° over snow cools the surface and warms the TOA, but the opposite effect is seen for TOA by the same layer over ocean. The layer over snow also warms by 64 W m−2AOD−1 more than the same plume over seawater. The layer over snow at SZA = 75° warms the TOA 96 W m−2AOD−1 less than it would at SZA = 55° over snow, and there is instead warming at the surface. We also find that plume aging can alter the magnitude of the radiative forcing. An aged plume over snow at SZA = 55° would warm the TOA and layer by 146 and 143 W m−2AOD−1 less than the fresh plume, while the aging plume cools the surface 3 W m−2AOD−1 more. Comparing results for the thin plume to those for a thick plume (~3–20 km), we find that the fresh, thick plume with AOD(550 nm) = 3, over seawater, and SZA = 55° heats the upper part of the plume in the SW ~28 K day−1 more and cools in the LW by ~6.3 K day−1 more than a fresh, thin plume under the same environmental conditions. We compare our assessments with those reported for other aerosols typical to the Arctic environment (smoke from wildfires, Arctic haze, and dust) to demonstrate the importance of volcanic aerosols.
Impact of the Desert dust on the summer monsoon system over Southwestern North America
Authors: Zhao C. , Liu X. , Leung L. R.
Published: April 2012

Abstract. The radiative forcing of dust emitted from the Southwest United States (US) deserts and its impact on monsoon circulation and precipitation over the North America monsoon (NAM) region are simulated using a coupled meteorology and aerosol/chemistry model (WRF-Chem) for 15 years (1995–2009). During the monsoon season, dust has a cooling effect (−0.90 W m−2) at the surface, a warming effect (0.40 W m−2) in the atmosphere, and a negative top-of-the-atmosphere (TOA) forcing (−0.50 W m−2) over the deserts on 24-h average. Most of the dust emitted from the deserts concentrates below 800 hPa and accumulates over the western slope of the Rocky Mountains and Mexican Plateau. The absorption of shortwave radiation by dust heats the lower atmosphere by up to 0.5 K day−1 over the western slope of the Mountains. Model sensitivity simulations with and without dust for 15 summers (June-July-August) show that dust heating of the lower atmosphere over the deserts strengthens the low-level southerly moisture fluxes on both sides of the Sierra Madre Occidental. It also results in an eastward migration of NAM-driven moisture convergence over the western slope of the Mountains. These monsoonal circulation changes lead to a statistically significant increase of precipitation by up to ~40 % over the eastern slope of the Mountains (Arizona-New~Mexico-Texas regions). This study highlights the interaction between dust and the NAM system and motivates further investigation of possible dust feedback on monsoon precipitation under climate change and the mega-drought conditions projected for the future.