Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas. JC Nault, S Datta, S Imbeaud, A Franconi, M Mallet, G Couchy, E Letouzé, C Pilati, B Verret, JF Blanc, C Balabaud, J Calderaro, A Laurent, M Letexier, P Bioulac-Sage, F Calvo, J Zucman-Rossi. Nat Genet 2015 Oct;47(10):1187-1193. “We found clonal integration of adeno-associated virus type 2 (AAV2) in 11 of 193 HCCs. These AAV2 integrations occurred in known cancer driver genes, namely CCNA2 (cyclin A2; four cases), TERT (telomerase reverse transcriptase; one case), CCNE1 (cyclin E1; three cases), TNFSF10 (tumor necrosis factor superfamily member 10; two cases) and KMT2B (lysine-specific methyltransferase 2B; one case), leading to overexpression of the target genes. Tumors with viral integration mainly developed in non-cirrhotic liver (9 of 11 cases) and without known risk factors (6 of 11 cases), suggesting a pathogenic role for AAV2 in these patients. In conclusion, AAV2 is a DNA virus associated with oncogenic insertional mutagenesis in human HCC.” Of the 11 patients, one had HCV, one HBV plus alcohol, and three tumors were alcohol-related. Three patients were female (Supplementary Table 2).
Cytomegalovirus infection accelerates epigenetic aging.
L Kananen, T Nevalainen, J Jylhävä, S Marttila, A Hervonen, M Jylhä, M Hurme. Exp Gerontol 2015 Oct 17 [Epub ahead of print].
Epigenetic mechanisms such as DNA methylation (DNAm) have a central role in the regulation of gene expression and thereby in cellular differentiation and tissue homeostasis. It has recently been shown that aging is associated with profound changes in DNAm. Several of these methylation changes take place in a clock-like fashion, i.e. correlating with the calendar age of an individual. Thus, the epigenetic clock based on these kind of DNAm changes could provide a new biomarker for human aging process, i.e. being able to separate the calendar and biological age. Information about the correlation of the time indicated by this clock to the various aspects of immunosenescence is still missing. As chronic cytomegalovirus (CMV) infection is probably one of the major driving forces of immunosenescence, we now have analyzed the correlation of CMV seropositivity with the epigenetic age in the Vitality 90 + cohort 1920 (122 nonagenarians and 21 young controls, CMV seropositivity rates 95% and 57%, respectively). The data showed that CMV seropositivity was associated with a higher epigenetic age in both of these age groups (median 26.5 vs. 24.0 (p < 0.02, Mann–Whitney U -test) in the young controls and 76.0 vs. 70.0 (p < 0.01) in the nonagenarians). Thus, these data provide a new aspect to the CMV associated pathological processes.
More about CMV and Aging
Meanwhile, AS USUAL, the anti-smokers are committing scientific fraud by ignoring the role of CMV infection in order to exploit the circumstance that smokers are more likely to have been infected by it, beginning in childhood. Continue reading
The Center for Medicare and Medicaid Innovation, which was created under Section 1115A of the Social Security Act (added by section 3021 of the Affordable Care Act), has commenced the initial stages of tyrannizing the details of older peoples’ lives in the name of supposedly reducing heart disease risks. Its “Million Hearts®: CVD Model” will be recruiting 360 control and 360 intervention practices, with about 150,000 Medicare fee-for-service patients in each group. Needless to say, the American Heart Association is the primary instigator. And it’s coming under cover of the US Secretary of Health and Human Services announcement of their intention to shift 85% of all traditional (fee for service) Medicare payments to “quality and value” [sic] by 2016. Continue reading
On April 16, 2015, several federal agencies released a barrage of regulatory issuances and guidances that further clarify their position on wellness programs. First, the EEOC released a proposed rule on the application of the Americans with Disabilities Act to Wellness programs. With the proposed rule, the EEOC released a fact sheet for small businesses and a question and answer set for the general public.
Second, the HHS Office of Civil Rights, which enforces the HIPAA privacy rules, released FAQs on the wellness programs and HIPAA privacy and security. Third, HHS and the Departments of Labor and Treasury released a set of frequently asked questions on wellness programs. Fourth, HHS released a separate set of FAQs regarding the relationship between the ACA insurance reforms and wellness programs.
Finally, the Department of Labor released a research report on workplace wellness programs. (Workplace Wellness Programs: Federal Agencies Weigh In. By Timothy Jost. Health Affairs, Apr. 17, 2015.)
As usual, smokers’ rights concerns are poorly addressed, if not completely trampled, by all. An example is what the departments of HHS, Labor and the Treasury consider to be a “reasonably designed” wellness program. “A program that collects a substantial level of sensitive personal health information without assisting individuals to make behavioral changes such as stopping smoking, managing diabetes, or losing weight, may fail to meet the requirement that the wellness program must have a reasonable chance of improving the health of, or preventing disease in, participating individuals.” But what about the rights of people who don’t want to quit smoking? What about the inherent coercion of so-called “incentives?”
And what about the fact that Workplace Wellness is founded on scientific and economic fraud in the first place? At least the economic nonsense is addressed in the last two paragraphs, summarizing the Department of Labor research report:
The study found that lifestyle management programs did not result in reduced utilization of health care services or reduced cost. No evidence was found of reduced costs from smoking cessation or pre-disease management programs. Greater exposure to interventions through telephonic counseling programs increased rather than reduced costs. Lower cardiovascular events attributable to wellness programs reduced costs, but did not come close to offsetting increased costs of participation.
Wellness programs, in sum, do not reduce health program cost, contrary to the assertions of program vendors and the beliefs of employers.
Relationship between Tobacco, cagA and vacA i1 Virulence Factors and Bacterial Load in Patients Infected by Helicobacter pylori.
Santibáñez M, Aguirre E, Belda S, Aragones N, Saez J, Rodríguez JC, Galiana A, Sola-Vera J, Ruiz-García M, Paz-Zulueta M, Sarabia-Lavín R, Brotons A, López-Girona E, Pérez E, Sillero C, Royo G.
PLoS One 2015 Mar 20;10(3):e0120444.
The academic editor of this paper evidently lacked expertise on the socioeconomics of H. pylori infection, because this group put one over on her. Continue reading
Neurology. 2015 Mar 4. pii: 10.1212/WNL.0000000000001420. [Epub ahead of print]
Epstein-Barr virus genetic variants are associated with multiple sclerosis.
Mechelli R, Manzari C, Policano C, Annese A, Picardi E, Umeton R, Fornasiero A, D’Erchia AM, Buscarinu MC, Agliardi C, Annibali V, Serafini B, Rosicarelli B, Romano S, Angelini DF, Ricigliano VA, Buttari F, Battistini L, Centonze D, Guerini FR, D’Alfonso S, Pesole G, Salvetti M, Ristori G.
We analyzed the Epstein-Barr nuclear antigen 2 (EBNA2) gene, which contains the most variable region of the viral genome, in persons with multiple sclerosis (MS) and control subjects to verify whether virus genetic variants are involved in disease development.
A seminested PCR approach and Sanger sequencing were used to analyze EBNA2 in 53 patients and 38 matched healthy donors (HDs). High-throughput sequencing by Illumina MiSeq was also applied in a subgroup of donors (17 patients and 17 HDs). Patients underwent gadolinium-enhanced MRI and human leucocyte antigen typing.
MS risk significantly correlated with an excess of 1.2 allele (odds ratio [OR] = 5.13; 95% confidence interval [CI] 1.84-14.32; p = 0.016) and underrepresentation of 1.3B allele (OR = 0.23; 95% CI 0.08-0.51; p = 0.0006). We identified new genetic variants, mostly 1.2 allele- and MS-associated (especially amino acid variation at position 245; OR = 9.4; 95% CI 1.19-78.72; p = 0.0123). In all cases, the consensus sequence from deep sequencing confirmed Sanger sequencing (including the cosegregation of newly identified variants with known EBNA2 alleles) and showed that the extent of genotype intraindividual variability was higher than expected: rare EBNA2 variants were detected in all HDs and patients with MS (range 1-17 and 3-19, respectively). EBNA2 variants did not seem to correlate with human leucocyte antigen typing or clinical/MRI features.
Our study unveils a strong association between Epstein-Barr virus genomic variants and MS, reinforcing the idea that Epstein-Barr virus contributes to disease development.
Smokers are more likely to have been infected by EBV, for socioeconomic reasons. But the latest Surgeon General report (2014, Ch. 10, p. 569), which blames smoking for multiple sclerosis, doesn’t even mention EBV! And this reveals how the anti-smokers commit scientific fraud, by cynically exploiting infection to lay false blame on smoking.
The FDA finally obeyed the District Court ruling of July 21, 2014, to reconstitute the Tobacco Products Scientific Advisory Committee (TPSAC), due to conflicts of interest with pharmaceutical companies. Its chairman, the infamous Jonathan Samet, is gone, along with three others – Claudia Barone, Joanna Cohen, and Suchitra Krishnan-Sarin, all militant anti-smokers, needless to say. Samet is truly the rottenest of the rotten, but my joy at seeing him gone is tempered with regret that it was for the wrong reason. It should have been because his flagrant scientific fraud in the Surgeon General reports, etc., made him unsuitable to occupy any federal position other than a cell in a penitentiary. Continue reading