bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Energy-Conserving Hydrogenase B in
Methanococcus maripaludis
Authors: Major Tiffany A. , Liu Yuchen , Whitman William B.
Published: May 2010

The
Methanococcus maripaludis
energy-conserving hydrogenase B (Ehb) generates low potential electrons required for autotrophic CO
2
assimilation. To analyze the importance of individual subunits in Ehb structure and function, markerless in-frame deletions were constructed in a number of
M. maripaludis ehb
genes. These genes encode the large and small hydrogenase subunits (
ehbN
and
ehbM
, respectively), a polyferredoxin and ferredoxin (
ehbK
and
ehbL
, respectively), and an ion translocator (
ehbF
). In addition, a gene replacement mutation was constructed for a gene encoding a putative membrane-spanning subunit (
ehbO
). When grown in minimal medium plus acetate (McA), all
ehb
mutants had severe growth deficiencies except the Δ
ehbO
::
pac
strain. The membrane-spanning ion translocator (Δ
ehbF
) and the large hydrogenase subunit (Δ
ehbN
) deletion strains displayed the severest growth defects. Deletion of the
ehbN
gene was of particular interest because this gene was not contiguous to the
ehb
operon. In-gel activity assays and Western blots confirmed that EhbN was part of the membrane-bound Ehb hydrogenase complex. The Δ
ehbN
strain was also sensitive to growth inhibition by aryl acids, indicating that Ehb was coupled to the indolepyruvate oxidoreductase (Ior), further supporting the hypothesis that Ehb provides low potential reductants for the anabolic oxidoreductases in
M. maripaludis
.
Medical decision-making and communication of risks: an ethical perspective
Authors: Breitsameter Christof
Published: May 2010

The medical decision-making process is currently in flux. Decisions are no longer made entirely at the physician's discretion: patients are becoming more and more involved in the process. There is a great deal of discussion about the ideal of ‘informed consent’, that is that diagnostic and therapeutic decisions should be made based on an interaction between physician and patient. This means that patients are informed about the advantages and disadvantages of a treatment as well as alternatives to the treatment; then, based on this information they can decide whether or not they want to undergo the treatment. However, recent studies show that the realisation of the ideal of ‘shared decision-making’ faces a number of difficulties related to the fact that patients are not provided with complete and accurate information. Using the example of breast cancer screening, this article examines the question of whether, in light of these difficulties, the ideal of informed decision-making is only an illusion or whether concrete steps can be taken towards the realisation of this ideal.
The parents' ability to take care of their baby as a factor in decisions to withhold or withdraw life-prolonging treatment in two Dutch NICUs
Authors: Moratti Sofia
Published: May 2010

In The Netherlands, it is openly acknowledged that the parents' ability to take care of their child plays a role in the decision-making process over administration of life-prolonging treatment to severely defective newborn babies. Unlike other aspects of such decision-making process up until the present time, the ‘ability to take care’ has not received specific attention in regulation or in empirical research. The present study is based on interviews with neonatologists in two Dutch NICUs concerning their definition of the ability to take care and its relevance in non-treatment decisions. All of the respondents think that the ability to take care consists of more than one factor. Most doctors mention the parents' emotional state, social network and cognitive abilities. Some doctors mention the presence of psychological conditions in the parents, their financial situation and physical condition. A few refer to the parents' experience and age, their chances to have another baby and their cultural background. Most doctors think the ability to take care has a secondary relevance in the decision-making process, while the primary concern is assessing the condition of the child. A substantial minority thinks the ability to take care does not play any role, while one doctor thinks it is a factor of primary importance. The study constitutes an important stepping-stone for future research in The Netherlands and elsewhere.
The ethical professional as endangered person: blog notes on doctor–patient relationships
Authors: Koch Tom , Jones Sarah
Published: May 2010

In theory, physicians subscribe to and in their actions personify a set of virtues whose performance demands personal engagement. At the same time, they are instructed in their professional roles to remain emotionally and personally distant from those they are called to treat. The result, the authors argue, is an ethical conflict whose nature is described through an analysis of two narratives drawn from an online blog for young physicians. Confusion over professional responsibilities and personal roles were found to affect physicians' perceptions of their clinical duties and their social roles. In addition, it sets in sharp relief contemporary debates on physician training and the ethical nature of medical professionalism. Practically, the authors suggest, the confusion may contribute to early physician burnout. Methodologically, this paper promotes the use of online discussion sites as rich repositories providing an insight into real dilemmas and the actual perception of physicians' attempts to address them. It thus promotes use of such sites as a resource in which assumptions about physicians' own perceptions about the nature of their role in contemporary society can be tested.
Sustained suppression of sympathetic activity and arterial pressure during chronic activation of the carotid baroreflex
Authors: Lohmeier Thomas E. , Iliescu Radu , Dwyer Terry M. , Irwin Eric D. , Cates Adam W. , Rossing Martin A.
Published: May 2010

Following sinoaortic denervation, which eliminates arterial baroreceptor input into the brain, there are slowly developing adaptations that abolish initial sympathetic activation and hypertension. In comparison, electrical stimulation of the carotid sinus for 1 wk produces sustained reductions in sympathetic activity and arterial pressure. However, whether compensations occur subsequently to diminish these responses is unclear. Therefore, we determined whether there are important central and/or peripheral adaptations that diminish the sympathoinhibitory and blood pressure-lowering effects of more sustained carotid sinus stimulation. To this end, we measured whole body plasma norepinephrine spillover and α1-adrenergic vascular reactivity in six dogs over a 3-wk period of baroreflex activation. During the first week of baroreflex activation, there was an ∼45% decrease in plasma norepinephrine spillover, along with reductions in mean arterial pressure and heart rate of ∼20 mmHg and 15 beats/min, respectively; additionally, plasma renin activity did not increase. Most importantly, these responses during week 1 were largely sustained throughout the 3 wk of baroreflex activation. Acute pressor responses to α-adrenergic stimulation during ganglionic blockade were similar throughout the study, indicating no compensatory increases in adrenergic vascular reactivity. These findings indicate that the sympathoinhibition and lowering of blood pressure and heart rate induced by chronic activation of the carotid baroreflex are not diminished by adaptations in the brain and peripheral circulation. Furthermore, by providing evidence that baroreflexes have long-term effects on sympathetic activity and arterial pressure, they present a perspective that is opposite from studies of sinoaortic denervation.
Divergent effects of low-O2tension and iloprost on ATP release from erythrocytes of humans with type 2 diabetes: implications for O2supply to skeletal muscle
Authors: Sprague Randy S. , Goldman Daniel , Bowles Elizabeth A. , Achilleus David , Stephenson Alan H. , Ellis Christopher G. , Ellsworth Mary L.
Published: May 2010

Erythrocytes release both O2and a vasodilator, ATP, when exposed to reduced O2tension. We investigated the hypothesis that ATP release is impaired in erythrocytes of humans with type 2 diabetes (DM2) and that this defect compromises the ability of these cells to stimulate dilation of resistance vessels. We also determined whether a general vasodilator, the prostacyclin analog iloprost (ILO), stimulates ATP release from healthy human (HH) and DM2 erythrocytes. Finally, we used a computational model to compare the effect on tissue O2levels of increases in blood flow directed to areas of increased O2demand (erythrocyte ATP release) with nondirected increases in flow (ILO). HH erythrocytes, but not DM2 cells, released increased amounts of ATP when exposed to reduced O2tension (Po2< 30 mmHg). In addition, isolated hamster skeletal muscle arterioles dilated in response to similar decreases in extraluminal O2when perfused with HH erythrocytes, but not when perfused with DM2 erythrocytes. In contrast, both HH and DM2 erythrocytes released ATP in response to ILO. In the case of DM2 erythrocytes, amounts of ATP released correlated inversely with glycemic control. Modeling revealed that a functional regulatory system that directs blood flow to areas of need (low O2-induced ATP release) provides appropriate levels of tissue oxygenation and that this level of the matching of O2delivery with demand in skeletal muscle cannot be achieved with a general vasodilator. These results suggest that the inability of erythrocytes to release ATP in response to exposure to low-O2tension could contribute to the peripheral vascular disease of DM2.
Ethnic differences in resistance artery contractility of normotensive pregnant women
Authors: Brewster L. M. , Taherzadeh Z. , Volger S. , Clark J. F. , Rolf T. , Wolf H. , VanBavel E. , van Montfrans G. A.
Published: May 2010

Black women are at a greater risk to develop hypertension during pregnancy, with a 4.5 times higher rate of fatal preeclampsia than white women. Therefore, it is important to identify factors that may affect this risk. Our group previously proposed that high activity of the central regulatory enzyme of energy metabolism, creatine kinase (CK), may increase ATP-buffering capacity and lead to enhanced vascular contractility and reduced nitric oxide bioavailability. Therefore, we assessed microvascular contractility characteristics in isolated resistance arteries from self-defined black and white normotensive pregnant women using a Mulvany-Halpern myograph. Additionally, morphology was assessed with electron microscopy. Resistance-sized arteries obtained from omentum donated during cesarean sections (11 black women and 20 white women, mean age: 34 yr) studied in series showed similar morphology but significantly greater maximum contractions to norepinephrine (10−5 M) in blacks [14.0 mN (1.8 SE)] compared with whites [8.9 mN (1.4 SE), P = 0.02]. Furthermore, we found greater residual contractility after the specific CK inhibitor dinitrofluorobenzene (10−6 M) in black women [55% (6 SE)] compared with white women [28% (4 SE), P = 0.001] and attenuated vasodilation after bradykinin (10−7 M) in black women [103% (6 SE)] compared with white women [84% (5 SE), P = 0.023], whereas responses to sodium nitroprusside (10−4 M) and amlodipine (10−6 M) were similar. We conclude that compared with white women, normotensive pregnant black women display greater resistance artery contractility and evidence of higher vascular CK activity with attenuated nitric oxide synthesis. These findings in normotensives may imply that the black population is at risk for a further incline in pregnancy-related hypertensive disorders.
Human thoracic duct in vitro: diameter-tension properties, spontaneous and evoked contractile activity
Authors: Telinius Niklas , Drewsen Nanna , Pilegaard Hans , Kold-Petersen Henrik , de Leval Marc , Aalkjaer Christian , Hjortdal Vibeke , Boedtkjer Donna Briggs
Published: May 2010

The current study characterizes the mechanical properties of the human thoracic duct and demonstrates a role for adrenoceptors, thromboxane, and endothelin receptors in human lymph vessel function. With ethical permission and informed consent, portions of the thoracic duct (2–5 cm) were resected and retrieved at T7–T9during esophageal and cardia cancer surgery. Ring segments (2 mm long) were mounted in a myograph for isometric tension (N/m) measurement. The diameter-tension relationship was established using ducts from 10 individuals. Peak active tension of 6.24 ± 0.75 N/m was observed with a corresponding passive tension of 3.11 ± 0.67 N/m and average internal diameter of 2.21 mm. The equivalent active and passive transmural pressures by LaPlace's law were 47.3 ± 4.7 and 20.6 ± 3.2 mmHg, respectively. Subsequently, pharmacology was performed on rings from 15 ducts that were normalized by stretching them until an equivalent pressure of 21 mmHg was calculable from the wall tension. At low concentrations, norepinephrine, endothelin-1, and the thromboxane-A2analog U-46619 evoked phasic contractions (analogous to lymphatic pumping), whereas at higher contractions they induced tonic activity (maximum tension values of 4.46 ± 0.63, 5.90 ± 1.4, and 6.78 ± 1.4 N/m, respectively). Spontaneous activity was observed in 44% of ducts while 51% of all the segments produced phasic contractions after agonist application. Acetylcholine and bradykinin relaxed norepinephrine preconstrictions by ∼20% and ∼40%, respectively. These results demonstrate that the human thoracic duct can develop wall tensions that permit contractility to be maintained across a wide range of transmural pressures and that isolated ducts contract in response to important vasoactive agents.
All-trans retinoic acid mediates DUOX2 expression and function in respiratory tract epithelium
Authors: Linderholm Angela Lee , Onitsuka June , Xu Changhong , Chiu Maggie , Lee Wai-Ming , Harper Richart W.
Published: May 2010

DUOX1 and DUOX2 are members of the NADPH oxidase family that are specifically regulated to produce hydrogen peroxide in epithelia of the thyroid, gastrointestinal tract, and respiratory tract. The determinants of DUOX1 or DUOX2 expression in various tissues have not been established. Using respiratory tract epithelial cells as a model, we investigated changes in DUOX mRNA and protein expression during the first 10 days of differentiation. By comparing a respiratory tract cell line, HBE1, with primary tracheobronchial epithelial (TBE) cells, we determined that DUOX2 was significantly expressed only in cell conditions that included all- trans retinoic acid (ATRA). In HBE1 cells, DUOX2 mRNA increased 6-fold after ATRA treatment. Similarly, ATRA induced a 19-fold increase in DUOX2 mRNA expression in primary TBE cells with parallel increases in DUOX protein and DUOX-mediated H2O2 production as well. In addition, DUOX2 induction by rhinovirus required the presence of ATRA. ATRA had no effect on DUOX1 expression for all the conditions studied. Our data indicate that for respiratory epithelial cells, ATRA is important in the regulation of DUOX2 expression, function, and rhinovirus-mediated DUOX2 inducibility.
Stretch augments TGF-β1 expression through RhoA/ROCK1/2, PTK, and PI3K in airway smooth muscle cells
Authors: Mohamed Junaith Shaik , Boriek Aladin M.
Published: May 2010

Transforming growth factor-β1 (TGF-β1) expression in smooth muscle cells may play an important role in the pathogenesis of asthma. However, mechanisms that are involved in the regulation of TGF-β1 gene expression in human airway smooth muscle cells (HASMCs) remain elusive. Here, we show that mechanical stretch of HASMCs augmented TGF-β1 expression through a de novo RNA synthesis mechanism. Luciferase reporter assays revealed that stretch-induced TGF-β1 expression was mediated through the enhanced activation of TGF-β1 promoter. Interestingly, selective inhibitors of PTK, PI3K, or MEK1/2 attenuated TGF-β1 expression through blocking ERK1/2 phosphorylation and TGF-β1 promoter activity in response to stretch. In addition, stretch rapidly and transiently augmented GTP-bound RhoA and Rac1 but not Cdc42 GTPase. Either blockade of RhoA GTPase using C3 transferase, ROCK1/2 using Y27632, or knockdown of endogenous RhoA using RhoA siRNA attenuated stretch-induced TGF-β1 expression through the inhibition of ERK1/2 phosphorylation. Moreover, stretch augmented DNA binding activity of AP-1 in a time-dependent manner. Either treatment of HASMCs with the inhibitors of RhoA, ROCK1/2, PTK, PI3K, MEK1/2, or AP-1 or transfection of HASMCs with AP-1 decoy oligonucleotide attenuated stretch-induced TGF-β1 expression through repressing the DNA binding activity of AP-1. Site-directed mutagenesis demonstrated that two AP-1 binding sites in the TGF-β1 promoter region are responsible for stretch-induced TGF-β1 expression. Overall, in HASMCs, mechanical stretch plays an important role in TGF-β1 gene upregulation through a stretch-induced signaling pathway, which could be a potential therapeutic intervention for TGF-β1-induced pathogenesis in asthma.
Fragmented QRS and Mortality Risk in Patients With Left Ventricular Dysfunction
Authors: Cheema Aamir , Khalid Adnan , Wimmer Alan , Bartone Cheryl , Chow Theodore , Spertus John A. , Chan Paul S.
Published: May 2010

Background—

Fragmented QRS (fQRS) has been shown to predict cardiac events in select patient populations. Whether fQRS improves patient selection for primary prevention patients eligible for implantable cardioverter-defibrillator (ICD) therapy remains unknown.

Methods and Results—

In a prospective, multisite cohort of 842 patients with left ventricular dysfunction (ejection fraction ≤35%) representing both ischemic and nonischemic etiology, the presence of fQRS on ECG was assessed using standardized criteria. The association between fQRS and all-cause and arrhythmic mortality was evaluated overall and stratified by ICD status using multivariable Cox regression models, adjusted for demographic, clinical, and treatment variables. Fragmented QRS was present in 274 (32.5%) patients, and there were 191 (22.7%) deaths during a mean follow-up of 40±17 months. Rates of all-cause mortality did not differ between the fQRS+ (19.7%) and fQRS− (24.1%) groups; adjusted hazard ratio, 0.88; 95% confidence interval, 0.63–1.22;
P
=0.43. Additionally, rates of arrhythmic mortality were similar between the fQRS+ (9.9%) and fQRS− (12.7%) groups: adjusted hazard ratio, 0.77; 95% confidence interval, 0.49–1.31;
P
=0.38. Subgroup analyses found no association between fQRS and mortality when the cohort was further stratified by ICD status, etiology of left ventricular dysfunction, wide (≥120 ms) versus narrow (<120 ms) QRS duration, or fQRS myocardial territory.

Conclusions—

In this prospective, multisite cohort of primary prevention patients with left ventricular dysfunction, the presence of fQRS on ECG was not associated with a higher risk of either all-cause or arrhythmic mortality. These findings do not provide evidence that fQRS would be effective in risk stratifying primary prevention patients eligible for ICD therapy.
Atrial Fibrillation Cycle Length Is a Sole Independent Predictor of a Substrate for Consecutive Arrhythmias in Patients With Persistent Atrial Fibrillation
Authors: Drewitz Imke , Willems Stephan , Salukhe Tushar V. , Steven Daniel , Hoffmann Boris A. , Servatius Helge , Bock Karsten , Aydin Muhammet Ali , Wegscheider Karl , Meinertz Thomas , Rostock Thomas
Published: May 2010

Background—

Termination of persistent atrial fibrillation (AF) can be achieved through ablation, with the majority of patients terminating to an atrial tachycardia (AT) and fewer directly to sinus rhythm (SR). We aimed to identify potential predictors for the existence of a substrate for AT on termination to SR.

Methods and Results—

We assessed 95 persistent AF patients (age, 60±10 years) who underwent catheter ablation to the end point of AF termination. Forty patients terminated directly to SR (SRterm) and 55 to ATs (ATterm). Compared with the ATterm group, the SRterm group were younger (56±10 versus 63±9 years,
P
=0.001), had shorter durations of AF before ablation (9±26 versus 14±20 months,
P
<0.001), smaller left atrial diameters (41±5 versus 45±5 mm,
P
=0.015), and longer baseline AF cycle lengths (178±23 versus 159±31 ms,
P
=0.005). However, AF cycle length was the sole independent predictor of direct termination to SR. The most frequent AF termination site in SRterm patients was the pulmonary veins (53%), whereas in ATterm patients this was within the left atrium (58%). After follow-up of 12±6 months, there was a trend toward a greater proportion of patients in SR among those who terminated directly to SR after a single procedure. The most frequent type of recurrence was paroxysmal AF in SRterm patients and AT in ATterm patients.

Conclusions—

Patients who terminate to SR through ablation without an intermediate AT are characterized by a less altered arrhythmogenic substrate. Baseline AF cycle lengths emerged as a sole independent predictor of a substrate for consecutive arrhythmias.
J Wave, QRS Slurring, and ST Elevation in Athletes With Cardiac Arrest in the Absence of Heart Disease
Authors: Cappato Riccardo , Furlanello Francesco , Giovinazzo Valerio , Infusino Tommaso , Lupo Pierpaolo , Pittalis Mario , Foresti Sara , De Ambroggi Guido , Ali Hussam , Bianco Elisabetta , Riccamboni Roberto , Butera Gianfranco , Ricci Cristian , Ranucci Marco , Pelliccia Antonio , De Ambroggi Luigi
Published: May 2010

Background—

QRS-ST changes in the inferior and lateral ECG leads are frequently observed in athletes. Recent studies have suggested a potential arrhythmogenic significance of these findings in the general population. The aim of our study was to investigate whether QRS-ST changes are markers of cardiac arrest (CA) of unexplained cause or sudden death in athletes.

Methods and Results—

In 21 athletes (mean age, 27 years; 5 women) with cardiac arrest or sudden death, the ECG recorded before or immediately after the clinical event was compared with the ECG of 365 healthy athletes eligible for competitive sport activity. We measured the height of the J wave and ST elevation and searched for the presence of QRS slurring in the terminal portion of QRS. QRS slurring in any lead was present in 28.6% of cases and in 7.6% of control athletes (
P
=0.006). A J wave and/or QRS slurring without ST elevation in the inferior (II, III, and aVF) and lateral leads (V
4
to V
6
) were more frequently recorded in cases than in control athletes (28.6% versus 7.9%,
P
=0.007). Among those with cardiac arrest, arrhythmia recurrences did not differ between the subgroups with and without J wave or QRS slurring during a median 36-month follow-up of sport discontinuation.

Conclusions—

J wave and/or QRS slurring was found more frequently among athletes with cardiac arrest/sudden death than in control athletes. Nevertheless, the presence of this ECG pattern appears not to confer a higher risk for recurrent malignant ventricular arrhythmias.
Community engagement for health promotion
Authors: Tse Samson , Laverack Glenn , Nayar Shoba , Foroughian Shirin
Published: May 2010

Objectives and Settings: A growing Asian population currently resides in New Zealand, yet under half of this population claim the support they are entitled to in the face of an accident and injury. This research is focused on identifying ways of effectively engaging the Chinese community in health-promotion programmes to prevent and/or reduce injuries.

Methods: Research field work was conducted based on a qualitative approach. Interviews were carried out with 32 members of the Chinese community and six experts from six different organizations working with the Chinese community in Auckland, New Zealand.

Results: Interviews revealed that issues of resettlement and relocation, lack of communication, community readiness and community capacity all impacted on the delivery of health-promotion activities within the Chinese community.

Conclusion: The findings led to a series of seven steps as guidelines to engage the Chinese community to prevent and/or reduce injuries towards improving the quality of their lives. The underlying principles of the guidelines helped in the development of a community engagement approach for Chinese communities in Auckland, New Zealand.
Examining differences between light and heavier smoking vocational students
Authors: de Araújo Vanessa A , Loukas Alexandra , Gottlieb Nell H
Published: May 2010

Objective: To examine differences between light and heavier smoking vocational/technical students in tobacco use, related behaviors, and cessation.

Design: Cross-sectional.

Setting and Methods: Two hundred and four smokers attending two vocational/technical colleges in east Texas, USA, completed an anonymous survey during a regularly scheduled class in Fall, 2004 or Spring, 2005.

Results: Heavier smokers (39.7 per cent of the sample) were more likely than light smokers to be European American, to be dependent on cigarettes, to use cigarettes in a variety of situations, to use medication to quit smoking, and to be less likely to report a desire to quit on their own. The two groups did not differ on gender or the use of cigars and chewing tobacco.

Conclusion: Given the disproportionately high rates of tobacco use among vocational/technical students, results from this study indicate that salient anti-tobacco programs that can be implemented at the vocational school and that target light and heavier smoking students are needed.
In vivo Dentin Microhardness beneath a Calcium-Phosphate Cement
Authors: Bresciani E. , Wagner W.C. , Navarro M.F.L. , Dickens S.H. , Peters M.C.
Published: May 2010

A minimally invasive caries-removal technique preserves potentially repairable, caries-affected dentin. Mineral-releasing cements may promote remineralization of soft residual dentin. This study evaluated the in vivo remineralization capacity of resin-based calcium-phosphate cement (Ca-PO4) used for indirect pulp-capping. Permanent carious and sound teeth indicated for extraction were excavated and restored either with or without the Ca-PO4 base (control), followed by adhesive restoration. Study teeth were extracted after 3 months, followed by sectioning and in vitro microhardness analysis of the cavity floor to 115-µm depth. Caries-affected dentin that received acid conditioning prior to Ca-PO4 basing showed significantly increased Knoop hardness near the cavity floor. The non-etched group presented results similar to those of the non-treated group. Acid etching prior to cement application increased microhardness of residual dentin near the interface after 3 months in situ.
Novel Cleft Susceptibility Genes in Chromosome 6q
Authors: Letra A. , Menezes R. , Fonseca R.F. , Govil M. , McHenry T. , Murphy M.J. , Hennebold J.D. , Granjeiro J.M. , Castilla E.E. , Orioli I.M. , Martin R. , Marazita M.L. , Bjork B.C. , Vieira A.R.
Published: May 2010

Cleft lip/palate is a defect of craniofacial development. In previous reports, chromosome 6q has been suggested as a candidate region for cleft lip/palate. A multipoint posterior probability of linkage analysis of multiplex families from the Philippines attributed an 88% probability of harboring a cleft-susceptibility gene to a narrower region on bands 6q14.2-14.3. We genotyped 2732 individuals from families and unrelated individuals with and without clefts to investigate the existence of possible cleft-susceptibility genes in this region. We found association of PRSS35 and SNAP91 genes with cleft lip/palate in the case-control cohort and in Caucasian families. Haplotype analyses support the individual associations with PRSS35. We found Prss35 expression in the head and palate of mouse embryos at critical stages for palatogenesis, whereas Snap91 was expressed in the adult brain. We provide further evidence of the involvement of chromosome 6q in cleft lip/palate and suggest PRSS35 as a novel candidate gene.
Oil and democracy: More than a cross-country correlation?
Authors: Aslaksen Silje
Published: May 2010

This article revisits the empirical relationship between oil and democracy. Existing studies establish a negative cross-country correlation between oil and democracy in a Pooled OLS framework. This insight has recently been challenged by claiming that it suffers from omitted variables, and that including country fixed effects removes the statistical association between oil and democracy. This article argues that because of the high persistence of democracy and oil, the findings of no effect of oil on democracy suffers from weak instrument problems and is not informative. Indeed, this article shows that levels of oil systematically predict both levels and changes in democracy in a sample of up to 156 countries between 1972 and 2002. By considering a different identification assumption for oil and by using additional and more informative moment conditions to instrument the regressors, this article demonstrates that the relationship between oil and democracy is negative also when country fixed effects are taken into account. This result holds for alternative measures of democracy and alternative measures of oil abundance; it is robust when including additional covariates and when removing major oil producers.
Theoretical Foundation of Patient v. Population Preferences in Calculating QALYs
Authors: Gandjour Afschin
Published: May 2010

The cost-effectiveness of health care interventions is often evaluated using quality-adjusted life years (QALYs) as a measure of outcome. There is a debate on whether QALYs should use patient preferences as opposed to community preferences. This article shows that patient preferences have a theoretical foundation in preference-utilitarian theory and welfare economics. In contrast, this study found no compelling theoretical basis for community preferences. There is a need for further development of a normative framework to inform the choice of preference source.
Poor But Not Powerless: Women Workers in Production Chain Factories in China
Authors: Lang Ma  , Jacobs Francine
Published: May 2010

The present study demonstrates the processes by which 12 young women working in four production chain factories in China shape their own lives — their developmental trajectories — during the period following their entry into factory work. One-on-one, in-depth, semi-structured interviews were conducted in August, 2005, as part of an evaluation project that assessed the labor practices and interpersonal relationships in production chain factories. These interviews revealed considerable personal agency among the women, and prompted us to examine how this agency manifests itself, and what individual and contextual factors influence it. Operating from a developmental systems perspective, and using a “grounded approach” to identify active, personal agency as the organizing construct for this investigation, we adopted the selective optimization with compensation (SOC) model to guide data analysis and presentation, after initial data coding indicated its suitability. Findings suggest that activity within these three components (selection, optimization, and compensation) is oriented toward fulfilling both the women’s family goals and their career goals. These workers sought to improve the well-being of their families and themselves through selecting to work in these particular production chain factories, optimizing their factory experiences, and compensating for the attendant losses — personal and career-related. Individual characteristics, such as marital status, migrant status, and educational background, in combination with contextual factors, such as family socio-economic background and factory labor practices, influenced these women worker’s decisions, and thus, their developmental course.
Cell Adhesion and Proliferation onto Chitosan-based Membranes Treated by Plasma Surface Modification
Authors: Luna Sandra M. , Silva Simone S. , Gomes Manuela E. , Mano João F. , Reis Rui L.
Published: May 2010

Surface properties play a vital role in the functioning of a biomaterial. Cellular adherence and growth onto biomaterials can be enhanced in biomaterial modifications of their surface. In this work, the cell behavior on chitosan membranes modified by argon and nitrogen-plasma treatments was investigated. Characterization of the membranes was performed using atomic force microscopy, contact angle measurements, and X-ray photoelectron spectroscopy. Cytotoxicity assessment and direct contact assay were carried out for untreated and treated chitosan membranes using L929 fibroblast-like cells. Cell morphology and cell viability were assessed to evaluate the cell attachment and proliferation. Changes in terms of roughness, surface chemistry, and hydrophilicity/hydrophobic balance of chitosan-modified membranes were observed. Regarding cell studies, the findings revealed that the extracts of all membranes do not induce cytotoxic effects. Moreover, the in vitro assays evidenced an improvement of the L929 adhesion and attachment when compared to untreated chitosan membranes. Overall, the data obtained clearly demonstrated that plasma treatments constitute an effective way of improving the biocompatibility of chitosan membranes towards to their use in biomedical applications.
Hepatocyte-targeted psiRNA Delivery Mediated by Galactosylated Poly(Ethylene Glycol)-Graft-Polyethylenimine In Vitro
Authors: Nie Changfu , Liu Chuntao , Chen Guihua , Dai Jian , Li Hua , Shuai Xintao
Published: May 2010

Gene silencing in liver disease could be achieved by delivering siRNA with nonviral vectors. However, the transfection efficiency of plasmid siRNA ( psiRNA) applied through this approach in hepatocytes is generally low. Based on the fact that the asialoglycoprotein receptors present on hepatocytes can recognize galactose, we synthesized galactosylated poly(ethylene glycol)-graft-polyethylenimine (Gal-PEG-PEI) as a nonviral psiRNA carrier for hepatocyte targeting. Our results indicate that 0.2% (molar percentage) of amine groups of PEI was conjugated with PEG having galactose on its distal end. Increasing the molar ratios of Gal-PEG-PEI to psiRNA in complexation led to a decrease in particle size but an increase in zeta potential of complexes. The transfection efficiency of nanocomplexes, that is, Gal-PEG-PEI/psiRNA, in HepG2 cell line depends on the N/P value, which reflects the molar ratio of Gal-PEG-PEI to psiRNA in the complex. The highest transfection efficiency was 37.34%, which was obtained at N/P 8. At the same N/P value, the transfection efficiency with the nontargeting PEG-PEI/ psiRNA or Lipofectamine 2000/ psiRNA was much lower. The transfection efficiency of Gal-PEG-PEI/ psiRNA dropped to 3.60% from 37.34% after an excessive amount of free galactose was added into the medium for HepG2 cell incubation. By contrast, the similar phenomenon was observed neither when using PEG-PEI or Lipofectamine 2000 as a delivery vector nor in human embryonic kidney 293 cell line lacking ASGR. Real-time PCR analysis and western blot assay demonstrate that the knockdown of HLA-E gene expression by psiRNA/Gal-PEG-PEI (N/P 8) can reach about 60% in HepG2 cells after a 48-h transfection.
Review Paper: DNA Delivery Strategies to Promote Periodontal Regeneration
Authors: Elangovan Satheesh , Karimbux Nadeem
Published: May 2010

Periodontal diseases are caused by bacteria with an inflammatory component that result in the loss of bone and soft tissue around the neck of the teeth. Recent therapies allow clinicians to regenerate some of the lost structures of the periodontium. Regeneration of these lost supporting structures is a highly orchestrated process, involving various cellular and molecular players, leading to the complete restoration of the periodontium (the tooth-supporting apparatus). The introduction of growth factors has positively influenced the clinical outcome of the existing regenerative procedures but the supra-physiological doses and the high cost associated with these growth factors can be drawbacks. Gene therapy may offer some interesting advantages to current therapies. In the field of periodontology, several studies have been conducted to explore the efficacy of delivering the DNA of key growth factors using viral vectors in both periodontal and peri-implant bone regeneration. Relatively few studies have explored the application of nonviral gene therapy in periodontal regeneration. This article is aimed at reviewing the studies conducted so far using viral and nonviral gene delivery approaches to achieve periodontal and peri-implant bone regeneration.
Surface Engineering of Polycaprolactone by Biomacromolecules and their Blood Compatibility
Authors: Khandwekar Anand P. , Patil Deepak P. , Shouche Yogesh , Doble Mukesh
Published: May 2010

Improving blood compatibility of biodegradable polymers is an area of intensive research in blood contacting devices. In this study, curdlan sulphate and heparin-modified poly (caprolactone) (PCL) hybrids were developed by physically entrapping these molecules on the PCL surface. This modification technique was performed by reversible gelation of the PCL surface region following exposure to a solvent and nonsolvent mixture. The presence of these biomacromolecules on the PCL surface was verified by atomic force microscopy (AFM) and scanning electron microscopy and energy dispersive X-ray analysis (SEM-EDAX) analysis, while wettability of the films was investigated by dynamic contact angle measurements. The blood compatibilities of the surface-modified films were examined using in vitro platelet and leukocyte adhesion and thrombus formation. Mouse RAW 264.7 macrophage cells were used to assess the cell adhesion and inflammatory response to the modified surface by quantifying mRNA expression levels of proinflammatory cytokines namely TNF-α and IL-1β using real-time polymerase chain reaction (RT-PCR). A lower platelet and leukocyte adhesion and activation was observed on the modified films incubated with whole human blood for 2 h. The thrombus formation on the PCL was significantly decreased upon immobilization of both curdlan sulphate (39%, *p<0.05) and heparin (28%, *p<0.01) when compared to bare PCL (80%). All of these results revealed that improved blood compatibility was obtained by surface entrapment of both curdlan sulphate (CURS) and heparin (HEP) onto PCL films. Both PCL-CURS and PCL-HEP films reduced RAW 264.7 macrophage cell adhesion (*p<0.05) with respect to the base unmodified PCL. The cellular inflammatory response was suppressed on the modified substrates. The mRNA expression levels of proinflammmatory cytokines (TNF-α and IL-1β) were upregulated on bare PCL, while it was significantly lower on PCL-CURS and PCL-HEP substrates (**p<0.001). Thus, this biomacromolecule entrapment process can be applied on PCL in order to achieve improved blood compatibility and reduced inflammatory host response for its future blood contacting applications.
Evaluation of a Customized Artificial Osteoporotic Bone Model of the Distal Femur
Authors: Wähnert Dirk , Hoffmeier Konrad L. , Stolarczyk Yves , Fröber Rosemarie , Hofmann Gunther O. , Mückley Thomas
Published: May 2010

In the development of new implants biomechanical testing is essential. Since human bones vary markedly in density and geometry their suitability for biomechanical testing is limited. In contrast artificial bones are of great uniformity and therefore appropriate for biomechanical testing. However, the applied artificial bones have to be proved as comparable to human bone. An anatomical shaped artificial bone representing the distal human femur was created by foaming polyurethane. To get a bone model with properties of osteoporotic bone a foam density of 150 kg/m3 was used. The biomechanical properties of our artificial bones were evaluated against eight mildly osteoporotic fresh frozen human femora by mechanical testing. At the artificial bones all tested parameters showed a very small variation. In contrast significant correlation between bone mass density and tested parameters was found for the human bones. The artificial bones reached 39% of the compression strength and 41% of the screw pullout force of the human bone. In indentation testing the artificial bones reached 27% (cancellous) and 59% (cortical) respectively of the human bones strength. Regarding Shore hardness artificial bone and human bone showed comparable results for the cortical layer and at the cancellous layer the artificial bone reached 57% of human bones hardness. Our described method for customizing of artificial bones regarding their shape and bone stock quality provides suitable results. In relation to the as mildly osteoporotic classified human bones we assume that the biomechanical properties matching to serve osteoporotic bone.
Impact of ionic liquids in environment and humans: An overview
Authors: Frade Raquel FM , Afonso Carlos AM
Published: May 2010

Ionic liquids enclose a large number of molecular structures consisting of a cation and an anion. Their physical state and their chemical properties can be tuned by different combination of the ions and a large number of ionic liquids have already been reported. Toxicity of ionic liquids is a subject of great importance concerning their likely use as greener solvents and new materials for a broad number of potential applications. This review provides relevant toxicological data published so far about this topic and includes a large range of ionic liquids based on different cations (imidazolium, pyridinium, pyrrolidinium, quaternary ammonium, quaternary phosphonium and guanidinium) and anions (halogens-Br, Cl, bis (trifluoromethyl)sulfonylamide, tetrafluoroborate, hexafluorophosphate, dicyanamide, acesulfame and saccharin, amongst others). In general, toxicity of ionic liquids depends on both ions and the effect of the cation alkyl chain length is very pronounced although the type of anion also exerts impact on the overall toxicity.
Beneficial interaction between clobenpropit and pyridoxine in prevention of electroshock-induced seizures in mice: Lack of histaminergic mechanisms
Authors: Uma Devi P. , Manocha A. , Khanam R. , Vohora D.
Published: May 2010

Clobenpropit, an H3receptor antagonist, has been reported to modulate both the release of neurotransmitters and also the activity of histidine decarboxylase (HDC). Therefore, a decarboxylase-positive modulator, namely pyridoxine, was taken for interaction studies with clobenpropit in the electroshock (ES) model of seizures in mice and subsequent changes in brain histamine levels were estimated. A significant inhibition of ES-induced seizures was seen after the simultaneous use of clobenpropit and pyridoxine. No significant effects were evident on the brain histamine levels following this combination. The combination of clobenpropit with pyridoxine appears to exhibit beneficial pharmacodynamic interaction for the prevention of ES-induced seizures, which might not be mediated by the histaminergic mechanisms.
Development of molecular docking-based binding energy to predict the joint effect of BPA and its analogs
Authors: Zhang Hong-Chang , Hu Xia-Lin , Yin Da-Qiang , Lin Zhi-Fen
Published: May 2010

A general proposal for predicting the joint effect of endocrine disrupting chemicals by examining binding energy models was developed in this study. 2,2-bis(4-hydroxyphenyl)propane (BPA) and 11 of its analogs were chosen, and the estrogenic activity of each compound was measured by determining its EC50 value using a recombinant gene yeast assay. Binding energies (BEs) were calculated using Surflex-Docking software. The analysis of the relationship between EC50 values and BEs showed that there is a linear correlation between the BEs and EC50 values. Furthermore, the analysis of the given binary and quaternary mixtures of BPA and three of its analogs showed that the joint effects of the mixtures were affected by the proportions of the chemicals in each mixture and their relative binding energy. The correlation between the joint effects of mixtures and the binding energy of the individual compounds has been described using one formula, which can be used to predict the joint effects of other mixtures.
Gypenosides inhibits migration and invasion of human oral cancer SAS cells through the inhibition of matrix metalloproteinase-2 -9 and urokinase-plasminogen by ERK1/2 and NF-kappa B signaling pathways
Authors: Lu Kung-Wen , Chen Jung-Chou , Lai Tung-Yuan , Yang Jai-Sing , Weng Shu-Wen , Ma Yi-Shih , Lu Pei-Jung , Weng Jing-Ru , Chueh Fu-Shin , Gibson Wood W. , Chung Jing-Gung
Published: May 2010

Gypenosides (Gyp), found in Gynostemma pentaphyllum Makino, has been used as a folk medicine in the Chinese population for centuries and is known to have diverse pharmacologic effects, including anti-proliferative and anti-cancer actions. However, the effects of Gyp on prevention from invasion and migration of oral cancer cells are still unsatisfactory. The purpose of this study was to investigate effects of Gyp treatment on migration and invasion of SAS human oral cancer cells. SAS cells were cultured in the presence of 90 and 180 μg/mL Gyp for 24 and 48 hours. Gyp induced cytotoxic effects and inhibited SAS cells migration and invasion in dose- and time-dependent response. Wound-healing assay and boyden chamber assay were carried out to investigate Gyp-inhibited migration and invasion of SAS cells. Gyp decreased the abundance of several proteins, including nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), extracellular signal-regulated kinase 1/2 (ERK1/ 2), matrix metalloproteinase-9, -2 (MMP-9, -2), sevenless homolog (SOS), Ras, urokinase-type plasminogen activator (uPA), focal adhesion kinase (FAK) and RAC-alpha serine/threonine-protein kinase (Akt), in a time-dependent manner. In addition, Gyp decreased mRNA levels of MMP-2, MMP-7, MMP-9 but did not affect FAK and Rho A mRNA levels in SAS cells. These results provide evidences for the role of Gyp as a potent anti-metastatic agent, which can markedly inhibit the metastatic and invasive capacity of oral cancer cells. The inhibition of NF-κB and MMP-2, -7 and -9 signaling may be one of the mechanisms that is present in Gyp-inhibited cancer cell invasion and migration.
A spatial beta-binomial model for clustered count data on dental caries
Authors: Bandyopadhyay Dipankar , Reich Brian J , Slate Elizabeth H
Published: May 2010

One of the most important indicators of dental caries prevalence is the total count of decayed, missing or filled surfaces in a tooth. These count data are often clustered in nature (several count responses clustered within a subject), over-dispersed as well as spatially referenced (a diseased tooth might be positively influencing the decay process of a set of neighbouring teeth). In this article, we develop a multivariate spatial betabinomial (BB) model for these data that accommodates both over-dispersion as well as latent spatial associations. Using a Bayesian paradigm, the re-parameterised marginal mean (as well as variance) under the BB framework are modelled using a regression on subject/tooth-specific co-variables and a conditionally autoregressive prior that models the latent spatial process. The necessity of exploiting spatial associations to model count data arising in dental caries research is demonstrated using a small simulation study. Real data confirms that our spatial BB model provides a superior estimation and model fit as compared to other sub-models that do not consider modelling spatial associations.
Perceptions of Effectiveness Among College Students: Toward Marriage and Family Counseling and Therapy
Authors: Tse Luke M. , Wantz Richard A. , Firmin Michael
Published: May 2010

Unlike perceptions toward professional counseling, public opinions do not typically associate marriage and family counseling or therapy with treatments of mental disorders. The current survey of college students in this sample confirmed that most would not recommend, specifically, marriage and family therapists (MFTs) for mental health evaluations, psychiatric symptoms, intelligence and personality assessments, drug abuses, among others. The only situation for which students would most recommend an MFT is issues pertaining to marriage and the family. Implications for professional promotion and credentialing include enhancing the visibility, availability, and qualifications of marriage and family counselors (MFCs) or therapists especially through educational venues such as schools as well as media outlets.