Spider Zygoma: a new implant rehabilitation technique for atrophic maxilla.

OAtrophic maxilla is a challenge in dental implant surgery, and new strategies are needed. We present a new minimally-invasive approach, called "Spider Zygoma", consisting of implant-supported prosthesis with the addition of customized maxillofacial plates and screws on surface of zygomatic bone. A 3D-model of the edentulous upper jaw was used as preoperative model. Two customized bone plates were created and used as guide for placement of implants and zygomatic screws. Although this is only a pilot study, this new surgical technique seems to be safe and accurate, confirmed by the maintenance of good aesthetic and functional results after 5-year follow-up.

Beliefs about the relative harm of "light" and "low tar" cigarettes: findings from the International Tobacco Control (ITC) China Survey.

BACKGROUND: Many smokers in Western countries perceive "light" or "low tar" cigarettes as less harmful and less addictive than "regular" or "full flavoured" cigarettes. However, there is little research on whether similar perceptions exist among smokers in low and middle incomes, including China. OBJECTIVE: To characterise beliefs about "light" and "low tar" cigarettes among adult urban smokers in China. METHODS: We analysed data from Wave 1 of the ITC China Survey, a face-to-face household survey of 4732 adult Chinese smokers randomly selected from six cities in China in 2006. Households were sampled using a stratified multistage design. FINDINGS: Half (50.0%) of smokers in our sample reported having ever tried a cigarette described as "light," "mild" or "low tar". The majority of smokers in our sample (71%) believed that "light" and/or "low tar" cigarettes are less harmful compared to "full flavoured" cigarettes. By far the strongest predictor of the belief that "light" and/or "low tar" cigarettes are less harmful was the belief that "light" and/or "low tar" cigarettes feel smoother on the respiratory system (p<0.001, OR=53.87, 95% CI 41.28 to 70.31). CONCLUSION: Misperceptions about "light" and/or "low tar" cigarettes were strongly related to the belief that these cigarettes are smoother on the respiratory system. Future tobacco control policies should go beyond eliminating labelling and marketing that promotes "light" and "low tar" cigarettes by regulation of product characteristics (for example, additives, filter vents) that reinforce perceptions that "light" and "low tar" cigarettes are smoother on the respiratory system and therefore less harmful.

A small molecule inhibitor of Pim protein kinases blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma.

The serine/threonine Pim kinases are up-regulated in specific hematologic neoplasms, and play an important role in key signal transduction pathways, including those regulated by MYC, MYCN, FLT3-ITD, BCR-ABL, HOXA9, and EWS fusions. We demonstrate that SMI-4a, a novel benzylidene-thiazolidine-2, 4-dione small molecule inhibitor of the Pim kinases, kills a wide range of both myeloid and lymphoid cell lines with precursor T-cell lymphoblastic leukemia/lymphoma (pre-T-LBL/T-ALL) being highly sensitive. Incubation of pre-T-LBL cells with SMI-4a induced G1 phase cell-cycle arrest secondary to a dose-dependent induction of p27(Kip1), apoptosis through the mitochondrial pathway, and inhibition of the mammalian target of rapamycin C1 (mTORC1) pathway based on decreases in phospho-p70 S6K and phospho-4E-BP1, 2 substrates of this enzyme. In addition, treatment of these cells with SMI-4a was found to induce phosphorylation of extracellular signal-related kinase1/2 (ERK1/2), and the combination of SMI-4a and a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor was highly synergistic in killing pre-T-LBL cells. In immunodeficient mice carrying subcutaneous pre-T-LBL tumors, treatment twice daily with SMI-4a caused a significant delay in the tumor growth without any change in the weight, blood counts, or chemistries. Our data suggest that inhibition of the Pim protein kinases may be developed as a therapeutic strategy for the treatment of pre-T-LBL.

PIM1 protein kinase regulates PRAS40 phosphorylation and mTOR activity in FDCP1 cells.

PIM1 is a serine/threonine kinase that has diverse biological roles in cell survival, proliferation and differentiation. PIM1 has been implicated in early transformation and tumor progression in haematopoietic malignancies and prostate carcinomas. The ability of PIM1 to regulate these processes is thought to be in part secondary to its activity in stimulating 4EBP1 phosphorylation and enhancement of protein synthesis. Because 4EBP1 is an mTOR substrate, we have investigated how PIM1 might regulate this latter enzyme. We have examined the ability of PIM1 to modulate PRAS40, a protein known to negatively regulate mTOR activity in FDCP1 cells. Upon phosphorylation, PRAS40 dissociates from the mTOR complex and increases mTOR kinase activity. We find that enforced overexpression of PIM1 increases PRAS40 phosphorylation at Thr(246), an AKT phosphorylation site, whether grown in complete media or deprived of IL-3 and serum. The increase in PRAS40 phosphorylation was independent of AKT activation and not inhibited by wortmannin. In vitro kinase assays indicate that the PIM1 protein kinase is capable of directly phosphorylating Thr(246) in PRAS40. PIM1 protein kinase overexpression reduced the association of PRAS40 with mTOR, and increased the mTOR directed phosphorylation of 4EBP1 and p70S6Kinase. Treatment of FDCP1 cells transfected with PIM1 (FD/mpim44) with small molecule inhibitors of PIM1 kinase activity reduced both PRAS40 and 4EBP1 phosphorylation. These results suggest that PIM1 regulates mTOR activity through phosphorylation of PRAS40. Thus, increases in mTOR activity mediated by the PIM protein kinase may have the potential to control cell growth.

Synthesis and evaluation of novel inhibitors of Pim-1 and Pim-2 protein kinases.

The Pim protein kinases are frequently overexpressed in prostate cancer and certain forms of leukemia and lymphoma. 5-(3-Trifluoromethylbenzylidene)thiazolidine-2,4-dione (4a) was identified by screening to be a Pim-1 inhibitor and was found to attenuate the autophosphorylation of tagged Pim-1 in intact cells. Although 4a is a competitive inhibitor with respect to ATP, a screen of approximately 50 diverse protein kinases demonstrated that it has high selectivity for Pim kinases. Computational docking of 4a to Pim-1 provided a model for lead optimization, and a series of substituted thiazolidine-2,4-dione congeners was synthesized. The most potent new compounds exhibited IC(50)s of 13 nM for Pim-1 and 2.3 microM for Pim-2. Additional compounds in the series demonstrated selectivities of more than 2500-fold and 400-fold for Pim-1 or Pim-2, respectively, while other congeners were essentially equally potent toward the two isozymes. Overall, these compounds are new Pim kinase inhibitors that may provide leads to novel anticancer agents.

What happened to smokers' beliefs about light cigarettes when "light/mild" brand descriptors were banned in the UK? Findings from the International Tobacco Control (ITC) Four Country Survey.

AIM: This paper examines how beliefs of smokers in the UK were affected by the removal of "light" and "mild" brand descriptors, which came into effect on 30 September 2003 for Member States of the European Union (EU). PARTICIPANTS: The data come from the first four waves (2002-2005) of the International Tobacco Control Policy Evaluation (ITC) Four-Country Survey, an annual cohort telephone survey of adult smokers in Canada, USA, UK and Australia (15 450 individual cases). DESIGN: The UK ban on misleading descriptors occurred around the second wave of data collection in the ITC survey, permitting us to compare beliefs about light cigarettes among adult smokers in the UK before and after the ban, with beliefs in the three other ITC countries unaffected by the ban. RESULTS: There was a substantial decline in reported beliefs about the benefits of light cigarettes in the UK following the policy change and an associated public information campaign, but by 2005 (ie, wave 4), these beliefs rebounded slightly and the change in beliefs was no greater than in the USA, where there was no policy change. CONCLUSIONS: The findings reveal that high levels of misperceptions about light cigarettes existed among smokers in all four countries before and after the EU ban took effect. We cannot conclude that the policy of removing some aspects of misleading labels has been effective in changing beliefs about light cigarettes. Efforts to correct decades of consumer misperceptions about light cigarettes must extend beyond simply removing "light" and "mild" brand descriptors.

Intracranial haemorrhage in patients on antithrombotics: clinical presentation and determinants of outcome in a prospective multicentric study in Italian emergency departments.

BACKGROUND: Intracranial haemorrhage (ICH) is the type of stroke associated with the highest death rate, and about 30% of ICH occurs in patients on antithrombotic treatment. This study relates clinical presentations and outcome of ICH patients on oral anticoagulant (OA) or antiplatelet (AP) therapy admitted to 33 Italian emergency departments (ED). METHODS: Consecutive patients were enrolled after cranial computed tomography (CT). Primary outcome was the Modified Rankin Scale (MRS) score at 3 months of follow-up. Common descriptive statistics were computed after stratification for traumatic or spontaneous ICH and identification of the anatomical location of bleeding. Multivariate logistic regression was used to assess predictors of death. RESULTS: We recruited 434 patients on AP therapy and 232 on OA. There were 432 spontaneous and 234 traumatic ICH patients. The proportions of AP and OA patients undergoing neurosurgery were 21.8 and 19.4%, respectively, while < 30% underwent procoagulant medical treatment. At the 3-month follow-up, the case fatality rate was 42.0%, while disability or death (MRS 3-6) was 68.1%. The odds ratio for death in OA versus AP patients was 2.63 (95% CI 1.73-4.00) in the whole population and 2.80 (95% CI 1.77-4.41) in intraparenchymal event patients. Glasgow Coma Scale, age, spontaneous event and anticoagulant use were found to be predictors of death both in traumatic and spontaneous events. CONCLUSION: This study confirms the high prevalence of death or disability in OA and AP patients with ICH. As far as the determinants of mortality and disability are concerned, the results of this study might be useful in the clinical management and allocation of resources in the ED setting. The observed low use of procoagulant therapy highlights the need for ED educational programmes to heighten the awareness of available and effective haemostatic treatments.

Histidine ligand protonation and redox potential in the rieske dioxygenases: role of a conserved aspartate in anthranilate 1,2-dioxygenase.

The Rieske dioxygenase, anthranilate 1,2-dioxygenase, catalyzes the 1,2-dihydroxylation of anthranilate (2-aminobenzoate). As in all characterized Rieske dioxygenases, the catalytic conversion to the diol occurs within the dioxygenase component, AntAB, at a mononuclear iron site which accepts electrons from a proximal Rieske [2Fe-2S] center. In the related naphthalene dioxygenase (NDO), a conserved aspartate residue lies between the mononuclear and Rieske iron centers, and is hydrogen-bonded to a histidine ligand of the Rieske center. Engineered substitutions of this aspartate residue led to complete inactivation, which was proposed to arise from elimination of a productive intersite electron transfer pathway [Parales, R. E., Parales, J. V., and Gibson, D. T. (1999) J. Bacteriol. 181, 1831-1837]. Substitutions of the corresponding aspartate, D218, in AntAB with alanine, asparagine, or glutamate also resulted in enzymes that were completely inactive over a wide pH range despite retention of the hexameric quaternary structure and iron center occupancy. The Rieske center reduction potential of this variant was measured to be approximately 100 mV more negative than that for the wild-type enzyme at neutral pH. The wild-type AntAB became completely inactive at pH 9 and exhibited an altered Rieske center absorption spectrum which resembled that of the D218 variants at neutral pH. These results support a role for this aspartate in maintaining the protonated state and reduction potential of the Rieske center. Both the wild-type and D218A variant AntABs exhibited substrate-dependent rapid phases of Rieske center oxidations in stopped-flow time courses. This observation does not support a role for this aspartate in a facile intersite electron transfer pathway or in productive substrate gating of the Rieske center reduction potential. However, since the single turnovers resulted in anthranilate dihydroxylation by the wild-type enzyme but not by the D218A variant, this aspartate must also play a crucial role in substrate dihydroxylation at or near the mononuclear iron site.

Enhancing the effectiveness of tobacco package warning labels: a social psychological perspective.

OBJECTIVE: To outline social psychological principles that could influence the psychosocial and behavioural effects of tobacco warning labels, and to inform the development of more effective tobacco warning labels. DATA SOURCES: PsycInfo and Medline literature searches and expert guided selection of principles and theories in social psychology and of tobacco warning labels, including articles, books, and reports. CONCLUSIONS: Tobacco warning labels represent a potentially effective method of influencing attitudes and behaviours. This review describes social psychological principles that could be used to guide the creation of more effective warning labels. The potential value of incorporating warning labels into a broader public health education campaign is discussed, and directions for future research are suggested.

X-ray crystal structure of benzoate 1,2-dioxygenase reductase from Acinetobacter sp. strain ADP1.

One of the major processes for aerobic biodegradation of aromatic compounds is initiated by Rieske dioxygenases. Benzoate dioxygenase contains a reductase component, BenC, that is responsible for the two-electron transfer from NADH via FAD and an iron-sulfur cluster to the terminal oxygenase component. Here, we present the structure of BenC from Acinetobacter sp. strain ADP1 at 1.5 A resolution. BenC contains three domains, each binding a redox cofactor: iron-sulfur, FAD and NADH, respectively. The [2Fe-2S] domain is similar to that of plant ferredoxins, and the FAD and NADH domains are similar to members of the ferredoxin:NADPH reductase superfamily. In phthalate dioxygenase reductase, the only other Rieske dioxygenase reductase for which a crystal structure is available, the ferredoxin-like and flavin binding domains are sequentially reversed compared to BenC. The BenC structure shows significant differences in the location of the ferredoxin domain relative to the other domains, compared to phthalate dioxygenase reductase and other known systems containing these three domains. In BenC, the ferredoxin domain interacts with both the flavin and NAD(P)H domains. The iron-sulfur center and the flavin are about 9 A apart, which allows a fast electron transfer. The BenC structure is the first determined for a reductase from the class IB Rieske dioxygenases, whose reductases transfer electrons directly to their oxygenase components. Based on sequence similarities, a very similar structure was modeled for the class III naphthalene dioxygenase reductase, which transfers electrons to an intermediary ferredoxin, rather than the oxygenase component.

Compensatory conviction in the face of personal uncertainty: going to extremes and being oneself.

Study 1 participants' self-integrity (C. M. Steele. 1988) was threatened by deliberative mind-set (S. E. Taylor & P. M. Gollwitzer, 1995) induced uncertainty. They masked the uncertainty with more extreme conviction about social issues. An integrity-repair exercise after the threat, however, eliminated uncertainty and the conviction response. In Study 2, the same threat caused clarified values and more self-consistent personal goals. Two other uncertainty-related threats, mortality salience and temporal discontinuity, caused similar responses: more extreme intergroup bias in Study 3, and more self-consistent personal goals and identifications in Study 4. Going to extremes and being oneself are seen as 2 modes of compensatory conviction used to defend against personal uncertainty. Relevance to cognitive dissonance and authoritarianism theories is discussed, and a new perspective on terror managenment theory (J. Greenberg, S. Solomom, & T. Pyszczynski, 1997) is proposed.

Alcohol, sexual arousal, and intentions to use condoms in young men: applying alcohol myopia theory to risky sexual behavior.

Data from 7 studies were aggregated to examine how reported sexual arousal and alcohol intoxication interact to affect attitudes and intentions toward engaging in unprotected sexual intercourse in college-age men (N = 358). When participants were in a sober or placebo condition, their self-reports of sexual arousal had no effect on their responses. When participants were intoxicated, however, those who felt sexually aroused reported more favorable attitudes, thoughts, and intentions toward having unprotected sex than did those who did not feel aroused. These findings support alcohol myopia theory (C. M. Steele & R. A. Josephs, 1990), which states that alcohol intoxication restricts attentional capacity so that people are highly influenced by the most salient cues in their environment. It is suggested that sexual arousal is a powerful internal cue that interacts with alcohol intoxication to enhance attitudes and intentions toward risky sexual behaviors.

Alcohol myopia and condom use: can alcohol intoxication be associated with more prudent behavior?

We tested 2 competing theories about the effects of alcohol on intentions to engage in risky behavior. Disinhibition predicts that intoxicated people will exhibit risky behavior regardless of environmental cues, whereas alcohol myopia (C. M. Steele & R. A. Josephs, 1990) predicts that intoxicated people will be more or less likely to exhibit risky behavior, depending on the cues provided. In 4 studies, we found an interaction between intoxication and cue type. When impelling cues were present, intoxicated people reported greater intentions to have unprotected sex than did sober people. When subtle inhibiting cues were present, intoxicated and sober people reported equally cautious intentions (Studies 1-3). When strong inhibiting cues were present, intoxicated people reported more prudent intentions than did sober people (Study 4). We suggest that alcohol myopia provides a more comprehensive account of the effects of alcohol than does disinhibition.

Polypharmacy. Reducing adverse events among the elderly in NJ.

This is the second of a two-part series that focuses on reducing polypharmacy and adverse drug events in the community-dwelling elderly. Part 2 focuses on the medical exception process (MEP), explains information flow relevant to the physician's practice, and provides clinical examples illustrating the potential of computer technology in improving outcomes of care. A combined approach, which employs computer-based technology, values physician judgment, and stresses patient and provider education, is described.

Polypharmacy. Reducing adverse events among the elderly in NJ. Part 1.

This is the first of a two-part series that focuses on reducing polypharmacy and adverse drug events in the community-dwelling elderly. Part 1 provides a rationale for the design of public health interventions to reduce this problem and explores technology development. The components of an integrated system linking computer-based technology, pharmacists, and physicians are outlined.

Community Intervention Trial for Smoking Cessation (COMMIT): changes in community attitudes toward cigarette smoking.

The success of the Community Intervention Trial for Smoking Cessation (COMMIT) in changing smoking attitudes is examined by testing two primary hypotheses: (1) the priority of smoking as a public health problem increased more in the intervention communities than in the comparison communities, and (2) norms and values that support non-smoking increased more in the intervention than in the comparison communities. One community within each of 11 matched pairs was randomly assigned to receive a 4-year (1989-92) community-based smoking control intervention. Community attitudes towards smoking were measured primarily by cross-sectional surveys in 1989 (n = 9875) and 1993 (n = 14117) but a cohort (n = 5450) also provided attitude information. The main trial effect was on heavy smokers in the intervention communities who showed significantly more change in their beliefs about smoking as a public health problem. Despite the absence of an intervention-comparison difference, the magnitude of change in community-wide norms and values was related to the level of smoking control activities. In the cohort, light-to-moderate smokers in the intervention communities came to have stronger beliefs about smoking as a serious public health problem. COMMIT's impact on the beliefs of heavy smokers about the seriousness of smoking as a public health problem has important public health implications.

Measuring attitudes towards smoking in the Community Intervention Trial for Smoking Cessation (COMMIT).

We present the development of indices using baseline data from the Evaluation Survey for the Community Intervention Trial for Smoking Cessation (COMMIT). The indices are designed to measure two primary attitude constructs that relate to smoking behavior: beliefs about smoking as a public health problem (SPHP); and norms and values concerning smoking (NVS). Two general approaches to index construction, the rational method and the factor analytic method, were used. Item analysis suggested good internal consistency for both indices (alpha > 0.75). Seven subconstructs emerged from the factor analysis accounting for 55.0% of the total variance. The SPHP and NVS items uniquely identify with four factors and three factors, respectively, confirming the validity of the two indices. Confirmatory factor analyses of a different data set provided further validation. Validity was also assessed by an examination of the relationships between index scores and smoking status. Smokers reported significantly higher scores than non-smokers on the two measures indicating, as anticipated, that smokers have more favorable attitudes towards smoking than non-smokers. These findings suggest that the two a priori constructs of SPHP and NVS are empirically distinguishable components of attitudes towards smoking, and that the indices developed here are reliable and valid measures of those constructs.

The conflicted individual: personality-based and domain-specific antecedents of ambivalent social attitudes.

Historically, attitude theory and research has assumed that attitudes are largely unconflicted and unidimensional summary statements of feelings and beliefs. More recent work has reexamined this assumption (Thompson, Zanna, & Griffin, in press). The present article details two studies that continue to investigate this notion, examining antecedent variables assumed important in the genesis of attitudinal ambivalence. The first study focuses upon personality-based factors such as individuals' Need for Cognition (NFC) and Personal Fear of Invalidity (PFI) (a heightened concern with error). The pattern of results was consistent with our predictions: High NFC was associated with less ambivalence and high PFI was associated with greater ambivalence. The second study investigated a domain-specific antecedent. It was predicted that higher involvement would reduce the level of ambivalence experienced. Further, involvement was expected to moderate the effect of the personality-based antecedents. Again, results confirmed our hypotheses. High NFC was associated with less ambivalence, especially under conditions of high involvement with the issues. Conversely, high PFI individuals who were highly involved with these issues experienced more ambivalence. These results are discussed in terms of their implications for attitude theory.