The effect of vertical gaze position on ocular tear film stability

Background: An enlarged exposed ocular surface area is known to degrade tear film stability. Little is known of how tear film stability alters with vertical gaze and the change of palpebral fissure height Methods: Tear film break‐up time (TBUT; fluorescent dye) and palpebral fissure height were measured in three vertical gaze positions (primary position and 20 degrees up and 20 degrees down) on 23 healthy volunteers. The effect of gaze direction on TBUT was analysed by ANOVA. Results: Gaze had a significant influence on tear film stability [F(2,44) = 27.6, p < 0.001]. In up‐gaze with an enlarged palpebral fissure height (11.1 ± 1.4 mm), TBUT was degraded (17.3 ± 12.7 seconds). In down‐gaze and decreased palpebral fissure height (6.7 ± 1.2 mm) TBUT was extended (43.5 ± 35.4 seconds). Conclusion: Ocular tear film stability alters with vertical gaze. Our hypothesis is that the change of the palpebral fissure height and the exposed ocular surface area alters the thickness of the lipid layer and with it tear film evaporation.     

Cervical and vulvar cancer risk in relation to the joint effects of cigarette smoking and genetic variation in interleukin 2

Cigarette smoking is an established cofactor to human papillomavirus (HPV) in the development of cervical and vulvar squamous cell carcinoma (SCC), and may influence risk through an immunosuppressive pathway. Genetic variation in interleukin 2 (IL2), associated in some studies with the inhibition of HPV-targeted immunity, may modify the effect of smoking on the risk of HPV-related anogenital cancers. We conducted a population-based case-only study to measure the departure from a multiplicative joint effect of cigarette smoking and IL2 variation on cervical and vulvar SCC. Genotyping of the four IL2 tagSNPs (rs2069762, rs2069763, rs2069777, and rs2069778) was done in 399 cervical and 486 vulvar SCC cases who had been interviewed regarding their smoking history. Compared with cases carrying the rs2069762 TT genotype, we observed significant departures from multiplicativity for smoking and carriership of the TG or GG genotypes in vulvar SCC risk [interaction odds ratio (IOR), 1.67; 95% confidence interval (CI), 1.16-2.41]. Carriership of one of three diplotypes, together with cigarette smoking, was associated with either a supramultiplicative (TGCT/GGCC; IOR, 2.09; 95% CI, 0.98-4.46) or submultiplicative (TTCC/TGTC; IOR, 0.37; 95% CI, 0.16-0.85 or TGCT/TGCC; IOR, 0.37; 95% CI, 0.15-0.87) joint effect in vulvar cancer risk. For cervical SCC, departure from multiplicativity was observed for smokers homozygous for the rs2069763 variant allele (TT versus GG or GT genotypes; IOR, 1.87; 95% CI, 1.00-3.48), and for carriership of the TTCC/TTCC diplotype (IOR, 2.08; 95% CI, 1.01-4.30). These results suggest that cervical and vulvar SCC risk among cigarette smokers is modified by genetic variation in IL2.     

A systematic review of the prevalence and attribution of human papillomavirus types among cervical, vaginal, and vulvar precancers and cancers in the United States

OBJECTIVES: To describe prevalence and estimated attribution of human papillomavirus (HPV) types in U.S. cervical, vaginal, and vulvar precancers and cancers. METHODS: U.S. studies reporting HPV typing for cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), and vaginal intraepithelial neoplasia (VaIN) and/or invasive cancers of those sites were gathered from the PubMed database (http://www.ncbi.nlm.nih.gov/sites/entrez/). Selected studies had PCR testing data for > or =10 cases for a disease endpoint. Analytic methods augmented prior reviews of cervical disease with an updated and expanded analysis (including vulvar and vaginal disease), new selection criteria for specimens, and adjustment for histologic type, where possible, among pooled cancer cases. In addition, for analyses of estimated attribution of HPV types, we incorporated accounting methods for lesions infected with multiple HPV types. RESULTS: Data from 22 U.S. studies meeting review eligibility criteria were tabulated. Following adjustment for the presence of multiple HPV types in a single specimen, the top two HPV types contributing to disease were CIN 1 (HPV 16/66; 15.3%), CIN 2/3 (HPV 16/31; 61.9%), cervical cancer (HPV 16/18; 79.2%), VIN 1 (HPV 6/11; 41.7%), VIN 3 (HPV 16/18; 84.0%), vulvar cancer (HPV 16/33; 55.5%), VaIN 3 (HPV 16/18; 65.1%), and vaginal cancer (HPV 16/18; 72.7%). CONCLUSIONS: The HPV type distribution and proportion of cases testing positive for any HPV type were observed to vary among U.S. cervical, vulvar, and vaginal neoplasias and by grade of disease. Adjustment for the presence of multitype HPV infections can have an important effect on the estimated attribution of HPV types to disease, particularly for types other than HPV 16.     

Evaluation der Kampagne ?Künftige Nichtraucher” des Schweizerischen Apothekerverbands

Mit dem Ziel, die Bevölkerung für das niederschwellige Beratungsangebot in Apotheken zu sensibilisieren, organisierte der Schweizerische Apothekerverband in 616 Apotheken die Kampagne Künftige Nichtraucher. Die Evaluation beurteilte die Beratungstätigkeit der Apotheken im Bereich Tabakentwöhnung und untersuchte die Einstellung der Projektverantwortlichen in den Apotheken gegenüber der Kampagne und der Tabakprävention. Die Dokumentation der Raucherberatungen erfolgte mittels Aktivitätsstatistik eine Woche vor und während der Aktion. Ein standardisierter Fragebogen erfasste an deren Ende die Einstellung gegenüber der Kampagne und der Tabakprävention. 32% der an der Kampagne teilnehmenden Apotheken führten die Aktivitätsstatistik. Der Rücklauf des Fragebogens zur Erfassung der Einstellung betrug 58%. Stärkster Prädiktor der Beratungshäufigkeit war die Variable Apotheke mit mehrheitlich Passantenkundschaft. Für die Beratungsintensität war es die Variable Besuch des Workshops und Weiterbildung des Apothekenteams, d. h. die bestmögliche Weiterbildung vor der Kampagne. Die positivste Einstellung gegenüber der Tabakprävention und das grösste Interesse an einer weiteren Kampagne zeigten Verantwortliche aus Apotheken mit mehrheitlich häufiger und intensiver Beratungstätigkeit. Mit der vorliegenden Studie kann gezeigt werden, dass Raucherentwöhnung in Apotheken durchführbar ist. Hauptvoraussetzungen dafür sind Motivation für die Prävention sowie eingehende Weiterbildung der Apothekerlnnen und des Apothekenteams.     

Using stated preference discrete choice modelling to evaluate the introduction of varicella vaccination

Applications of stated preference discrete choice modelling (SPDCM) in health economics have been used to estimate consumer willingness to pay and to broaden the range of consequences considered in economic evaluation. This paper demonstrates how SPDCM can be used to predict participation rates, using the case of varicella (chickenpox) vaccination. Varicella vaccination may be cost effective compared to other public health programs, but this conclusion is sensitive to the proportion of the target population immunised. A choice experiment was conducted on a sample of Australian parents to predict uptake across a range of hypothetical programs. Immunisation rates would be increased by providing immunisation at no cost, by requiring it for school entry, by increasing immunisation rates in the community and decreasing the incidence of mild and severe side effects. There were two significant interactions; price modified the effect of both support from authorities and severe side effects. Country of birth was the only significant demographic characteristic. Depending on aspects of the immunisation program, the immunisation rates of children with Australian-born parents varied from 9% to 99% while for the children with parents born outside Australia they varied from 40% to 99%. This demonstrates how SPDCM can be used to understand the levels of attributes that will induce a change in the decision to immunise, the modification of the effect of one attribute by another, and subgroups in the population. Such insights can contribute to the optimal design and targeting of health programs.     

Vinyl sulfide cyclized analogues of angiotensin II with high affinity and full agonist activity at the AT(1) receptor

Vinyl sulfide cyclized analogues of the octapeptide angiotensin II that are structurally related to the cyclic disulfide agonist c[Hcy(3,5)]Ang II have been prepared. The synthesis relies on the reaction of the mercapto group of a cysteine residue in position 3 with the formyl group of allysine incorporated in position 5 of angiotensin II. A mixture of the cis and the trans isomers was formed, and these were separated and isolated by RP-HPLC. Thus, the three-atom CH(2)[bond]S[bond]S element of the AT(1) receptor agonist c[Hcy(3,5)]Ang II has been displaced by a bioisosteric three-atom S[bond]CH[double bond]CH element. A comparative conformational analysis of the 13-membered ring systems of c[Hcy(3,5)]Ang II and the 13-membered cyclic vinyl sulfides with cis and trans configuration, respectively, suggested that all three systems adopted very similar low-energy conformations. This similarity was also reflected in the bioactivity. Both of the compounds that contained the ring systems encompassing the cis or trans vinyl sulfide elements between positions 3 and 5 exhibited K(i) values less than 2 nM and exerted full agonism at the AT(1) receptor. In contrast, vinyl sulfide cyclization involving the amino acid residues 5 and 7 rendered inactive compounds. The cyclic vinyl sulfides that have agonist activity were both shown to possess low-energy conformers compatible with the previously proposed 3D model for the bioactive conformation of Ang II.     

Retinoids: therapeutic applications and mechanisms of action in cutaneous T-cell lymphoma

Retinoids, natural and synthetic derivatives of vitamin A, are biological regulators of differentiation, proliferation, apoptosis, and immune response. Retinoic-acid-receptor-selective retinoids (all-trans retinoic acid, 13-cis-retinoic acid, and the synthetic analogs isotretinoin, etretinate and acitretin) have been used for years as monotherapy and/or in combination for treatment of cutaneous T-cell lymphoma (CTCL). Orally administered bexarotene, the first synthetic highly selective retinoid-X-receptor retinoid to be approved by the FDA for CTCL, was shown to be active against the cutaneous manifestations of all stages of CTCL. The topical gel formulation was also effective for early cutaneous manifestations of CTCL or as an adjunct to systemic or phototherapy. Bexarotene treatment induces apoptosis of CTCL cells with down-regulation of its receptors and of survivin, an inhibitor of apoptosis. Identification of new receptor subtype-selective retinoids, combination of various receptor-selective retinoids or other agents, and a new drug delivery system may improve the clinical efficacy of retinoids in the future.     

Neutrophils in asthma pathophysiology

Although the role of eosinophils, mast cells, and T cells in asthma has long been recognized, several reports suggest that neutrophils may also be involved. In most studies of people with mild asthma, neutrophil numbers in the airways are not different from controls. However, in severe asthma, including asthma deaths, neutrophils are usually raised. Furthermore, most pediatric studies suggest that neutrophils are raised in some children, in particular in the young or infantile wheeze group. Measurements of inflammatory mediators in the airways of asthmatic subjects suggest that neutrophils are activated.     

p53 codon 72 Arg homozygotes are associated with an increased risk of cutaneous melanoma

The p53 gene plays an important role in cell cycle control, facilitating DNA repair activities in response to DNA damage. Aberrant cell cycle control impairs DNA repair and increases the probability of mutations that can lead to carcinogenesis. The p53 gene is polymorphic at codon 72 (Arg/Pro) of its protein, which is functionally distinct, leading to inquiry into its role in carcinogenesis. In this hospital-based case-control study of 289 newly diagnosed patients with melanoma and 308 cancer-free control subjects, we evaluated whether the p53 codon 72 variant is associated with risk of cutaneous melanoma (CM). The controls were frequency-matched to the cases by age, sex, and ethnicity. The frequency of the p53 Arg allele was 78.2% in cases and 73.2% in controls (p=0.045), and the genotype frequencies of p53 Arg/Arg, Arg/Pro, and Pro/Pro were 62.6%, 31.1%, and 6.3%, respectively, in the cases, and 53.9%, 38.6%, and 7.5%, respectively, in the controls (p=0.096). Logistic regression analysis revealed that the p53 Arg/Arg genotype was associated with a significantly increased risk of melanoma (adjusted odds ratio (OR)=1.43; 95% confidence interval (CI)=1.02-2.02) compared with other genotypes, and this association was more evident in subgroups of older subjects (OR=2.32; 95% CI=1.39-388), and subjects with Fitzpatrick's skin type III or IV (OR=1.69; 95% CI=1.11-2.59). In conclusion, this study found some evidence that in subjects over 50, p53 Arg/Arg genotype is associated with increased risk of CM as compared to genotypes Arg/Pro or Pro/Pro. Further larger studies are needed to substantiate our findings.     

Fanconi anemia genes are highly expressed in primitive CD34<Superscript>+</Superscript>hematopoietic cells

Background  

Fanconi anemia (FA) is a complex recessive genetic disease characterized by progressive bone marrow failure (BM) and a predisposition to cancer. We have previously shown using the Fancc mouse model that the progressive BM failure results from a hematopoietic stem cell defect suggesting that function of the FA genes may reside in primitive hematopoietic stem cells.