Can tobacco use promote HCV-induced miR-122 hijacking and hepatocarcinogenesis?

Chronic hepatitis C virus (HCV) infection is a well-recognized risk factor for hepatocellular carcinoma (HCC). As a co-risk factor, the role of tobacco use in HCV-driven carcinogenesis and relevant underlying mechanisms remain largely unclear. The latest discoveries about HCV replication have shown that HCV RNA hijacks cellular miRNA-122 by forming an Ago2-HCV-miR-122 complex that stabilizes the HCV genome and enhances HCV replication. Our previous work has demonstrated that aqueous tobacco smoke extract (TSE) is a potent activator of HIV replication via TSE-mediated viral protection from oxidative stress and activation of a set of genes that can promote viral replication. Since HCV is, like HIV, an enveloped virus that should be equally susceptible to lipid peroxidation, and since one of the TSE-upregulated genes, the DDX3 helicase, is known to facilitate HCV replication, we hypothesize that (1) tobacco use can similarly enhance HCV viability and replication, and promote HCC progression by up-regulation of DDX3, and (2) by competing for binding with miR-122 as a competing endogenous RNA (ceRNA), HCV replication can liberate miR-122’s direct target, oncogenic gene cyclin G1 (CCNG1); furthermore, simultaneous tobacco use can synergistically enhance this competing effect via HCV upregulation. Our hypotheses may lay a foundation for better understanding of carcinogenesis in HCV-driven HCC and the potential role of tobacco as a cofactor. Disrupting the HCV ceRNA effect may provide a new strategy for designing anti HCV/HCC drugs.     

The association of health literacy with illness and medication beliefs among older adults with asthma

Objective

Suboptimal health literacy (HL) and asthma beliefs are associated with poor asthma self-management and outcomes. We tested the hypothesis that low HL is associated with inaccurate beliefs.

Methods

Asthmatics ≥60 were recruited from hospital and community practices in New York, NY and Chicago, IL (n = 420). HL was measured with the Short Test of Functional Health Literacy in Adults; validated instruments derived from the self regulation model were used to assess beliefs. The association of beliefs with HL was evaluated with multivariate models.

Results

Thirty-six percent of patients had low HL; 54% believed they only have asthma when symptoms are present, 29% believed they will not always have asthma and 20% believed that their doctor can cure asthma. HL was associated with beliefs of not having asthma all the time and that asthma can be cured (OR: 1.84, 95% CI: 1.2–2.82; OR: 2.22, 95% CI: 1.29–3.82, respectively). Patients with low HL were also more likely to be concerned about medication use (β = 0.92, p = .05), despite recognizing their necessity (β = −1.36, p = .01).

Conclusions

Older asthmatics with low HL endorse erroneous asthma beliefs.

Practice implications

Health communications for improving self-management behaviors in asthma should employ both health literacy-appropriate strategies and messages to counter illness-related misconceptions.     

Will diminishing cochlear delay affect speech perception in noise?

Objective: Normal auditory systems appear well habituated to time/phase delays inherent to sound encoding along the hearing organ, sending frequency information non-simultaneously to the central auditory system. Eliminating, or simply perturbing, the cochlear delay might be expected to decrease speech recognition ability, especially under demanding listening conditions. Resources of a larger-scale investigation permitted a preliminary examination of this issue, particularly on a relevant timescale of empirically demonstrated cochlear delays. Design: In a randomized controlled trial study, word recognition was tested for mono-syllabic tokens treated digitally to exacerbate, if not diminish/nullify, such delays. Speech-weighted noise was used to interfere with listening to time-frequency reversed (nominally no delay) versus non-reversed (natural timing) transforms under three treatments of speech tokens: (1) original-digitally recorded; digitally processed to emphasize (2) transient versus (3) quasi-steady-state components. Study sample: Ten normal-hearing young-adult females. Results: The findings failed to demonstrate statistically significant differences between delay conditions for any of the three speech-token treatments. Conclusions: An algorithm putatively diminishing frequency-dependent cochlear delays failed to systematically deteriorate performance in all subjects for the fixed time-frequency transform, stimulus parameters, and test materials employed. Yet, trends were evident such that some effect of perturbing cochlear delays could not be ruled out completely.     

Clinical Profile of Nonresponders to Surgical Myectomy with Obstructive Hypertrophic Cardiomyopathy

Background

Surgical myectomy reverses heart failure symptoms in the vast majority of obstructive hypertrophic cardiomyopathy patients. However, a small subgroup fails to experience sustained postoperative improvement despite relief of obstruction. Clinical profile of such patients has not been well defined.

Prevalence and determinants of exocrine pancreatic insufficiency among older adults: results of a population-based study

OBJECTIVE: The prevalence and main determinants of exocrine pancreatic insufficiency were investigated in a large population-based sample of older adults by measuring pancreatic elastase-1 in stool. MATERIAL AND METHODS: The study comprised 914 participants aged 50 to 75 years recruited by their general practitioner during a general health examination. All participants and their physicians were asked to fill out a standardized questionnaire which contained information on socio-demographic and lifestyle factors as well as medical history. Native stool was examined for pancreatic elastase-1 with a commercially available ELISA (ScheBo Tech, Giessen, Germany). RESULTS: Overall, 524 women and 390 men aged 50 to 75 years (mean age 61.9 years) were included in the analysis. In total, 105 (11.5%) of the 914 subjects showed signs of exocrine pancreatic insufficiency (EPI) with =200 microg elastase-1/g stool, and 47 (5.1%) subjects showed signs of a severe exocrine pancreatic insufficiency (SEPI, < 100 microg elastase-1/g stool). There was a clear increase in EPI with age. Patients taking angiotensin-converting enzyme (ACE) inhibitors had a lower prevalence than subjects without this medication; these associations persisted after adjustment for covariates. CONCLUSIONS: Prevalence of EPI increases with age and seems to be tentatively higher in men than in women. However, smoking seems to be an independent risk factor for EPI and SEPI whereas ACE-inhibitor intake might be a protective factor. The latter finding may even point to new options in the treatment of chronic pancreatitis.