Rethinking daily aspirin for primary prevention

An updated meta-analysis of newer RCTs seems to settle the matter as to whether to use aspirin in individuals with no known history of atherosclerotic CVD. PRACTICE CHANGER: Do not routinely use aspirin for primary prevention of cardiovascular disease (CVD). There is no identifiable mortality benefit for those without established CVD--regardless of risk factors. And aspirin therapy increases the risk of major bleeding. STRENGTH OF RECOMMENDATION: Based on a meta-analysis of 11 randomized trials involving 157,248 patients who received aspirin for primary prevention

Promoter methylation of cancer-related genes in gastric carcinoma

Genetic changes associated with gastric cancer are not completely known, but epigenetic mechanisms involved in this disease seem to play an important role in its pathophysiology. One of these mechanisms, an aberrant methylation in the promoter regions of genes involved in cancer induction and promotion, may be of particular importance in gastric cancer. Aim: To analyze the methylation status of eight genes: Apaf-1, Casp8, CDH1, MDR1, GSTP1, BRCA1, hMLH1, Fas in gastric cancer patients. Methods: The methylation pattern of the genes was assessed by methylation specific restriction enzyme PCR (MSRE-PCR) in gastric tumors taken during surgery of 27 patients and compared with the methylation pattern in material obtained from biopsy in 25 individuals without cancer and pre-cancerous lesions. Results: We observed a promoter hypermethylation in the Casp8, hMLH1, CDH1 and MDR1 in gastric cancer patients as compared with the controls. Additionally, we investigated the relationship between promoter hypermethylation and age, gender, smoking and gastric cancer family history. The hypermethylation of the hMLH1 gene occurred more frequently in female than in men, and the hypermethylation of the CDH1 gene was observed preferentially in smoking than in non-smoking individuals. Conclusion: The data obtained indicate that changes in DNA methylation may contribute to gastric carcinogenesis.Генетические изменения, ассоциированные с опухолью желудка, изучены не в полной мере. В то же время эпигенетические механизмы скорее всего играют ключевую роль и лежат в основе возникновения этого заболевания. Один из таких механизмов– нарушенияметилирования промоторов генов, которые регулируют злокачественнуютрансформациюи прогрессирование опухолевого процесса, может быть особенно важным в развитии рака желудка. Цель: проанализировать статус метилирования промоторов восьми генов: Apaf-1, Casp8, CDH1, MDR1, GSTP1, BRCA1, hMLH1, Fas у больных раком желудка. Методы: метилирование промоторов генов изучали с помощьюспецифической к сайтамметилирования рестрикцией с ПЦР (MSRE-PCR) на хирургическомматериале (опухоли желудка) 27 пациентов. Вкачестве контроля использовали иопсийныйматериал, полученный от 25 больных, у которых не было выявлено рака или предраковых состояний. Результаты: отмечали гиперметилирование промоторов генов Casp8, hMLH1, CDH1 и MDR1 в опухолевой ткани желудка по сравнению с контрольными образцами. Кроме того, нами была прослежена взаимосвязь между гиперметилированием промоторов генов и возрастом, полом пациентов, курением и семейной историей заболевания раком желудка. Гиперметилирование гена hMLH1 выявляли чаще у женщин, чем у мужчин, а гиперметилирование гена CDH1 — в основном у курильщиков. Выводы: полученные данные свидетельствуют о том, что метилирование ДНК может играть важную роль при развитии рака желудка

Equilibrium hydrostatic equation and Newtonian limit of the singular f(R) gravity

We derive the equilibrium hydrostatic equation of a spherical star for any gravitational Lagrangian density of the form $L=\sqrt{-g}f(R)$. The Palatini variational principle for the Helmholtz Lagrangian in the Einstein gauge is used to obtain the field equations in this gauge. The equilibrium hydrostatic equation is obtained and is used to study the Newtonian limit for $f(R)=R-\frac{a^{2}}{3R}$. The same procedure is carried out for the more generally case $f(R)=R-\frac{1}{n+2}\frac{a^{n+1}}{R^{n}}$ giving a good Newtonian limit.Comment: Revised version, to appear in Classical and Quantum Gravity

Modified gravity and its reconstruction from the universe expansion history

We develop the reconstruction program for the number of modified gravities: scalar-tensor theory, $f(R)$, $F(G)$ and string-inspired, scalar-Gauss-Bonnet gravity. The known (classical) universe expansion history is used for the explicit and successful reconstruction of some versions (of special form or with specific potentials) from all above modified gravities. It is demonstrated that cosmological sequence of matter dominance, decceleration-acceleration transition and acceleration era may always emerge as cosmological solutions of such theory. Moreover, the late-time dark energy FRW universe may have the approximate or exact $\Lambda$CDM form consistent with three years WMAP data. The principal possibility to extend this reconstruction scheme to include the radiation dominated era and inflation is briefly mentioned. Finally, it is indicated how even modified gravity which does not describe the matter-dominated epoch may have such a solution before acceleration era at the price of the introduction of compensating dark energy.Comment: LaTeX file, 24 pages, no figure, prepared for the proceedings of ERE 2006, minor correction

Memory Acquisition and Retrieval Impact Different Epigenetic Processes that Regulate Gene Expression

Background: A fundamental question in neuroscience is how memories are stored and retrieved in the brain. Long-term memory formation requires transcription, translation and epigenetic processes that control gene expression. Thus, characterizing genome-wide the transcriptional changes that occur after memory acquisition and retrieval is of broad interest and importance. Genome-wide technologies are commonly used to interrogate transcriptional changes in discovery-based approaches. Their ability to increase scientific insight beyond traditional candidate gene approaches, however, is usually hindered by batch effects and other sources of unwanted variation, which are particularly hard to control in the study of brain and behavior. Results: We examined genome-wide gene expression after contextual conditioning in the mouse hippocampus, a brain region essential for learning and memory, at all the time-points in which inhibiting transcription has been shown to impair memory formation. We show that most of the variance in gene expression is not due to conditioning and that by removing unwanted variance through additional normalization we are able provide novel biological insights. In particular, we show that genes downregulated by memory acquisition and retrieval impact different functions: chromatin assembly and RNA processing, respectively. Levels of histone 2A variant H2AB are reduced only following acquisition, a finding we confirmed using quantitative proteomics. On the other hand, splicing factor Rbfox1 and NMDA receptor-dependent microRNA miR-219 are only downregulated after retrieval, accompanied by an increase in protein levels of miR-219 target CAMKIIγ. Conclusions: We provide a thorough characterization of coding and non-coding gene expression during long-term memory formation. We demonstrate that unwanted variance dominates the signal in transcriptional studies of learning and memory and introduce the removal of unwanted variance through normalization as a necessary step for the analysis of genome-wide transcriptional studies in the context of brain and behavior. We show for the first time that histone variants are downregulated after memory acquisition, and splicing factors and microRNAs after memory retrieval. Our results provide mechanistic insights into the molecular basis of cognition by highlighting the differential involvement of epigenetic mechanisms, such as histone variants and post-transcriptional RNA regulation, after acquisition and retrieval of memory

Compactifying the state space for alternative theories of gravity

In this paper we address important issues surrounding the choice of variables when performing a dynamical systems analysis of alternative theories of gravity. We discuss the advantages and disadvantages of compactifying the state space, and illustrate this using two examples. We first show how to define a compact state space for the class of LRS Bianchi type I models in $R^n$-gravity and compare to a non--compact expansion--normalised approach. In the second example we consider the flat Friedmann matter subspace of the previous example, and compare the compact analysis to studies where non-compact non--expansion--normalised variables were used. In both examples we comment on the existence of bouncing or recollapsing orbits as well as the existence of static models.Comment: 18 pages, revised to match published versio

Dental methacrylates may exert genotoxic effects via the oxidative induction of DNA double strand breaks and the inhibition of their repair

Methacrylate monomers used in dentistry have been shown to induce DNA double strand breaks (DSBs), one of the most serious DNA damage. In the present work we show that a model dental adhesive consisting of 45% 2-hydroxyethyl methacrylate (HEMA) and 55% bisphenol A-diglycidyl dimethacrylate (Bis-GMA) at concentrations up to 0.25 mM Bis-GMA induced oxidative DNA in cultured primary human gingival fibroblasts (HGFs) as evaluated by the comet assay and probed with human 8-hydroxyguanine DNA-glycosylase 1. HEMA/Bis-GMA induced DSBs in HGFs as assessed by the neutral comet assay and phosphorylation of the H2AX histone and sodium ascorbate or melatonin (5-methoxy-N-acetyltryptamine) both at 50 μM reduced the DSBs, they also inhibited apoptosis induced by HEMA/Bis-GMA. The adhesive slowed the kinetics of the repair of DNA damage induced by hydrogen peroxide in HGFs, while sodium ascorbate or melatonin improved the efficacy of H2O2-induced damage in the presence of the methacrylates. The adhesive induced a rise in the G2/M cell population, accompanied by a reduction in the S cell population and an increase in G0/G1 cell population. Sodium ascorbate or melatonin elevated the S population and reduced the G2/M population. In conclusion, HEMA/Bis-GMA induce DSBs through, at least in part, oxidative mechanisms, and these compounds may interfere with DSBs repair. Vitamin C or melatonin may reduce the detrimental effects induced by methacrylates applied in dentistry

Dynamics of f(R)-cosmologies containing Einstein static models

We study the dynamics of homogeneous isotropic FRW cosmologies with positive spatial curvature in $f(R)$-gravity, paying special attention to the existence of Einstein static models and only study forms of $f(R)=R^n$ for which these static models have been shown to exist. We construct a compact state space and identify past and future attractors of the system and recover a previously discovered future attractor corresponding to an expanding accelerating model. We also discuss the existence of universes which have both a past and future bounce, a phenomenon which is absent in General Relativity.Comment: 14 pages, 6 figure