Secondhand smoke exposure and risk of incident peripheral arterial disease and mortality: a Scotland-wide retrospective cohort study of 4045 non-smokers with cotinine measurement

Background: Active smoking is an important risk factor for all-cause mortality and peripheral arterial disease (PAD). In contrast, published studies on the associations with secondhand smoke (SHS) are limited. The aim of this study was to examine the associations between SHS exposure and incident PAD, as well as mortality, among middle-aged non-smokers. Methods: We undertook a retrospective, cohort study using record linkage of the Scottish Health Surveys between 1998 and 2010 to hospital admissions and death certificates. Inclusion was restricted to participants aged > 45 years. Cox proportional hazard models were used to examine the association between SHS exposure and incident PAD (hospital admission or death) and all-cause mortality, with adjustment for potential confounders. Results: Of the 4045 confirmed non-smokers (self-reported non-smokers with salivary cotinine concentrations < 15 ng/mL), 1163 (28.8%) had either moderate or high exposure to SHS at baseline. In men, high exposure to SHS (cotinine ≥2.7 ng/mL) was associated with increased risk of all-cause mortality (fully adjusted hazard ratio [HR] 1.54, 95% CI 1.07–2.22, p = 0.020) with evidence of a dose-relationship (p for trend = 0.004). In men, high exposure to SHS was associated with increased risk of incident PAD over the first five years of follow-up (fully adjusted HR 4.29, 95% CI 1.14–16.10, p = 0.031) but the association became non-significant over longer term follow-up. Conclusions: SHS exposure was independently associated with all-cause mortality and may be associated with PAD, but larger studies, or meta-analyses, are required to confirm the latter

Association between active smoking, secondhand smoke and peripheral arterial disease

Worldwide, cardiovascular disease (CVD) is the leading cause of death. It is widely accepted that both active smoking and exposure to secondhand smoke (SHS) are associated with CVD. About 20% of the global population smoke tobacco or tobacco-related products. The global prevalence of smoking is increasing, although it is decreasing in some high-income and upper middle-income countries. Globally, about a third of adults and 40% children are regularly exposed to SHS. According to the World Health Organisation (WHO), only 16% of the global population is protected by a comprehensive smoke-free legislation. Coronary heart disease (CHD), stroke and peripheral arterial disease (PAD) are all types of atherosclerosis and often co-exist in the same patients. Therefore, they share many common risk factors including cigarette smoking. However, previous epidemiological studies on CVD including those on cigarette smoking mainly focused on CHD and stroke and pay little attention to PAD. Evidence is increasing in support of the association between exposure to SHS and both CHD and stroke. In contrast, there is a paucity of studies on SHS and the risk of PAD. The overarching aim of this thesis was to collate the published evidence on the association between active cigarette smoking and PAD, and examine the association between exposure to SHS and PAD in the general population. This thesis starts with a systematic review on the association between active cigarette smoking, SHS and PAD undertaken using four databases: Medline, Embase, PubMed and Web of Science to identify existing published evidence up to 30 April 2012 (Chapter 2). Prior to the published studies contained in this thesis, there had been no meta-analyses on the association between active cigarette smoking and PAD and only two studies published on the association between SHS and PAD. Therefore, this systematic review was followed by a meta-analysis on the association between active cigarette smoking and PAD. This meta-analysis identified 55 studies: 43 cross-sectional, 10 cohort and 2 case-control. Of the 68 results for current smokers, 59 (86.8%) were statistically significant and the pooled odds ratio (OR) was 2.72 (95% confidence interval [CI] 2.28-3.21). Of the 40 results for ex-smokers, 29 (72.5%) were statistically significant and the pooled OR was 1.67 (95% CI 1.54-1.81). Active cigarette smoking significantly increases the risk of PAD, compared with never smokers. The magnitude of association between active cigarette smoking and PAD was greater in current smokers than ex-smokers. In contrast, prior to my studies in this thesis, only two studies on SHS were identified. Only one showed an overall association between self-report SHS and PAD in Chinese never smokers, with a clear dose-response relationship. The other study used serum cotinine as measure for SHS exposure and found neither an overall association nor a dose-response relationship but suggested a very high cotinine concentration as threshold. Chapter 3 examines the association between SHS exposure and PAD in adult non-smokers in Scotland. This chapter includes two cross-sectional studies using the Generation Scotland: Scottish Family Health Study (GS: SFHS) and the Scottish Health Survey (SHeS), and one retrospective cohort study using the record linkage of the SHeS. In the cross-sectional study using SFHS, PAD was measured using ankle brachial pressure index (ABPI) but SHS exposure was self-report. Of the 5,686 never smokers, 134 (2.4%) had PAD (defined as an ABPI <0.9). Participants who reported overall high level of SHS exposure (exposed to ≥40 hours per week) were more likely to have PAD, compared with those who reported no exposure to SHS. After adjustment for potential confounders, the association between SHS and PAD persisted (adjusted OR 4.53, 95% CI 1.51-13.56, p=0.007), with suggestion of a dose-response relationship. In the other cross-sectional study using SHeS, SHS exposure was measured objectively using cotinine concentration but PAD was based on self-report symptoms of intermittent claudication (IC) using the Edinburgh Claudication Questionnaire. Of the 4,231 non-smokers (defined as self-reported non-smokers with a salivary cotinine concentration <15 ng/mL), 134 (3.2%) had IC. Participants with high exposure to SHS (cotinine ≥2.7 ng/mL) were at significantly higher risk of IC, after adjustment for potential confounders (adjusted OR 1.76, 95% CI 1.04-3.00, p=0.036). A dose-response relationship was suggested, whereby the risk of IC increased with increasing cotinine concentration. However, the association varied by age category. Participants aged <60 were more strongly associated with PAD. This may be explained by survival bias. For the third, retrospective cohort study in Chapter 3, I used record linkage of SHeS to Scottish Morbidity Record 01 (SMR01) records and death certificates to identify the first hospital admission/death following the SHeS in which PAD was recorded as the primary or secondary cause. Of the 4,045 confirmed non-smokers who were free of baseline IC were included. Over the follow-up period (mean follow-up 9 years), there were 568 deaths, none of which were coded as due to PAD, and 64 participants were hospitalised for PAD. High exposure to SHS was associated with increased risk of all-cause mortality (adjusted hazard ratio [HR] 1.42, 95% CI 1.09- 1.86, p=0.011) among all non-smokers and increased risk of incident PAD (adjusted HR 2.82, 95% CI 1.14-6.96, p=0.024) among male non-smokers. Increased cotinine concentrations at baseline were associated with increased risk of all-cause mortality, with a dose-response relationship. SHS contains both sidestream smoke, from burning cigarette tips, and exhaled mainstream smoke. Shortened telomere length is broadly viewed as a biomarker for biological ageing including atherosclerosis phenotypes such as PAD. Evidence is strong that active smoking increases telomere length attrition but whether such association occurs between SHS and telomere length is unknown. Therefore, Chapter 4 aimed to add to growing evidence that exposure to SHS is associated with disproportionately higher biomarkers of cardiovascular risk compared with active smoking and may accelerate normal biological ageing. This chapter includes two cross-sectional studies. The first study investigated the relationship between salivary cotinine and several preclinical cardiovascular biomarkers: C-reactive protein (CRP), high-density lipoprotein (HDL) cholesterol, TC/HDL cholesterol ratio and fibrinogen in 10,081 adults from the SHeS. CRP concentration and the TC/HDL cholesterol ratio increased, and HDL cholesterol concentration decreased with increasing cotinine concentration among both non-smokers and active smokers. There were step changes in the relationship between tobacco exposure and cardiovascular biomarkers at the interface of non-smokers exposed to SHS and active smokers. Non-smokers with high exposure to SHS had lower cotinine concentrations than light active smokers but comparable concentrations of CRP (p=0.709), HDL cholesterol (p=0.931) and the TC/HDL cholesterol ratio (p=0.405). Fibrinogen concentration was less clear-cut and only increased in moderate and heavy active smokers. The second study in this chapter explored the association between self-reported levels of SHS exposure and telomere shortening per annum using a subgroup of participants from the SFHS. Of the 1,303 non-smokers, telomere length decreased more rapidly with increasing age among participants with high level of SHS exposure, compared with both those with no exposure (adjusted coefficient -0.006, 95% CI -0.008- -0.004) (high vs no SHS: p=0.010) or low exposure (adjusted coefficient -0.005, 95% CI -0.007- -0.003) (high vs low SHS: p=0.005). In summary, there is now substantial evidence of an association between active cigarette smoking and PAD. This thesis adds to the limited existing evidence on SHS as an independent risk factor for PAD. There was an overall association between exposure to SHS and PAD, with suggestion of a dose-response relationship. However, the association varied by age category. Individuals aged <60 were more strongly associated with the prevalence of IC. SHS was significantly associated with incident PAD only in men. This thesis further demonstrates that exposure to SHS carries a disproportionately higher cardiovascular risk than active smoking for a given level of smoke exposure. Telomere shortening per year of age may be an intermediate step between SHS and CVD including PAD. This also supports the association between SHS exposure and the atherosclerosis-related biomarkers, which play an important role in the pathophysiology of PAD. Further research is needed in the future to better understand the association between SHS and PAD, and the underlying mechanisms. The research in this thesis supports the need to protect the general public from exposure to SHS

Association between exposure to second-hand smoke and telomere length: cross-sectional study of 1303 non-smokers

Background: Both active smoking and second-hand smoke (SHS) are important risk factors for many age-related diseases. Active smoking is associated with shortened telomere length. However, whether SHS accelerates telomere attrition with age is uncertain. The aim of this study was to examine the association between SHS exposure and shortening by age of leukocyte telomere length among adult non-smokers. Methods: We undertook a cross-sectional study of the association between self-reported levels of SHS exposure and telomere length shortening per annum on a subgroup of participants from the Scottish Family Health Study. Inclusion was restricted to non-smokers aged ≥ 18 years, who had provided self-reported overall usual SHS exposure (total hours per week) and blood samples for telomere analysis. Linear regression models were used to compare the ratio of telomere repeat copy number to single copy gene number (T/S)by age according to SHS exposure. Results: Of the 1303 eligible participants, 779 (59.8%) reported no SHS exposure, 495 (38.0%) low exposure (1–19 h per week) and 29 (2.2%) high exposure (≥20 h per week). In the univariate linear regression analyses, relative T/S ratio declined with increasing age in all exposure groups. Telomere length decreased more rapidly with increasing age among those with high exposure to SHS [adjusted coefficient −0.019, 95% confidence interval (CI) −0.031- −0.007) when compared with both those with no exposure to SHS (adjusted coefficient −0.006, 95% CI −0.008- −0.004) (high vs no SHS: P = 0.010) and those with low exposure to SHS (adjusted coefficient −0.005, 95% CI −0.007- −0.003) (high vs low SHS: P = 0.005). Conclusions: Our findings suggest that high SHS exposure may accelerate normal biological ageing, and support efforts to protect the public from SHS exposure. Further studies on relevant mechanisms should be conducted

Facile synthesis of CdS nanocrystals using thioglycolic acid as a sulfur source and stabilizer in aqueous solution

A novel method has been developed for the synthesis of CdS nanocrystals (NCs) using thioglycolic acid (TGA) as a sulfur source and stabilizer with the presence of hydrogen peroxide in an aqueous medium. The products were characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy. The results indicate that the product was of zinc-blend crystal structure in a sphere-like shape. The room-temperature luminescence spectra revealed that the emission peak of CdS NCs prepared in relatively short refluxing times (10-120 min) could be tuned from 518 nm to 610 nm, and the photoluminescence quantum yield of the as-prepared CdS NCs could reach as high as 12.6%. In addition, the mechanism of the CdS nanocrystals formation was preliminarily discussed.KEY WORDS: Chemical synthesis, CdS, Nanostructures, Optical properties, Photoluminescence spectroscopy Bull. Chem. Soc. Ethiop. 2011, 25(3), 393-398

Cancer-related financial hardship among head and neck cancer survivors: risk factors and associations with health-related quality of life

Objective: Cancer survivors are susceptible to financial hardship. In head and neck cancer (HNC) survivors, we investigated (a) predictors for cancer‐related financial hardship and (b) associations between financial hardship and health‐related quality of life (HRQoL). Methods: We conducted a cross‐sectional study in HNC survivors identified from the National Cancer Registry Ireland. HRQoL was based on the Functional Assessment for Cancer Therapy General (FACT‐G) plus Head and Neck Module (FACT‐HN). Objective cancer‐related financial hardship (financial stress) was assessed as household ability to make ends meet due to cancer and subjective financial hardship (financial strain) as feelings about household financial situation due to cancer. Modified Poisson regression was used to identify predictors for financial hardship. Bootstrap linear regression was used to estimate associations between hardship and FACT domain scores. Results: Pre‐diagnosis retirement (relative risk [RR] 0.50, 95% confidence interval [CI] 0.37‐0.67), pre‐diagnosis financial stress (RR 1.85, 95% CI 1.58‐2.15), and treatment were significantly associated with objective financial hardship. Predictors of subjective financial hardship were similar: aged greater than or equal to 65 years, pre‐diagnosis financial stress, and treatment. Participants with objective financial hardship reported significantly lower physical (coefficient −3.45, 95% CI −4.39 to −2.44), emotional (−2.01, 95% CI −2.83 to −1.24), functional (−2.56, 95% CI −3.77 to −1.33) and HN‐specific HRQoL (−3.55, 95% CI −5.04 to −2.23). Physical, emotional, and functional HN‐specific HRQoL were also significantly lower in participants with subjective financial hardship. Conclusion: Cancer‐related financial hardship is common and associated with worse HRQoL among HNC survivors. This supports the need for services and supports to address financial concerns among HNC survivors

Anticonvulsant and sedative effect of Fufang Changniu pills and probable mechanism of action in mice

Purpose: To investigate the anticonvulsant and sedative effects of Fufang Changniu Pills (FCP) and its probable mechanism of action in mice.Methods: The water decoction of FCP was prepared and the main constituents were determined by high performance liquid chromatography (HPLC). The anticonvulsant activities of FCP were evaluated by maximal electroshock (MES) and  pentylenetetrazole (PTZ)-induced seizures in mice. Pentobarbital sodium-induced sleeping time and locomotor activity measurements were performed to evaluate the sedative effects of FCP in mice. Finally, PTZ-induced chronic seizures were  established, and expressions of gamma-aminobutyric acid A receptor (GABA-A) and glutamic acid decarboxylase 65 (GAD65) in the brains of the mice were assayed by western blot in order to explore the probable mechanisms of action of the drug.Results: Gallic acid, liquiritin, cinnamyl alcohol, cinnamic acid and glycyrrhizic acid were detected in FCP decoction. FCP (50, 100 and 200 mg/kg) showed significant anticonvulsant and sedative effects on epileptic mice induced by MES (p &lt; 0.05) and PTZ (p &lt; 0.05). Moreover, pentobarbital sodium-induced sleeping time and  locomotor activity tests showed that FCP possesses sedative effect (p &lt; 0.05). Western blot data indicate that FCP significantly up-regulated GABA-A and GAD 65 in the brains of chronic epileptic rats (p &lt; 0.05).Conclusion: FCP has significant anticonvulsant and sedative effects, and the  mechanism of its action may be related to the up-regulation of GABA-A and GAD 65 in mice brain.Keywords: Epilepsy, Fufang Changniu pills, Anticonvulsant, Sedative effect,  Gamma-aminobutyric acid, Glutamate dehydrogenas

Exposure to secondhand smoke and risk of peripheral arterial disease in southern Chinese non-smokers: the Guangzhou Biobank Cohort Study-Cardiovascular Disease Sub-cohort

Objectives: We studied the association between secondhand smoke (SHS) exposure and peripheral arterial disease (PAD) in Chinese non-smokers. Methods: We conducted a cross-sectional study using baseline data from the Guangzhou Biobank Cohort Study: Cardiovascular Disease Sub-cohort Study (GBCS-CVD). Guangzhou residents aged ≥ 50 years were recruited between 2003 and 2008. Baseline data included measurement of ankle brachial pressure index (ABPI) and self-reported smoking status and SHS exposure. Univariate and multivariate logistic regression analyses were used to analyze the association between SHS and PAD (defined as ABPI &lt; 0.9). Results: Of the 1507 non-smokers, 24 (1.6%) had PAD. Of these, 12 were men and 12 were women. Exposure to SHS at home of ≥25 h per week was reported by 16.7% of PAD cases compared with 3.8% of those without PAD (χ2 test, p = 0.003). After adjustment for potential confounders, exposure to ≥25 h per week at home was still associated with PAD (adjusted OR 7.86, 95% CI 2.00–30.95, p = 0.003), with suggestion of a dose-response relationship. Conclusions: Our results extend the US Surgeon General’s 2006 report that SHS exposure is an independent risk factor for PAD. National smoke-free legislation is needed to protect all people from exposure

Extracranial Artery Stenosis Is Associated With Total MRI Burden of Cerebral Small Vessel Disease in Ischemic Stroke Patients of Suspected Small or Large Artery Origins

Background and Purpose: Extracranial artery stenosis (ECAS) is related to individual imaging markers of cerebral small vessel disease (cSVD). However, little has been reported on the association between ECAS and the total burden of cSVD as assessed by magnetic resonance imaging (MRI). The purpose of this study was to investigate the relationship between ECAS and cSVD burden in patients with ischemic stroke of suspected small or large artery origin.Methods: We reviewed consecutive patients with ischemic stroke of suspected small or large artery origin who underwent color Doppler ultrasonography and brain MRI. Bilateral extracranial cerebral arteries including common carotid artery, internal carotid artery (ICA), and proximal vertebral artery (VA, ostium, V2–3 segments) were assessed using color Doppler ultrasonography. ECAS severity was classified as no/mild stenosis, moderate stenosis, severe stenosis, or occlusion. The total cSVD score was assessed by awarding one point according to the load of each of these cSVD markers as determined using MRI; lacunar infarction, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces. The relationship between ECAS severity and cSVD burden according to MRI was examined.Results: Two hundred and twenty one patients were included in this study (mean age 61 ± 12 years, 75.6% male). Hypertension, current smoking, hyperlipidaemia, and diabetic mellitus were frequent among the patients (67.4, 45.7, 43.9, and 36.7%, respectively), while the other vascular risk factors including previous stroke or TIA and alcohol excess were less frequent (19.0 and 15.4%, respectively). Patients with higher total cSVD burden was significantly older and had severer ECAS. The frequency of hypertension was significantly higher in patients with higher total cSVD burden. This analysis indicated that that increasing ECAS severity (from no stenosis through to 100%) was independently associated with increasing total cSVD score after adjusting for other vascular risk factors (odds ratio 1.76, 95% CI [1.16–2.69]).Conclusions: In this study, high levels of ECAS from ultrasound evidence were associated with coexisting advanced cerebral cSVD in ischemic stroke patients of suspected small or large artery origin. Further studies are required to determine if and how extracranial arterial imaging helps reduce cSVD burden or improves cognitive function

Glucitol-core containing gallotannins-enriched red maple (Acer rubrum) leaves extract alleviated obesity via modulating short-chain fatty acid production in high-fat diet-fed mice

Glucitol-core containing gallotannins (GCGs) are characteristic constituents of the red maple (Acer rubrum) species. To pursue the development of red maple for nutraceutical applications, GCGs-enriched red maple leaves extract (MLE) was evaluated for its effects on obesity, gut dysbiosis and short chain fatty acids (SCFAs) production. Our results demonstrated that MLE alleviated high-fat diet-induced obesity, reduced body weight gain and fat mass, improved liver steatosis and insulin resistance, and mitigated adipose hypertrophy and inflammation. Additionally, MLE increased total SCFAs, acetic acid and n-butyric acid content, but exerted no impact on propionic acid production. Moreover, MLE modulated gut microbiota community structure and certain bacteria relative abundance, including Prevotella and Eubacterium. Our work firstly reports a potential association between colon-derived SCFAs production and metabolic improvement due to GCGs-enriched red maple leaves extract administration, and highlights the utilization of red maple gallotannins as a dietary ingredient for preventing obesity and related metabolic diseases