bluuebunny/crossref_metadata_2025 huggingface dataset:
N′1,N′3-Dimethyl-N′1,N′3-bis(phenylcarbonothioyl) Propanedihydrazide (Elesclomol) Selectively Kills Cisplatin Resistant Lung Cancer Cells through Reactive Oxygen Species (ROS)
Authors: Wangpaichitr Medhi , Wu Chunjing , You Min , Maher Johnathan C. , Dinh Vy , Feun Lynn G. , Savaraj Niramol
Published: December 2009

Cisplatin is an important chemotherapeutic agent in lung cancer treatment. The mechanism of drug resistance to cisplatin is complex and historically has been difficult to overcome. We report here that cisplatin resistant lung cancer cell lines possess high basal levels of reactive oxygen species (ROS) when compared to normal cells and their parental cell counterparts. These resistant cells also have low thioredoxin (TRX) levels which may be one of the contributory factors to high ROS. N′1,N′3-dimethyl-N′1,N'3-bis(phenylcarbonothioyl) propanedihydrazide (elesclomol), an agent known to increase ROS is selectively toxic to cisplatin-resistant cells, while sparing normal cells and the parental counterpart. The cytotoxic effect of elesclomol in resistant cells is accompanied by further decreases in TRX and glutathione (GSH) antioxidant systems, while opposite results were found in parental cells. The ID50 of elesclomol in cisplatin-resistant cells ranged from 5–10 nM, which is well within clinically achievable ranges. N-Acetylcysteine (NAC), which is known to neutralize ROS, can abolish the cytotoxic effect of elesclomol, suggesting that the cytotoxic effect results from increased ROS. Overall, our data suggest that elesclomol selectively kills cisplatin-resistant tumor cells through increased ROS. This agent may hold potential to overcome cisplatin resistance and should be further explored to treat patients who have failed cisplatin therapy.
Sustainability between Necessity, Contingency and Impossibility
Authors: Bruckmeier Karl
Published: December 2009

Sustainable use of natural resources seems necessary to maintain functions and services of eco- and social systems in the long run. Efforts in policy and science for sustainable development have shown the splintering of local, national and global strategies. Sustainability becomes contingent and insecure with the actors´ conflicting knowledge, interests and aims, and seems even impossible through the “rebound”-effect. To make short and long term requirements of sustainability coherent requires critical, comparative and theoretical analysis of the problems met. For this purpose important concepts and theories are discussed in this review of recent interdisciplinary literature about resource management.
Clinical Features and Prognosis of Late-onset Systemic Lupus Erythematosus: Results from the 1000 Faces of Lupus Study
Authors: LALANI SHELIZA , POPE JANET , de LEON FAYE , PESCHKEN CHRISTINE
Published: December 2009

Objective.

There is controversy whether older-onset systemic lupus erythematosus (SLE) is associated with a different, more benign disease course than in younger-onset SLE. Our objective was to characterize the clinical features and prognosis of late-onset SLE in a large, multicenter cohort.

Methods.

We studied adult-onset lupus in the 1000 Canadian Faces of Lupus cohort (n = 1528) of whom 10.5% had onset at age ≥ 50 years versus a control group with onset at < 50 years.

Results.

Disease duration was different in early- and late-onset groups (15 yrs in early vs 9.3 yrs in late; p < 0.001). Caucasians were represented more in the later-onset SLE group (55.6% vs 74.5%), while Asians and Blacks were more prevalent in the younger group. Younger-onset SLE subjects fulfilled more American College of Rheumatology criteria for SLE (< 50 yrs: 5.98 ± 1.68; ≥ 50 yrs: 5.24 ± 1.44; p < 0.0001). Despite an equal prevalence of anti-dsDNA, the younger-onset group more often had positive anti-Smith autoantibody, ribonucleoprotein, and hypocomplementemia, and more nephritis, rash, and cytopenias than the older-onset group. However, disease activity and damage accrual were higher in the older-onset group. The older patients received less prednisone and immunosuppressives (current and ever-use). As expected, comorbidity was higher in the older-onset SLE group.

Conclusion.

This study suggests that older age-onset SLE is not benign. There may be an interaction between lupus and age in which, although there is less lupus nephritis in the elderly, more disease activity and damage are present.
Possible Reactivation of Potential Hepatitis B Virus Occult Infection by Tumor Necrosis Factor-α Blocker in the Treatment of Rheumatic Diseases
Authors: KIM YUN JUNG , BAE SANG-CHEOL , SUNG YOON-KYOUNG , KIM TAE-HWAN , JUN JAE-BUM , YOO DAE-HYUN , KIM TAE YEOB , SOHN JOO HYUN , LEE HYE-SOON
Published: December 2009

Objective.

To assess the safety of anti-tumor necrosis factor (TNF-α) therapy in patients with rheumatic diseases in terms of the reactivation of potential hepatitis B virus (HBV) occult infection.

Methods.

Patients who had taken anti-TNF-α for the treatment of rheumatic diseases from January 2002 to May 2008 were included in the study. In this patient group, we retrospectively investigated a series of serum aminotransferase levels, HBV serologic status, the type of anti-TNF-α therapy, duration of the anti-TNF-α treatment, and concurrent use of hepatotoxic drugs.

Results.

A total of 266 cases were documented using 3 serologic markers for HBV infection: HBV surface antigen (HBsAg), HBV surface antibody (HBsAb), and HBV core IgG Ab (HBcAb). Of these, 8 cases had chronic hepatitis B (HBsAg+), 170 cases were HBcAb-negative, and 88 cases were identified as having potential HBV occult infections represented by HBsAg-negative and HBcAb-positive, irrespective of the status of the HBsAb.

The frequency of clinically significant (> 2 times normal value) and persistent increase (> 2 consecutive tests) of aminotransferase levels was significantly higher in the group with a potential HBV occult infection compared to the HBcAb-negative group. In the multiple logistic regression analysis controlling for various potential confounding factors such as prophylactic anti-tuberculosis medication, methotrexate, nonsteroidal antiinflammatory drugs, and the type of anti-TNF-α therapy, only potential HBV occult infection was a significant risk factor for abnormal liver function test (LFT).

Conclusion.

All rheumatic patients who plan to take anti-TNF-α treatment should undergo a test for HBV serology, including HBcAb, and have a close followup with an LFT test during therapy. Further prospective studies for hepatitis B viral load using HBV-polymerase chain reaction in patients who are HbcAb positive are needed to identify whether the abnormal LFT comes from the reactivation of occult HBV infection.
Medium-Chain Acyl-CoA Dehydrogenase Deficiency in an Infant with Dilated Cardiomyopathy
Authors: Marcì Marcello , Ajovalasit Patrizia
Published: December 2009

We report about an infant affected by dilated cardiomyopathy (CMP) in whom metabolic investigations evidenced medium-chain-acyl-CoA dehydrogenase deficiency (MCADD), that is one of three types of inherited disorders of mitochondrial fatty-acid -oxidation. Long-chain and very long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficits are recognized as responsible of hypertrophic or, less frequently, dilated cardiomyopathy (CMP) in childhood. Otherwise, to our knowledge, no case of MCADD associated to dilated CMP has been reported in literature.
A General Approach for Fabricating Arc‐Shaped Composite Nanowire Arrays by Pulsed Laser Deposition
Authors: Shen Yue , Hong Jung‐Il , Xu Sheng , Lin Shisheng , Fang Hao , Zhang Su , Ding Yong , Snyder Robert L. , Wang Zhong Lin
Published: December 2009

Here, a new method is demonstrated that uses sideways pulsed laser deposition to deliberately bend nanowires into a desired shape after growth and fabricate arc‐shaped composite nanowire arrays of a wide range of nanomaterials. The starting nanowires can be ZnO, but the materials to be deposited can be metallic, semiconductor, or ceramic depending on the application. This method provides a general approach for rational fabrication of a wide range of side‐by‐side or “core–shell” nanowire arrays with controllable degree of bending and internal strain. Considering the ZnO is a piezoelectric and semiconductive material, its electrical properties change when deformed. This technique has potential applications in tunable electronics, optoelectronics, and piezotronics.
Dasatinib 140 mg once daily versus 70 mg twice daily in patients with Ph‐positive acute lymphoblastic leukemia who failed imatinib: Results from a phase 3 study
Authors: Lilly Michael B. , Ottmann Oliver G. , Shah Neil P. , Larson Richard A. , Reiffers Josy J. , Ehninger Gerhard , Müller Martin C. , Charbonnier Aude , Bullorsky Eduardo , Dombret Herve , Brigid Bradley‐Garelik Mary , Zhu Chao , Martinelli Giovanni
Published: December 2009

Dasatinib 70 mg twice daily is indicated for Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ ALL) intolerant or resistant to imatinib. In patients with chronic‐phase chronic myelogenous leukemia, once‐daily dosing has similar efficacy with improved safety, compared with twice‐daily dosing. A phase 3 study (n = 611) assessed the efficacy and safety of dasatinib 140 mg once daily versus 70 mg twice‐daily in patients with advanced phase chronic myelogenous leukemia or Ph+ ALL resistant or intolerant to imatinib. Here, results from the Ph+ ALL subset (n = 84) with a 2‐year follow‐up are reported. Patients were randomly assigned to receive dasatinib either 140 mg once daily (n = 40) or 70 mg twice daily (n = 44). The rate of confirmed major hematologic response with once‐daily dosing (38%) was similar to that with twice‐daily dosing (32%). The rate of major cytogenetic response with once‐daily dosing (70%) was higher than that with twice‐daily dosing (52%). Compared with the twice‐daily schedule, the once‐daily schedule had longer progression‐free survival (median, 3.0 months versus 4.0 months, respectively) and shorter overall survival (median, 9.1 months versus 6.5 months, respectively). Overall safety profiles were similar between two groups, with nonhematologic adverse events being mostly grade 1 or 2. Pleural effusion was less frequent with once‐daily dosing than with twice‐daily dosing (all grades, 18% versus 32%). Notably, none of the differences between the two schedules was statistically significant. Compared with the 70 mg twice daily, dasatinib 140 mg once daily had similar overall efficacy and safety in patients with imatinib‐resistant or intolerant Ph+ ALL. (clinicaltrials.gov identifier: NCT00123487). Am. J. Hematol. 2010. © 2009 Wiley‐Liss, Inc.
Case–control study of pleural mesothelioma in workers with social security in Mexico
Authors: Aguilar‐Madrid Guadalupe , Robles‐Pérez Eduardo , Juárez‐Pérez Cuauhtémoc Arturo , Alvarado‐Cabrero Isabel , Rico‐Méndez Flavio Gerardo , Javier Kelly‐García
Published: December 2009

Background

Environmental and occupational exposure to asbestos in Mexico in the past has been a cause of deaths and health damages. Its magnitude is unknown to date. Our objective was to identify the proportion of cases of malignant pleural mesothelioma (MPM) that can be attributed to and occupational exposure to asbestos.

Methods

We carried out a case–control study of MPM in 472 workers insured by the Mexican Institute of Social Security, all Valley of Mexico residents, with 119 incident cases and 353 controls. Cases were histologically confirmed. Participants were questioned concerning their occupational history and sociodemographic data. Assignment to one of the four exposures was performed qualitatively by an expert hygienist. Odds ratios (ORs) and attributable risks (ARs) were calculated using a non‐conditional logistic regression model.

Results

A total of 80.6% of cases and 31.5% of controls had occupational exposure to asbestos. ORs were adjusted for age and gender and by exposure category, and exhibited an increase with probability of exposure as follows: 3.7(95% CI 1.3–10.4) for the likely category and 14.3(95% CI 8–26) for the certain category; AR in the group occupationally exposed to asbestos was 83.2%, and the population AR was 44%.

Conclusions

Our results show that the relationship between industrial uses of all forms of asbestos is generating an increase in mesothelioma‐related diseases and deaths among Mexican workers. As a public health policy, Mexico should prohibit the use of asbestos in all production processes with the aim of controlling the epidemic and preventing the occurrence of new cases of MPM. Am. J. Ind. Med. 53:241–251, 2010. © 2009 Wiley‐Liss, Inc.
Hearing problems among a cohort of nationally certified EMS professionals
Authors: Fernandez Antonio R. , Crawford J. Mac , Studnek Jonathan R. , Wilkins J.R.
Published: December 2009

Purpose

The objectives of this study were to estimate the prevalence of hearing problems among a national cohort of emergency medical service (EMS) professionals, determine factors associated with hearing problems, and estimate the percentage of EMS professionals who utilize hearing protection.

Methods

Utilizing results from a questionnaire, individuals who reported hearing problems were compared to individuals who had not. Multivariable logistic regression was performed to identify variables associated with hearing problems. Finally, items regarding use of hearing protection were assessed to estimate the percentage of usage among EMS professionals.

Results

In total, 1,058 (57%) participants responded to the questionnaire. Of those, 1,024 (97%) who completed the hearing problems question were utilized for analysis. There were 153 (14.9%) cases of self‐reported hearing problems. The final logistic regression model included lifetime occupational noise exposure 0.99 (95% CI = 0.9997–1.0002), report of previous back problems (odds ratio (OR) = 2.74, 95% CI = 1.8340–4.1042), large community size (OR = 1.67, 95% CI = 1.1211–2.4843), and minority status (OR = 0.61, 95% CI = 0.3719–0.9867). Finally, 213 (20.8%) individuals reported utilizing some form of hearing protection at their main EMS job.

Conclusion

The results from this analysis are the first national estimates of the prevalence of self reported hearing problems among EMS professionals. This study was also the first to estimate the percentage of EMS professionals who self reported the utilization of hearing protection. Am. J. Ind. Med. 53:264–275, 2010. © 2009 Wiley‐Liss, Inc.
Association of high‐dose bifonazole administration during early pregnancy and severe limb reduction defects in the newborn
Authors: Linder Nehama , Amarilla Mandola , Hernandez Adriana , Tamiri Tsippy , Sirota Lea , Klinger Gil , Levy Itzhak , Merlob Paul
Published: December 2009

BACKGROUND:

Neonatal limb reduction defects may be caused by exposure to an external agent. The azole derivatives are used in the treatment of systemic and dermal mycoses. Their relative teratogenic risk is still controversial.

CASES:

We describe two newborns with severe limb defects who were exposed to high doses of oral (an unacceptable route) and/or intravaginal bifonazole during the entire first trimester of pregnancy.

CONCLUSION:

Although only two cases are insufficient to establish a relationship, our data suggest thatmaternal intake of bifonazole in early pregnancy poses a risk of morphogenic malformations. The literature suggests several possible mechanisms. Birth Defects Research (Part A) 2010. © 2009 Wiley‐Liss, Inc.
Hyperosmotic stress induces autophagy and apoptosis in recombinant Chinese hamster ovary cell culture
Authors: Han Young Kue , Kim Yeon‐Gu , Kim Jee Yon , Lee Gyun Min
Published: December 2009

During recombinant Chinese hamster ovary (rCHO) cell culture, various events, such as feeding with concentrated nutrient solutions or the addition of base to maintain an optimal pH, increase the osmolality of the medium. To determine the effect of hyperosmotic stress on two types of programmed cell death (PCD), apoptosis and autophagy, of rCHO cells, two rCHO cell lines, producing antibody and erythropoietin, were subjected to hyperosmotic stress resulting from NaCl addition (310–610 mOsm/kg). For both rCHO cell lines, hyperosmolality up to 610 mOsm/kg increased cleaved forms of PARP, caspase‐3, caspase‐7, and fragmentation of chromosomal DNA, confirming the previous observation that apoptosis was induced by hyperosmotic stress. Concurrently, hyperosmolality increased the level of accumulation of LC3‐II, a widely used autophagic marker, which was determined by Western blot analysis and confocal microscopy. When glucose and glutamine concentrations were measured during the cultures, glucose and glutamine concentrations in the culture medium at various osmolalities (310–610 mOsm/kg) showed no significant differences. This result suggests that induction of PCD by hyperosmotic stress occurred independently of nutrient depletion. Taken together, autophagy as well as apoptosis was observed in rCHO cells subjected to hyperosmolality. Biotechnol. Bioeng. 2010;105: 1187–1192. © 2009 Wiley Periodicals, Inc.
Semi‐permeable membrane retention of synovial fluid lubricants hyaluronan and proteoglycan 4 for a biomimetic bioreactor
Authors: Blewis Megan E. , Lao Brian J. , Jadin Kyle D. , McCarty William J. , Bugbee William D. , Firestein Gary S. , Sah Robert L.
Published: December 2009

Synovial fluid (SF) contains lubricant macromolecules, hyaluronan (HA), and proteoglycan 4 (PRG4). The synovium not only contributes lubricants to SF through secretion by synoviocyte lining cells, but also concentrates lubricants in SF due to its semi‐permeable nature. A membrane that recapitulates these synovium functions may be useful in a bioreactor system for generating a bioengineered fluid (BF) similar to native SF. The objectives were to analyze expanded polytetrafluoroethylene membranes with pore sizes of 50 nm, 90 nm, 170 nm, and 3 µm in terms of (1) HA and PRG4 secretion rates by adherent synoviocytes, and (2) the extent of HA and PRG4 retention with or without synoviocytes adherent on the membrane. Experiment 1: Synoviocytes were cultured on tissue culture (TC) plastic or membranes ± IL‐1β + TGF‐β1 + TNF‐α, a cytokine combination that stimulates lubricant synthesis. HA and PRG4 secretion rates were assessed by analysis of medium. Experiment 2: Bioreactors were fabricated to provide a BF compartment enclosed by membranes ± adherent synoviocytes, and an external compartment of nutrient fluid (NF). A solution with HA (1 mg/mL, MW ranging from 30 to 4,000 kDa) or PRG4 (50 µg/mL) was added to the BF compartment, and HA and PRG4 loss into the NF compartment after 2, 8, and 24 h was determined. Lubricant loss kinetics were analyzed to estimate membrane permeability. Experiment 1: Cytokine‐regulated HA and PRG4 secretion rates on membranes were comparable to those on TC plastic. Experiment 2: Transport of HA and PRG4 across membranes was lowest with 50 nm membranes and highest with 3 µm membranes, and transport of high MW HA was decreased by adherent synoviocytes (for 50 and 90 nm membranes). The permeability to HA mixtures for 50 nm membranes was ∼20 × 10−8 cm/s (− cells) and ∼5 × 10−8 cm/s (+ cells), for 90 nm membranes was ∼35 × 10−8 cm/s (− cells) and ∼19 × 10−8 cm/s (+ cells), for 170 nm membranes was ∼74 × 10−8 cm/s (± cells), and for 3 µm membranes was ∼139 × 10−8 cm/s (± cells). The permeability of 450 kDa HA was ∼40× lower than that of 30 kDa HA for 50 nm membranes, but only ∼2.5× lower for 3 µm membranes. The permeability of 4,000 kDa HA was ∼250× lower than that of 30 kDa HA for 50 nm membranes, but only ∼4× lower for 3 µm membranes. The permeability for PRG4 was ∼4 × 10−8 cm/s for 50 nm membranes, ∼48 × 10−8 cm/s for 90 nm membranes, ∼144 × 10−8 cm/s for 170 nm membranes, and ∼336 × 10−8 cm/s for 3 µm membranes. The associated loss across membranes after 24 h ranged from 3% to 92% for HA, and from 3% to 93% for PRG4. These results suggest that semi‐permeable membranes may be used in a bioreactor system to modulate lubricant retention in a bioengineered SF, and that synoviocytes adherent on the membranes may serve as both a lubricant source and a barrier for lubricant transport. Biotechnol. Bioeng. 2010; 106: 149–160. © 2009 Wiley Periodicals, Inc.
Sensitive multiplex RNA quantification using capillary electrophoresis‐based single‐strand conformation polymorphism
Authors: Shin Gi Won , Hwang Hee Sung , Nam Hong Gil , Oh Mi‐Hwa , Jung Gyoo Yeol
Published: December 2009

Quantification of RNA provides information crucial for various biological studies, including analysis of mRNA expression and that of microRNAs. Reverse transcription (RT) coupled with real‐time polymerase chain reaction (PCR) is known to be the most accurate method for quantifying nucleic acids, and thus represents the state‐of‐the‐art for RNA quantification. However, the use of real‐time PCR for RNA quantification is limited to a single target per analytical run because of reductions in quantification power and limitations of fluorescence dyes associated with multiplex applications. Here, we report a novel multiplex RNA quantification method that uses capillary electrophoresis single‐strand conformation polymorphism (CE‐SSCP) coupled with modified RT and asymmetric PCR. The reverse transcripts of seven in vitro transcribed RNAs were modified with common sequence tags and amplified by asymmetric PCR using primers specific to the common tags. The resulting amplicons were separated and quantified by CE‐SSCP. A series of experiments using different amounts of RNA demonstrated that the assay had a limit of detection of 2 amol and a dynamic range of ∼105. These results clearly indicate the potential of this method to provide robust and precise multiplex RNA quantification. Biotechnol. Bioeng. 2010; 106: 167–172. © 2009 Wiley Periodicals, Inc.
Hypoxia enhances proliferation of mouse embryonic stem cell‐derived neural stem cells
Authors: Rodrigues Carlos A.V. , Diogo Maria Margarida , da Silva Cláudia Lobato , Cabral Joaquim M.S.
Published: December 2009

Neural stem (NS) cells can provide a source of material with potential applications for neural drug testing, developmental studies, or novel treatments for neurodegenerative diseases. Herein, the ex vivo expansion of a model system of mouse embryonic stem (mES) cell‐derived NS cells was characterized and optimized, cells being cultivated under adherent conditions. Culture was first optimized in terms of initial cell plating density and oxygen concentration, known to strongly influence brain‐derived NS cells. To this end, the growth of cells cultured under hypoxic (2%, 5%, and 10% O2) and normoxic (20% O2) conditions was compared. The results showed that 2–5% oxygen, without affecting multipotency, led to fold increase values in total cell number about twice higher than observed under 20% oxygen (20‐fold vs. 10‐fold, respectively) this effect being more pronounced when cells were plated at low density. With an optimal cell density of 104 cells/cm2, the maximum growth rates were 1.9 day−1 under hypoxia versus 1.7 day−1 under normoxia. Cell division kinetics analysis by flow cytometry based on PKH67 tracking showed that when cultured in hypoxia, cells are at least one divisional generation ahead compared to normoxia. In terms of cell cycle, a larger population in a quiescent G0 phase was observed in normoxic conditions. The optimization of NS cell culture performed here represents an important step toward the generation of a large number of neural cells from a reduced initial population, envisaging the potential application of these cells in multiple settings. Biotechnol. Bioeng. 2010;106: 260–270. © 2009 Wiley Periodicals, Inc.
Analysis of endogenous glutathione‐adducts and their metabolites
Authors: Blair Ian A.
Published: December 2009

The ability to conduct validated analyses of glutathione (GSH)‐adducts and their metabolites is critically important in order to establish whether they play a role in cellular biochemical or pathophysiological processes. The use of stable isotope dilution (SID) methodology in combination with liquid chromatography–tandem mass spectrometry (LC‐MS/MS) provides the highest bioanalytical specificity possible for such analyses. Quantitative studies normally require the high sensitivity that can be obtained by the use of multiple reaction monitoring (MRM)/MS rather than the much less sensitive but more specific full scanning methodology. The method employs a parent ion corresponding to the intact molecule together with a prominent product ion that obtained by collision induced dissociation. Using SID LC‐MRM/MS, analytes must have the same relative LC retention time to the heavy isotope internal standard established during the validation procedure, the correct parent ion and the correct product ion. This level of specificity cannot be attained with any other bioanalytical technique employed for biomarker analysis. This review will describe the application of SID LC‐MR/MS methodology for the analysis of GSH‐adducts and their metabolites. It will also discuss potential future directions for the use of this methodology for rigorous determination of their utility as disease and exposure biomarkers. Copyright © 2010 John Wiley & Sons, Ltd.
An application of terror management theory in the design of social and health‐related anti‐smoking appeals
Authors: Martin Ingrid M. , Kamins Michael A.
Published: December 2009

Marketers and public policy makers continue to be plagued with the problem of creating effective communications, which can increase the probability of complying with risk avoidance behavior related to smoking. Using Terror Management Theory (TMT) as a theoretical basis, we provide a rationale as to why traditional anti‐smoking appeals focusing on negative health consequences are not impactful. We use the implications of the theory to predict and show that an appeal focusing on social exclusion should be more motivating than a health appeal to encourage smokers to quit in the short and long run. Specifically, we conduct an experiment designed to investigate the impact of mortality salience and self‐esteem on whether college‐age smokers will comply with anti‐smoking messages. We observe that social exclusion messages compared to health effect messages are particularly effective in reducing intentions to smoke for college‐age smokers who derive their self‐esteem in part from smoking. Overall, our results show that mortality salience interacts with self‐esteem in terms of influencing the probability of smoking in the short run and that social exclusion appeals have a stronger impact than health‐related appeals both in reducing long run smoking intention and emphasizing the salience of health‐related consequences of smoking.

Copyright © 2009 John Wiley & Sons, Ltd.
Electrochemical Machining of Gold Microstructures in LiCl/Dimethyl Sulfoxide
Authors: Ma Xinzhou , Bán Andreas , Schuster Rolf
Published: December 2009

LiCl/dimethyl sulfoxide (DMSO) electrolytes were applied for the electrochemical micromachining of Au. Upon the application of short potential pulses in the nanosecond range to a small carbon‐fiber electrode, three‐dimensional microstructures with high aspect ratios were fabricated. We achieved machining resolutions down to about 100 nm. In order to find appropriate machining parameters, that is, tool and workpiece rest potentials, the electrochemical behavior of Au in LiCl/DMSO solutions with and without addition of water was studied by cyclic voltammetry. In waterless electrolyte Au dissolves predominantly as Au(I), whereas upon the addition of water the formation of Au(III) becomes increasingly important. Because of the low conductivity of LiCl/DMSO compared with aqueous electrolytes, high machining precision is obtained with moderately short pulses. Furthermore, the redeposition of dissolved Au can be effectively avoided, since Au dissolution in LiCl/DMSO is highly irreversible. Both observations render LiCl/DMSO an appropriate electrolyte for the routine electrochemical micromachining of Au.
Mechanism of the Aerobic Oxidation of α‐Pinene
Authors: Neuenschwander Ulrich , Guignard Florian , Hermans Ive
Published: December 2009

A combined experimental and theoretical approach is used to study the thermal autoxidation of α‐pinene. Four different types of peroxyl radicals are generated; the verbenyl peroxyl radical being the most abundant one. The peroxyl radicals propagate a long radical chain, implying that chain termination does not play an important role in the production of the products. Two distinct types of propagation steps are active in parallel: the abstraction of allylic H atoms and the addition to the unsaturated CC bond. The efficiency for both pathways appears to depend on the structure of the peroxyl radical. The latter step yields the corresponding epoxide product, as well as alkoxyl radicals. Under the investigated reaction conditions the alkoxyl radicals seem to produce both the alcohol and ketone products, the ketone presumably being formed upon the abstraction of the weakly bonded αH atom by O2. This mechanism explains the predominantly primary nature of all quantified products. At higher conversion, co‐oxidation of the hydroperoxide products constitutes an additional, albeit small, source of alcohol and ketone products.
Maternal hypoxia increases the activity of MMPs and decreases the expression of TIMPs in the brain of neonatal rats
Authors: Tong Wenni , Chen Wanqiu , Ostrowski Robert P. , Ma Qingyi , Souvenir Rhonda , Zhang Lubo , Zhang John H. , Tang Jiping
Published: December 2009

A recent study has shown that increased activity of matrix metalloproteinases‐2 and metalloproteinases‐9 (MMP‐2 and MMP‐9) has detrimental effect on the brain after neonatal hypoxia. The present study determined the effect of maternal hypoxia on neuronal survivability and the activity of MMP‐2 and MMP‐9, as well as the expression of tissue inhibitors of metalloproteinase 1 and 2 (TIMP‐1 and TIMP‐2) in the brain of neonatal rats. Pregnant rats were exposed to 10.5% oxygen for 6 days from the gestation day 15 to day 21. Pups were sacrificed at day 0, 4, 7, 14, and 21 after birth. Body weight and brain weight of the pups were measured at each time point. The activity of MMP‐2 and MMP‐9 and the protein abundance of TIMP‐1 and TIMP‐2 were determined by zymography and Western blotting, respectively. The tissue distribution of MMPs was examined by immunofluorescence staining. The neuronal death was detected by Nissl staining. Maternal hypoxia caused significant decreases in body and brain size, increased activity of MMP‐2 at day 0, and increased MMP‐9 at day 0 and 4. The increased activity of the MMPs was accompanied by an overall tendency towards a reduced expression of TIMPs at all ages with the significance observed for TIMPs at day 0, 4, and 7. Immunofluorescence analysis showed an increased expression of MMP‐2, MMP‐9 in the hippocampus at day 0 and 4. Nissl staining revealed significant cell death in the hippocampus at day 0, 4, and 7. Functional tests showed worse neurobehavioral outcomes in the hypoxic animals. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2010
Tables of key findings and quality of included trials for ‘Interventions for treating obesity in children’
Authors: van Dalen E. C. , Kremer L. C. M.
Published: December 2009

These are tables of key findings and quality of included trials of a Cochrane review, published in this issue of EBCH, first published as: Oude Luttikhuis H, Baur L, Jansen H, Shrewsbury VA, O'Malley C, Stolk RP, Summerbell CD. Interventions for treating obesity in children. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD001872. DOI: 10.1002/14651858.CD001872.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Commentary and Summary. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Summary of ‘Newborn screening for cystic fibrosis’, including tables of key findings and quality of included trials
Authors: Southern K. W. , Mérelle M. E. , Dankert‐Roelse J. E. , Nagelkerke A. , van Dalen E.C. , Kremer L.C.M.
Published: December 2009

This is a summary, including tables of key findings and quality of included trials, of a Cochrane review, published in this issue of EBCH, first published as: Southern KW, Mérelle ME, Dankert‐Roelse JE, Nagelkerke A. Newborn screening for cystic fibrosis. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD001402. DOI: 10.1002/14651858.CD001402.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Commentary. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Summary of ‘Drug management for acute tonic‐clonic convulsions including convulsive status epilepticus in children’, including tables of key findings and quality of included trials
Authors: Appleton R. , Macleod S. , Martland T. , van Dalen E.C. , Kremer L.C.M.
Published: December 2009

This is a summary, including tables of key findings and quality of included trials, of a Cochrane review, published in this issue of EBCH, first published as: Appleton R, Macleod S, Martland T. Drug management for acute tonic‐clonic convulsions including convulsive status epilepticus in children. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD001905. DOI: 10.1002/14651858.CD001905.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Commentary. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Commentary on ‘Oral Zinc for treating diarrhoea in children’, with a response from the review authors
Authors: Roth Daniel E. , Lazzerini Marzia , Ronfani Luca
Published: December 2009

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Lazzerini M, Ronfani L. Oral zinc for treating diarrhoea in children. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD005436. DOI: 10.1002/14651858.CD005436.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Commentary on ‘Drug management for acute tonic‐clonic convulsions including convulsive status epilepticus in children’, with a response from the review authors
Authors: McGillivray David , Dayan Peter , Pusic Martin , Appleton R. , Macleod S. , Martland T.
Published: December 2009

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Appleton R, Macleod S, Martland T. Drug management for acute tonic‐clonic convulsions including convulsive status epilepticus in children. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD001905. DOI: 10.1002/14651858.CD001905.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Two commentaries on ‘Impact of tuberculosis preventive therapy on tuberculosis and mortality in HIV‐infected children’
Authors: Coovadia Hoosen , Bland Ruth M. , Walls Tony
Published: December 2009

These are commentaries on a Cochrane review, published in this issue of EBCH, first published as: Gray DM, Young T, Cotton M, Zar H. Impact of tuberculosis preventive therapy on tuberculosis and mortality in HIV‐infected children. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD006418. DOI:10.1002/14651858.CD006418.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
IL‐4 induces protection of vascular endothelial cells against killing by complement and melittin through lipid biosynthesis
Authors: Black Sylvester M. , Schott Megan E. , Batdorf Bjorn H. , Benson Barbara A. , Rutherford Mark S. , Levay‐Young Brett K. , Dalmasso Agustin P.
Published: December 2009

We have shown previously that cytokines IL‐4 and IL‐13 induce protection in porcine vascular endothelial cells (EC) against killing by the membrane attack complex (MAC) of human complement. This protection is intrinsic, not due to changes in complement regulatory proteins, and requires activation of Akt and sterol receptor element binding protein‐1 (SREBP‐1), which regulates fatty acid and phospholipid synthesis. Here we report that, compared to EC incubated in medium, IL‐4‐treated EC had a profound reduction in complement‐mediated ATP loss and in killing assessed by vital dye uptake, but only a slight reduction in permeability disruption measured by calcein release. While controls exposed to complement lost mitochondrial membrane potential and subsequently died, protected EC maintained mitochondrial morphology and membrane potential, and remained alive. SREBP‐1 and fatty acid synthase activation were required for protection and fatty acid and phospholipid synthesis, including cardiolipin, were increased after IL‐4 stimulation, without increase in cholesterol content or cell proliferation. IL‐4 also induced protection of EC from killing by the channel forming protein melittin, similar to protection observed for the MAC. We conclude that IL‐4 induced activation of Akt/SREBP‐1/lipid biosynthesis in EC, resulting in protection against MAC and melittin, in association with mitochondrial protection.
Mycobacterium tuberculosis Rv1419 encodes a secreted 13 kDa lectin with immunological reactivity during human tuberculosis
Authors: Nogueira Lucas , Cardoso Fernanda C. , Mattos Ana M. , Bordignon Juliano , Figueiredo Cláudia P. , Dahlstrom Pedro , Frota Cristiane C. , Duarte dos Santos Cláudia N. , Chalhoub Marcelo , Cavada Benildo S. , Teixeira Henrique C. , Oliveira Sérgio C. , Barral‐Netto Manoel , Báfica André
Published: December 2009

In this study, we have identified a secreted 13 kDa lectin from Mtb (Mtb, Mycobacterium tuberculosis; sMTL‐13) by homology search of a non‐redundant lectin database. Bioinformatic analysis revealed that sMTL‐13 belongs to the ricin‐type β‐trefoil family of proteins containing a Sec‐type signal peptide present in Mtb complex species, but not in non‐tuberculous mycobacteria. Following heterologous expression of sMTL‐13 and generation of an mAb (clone 276.B7/IgG1κ), we confirmed that this lectin is present in culture filtrate proteins from Mtb H37Rv, but not in non‐tuberculous mycobacteria‐derived culture filtrate proteins. In addition, sMTL‐13 leads to an increased IFN‐γ production by PBMC from active tuberculosis (ATB) patients. Furthermore, sera from ATB patients displayed high titers of IgG Ab against sMTL‐13, a response found to be decreased following successful anti‐tuberculosis therapy. Together, our findings reveal a secreted 13 kDa ricin‐like lectin from Mtb, which is immunologically recognized during ATB and could serve as a biomarker of disease treatment.
Modified vaccinia Ankara‐expressing Ag85A, a novel tuberculosis vaccine, is safe in adolescents and children, and induces polyfunctional CD4+ T cells
Authors: Scriba Thomas J. , Tameris Michele , Mansoor Nazma , Smit Erica , van der Merwe Linda , Isaacs Fatima , Keyser Alana , Moyo Sizulu , Brittain Nathaniel , Lawrie Alison , Gelderbloem Sebastian , Veldsman Ashley , Hatherill Mark , Hawkridge Anthony , Hill Adrian V. S. , Hussey Gregory D. , Mahomed Hassan , McShane Helen , Hanekom Willem A.
Published: December 2009

Modified vaccinia Ankara‐expressing Ag85A (MVA85A) is a new tuberculosis (TB) vaccine aimed at enhancing immunity induced by BCG. We investigated the safety and immunogenicity of MVA85A in healthy adolescents and children from a TB endemic region, who received BCG at birth. Twelve adolescents and 24 children were vaccinated and followed up for 12 or 6 months, respectively. Adverse events were documented and vaccine‐induced immune responses assessed by IFN‐γ ELISpot and intracellular cytokine staining. The vaccine was well tolerated and there were no vaccine‐related serious adverse events. MVA85A induced potent and durable T‐cell responses. Multiple CD4+ T‐cell subsets, based on expression of IFN‐γ, TNF‐α, IL‐2, IL‐17 and GM‐CSF, were induced. Polyfunctional CD4+ T cells co‐expressing IFN‐γ, TNF‐α and IL‐2 dominated the response in both age groups. A novel CD4+ cell subset co‐expressing these three Th1 cytokines and IL‐17 was induced in adolescents, while a novel CD4+ T‐cell subset co‐expressing Th1 cytokines and GM‐CSF was induced in children. Ag‐specific CD8+ T cells were not detected. We conclude that in adolescents and children MVA85A safely induces the type of immunity thought to be important in protection against TB. This includes induction of novel Th1‐cell populations that have not been previously described in humans.
Energy addiction and lymphocyte differentiation: A new role for the liver kinase B1 kinase
Authors: Aifantis Iannis , Sawai Catherine
Published: December 2009

Lymphocyte development is a process in which proliferation is coupled to differentiation. In order to undergo efficient proliferation, lymphocytes must coordinate the entry into cell cycle with increased metabolism. The signaling pathways, like those downstream of antigen and cytokine receptors, and specific regulators that directly control cell metabolism are only beginning to be defined. A study in this issue of the European Journal of Immunology, demonstrates that the liver kinase B1 (LKB1) is a regulator of cellular metabolism. Deficiency in LKB1 results in a block in T‐cell differentiation, increased apoptosis, as well as impaired survival of mature T cells. This study highlights the importance of LKB1 in T‐cell development and function, but as discussed in this Commentary, a number of intriguing questions concerning the regulation and additional functions of LKB1 remain.
Stable Selenenium Cations: Unusual Reactivity and Excellent Glutathione Peroxidase‐Like Activity
Authors: Singh Vijay P. , Singh Harkesh B. , Butcher Ray J.
Published: December 2009

The syntheses of the three selenenium cations 17–19 derived from N‐[n‐butyl‐(3‐nitrobenzylimino)]phenyl selenide (14) are described. Precursor 14 was synthesized by treating N‐(2‐bromo‐3‐nitrobenzylimino)benzene (12) with in situ generated nBuSeNa. The selenenium cation 17 with chloride as counteranion was isolated when 14 was treated with sulfuryl chloride (SO2Cl2) in the presence of triethylamine (Et3N). The selenenium cations with bromide (18) and tribromide (19) as counteranions, were synthesized by treating 14 with Br2 in the presence of Et3N. Reaction of 19 with thiophenol afforded two unexpected products: the cyclic diselenide 20 and the bicyclic selenide 21. Oxidation of 18 with hydrogen peroxide afforded the ebselen derivative, 2‐(4‐bromophenyl)‐7‐nitro‐1,2‐benzisoselenazol(2H)‐3‐one Se‐oxide (22). The presence of nonbonding Se···O/Se–N intramolecular interactions in 18 and 19 have been confirmed by single‐crystal X‐ray studies. Glutathione peroxidase‐like antioxidant activities of 17–19 and related compounds have been determined by the coupled reductase assay. It is proved that the high GPx‐like activities of cations involve the formation of corresponding intermediate selenoxide in the catalytic cycle. The isolated selenoxide 22 shows the highest GPx‐like activity among the series of compounds. The compounds have been further investigated by density functional theory calculations at the B3LYP level of theory using the 6‐31+G(d) basis set to identify nonbonding Se···O/N interactions. The second perturbation energy was obtained through natural bond orbital (NBO) analysis and NBO charges were calculated to ascertain the positive charge at the selenium atom. Nucleus‐independent chemical shifts (NICS) calculations have also been carried out.
N‐Phenyl‐1,2,4‐triazoline‐3,5‐dione (PTAD) as a Dienophilic Dinitrogen Equivalent: A Simple Synthesis of 3‐Amino‐1,2,4‐benzotriazines from Arylcarbodiimides
Authors: Alajarin Mateo , Bonillo Baltasar , Marin‐Luna Marta , Sanchez‐Andrada Pilar , Vidal Angel
Published: December 2009

N‐Arylcarbodiimides react with PTAD to provide [1,2,4]triazolo[1,2‐a][1,2,4]benzotriazines by a [4+2] cycloaddition reaction. When asymmetrically substituted diarylcarbodiimides are used, the cycloaddition proceeds with total chemoselectivity because only the more electron‐rich aryl nucleus is involved. This observation has been rationalized by a computational study using DFT methods that shows that, in the reaction of HTAD with arylcarbodiimides, the magnitude of the energy barriers depend on the electronic features of the substituents at the aryl nucleus; the calculations also indicate that the reaction proceeds through asynchronous states with polar characteristics. The treatment of the final cycloadducts with potassium hydroxide affords 3‐aryl(alkyl)amino‐1,2,4‐benzotriazines.
CuI‐Catalyzed Azide–Alkyne Intramolecular i‐to‐(i+4) Side‐Chain‐to‐Side‐Chain Cyclization Promotes the Formation of Helix‐Like Secondary Structures
Authors: Scrima Mario , Le Chevalier‐Isaad Alexandra , Rovero Paolo , Papini Anna Maria , Chorev Michael , D'Ursi Anna Maria
Published: December 2009

A solid‐phase assembly of model peptides derived from human parathyroid hormone‐related protein (11–19) containing ω‐azido‐ and ω‐yl‐α‐amino acid residues in positions i and i+4 was cyclised in solution by an intramolecular CuI‐catalyzed azide–alkyne 1,3‐dipolar Huisgen cycloaddition. These series of heterodetic cyclo‐nonapeptides varied in the size of the disubstituted 1,2,3‐triazolyl‐containing bridge, the location and the orientation of the 1,2,3‐triazolyl moiety within the bridge. The 1,2,3‐triazolyl moiety, presented at either 1,4‐ or 4,1‐orientation, is flanked by side chains containing 1–4 CH2 groups that result in bridges comprised from 4–7 CH2 groups connecting residues 13 and 17. Comprehensive conformational analysis employing CD, NMR and molecular dynamics reveals the conformational propensities of these heterodetic cyclo‐nonapeptides. Cyclo‐nonapeptides containing either the 7 methylene bridge (VII and VIII) or the 4 methylene bridge (II) are unstructured in structure‐promoting solvent. Cyclo‐nonapeptide I in which the 1,4‐disubstituted 1,2,3‐triazolyl is flanked by 3 and 1 CH2 groups in proximity to the respective residues 13 and 17, is stabilized in a non‐canonical structure. All the other heterodetic cyclo‐nonapeptides (III–VI) in which the 1,2,3‐triazolyl is flanked by a total of 5 or 6 CH2 groups nicely accommodate α‐helical structures and reproduce very closely the helical structure stabilized by the analogous cyclo‐nonapeptide in which Lys13 and Asp17 are bridged by the isosteric lactam. These studies suggest that the bioorthogonal i‐to‐(i+4) side‐chain‐to‐side‐chain cyclization via the prototypic “click reaction” offers a new and powerful approach for generating stable helix mimetic structures.