bluuebunny/crossref_metadata_2025 huggingface dataset:
Murine Leukemia Virus R Peptide Inhibits Influenza Virus Hemagglutinin-Induced Membrane Fusion
Authors: Li Min , Li Zhu-Nan , Yao Qizhi , Yang Chinglai , Steinhauer David A. , Compans Richard W.
Published: May 2006

The cytoplasmic tail of the murine leukemia virus (MuLV) envelope (Env) protein is known to play an important role in regulating viral fusion activity. Upon removal of the C-terminal 16 amino acids, designated as the R peptide, the fusion activity of the Env protein is activated. To extend our understanding of the inhibitory effect of the R peptide and investigate the specificity of inhibition, we constructed chimeric influenza virus-MuLV hemagglutinin (HA) genes. The influenza virus HA protein is the best-studied membrane fusion model, and we investigated the fusion activities of the chimeric HA proteins. We compared constructs in which the coding sequence for the cytoplasmic tail of the influenza virus HA protein was replaced by that of the wild-type or mutant MuLV Env protein or in which the cytoplasmic tail sequence of the MuLV Env protein was added to the HA cytoplasmic domain. Enzyme-linked immunosorbent assays and Western blot analysis showed that all chimeric HA proteins were effectively expressed on the cell surface and cleaved by trypsin. In BHK21 cells, the wild-type HA protein had a significant ability after trypsin cleavage to induce syncytium formation at pH 5.1; however, neither the chimeric HA protein with the full-length cytoplasmic tail of MuLV Env nor the full-length HA protein followed by the R peptide showed any syncytium formation. When the R peptide was truncated or mutated, the fusion activity was partially recovered in the chimeric HA proteins. A low-pH conformational-change assay showed that similar conformational changes occurred for the wild-type and chimeric HA proteins. All chimeric HA proteins were capable of promoting hemifusion and small fusion pore formation, as shown by a dye redistribution assay. These results indicate that the R peptide of the MuLV Env protein has a sequence-dependent inhibitory effect on influenza virus HA protein-induced membrane fusion and that the inhibitory effect occurs at a late stage in fusion pore enlargement.
Human Cytomegalovirus (HCMV) UL82 Gene Product (pp71) Relieves hDaxx-Mediated Repression of HCMV Replication
Authors: Cantrell Stacy R. , Bresnahan Wade A.
Published: May 2006

This study examines the role of the cellular protein hDaxx in controlling human cytomegalovirus (HCMV) immediate-early (IE) gene expression and viral replication. Using permissive cell lines that either overexpress hDaxx or are depleted of hDaxx expression by the use of short hairpin RNA, we demonstrate that hDaxx functions as a repressor of HCMV IE gene expression and replication. In addition, we demonstrate that the impaired growth phenotype associated with the UL82 (pp71) deletion mutant is abolished when hDaxx knockdown cells are infected, suggesting that pp71 functions to relieve hDaxx-mediated repression during HCMV infection.
Biochemical Activities of Highly Purified, Catalytically Active Human APOBEC3G: Correlation with Antiviral Effect
Authors: Iwatani Yasumasa , Takeuchi Hiroaki , Strebel Klaus , Levin Judith G.
Published: May 2006

APOBEC3G (APO3G), a cytidine deaminase with two zinc finger domains, inhibits
human immunodeficiency virus type 1 replication in the absence of Vif.
Here, we provide a comprehensive molecular analysis of the deaminase
and nucleic acid binding activities of human APO3G using a pure system
containing only one protein component, i.e., highly purified,
catalytically active enzyme expressed in a baculovirus system. We
demonstrate that APO3G deaminates cytosines in single-stranded DNA
(ssDNA) only, whereas it binds efficiently to ssDNA and ssRNA, about
half as well to a DNA/RNA hybrid, and poorly to double-stranded DNA and
RNA. In addition, the base specificities for deamination and binding of
ssDNA are not correlated. The minimum length required for detection of
APO3G binding to an ssDNA oligonucleotide in an electrophoretic
mobility shift assay is 16 nucleotides. Interestingly, if nucleocapsid
protein and APO3G are present in the same reaction, we find that they
do not interfere with each other's binding to RNA and a complex
containing the RNA and both proteins is formed. Finally, we also
identify the functional activities of each zinc finger domain. Thus,
although both zinc finger domains have the ability to bind nucleic
acids, the first zinc finger contributes more to binding and APO3G
encapsidation into virions than finger two. In contrast, deamination is
associated exclusively with the second zinc finger. Moreover, zinc
finger two is more important than finger one for the antiviral effect,
demonstrating a correlation between deaminase and antiviral
activities.
Peptide Aptamers That Bind to a Geminivirus Replication Protein Interfere with Viral Replication in Plant Cells
Authors: Lopez-Ochoa Luisa , Ramirez-Prado Jorge , Hanley-Bowdoin Linda
Published: May 2006

The AL1 protein of tomato golden mosaic virus (TGMV), a member of the geminivirus family, is essential for viral replication in plants. Its N terminus contains three conserved motifs that mediate origin recognition and DNA cleavage during the initiation of rolling-circle replication. We used the N-terminal domain of TGMV AL1 as bait in a yeast two-hybrid screen of a random peptide aptamer library constrained in the active site of the thioredoxin A (TrxA) gene. The screen selected 88 TrxA peptides that also bind to the full-length TGMV AL1 protein. Plant expression cassettes corresponding to the TrxA peptides and a TGMV A replicon encoding AL1 were cotransfected into tobacco protoplasts, and viral DNA replication was monitored by semiquantitative PCR. In these assays, 31 TrxA peptides negatively impacted TGMV DNA accumulation, reducing viral DNA levels to 13 to 64% of those of the wild type. All of the interfering aptamers also bound to the AL1 protein of cabbage leaf curl virus. A comparison of the 20-mer peptides revealed that their sequences are not random. The alignments detected seven potential binding motifs, five of which are more highly represented among the interfering peptides. One motif was present in 18 peptides, suggesting that these peptides interact with a hot spot in the AL1 N terminus. The peptide aptamers characterized in these studies represent new tools for studying AL1 function and can serve as the basis for the development of crops with broad-based resistance to single-stranded DNA viruses.
Activation of Vav by the Gammaherpesvirus M2 Protein Contributes to the Establishment of Viral Latency in B Lymphocytes
Authors: Rodrigues Lénia , Pires de Miranda Marta , Caloca María J. , Bustelo Xosé R. , Simas J. Pedro
Published: May 2006

Gammaherpesviruses subvert eukaryotic signaling pathways to favor latent infections in their cellular reservoirs. To this end, they express proteins that regulate or replace functionally specific signaling proteins of eukaryotic cells. Here we describe a new type of such viral-host interaction that is established through M2, a protein encoded by murine gammaherpesvirus 68. M2 associates with Vav proteins, a family of phosphorylation-dependent Rho/Rac exchange factors that play critical roles in lymphocyte signaling. M2 expression leads to Vav1 hyperphosphorylation and to the subsequent stimulation of its exchange activity towards Rac1, a process mediated by the formation of a trimolecular complex with Src kinases. This heteromolecular complex is coordinated by proline-rich and Src family-dependent phosphorylated regions of M2. Infection of Vav-deficient mice with gammaherpesvirus 68 results in increased long-term levels of latency in germinal center B lymphocytes, corroborating the importance of the M2/Vav cross talk in the process of viral latency. These results reveal a novel strategy used by the murine gammaherpesvirus family to subvert the lymphocyte signaling machinery to its own benefit.
Bovine Herpesvirus 1 UL49.5 Protein Inhibits the Transporter Associated with Antigen Processing despite Complex Formation with Glycoprotein M
Authors: Lipińska Andrea D. , Koppers-Lalic Danijela , Rychłowski Michał , Admiraal Pieter , Rijsewijk Frans A. M. , Bieńkowska-Szewczyk Krystyna , Wiertz Emmanuel J. H. J.
Published: May 2006

Bovine herpesvirus 1 (BHV-1) interferes with peptide translocation by the transporter associated with antigen processing (TAP). Recently, the UL49.5 gene product of BHV-1 was identified as the protein responsible for the observed inhibition of TAP. In BHV-1-infected cells and virions, the UL49.5 protein forms a complex with glycoprotein M (gM). Hence, it was investigated whether UL49.5 can combine the interactions with gM and the TAP complex. In cell lines constitutively expressing both UL49.5 and gM, UL49.5 appears to be required for functional processing of gM. Immunofluorescence-confocal laser scanning microscopy demonstrated that both proteins are interdependent for their redistribution from the endoplasmic reticulum to the
trans
-Golgi network. Remarkably, expression of cloned gM results in the abrogation of the UL49.5-mediated inhibition of TAP and prevents the degradation of the transporter. However, in BHV-1-infected cells, differences in UL49.5 and gM expression kinetics were seen to create a window of opportunity at the early stages of infection, during which time the UL49.5 protein can act on TAP without gM interference. Moreover, in later periods, non-gM-associated UL49.5 can be detected in addition to the UL49.5/gM complex. Thus, it has been deduced that different functions of UL49.5, editing of gM processing and inhibition of TAP, can be combined during BHV-1 infection.
Sindbis Virus Nonstructural Protein nsP2 Is Cytotoxic and Inhibits Cellular Transcription
Authors: Garmashova Natalia , Gorchakov Rodion , Frolova Elena , Frolov Ilya
Published: May 2006

Replication of alphaviruses in vertebrate cells strongly affects cell physiology and ultimately leads to development of a cytopathic effect (CPE) and cell death. Sindbis virus (SIN) replication causes major changes in cellular macromolecular synthesis, in which the strong downregulation of transcription of cellular mRNAs and rRNAs plays a critical role. SIN nonstructural protein nsP2 was previously proposed as one of the main regulators of virus-host cell interactions, because point mutations in the carboxy-terminal part of nsP2 could make SIN and other alphaviruses and replicons less cytopathic and capable of persisting in some vertebrate cell lines. These mutants were incapable of inhibiting transcription and downregulating a viral stress-induced cell response. In the present work, we demonstrate that (i) SIN nsP2 is critically involved in CPE development, not only during the replication of SIN-specific RNAs, but also when this protein is expressed alone from different expression cassettes; (ii) the cytotoxic effect of SIN nsP2 appears to be at least partially determined by its ability to cause transcriptional shutoff; (iii) these functions of SIN nsP2 are determined by the integrity of the carboxy-terminal peptide of this protein located outside its helicase and protease domains, rather than by its protease activity; and (iv) the cytotoxic activity of SIN nsP2 depends on the presence of this protein in a free form, and alterations in P123 processing abolish the ability of nsP2 to cause CPE.
3-
O
-(3′,3′-Dimethysuccinyl) Betulinic Acid Inhibits Maturation of the Human Immunodeficiency Virus Type 1 Gag Precursor Assembled In Vitro
Authors: Sakalian Michael , McMurtrey Curtis P. , Deeg Frederick J. , Maloy Christopher W. , Li Feng , Wild Carl T. , Salzwedel Karl
Published: May 2006

3-
O
-(3′,3′-Dimethysuccinyl) betulinic acid (PA-457) has been shown to potently inhibit human immunodeficiency virus (HIV) replication in culture. In contrast to inhibitors that act upon the viral proteinase, PA-457 appears to block only the final maturational cleavage of p25CA-p2 to p24CA. However, attempts to replicate this effect in vitro using recombinant Gag have failed, leading to the hypothesis that activity is dependent upon the assembly state of Gag. Using a synthesis/assembly system for chimeric HIV type 1 Gag proteins, we have replicated the activity of PA-457 in vitro. The processing of assembled chimeric Gag can be inhibited by the addition of drug with only the final cleavage of p25CA-p2 to p24CA blocked. Consistent with our hypothesis and with previous findings, inhibition appears specific to Gag assembled into an immature capsid-like structure, since synthetic Gag that remains unassembled is properly processed in the presence of the compound. To further analyze the authenticity of the assay, PA-457 was tested in parallel with its inactive parental compound, betulinic acid. Betulinic acid had no effect upon p25 processing in this system. Analysis of a PA-457-resistant mutant, A1V, in this system pointed to more rapid cleavage as a possible mechanism for resistance. However, characterization of additional mutations at the cleavage site and in p2 suggests that resistance does not strictly correlate with the rate of cleavage. With the establishment of an in vitro assay for the detection of PA-457 activity, a more detailed characterization of its mechanism of action will be possible.
My approach to the diagnosis of mesothelial lesions
Authors: Butnor K J
Published: May 2006

Mesothelial lesions pose considerable diagnostic challenges not only because benign tumours, reactive proliferations and malignant mesothelioma can mimic one another, but also because the morphological patterns displayed by malignant mesothelioma can simulate a variety of epithelial and non-epithelial malignancies. Immunohistochemical markers can aid in distinguishing epithelioid malignant mesothelioma from metastatic adenocarcinoma, but because no single marker reliably separates all cases, a panel of stains is recommended. Immunohistochemical studies are of more limited value in sarcomatoid malignant mesothelioma, and other features often play an essential role. The separation of reactive mesothelial proliferations from malignant mesothelioma on small biopsy can be quite difficult, as distinguishing features, such as stromal invasion, often cannot be adequately assessed. In adequately sampled lesions, however, the distinction between malignant mesothelioma, benign mesothelial proliferations and other tumours can be achieved in most cases by using a carefully intergrated approach that incorporates clinical and radiographic data, immunohistochemical studies and, in selected cases, histochemical and ultrastructural techniques.
“Cutaneous-type” angiosarcoma arising in a mature cystic teratoma of the ovary
Authors: den Bakker M A , Ansink A C , Ewing-Graham P C
Published: May 2006

Benign and malignant somatic tumours arising in mature cystic teratomas of the ovary are a rare but recognised phenomenon. Squamous cell carcinoma is the most common somatic malignancy arising in ovarian teratomas, although many other types of tumour have been described. An angiosarcoma with “cutaneous” type typical features arising in a dermoid cyst of the ovary is reported. Vascular tumours have only rarely been described as secondary somatic tumours in ovarian teratomas. The diagnostic features and complications of such tumours are described.
Testing by Sysmex UF-100 flow cytometer and with bacterial culture in a diagnostic laboratory: a comparison
Authors: Evans R , Davidson M M , Sim L R W , Hay A J
Published: May 2006

A large proportion of the samples tested in routine diagnostic microbiology laboratory are urine samples. The gold standard is bacterial culture, but a high proportion of samples cultured are negative. Unnecessary testing can be reduced and an improved service provided by an effective screening test. The Sysmex UF-100 flow cytometer has been developed to count cells and casts accurately in urine samples. Its performance in a screening test was compared with bacterial culture by using 1005 consecutive urine samples, and cut-off criteria were established. Cut-off values of 3000 bacteria/μl and 111 WBC/μl provided the best discrimination. Of 1005 samples, 606 (60%) would be cultured. Sixteen samples that were not selected according to these criteria were culture positive. This was considered acceptable for our routine use. The use of a testing algorithm incorporating the Sysmex UF-100 flow cytometer has improved the quality and efficiency of urine testing within the routine microbiology laboratory.
Finnish doctors and the realisation of patient autonomy in the context of end of life decision making
Authors: Hildén H-M , Honkasalo M-L , Louhiala P
Published: May 2006

Patient autonomy is a fundamental principle in end of life decision making. However, its realisation may take a variety of forms. Discourse analysis was conducted in a qualitative interview study of 19 physicians. The physicians made use of three different discourses, each of which contained a specific understanding of patient autonomy and a physician’s proper activities in the context of end of life decision making.
Primary care confidentiality for Spanish adolescents: fact or fiction?
Authors: Pérez-Cárceles M D , Pereñiguez J E , Osuna E , Pérez-Flores D , Luna A
Published: May 2006

Background:By providing healthcare to adolescents, a major opportunity is created to help them cope with the challenges in their lives, develop healthy behaviour and become responsible healthcare consumers. Confidentiality is a major issue in adolescent healthcare, and its perceived absence may be the main barrier to an adolescent seeking medical care. Little is known, however, about confidentiality for adolescents in primary care practices in Spain.

Objective:To ascertain the attitudes of Spanish family doctors towards the right of adolescents to confidentiality in different healthcare situations and in the prescription of treatment.

Method:A descriptive postal questionnaire was self-administered by family doctors.

Results:Parents of patients under 18 years are always informed by 18.5% of family doctors, whereas parents of those under 16 years are informed by 38.8% of doctors. The patients are warned of this likelihood by 79.3% of doctors. The proportion of doctors supporting confidentiality for adolescents increases with the age and maturity of the patients, whereas workload and previous training has a negative effect.

Conclusions:Spanish laws on adolescent healthcare are not reflected by the paternalistic attitude that Spanish primary care doctors have towards their adolescent patients. Doctors need to be provided with up-to-date and clinically relevant explanations on contemporary legal positions. In primary care, more attention should be paid to adolescents’ rights to information, privacy and confidentiality. Doctors should be more aware of the need to encourage communication between teenagers and their parents, while also safeguarding their patients’ rights to confidential care.
Partnership as an ethical model for medical research in developing countries: the example of the “implementation trial”
Authors: Dowdy D W
Published: May 2006

The existing model for ethical review of medical research consists primarily of regulations designed to prevent exploitation of participants. This model may fail when reviewing other ethical obligations, particularly the responsibility to provide valuable knowledge to society. Such failure is most apparent in developing countries, in which many stakeholders lack incentives or power to uphold society’s interests. An alternative ethical model is that of partnership, which actively involves all partners during ethical review and aims to secure partners’ best interests through compromise. Unlike the existing “regulatory” model, the partnership model effectively addresses ethical obligations to provide positive benefits to society. For the partnership model to be effective, power must be shared among partners; thus, the partnership model can be harmonised with the “regulatory” model through explicit consideration of power structures. One opportunity for crafting power balance in developing countries is apparent in “implementation trials”—randomised trials motivated by and integrated into the implementation of long term public health interventions. Given the failings of the existing ethical review model, alternative models—for example, partnership—and means to balance power—for example, implementation trials—must be explored to ensure that medical research provides knowledge of value to societies in the developing world.
“I am living in my own corpse”—the experience of tuberculosis in poems by A B Šimić
Authors: Dürrigl M-A , Fatović-Ferenčić S
Published: May 2006

This paper focuses on seven poems dealing with various aspects of his experience of tuberculosis and uncovers different shades of poetic self within his verses: the notions of self transforming from a helpless child to a ghostly, transparent creature in the secluded world of a hospital ward, and to decaying flesh and “living in a cadaver” are pinpointed. Poetry as creation is the opposite of physical demise; in poetry Šimić finds escape not from the inevitable end, but from suffering. These poems are not confessions of a sick young man; they are relevant works of art touching readers’ sensitivity and imagination. They may be relevant for medical professionals in enabling them to view disease—in this case tuberculosis—in a wider context and to be open to the many and different ways in which the experience of illness can be expressed.
Body and self: a phenomenological study on the ageing body and identity
Authors: Bullington J
Published: May 2006

The aim of the study was to investigate how older people (60+) experience the ageing body and how these experiences affect aged peoples’ sense of identity. Explorative, open ended, interviews were conducted with 13 respondents between the ages of 63 and 82, recruited from a retired peoples’ organisation, Church organisations, and from the working population. The qualitative data was analysed with a phenomenological method, the so called EPP method, the empirical phenomenological psychological method. The results showed that generally the experience of the ageing body has to do with a changed life world, reactions to this change in terms of body and self, and finding ways to feel at home in this changed situation. Results are presented as three typologies, reflecting the different ways in which the respondents described this general experience: existential awakening, making it good enough, and new possibilities. The results give support to the research that points out the importance of activity for the self esteem of the elderly. According to this study, however, the meaning of “activity” can vary and can have different sources of motivation. Respondents in only one typology expressed frustration over limitations of the ageing body. Respondents exhibited entirely different ways of relating to the fact that death was approaching, which raises questions about how the elderly experience this impending horizon. Finally, the gender differences in this small study were quite clear: all the male respondents belonged to the typology “New possibilities”, raising questions about gender aspects concerning the meaning of freedom, appearance, activity, and self esteem.
Medical ethics as therapy
Authors: Zucker A
Published: May 2006

In this paper, the author examines a style of teaching for a medical ethics course designed for medical students in their clinical years, a style that some believe conflicts with a commitment to analytic philosophy. The author discusses (1) why some find a conflict, (2) why there really is no conflict, and (3) the approach to medical ethics through narratives. The author will also argue that basing medical ethics on the use of narratives has problems and dangers not fully discussed in the literature.
Dr Bruno Sachs addresses an audience of first year medical students: an extract from the writing of Martin Winckler, French doctor and writer
Authors: Jeffries D , Winckler M
Published: May 2006

One of the authors of this paper (DJ) has been impressed by the work of the second author (MW) for some time. On reading one of his works,Les Trois Médecins, DJ was so struck by a particular passage that he attempted a translation. He received not only permission from Winckler to seek publication but also help with the translation. Along with that translation, which forms the body of this article, the passage has been set in context by MW, who also provides some explanation of it. It is DJ’s hope that the article will prove stimulating in its own right, and also lead some readers at least to seek out more of Winckler’s work.
Paradoxical increase in cigarette smuggling after the market opening in Taiwan
Authors: Wen C P , Peterson R A , Cheng T Y D , Tsai S P , Eriksen M P , Chen T
Published: May 2006

Objectives:To assess the magnitude of cigarette smuggling after the market opened in Taiwan.

Methods:Review of tobacco industry documents for references to smuggling activities related to Taiwan and government statistics on seizure of smuggled cigarettes.

Results:The market opening in 1987 led to an increase in smuggling. Contraband cigarettes became as available as legal ones, with only a small fraction (8%) being seized. Being specifically excluded from the market-opening, Japan entered the Taiwan market by setting up a Swiss plant as a legal cover for smuggling 10–20 times its legal quota of exports to Taiwan. Smuggling in Taiwan contributed to increased consumption of foreign brands, particularly by the young. Taiwan, not a member of the World Health Organization, was excluded from the East Asian 16-member “Project Crocodile”, a regional anti-smuggling collaborative effort to implement the Framework Convention on Tobacco Control.

Conclusions:Taiwan showed a sharp increase in smuggling after market liberalisation. Being excluded from the international community, Taiwan faces an uphill battle to fight smuggling alone. If Taiwan remained as its weakest link, global efforts to reduce tobacco use will be undermined, particularly for countries in the East Asian region.
The Philip Morris External Research Program: results from the first round of projects
Authors: Hirschhorn N , Bialous S Aguinaga , Shatenstein S
Published: May 2006

Background:Philip Morris (PM) launched the Philip Morris External Research Program (PMERP) in 2000, two years after the company agreed to the dissolution of two industry-wide, external research programmes: the Council for Tobacco Research (CTR) and the Center for Indoor Air Research (CIAR). Our previous analysis of PMERP’s Request for Applications noted that PMERP’s structure, while ostensibly concerned with new product development, was remarkably similar to that of CIAR. We also found the majority of designated peer-reviewers had previous ties to the tobacco industry and the research solicitation seemed to invite mitigating evidence concerning cigarettes and constituent risks. We concluded that a prime reason for PMERP’s existence was to garner scientific credibility for PM.

Objective:To examine the grants awarded in the first round of PMERP and subsequent peer-reviewed publications.

Methods:Searches of industry documents available on the internet using PMERP and its variations as initial keywords; searches on Medline for publications from PMERP grantees.

Results:Of 153 applications, 61 proposals were funded, 36 of which generated 78 scientific publications. Of these, 65% deal specifically with the tobacco plant or constituents. Over half the researchers listed as PMERP participants had previously received or applied for tobacco funding. One internal document indicated PMERP’s objectives included gaining “credibility” and “goodwill”, and finding “young scientists”. In addition, PM has launched its own and more extensive internal product design research programme.

Conclusion:PMERP appears to exist less as a conduit for critical scientific inquiry than to fit into a corporate strategy intended to burnish PM’s public image.
Risk factors for tobacco dependence in adolescent smokers
Authors: Karp I , O’Loughlin J , Hanley J , Tyndale R F , Paradis G
Published: May 2006

Objective:To study the incidence of conversion to tobacco dependence (TD) and the prevalence of the TD state in relation to several potential determinants in a sample of adolescent smokers.

Methods:Questionnaires were administered every 3–4 months to document TD symptoms, amount of cigarette consumption, and depression symptoms in a prospective cohort of 1293 grade 7 students in a convenience sample of 10 schools.

Results:Over 54 months of follow-up, 113 of 344 novice smokers converted to TD. The referent series for the analysis of incidence comprised 823 person-surveys. The prevalence series included 1673 person-surveys, contributed by 429 smokers. Conversion to TD and TD status were associated with the intensity of recent (that is, past 3-month) cigarette consumption (adjusted incidence rate ratio (aIRR) 1.63 (95% confidence interval (CI) 1.36 to 1.97) and adjusted prevalence odds ratio (aPOR) 1.35 (95% CI 1.23 to 2.48) per 100 cigarettes per month), slowest CYP2A6 activity (aIRR 4.19 (95% CI 1.38 to 12.76) and aPOR 2.30 (95% CI 1.29 to 4.09)), depression score (aIRR 1.61 (95% CI 1.17 to 2.21) and aPOR 1.47 (95% CI 1.22, 1.75) per 1-unit change). Additional determinants included, for conversion to TD, time since onset of cigarette use (aIRR 0.76 (95% CI 0.58 to 1.00) per year) and, for the TD state, positive TD status six months ago (aPOR 3.53 (95% CI 2.41 to 5.19)).

Conclusions:TD risk in adolescents is associated with intensity of recent cigarette consumption, while the role of more distant cigarette consumption appears small; subjects with slow nicotine metabolism and those with more depression symptoms are at increased risk of becoming tobacco dependent. The risk of being tobacco dependent is considerably higher in subjects who had previously developed the TD state.
Why are urban Indian 6th graders using more tobacco than 8th graders? Findings from Project MYTRI
Authors: Stigler M H , Perry C L , Arora M , Reddy K S
Published: May 2006

Objective:To investigate why urban Indian 6th graders may be using more tobacco than urban Indian 8th graders.

Design:Cross-sectional survey of students conducted in the summer of 2004, as the baseline evaluation tool for a group-randomised tobacco prevention intervention trial (Project MYTRI). Mixed-effects regression models were used to (1) examine the relationship between 15 psychosocial risk factors and current use of any tobacco, by grade; and (2) examine differences in psychosocial risk factors, by grade.

Setting:Thirty-two private (high socioeconomic status (SES)) and government (low-mid SES) schools in two large cities in India (Delhi and Chennai).

Subjects:Students in the 6th and 8th grade in these schools (n  =  11642). Among these, 50.6% resided in Delhi (vChennai), 61.4% attended a government school (va private school), 52.9% were enrolled in 6th grade (v8th), and 54.9% were male (vfemale).

Main outcome measure:Current (past 30 day) use of any tobacco, including chewing tobacco (for example, gutkha), bidis, or cigarettes.

Result:Almost all psychosocial factors were significantly related to tobacco use, for students in both grades. Some of the strongest correlates included social susceptibility to and social norms about use. Exposure to tobacco advertising was a strong correlate of tobacco use for 6th graders, but not for 8th graders. Sixth graders scored lower than 8th graders on almost all factors, indicating higher risk.

Conclusions:The “risk profile” of 6th graders suggests they would be vulnerable to use and to begin using tobacco, as well as to outside influences that may encourage use.
China at the crossroads: the economics of tobacco and health
Authors: Hu T-W , Mao Z , Ong M , Tong E , Tao M , Jiang H , Hammond K , Smith K R , de Beyer J , Yurekli A
Published: May 2006

Objective:To analyse economic aspects of tobacco control policy issues in China.

Methods:Published and collected survey data were used to analyse economic consequences of smoking. Economic analysis was used to address the role of tobacco farmers and the cigarette industry in the Chinese economy.

Results:In the agricultural sector, tobacco has the lowest economic rate of return of all cash crops. At the same time, the tobacco industry’s tax contribution to the central government has been declining.

Conclusion:Economic gains become less important as the negative health impact of smoking on the population garners more awareness. China stands at a crossroads to implement the economic promises of the World Health Organization’s Framework Convention on Tobacco Control and promote the health of its population.
Building capacity for tobacco control research and policy: Table 1
Authors: Stillman F , Yang G , Figueiredo V , Hernandez-Avila M , Samet J
Published: May 2006

The Fogarty International Center (FIC) initiative, “International Tobacco and Health Research Capacity Building Program” represents an important step in US government funding for global tobacco control. Low- and middle-income countries of the world face a rising threat to public health from the rapidly escalating epidemic of tobacco use. Many are now parties to the Framework Convention on Tobacco Control (FCTC) and capacity development to meet FCTC provisions. One initial grant provided through the FIC was to the Institute for Global Tobacco Control (IGTC) at the Johns Hopkins Bloomberg School of Public Health (JHSPH) to support capacity building and research programmes in China, Brazil, and Mexico. The initiative’s capacity building effort focused on: (1) building the evidence base for tobacco control, (2) expanding the infrastructure of each country to deliver tobacco control, and (3) developing the next generation of leaders as well as encouraging networking throughout the country and with neighbouring countries. This paper describes the approach taken and the research foci, as well some of the main outcomes and some identified challenges posed by the effort. Individual research papers are in progress to provide more in-depth reporting of study results.
The tobacco epidemic in Syria
Authors: Ward K D , Eissenberg T , Rastam S , Asfar T , Mzayek F , Fouad M F , Hammal F , Mock J , Maziak W
Published: May 2006

Background:The Syrian Center for Tobacco Studies (SCTS) was established in response to the smoking epidemic in Syria and lack of local knowledge and expertise to confront it.

Objectives:To (1) study tobacco use and local smoking practices using both qualitative and quantitative research methods; (2) develop and test an effective smoking cessation intervention for the Syrian environment; and (3) train Syrian researchers.

Methods and results:The Aleppo Household Survey involved a representative sample of adults in Aleppo (2038 subjects, 45.2% men, mean age 35.3 years, response rate 86%). The prevalence of cigarette smoking was 56.9% among men and 17.0% among women, while the prevalence of waterpipe smoking was 20.2% among men and 4.8% among women. Daily use predominated for cigarettes (29.0%), while the opposite was seen in waterpipe use with 10.6% smoking occasionally. Interest in quitting was greater for cigarette than waterpipe smokers (74.0%v48.6%), while quit rates were higher for waterpipe compared to cigarettes (28.2%v16.5%). In-depth ethnographic interviews with smokers show that smoking waterpipe is often viewed as an aesthetic enjoyable experience, while smoking cigarettes is viewed as a mundane anxiety-relieving addiction. Clinical laboratory studies reveal that both waterpipe and cigarette smokers in Syria are exposed to smoke toxicants and exhibit dependence symptoms.

Conclusions:All these data have been used iteratively to adapt smoking cessation interventions from developed countries to suit the local Syrian environment. Research conducted in the SCTS to date has provided a fertile training ground for Syrian researchers, as well as for the building of regional collaborations.
Personal, interpersonal, and cultural predictors of stages of cigarette smoking among adolescents in Johannesburg, South Africa
Authors: Brook J S , Morojele N K , Brook D W , Zhang C , Whiteman M
Published: May 2006

Objective:This study examined the personal, parental, peer, and cultural predictors of stage of smoking among South African urban adolescents.

Design:A cross-sectional design was employed. A stratified random approach based on census data was used to obtain the sample. Analyses were conducted using logistic regression.

Setting:The study took place in communities in and around Johannesburg, South Africa.

Subjects:Participants consisted of 731 adolescents in the age range of 12–17 years old. The sample was 47% male and 53% female, and contained four ethnic classifications: white, black, Indian, and “coloured” (a South African term for mixed ancestry).

Methods:A structured, in-person interview was administered to each participant in private by a trained interviewer, after obtaining consent.

Main outcome measures:The dependent variables consisted of three stages of smoking: non-smoking, experimental smoking, and regular smoking. The independent measures were drawn from four domains: personal attributes, parental, peer, and cultural influences.

Results:Factors in all four domains significantly predicted three different stages of smoking. Personal attributes (internalising and externalising) distinguished among the three stages. Parental factors (for example, affection) reduced the odds of being a regular smoker compared with an experimental smoker or non-smoker, but did not differentiate experimental smokers from non-smokers. Findings from the peer domain (for example, peer substance use) predicted an increase in the risk of being a regular smoker compared with an experimental smoker or non-smoker. In the cultural domain, ethnic identification predicted a decrease in the risk of being a regular smoker compared with an experimental smoker, whereas discrimination and victimisation predicted an increase in the risk of being an experimental smoker compared with a non-smoker.

Conclusions:All the domains were important for all four ethnic groups. Four psychosocial domains are important in distinguishing among the three stages of smoking studied. Some predictors differentiated all stages of smoking, others between some of the stages of smoking. Therefore, intervention and prevention programmes which are culturally and linguistically sensitive and appropriate should consider the individual’s stage of smoking.
Vulnerability to smoking after trying a single cigarette can lie dormant for three years or more
Authors: Fidler J A , Wardle J , Henning Brodersen N , Jarvis M J , West R
Published: May 2006

Objective:To examine the development of smoking behaviour among adolescents who, at age 11, had tried cigarettes just once.

Design:A five-year prospective study.

Setting:36 schools in South London, England.

Subjects:A socioeconomically and ethnically diverse sample of students completed questionnaires annually from age 11–16. A total of 5863 students took part, with an annual response rate ranging from 74–85%. 2041 (35%) provided smoking status data every year.

Main outcome measures:Current smoking (smoking sometimes or more often) for the first time. Cotinine assays provided biochemical verification of smoking status.

Results:Students who at age 11 reported having tried smoking cigarettes just once (n = 260), but were not smoking at the time, were more likely to take-up smoking at a later age than those that had not tried smoking (n = 1719), even after a gap of up to three years of not smoking. The odds of starting to smoke at age 14 were 2.1 times greater (95% confidence interval 1.2 to 3.5) in the age 11 “one time triers” than the “non-triers”, even once sex, ethnicity, deprivation, parental smoking and conduct disorder were adjusted for.

Conclusions:This is the first clear demonstration of a “sleeper effect” or period of dormant vulnerability. Our findings have implications for understanding the development of cigarette use and for policies to reduce smoking in young people. Preventing children from trying even one cigarette may be important, and the design of interventions should recognise adolescents who have smoked just once, several years previously, as potentially vulnerable to later smoking uptake.
Role of snus in initiation and cessation of tobacco smoking in Sweden
Authors: Ramström L M , Foulds J
Published: May 2006

Objective:To examine patterns of smoking and snus use and identify individual pathways of Swedish tobacco users in order to clarify whether snus use is associated with increased or decreased smoking.

Methods:Retrospective analysis of data from a cross-sectional survey completed by 6752 adult Swedes in 2001–2 focusing on identifying tobacco use history by survey items on current and prior tobacco use and smoking initiation and cessation procedures.

Results:15% of the men and 19% of the women completing the survey were daily smokers. 21% of the men and 2% of the women were daily snus users. Almost all (91%) male daily smoking began before the age of 23 years, whereas initiation of daily snus use continued throughout the age range (33% of initiation after age 22). 20% of male primary snus users started daily smoking compared to 47% of non-primary snus users. Thus, the odds of initiating daily smoking were significantly lower for men who had started using snus than for those who had not (odds ratio (OR) 0.28, 95% confidence interval (CI) 0.22 to 0.36). Among male primary smokers, 28% started secondary daily snus use and 73% did not. 88% of those secondary snus users had ceased daily smoking completely by the time of the survey as compared with 56% of those primary daily smokers who never became daily snus users (OR 5.7, 95% CI 4.9 to 8.1). Among men who made attempts to quit smoking, snus was the most commonly used cessation aid, being used by 24% on their latest quit attempt. Of those men who had used one single cessation aid 58% had used snus, as compared with 38% for all nicotine replacement therapy products together. Among men who used snus as a single aid, 66% succeeded in quitting completely, as compared with 47% of those using nicotine gum (OR 2.2, 95% CI 1.3 to 3.7) or 32% for those using the nicotine patch (OR 4.2, 95% CI 2.1 to 8.6). Women using snus as an aid were also significantly more likely to quit smoking successfully than those using nicotine patches or gum.

Conclusion:Use of snus in Sweden is associated with a reduced risk of becoming a daily smoker and an increased likelihood of stopping smoking.
Mentoring Cambodian and Lao health professionals in tobacco control leadership and research skills
Authors: Ferry L Hyder , Job J , Knutsen S , Montgomery S , Petersen F , Rudatsikira E , Singh P
Published: May 2006

Design:The aim of the programme was to ultimately affect public health practice and policy in the Kingdom of Cambodia and Lao People’s Democratic Republic (Lao PDR) by training key health professionals to conduct tobacco control research.

Setting:Encouraged by the World Health Organization’s Framework Convention on Tobacco Control, a global partnership formed to build effective leadership to develop and guide national tobacco control agendas. The partners were the Ministries of Health (Cambodia and Lao PDR), non-government organisations (Adventist Development and Relief Agency in Cambodia and Laos) and an academic institution (Loma Linda University, Loma Linda, California, USA).

Subjects:16 health professionals, 10 from Cambodia and 6 from Lao PDR, were selected by local advisory committees to enter a two-year, intensive tobacco research graduate certificate and research training programme.

Intervention:We developed a “Global Tobacco Control Methods” (GTCM) 28 unit certificate programme that was offered in five sessions from September 2003 to September 2005 at the National Institute of Public Health, Phnom Penh, Cambodia. As part of their coursework, the 16 trainees actively participated in the development and implementation of two research projects. In the first project, “Healthy Doc Healthy Patient” (HDHP), trainees adapted an existing, self-administered questionnaire designed to assess health practices and beliefs of medical students in Cambodia and Lao PDR. The second project involved the design of a national prevalence of tobacco use and health beliefs study in Cambodia using a multi-stage, cluster sample method. Trainees were sponsored to attend and present at international tobacco control conferences to enhance their awareness of the tobacco epidemic.

Results:As of September 2005, 14 trainees (8 from Cambodia and 6 from Lao PDR) completed the courses in the GTCM certificate programme. The HDHP study sampled four medical school classes (years 3, 4, 5 and 6) in both Cambodia (n  =  330, 71.1% response rate) and Lao PDR (n  =  386, 87.3% response rate). As part of the Cambodian adult tobacco prevalence study in Cambodia, 13 988 adults (ages ⩾ 18 years) were interviewed from all 22 provinces during the summer of 2005. Over the two years, more than half of the trainees participated substantially in local and regional tobacco control and research activities. Programme challenges included the trainees’ limited English language and computer proficiency skills, both of which improved during the two years.

Conclusions:With the successful completion of the certificate programme, the remaining two years of the grant will be used to prepare the trainees for positions of leadership within their Ministries of Health and other agencies to implement effective tobacco control policies based on locally-derived research findings.
Economic burden of smoking in China, 2000
Authors: Sung H-Y , Wang L , Jin S , Hu T-W , Jiang Y
Published: May 2006

Objective:To assess the health-related economic burden attributable to smoking in China for persons aged 35 and older.

Methods:A prevalence-based, disease-specific approach was used to estimate the smoking attributable direct costs, indirect morbidity costs, and costs of premature deaths caused by smoking-related diseases. The primary data source was the 1998 China National Health Services Survey, which contains the smoking status, medical utilisation, and expenditures for 216 101 individuals.

Results:The economic costs of smoking in 2000 amounted to $5.0 billion (measured in 2000, US$) in total and $25.43 per smoker (⩾ age 35). The share of the economic costs was greater for men than women, and greater in rural areas than in urban areas. Of the $5.0 billion total costs, direct costs were $1.7 billion (34% of the total), indirect morbidity costs were $0.4 billion (8%), and indirect mortality costs were $2.9 billion (58%). The direct costs of smoking accounted for 3.1% of China’s national health expenditures in 2000.

Conclusion:The adverse health effects of smoking constitute a huge economic burden to the Chinese society. To reduce this burden in the future, effective tobacco control programmes and sustained efforts are needed to curb the tobacco epidemic and economic losses.
AN AXISYMMETRIC INCOMPRESSIBLE LATTICE BOLTZMANN MODEL FOR PIPE FLOW
Authors: LEE T. S. , HUANG HAIBO , SHU C.
Published: May 2006

In this paper an accurate axisymmetric lattice Boltzmann D2Q9 model is proposed to simulate the steady and pulsatile flows in circular pipes. Present model is derived from an incompressible D2Q9 model and some errors in a previous model [Halliday et al., Phys. Rev. E64, 011208 (2001)] are revised. In the previous model, some terms relative to the radial velocity are missing and would lead to large error for constricted or expanded pipe flows. Present model is validated by cases of laminar steady flow through constricted tubes and 3D Womersley flow. Comparing with the previous model, our model is much more accurate for steady flow in constricted circular pipes. For 3D Womersley flow, it is also observed that the present model can reduce the compressibility effect in previous model.