A cross-sectional survey of factors associated with the uptake of smoking cessation aids among smokers and ex-smokers

Background: A cross-sectional survey was conducted in Germany via the online panel PsyWeb with the aim of assessing factors associated with the uptake of smoking cessation aids among smokers and ex-smokers.

Methods: Of the 10,000 panel members invited to participate in the survey, 624 took part.

Main Outcome Measures: Outcomes were measured via questionnaires to assess the uptake of smoking cessation aids, health literacy, readiness to change smoking behavior, and the Fagerström Test for Nicotine Dependence.

Results: There was no association between gender or educational status and use of smoking cessation aids according to chi-square tests of independence. Logistic regression showed that health literacy, degree of tobacco dependence, and readiness to change were significantly associated with the uptake of smoking cessation aids. Smokers with a high degree of nicotine dependence, high readiness to change, and low health literacy were more likely to use aids.

Conclusion: The survey results can be used to develop psychological approaches and interventions to promote smoking cessation, e.g., interventions to increase readiness to change among smokers may increase the uptake of aids. Moreover, the results may help to improve patient care by disseminating information on effective aids and thereby promoting smoking cessation among relevant patient groups.     

Light to moderate alcohol consumption and mortality in the elderly.

OBJECTIVE: To determine whether there is a relationship of low to moderate alcohol consumption with cardiovascular mortality in the elderly. DESIGN: Prospective cohort studies with 5-year mortality follow-up. SETTING: Three populations of community-dwelling elders. PARTICIPANTS: Population-based cohorts of men and women, aged 65 or older, in three populations. Subjects with prior myocardial infarction, stroke, or cancer, as well as those lacking alcohol consumption data, were excluded from statistical analyses leaving 2,694 subjects in East Boston, Massachusetts, 2,293 subjects in Iowa, and 1,904 subjects in New Haven, Connecticut. MAIN OUTCOME MEASUREMENTS: Alcohol consumption, total mortality, cardiovascular mortality, and cancer mortality. RESULTS: Low to moderate alcohol consumption was associated with statistically significant lowered total as well as cardiovascular mortality in East Boston and New Haven. The relative risks of total mortality for low to moderate consumers of alcohol compared to those consuming no alcohol in the previous year were 0.7 (95% CI 0.6-0.8) in East Boston and 0.6 (95% CI 0.5-0.8) in New Haven. For cardiovascular mortality, the RRs were 0.6 in East Boston and 0.5 in New Haven (95% CI's exclude null). These results persisted after control for potential confounding variables. In Iowa, there were no significant differences in total or cardiovascular mortality according to alcohol consumption patterns. For cancer mortality, there were no significant associations with alcohol consumption in any of the three populations. CONCLUSIONS: These data suggest that the relationship of low to moderate alcohol consumption with reduced total and cardiovascular mortality, which are well documented in middle age, also occur in older populations.     

Associations between Borg’s rating of perceived exertion and physiological measures of exercise intensity

Borg’s rating of perceived exertion (RPE) is a widely used psycho-physical tool to assess subjective perception of effort during exercise. We evaluated the association between Borg’s RPE and physiological exercise parameters in a very large population. In this cohort study, 2,560 Caucasian men and women [median age 28 (IQR 17–44) years] completed incremental exercise tests on treadmills or cycle ergometers. Heart rate, blood lactate concentration, and RPE (Borg scale 6–20) were simultaneously measured at the end of each work load. Rating of perceived exertion was strongly correlated with heart rate (r = 0.74, p < 0.001) and blood lactate (r = 0.83, p < 0.001). The mean values for lactate threshold (LT) and individual anaerobic threshold corresponded to an RPE of 10.8 ± 1.8 and 13.6 ± 1.8, respectively. Fixed lactate thresholds of 3 and 4 mmol/L corresponded to RPEs of 12.8 ± 2.1 and 14.1 ± 2.0. Gender, age, coronary artery disease (CAD), physical activity status and exercise testing modality did not influence this association significantly (all p > 0.05). Borg’s RPE seems to be an affordable, practical and valid tool for monitoring and prescribing exercise intensity, independent of gender, age, exercise modality, physical activity level and CAD status. Exercising at an RPE of 11–13 (“low”) is recommended for less trained individuals, and an RPE of 13–15 may be recommended when more intense but still aerobic training is desired.     

CYLD deletion triggers nuclear factor-κB-signaling and increases cell death resistance in murine hepatocytes

AIM:To analyze the role of CYLD for receptor-mediated cell death of murine hepatocytes in acute liver injury models.METHODS:Hepatocyte cell death in CYLD knockout mice(CYLD-/-)was analyzed by application of liver injury models for CD95-(Jo2)and tumor necrosis factor(TNF)-α-[D-Gal N/lipopolysaccharide(LPS)]induced apoptosis.Liver injury was assessed by measurement of serum transaminases and histological analysis.Apoptosis induction was quantified by cleaved PARP staining and Western blotting of activated caspases.Nuclear factor(NF)-κB,ERK,Akt and jun amino-terminal kinases signaling were assessed.Primary Hepatocytes were isolated by two step-collagenase perfusion and treated with recombinant TNF-αand with the CD95-ligand Jo2.Cell viability was analyzed by MTT-assay.RESULTS:Livers of CYLD-/-mice showed increased anti-apoptotic NF-κB signaling.In both applied liver injury models CYLD-/-mice showed a significantly reduced apoptosis sensitivity.After D-Gal N/LPS treatment CYLD-/-mice exhibited significantly lower levels of alanine aminotransferase(ALT)(295 U/L vs 859 U/L,P<0.05)and aspartate aminotransferase(AST)(560 U/L vs 1025 U/L,P<0.01).After Jo injection CYLD-/-mice showed 2-fold lower ALT(50 U/L vs 110 U/L,P<0.01)and lower AST(250 U/L vs 435 U/L,P<0.01)serumlevels compared to WT mice.In addition,isolated CYLD-/-primary murine hepatocytes(PMH)were less sensitive towards death receptor-mediated apoptosis and showed increased levels of Bcl-2,XIAP,c IAP1/2,survivin and c-FLIP expression upon TNF-and CD95-receptor triggering,respectively.Inhibition of NF-κB activation by the inhibitor of NF-κB phosphorylation inhibitor BAY 11-7085 inhibited the expression of antiapoptotic proteins and re-sensitized CYLD-/-PMH towards TNF-and CD95-receptor mediated cell death.CONCLUSION:CYLD is a central regulator of apoptotic cell death in murine hepatocytes by controlling NF-κB dependent anti-apoptotic signaling.     

Human stem cell models of neurodegeneration: a novel approach to study mechanisms of disease development

The number of patients with neurodegenerative diseases is increasing significantly worldwide. Thus, intense research is being pursued to uncover mechanisms of disease development in an effort to identify molecular targets for therapeutic intervention. Analysis of postmortem tissue from patients has yielded important histological and biochemical markers of disease progression. However, this approach is inherently limited because it is not possible to study patient neurons prior to degeneration. As such, transgenic and knockout models of neurodegenerative diseases are commonly employed. While these animal models have yielded important insights into some molecular mechanisms of disease development, they do not provide the opportunity to study mechanisms of neurodegeneration in human neurons at risk and thus, it is often difficult or even impossible to replicate human pathogenesis with this approach. The generation of patient-specific induced pluripotent stem (iPS) cells offers a unique opportunity to overcome these obstacles. By expanding and differentiating iPS cells, it is possible to generate large numbers of functional neurons in vitro, which can then be used to study the disease of the donating patient. Here, we provide an overview of human stem cell models of neurodegeneration using iPS cells from patients with Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington’s disease, spinal muscular atrophy and other neurodegenerative diseases. In addition, we describe how further refinements of reprogramming technology resulted in the generation of patient-specific induced neurons, which have also been used to model neurodegenerative changes in vitro.     

Single-stranded DNA oligonucleotides inhibit TLR3-mediated responses in human monocyte-derived dendritic cells and in vivo in cynomolgus macaques

TLR3 is a key receptor for recognition of double-stranded RNA and initiation of immune responses against viral infections. However, hyperactive responses can have adverse effects, such as virus-induced asthma. Strategies to prevent TLR3-mediated pathology are therefore desired. We investigated the effect of single-stranded DNA oligonucleotides (ssDNA-ODNs) on TLR3 activation. Human monocyte-derived dendritic cells up-regulate maturation markers and secrete proinflammatory cytokines on treatment with the synthetic TLR3 ligand polyinosine-polycytidylic acid (poly I:C). These events were inhibited in cultures with ssDNA-ODNs. Poly I:C activation of nonhematopoietic cells was also inhibited by ssDNA-ODNs. The uptake of poly I:C into cells was reduced in the presence of ssDNA-ODNs, preventing TLR3 engagement from occurring. To confirm this inhibition in vivo, we administered ssDNA-ODNs and poly I:C, alone or in combination, via the intranasal route in cynomolgus macaques. Proinflammatory cytokines were detected in nasal secretions in the poly I:C group, while the levels were reduced in the groups receiving ssDNA-ODNs or both substances. Our results demonstrate that TLR3-triggered immune activation can be modulated by ssDNA-ODNs and provide evidence of dampening proinflammatory cytokine release in the airways of cynomolgus macaques. These findings may open novel perspectives for clinical strategies to prevent or treat inflammatory conditions exacerbated by TLR3 signaling.     

Early dental caries risk assessment and prevention in pre-school children: evaluation of a new strategy for dental care in a field study

The aim of the present field study was to evaluate a new strategy for the dental care of pre-school children which includes an early caries risk assessment and early preventive care. One hundred and sixty-seven children were studied from 1 to 6 years of age (intervention group). A group of 125 children from the same clinic (historical control) was used as a comparison group. On the basis of the clinical examinations of the children and the interviews with the parents when the children were 3 years of age, the children in the intervention group were divided into four different risk groups: no (n = 95),low (n = 33), moderate (n = 30), and high caries risk (n = 9). Only 8 of the 95 children who had been placed in the no caries risk group at 3 years of age developed manifest carious lesions in their primary cuspids and molars by 6 years of age. At 6 years of age 81% in the intervention group were free of manifest carious lesions, compared with 55% in the comparison group (P < 0.001). Furthermore, the mean numbers of defs were 0.6 for children in the intervention group and 2.7 in the comparison group. Thus, this field study indicates that early primary prevention (before the onset of caries attack) and a structured and systematic approach to dental care for pre-school children result in good oral health for the children and may be economically profitable for a society with organized public dental service for pre-school children.