A Pilot Study to Examine the Effect of Chronic Treatment with Immunosuppressive Drugs on Mucociliary Clearance in a Vagotomized Murine Model

Background

Previously, we have demonstrated that mucociliary clearance (MCC) is diminished within the first months after surgery in lung transplant patients and the explanation for the reduction in MCC is unknown. We hypothesized that chronic treatment with a commonly prescribed regimen of immunosuppressive drugs significantly impairs MCC. We tested this hypothesis in a murine model of lung transplantation.

Methods

Fifteen C57BL/6 mice underwent vagotomy on the right side to simulate denervation associated with lung transplantation in humans. For 6 days, seven mice (controls) were intraperitoneally injected with three 100 µL doses of phosphate buffered saline and eight mice (immunosuppressed) were injected with three 100 µL injections of tacrolimus (1 mg/kg), mycophenolate mofetil (30 mg/kg), and prednisone (2 mg/kg) once daily. Then, mice inhaled the radioisotope ^99mtechnetium and underwent gamma camera imaging of their lungs for 6.5 hrs. Counts in the right lung at 1–1.5 hrs and at 6–6.5 hrs were first background-corrected and then decay-corrected to time 0 counts. Decay-corrected counts were then divided by time 0 counts. Retention at each time point was subtracted from 1.00 and multiplied by 100% to obtain percent removed by mucociliary clearance.

Results

Although there was a slowing of MCC at 1–1.5 hrs for the immunosuppressed mice, there was no statistical difference in MCC measured at 1–1.5 hrs for the two groups of mice. At 6–6.5 hrs, MCC was significantly slower in the immunosuppressed mice, compared to controls, with 7.78±5.9% cleared versus 23.01±11.7% cleared, respectively (p = 0.006).

Conclusions

These preliminary results suggest that chronic treatment with immunosuppressive medications significantly slows MCC in vagotomized C57BL/6 mice. These findings could shed light on why MCC is reduced in lung transplant patients whose lungs are denervated during surgery and who are chronically treated with immunosuppressive drugs post surgery.     

A New Method to Monitor the Contribution of Fast Food Restaurants to the Diets of US Children

Background

American adults consume 11.3% of total daily calories from foods and beverages from fast food restaurants. The contribution of different types of fast food restaurants to the diets of US children is unknown.

Objective

To estimate the consumption of energy, sodium, added sugars, and solid fats among US children ages 4–19 y by fast food restaurant type.

Methods

Analyses used the first 24-h recall for 12,378 children in the 2003–2010 cycles of the nationally representative National Health and Nutrition Examination Survey (NHANES 2003–2010). NHANES data identify foods by location of origin, including stores and fast food restaurants (FFR). A novel custom algorithm divided FFRs into 8 segments and assigned meals and snacks to each. These included burger, pizza, sandwich, Mexican, Asian, fish, and coffee/snack restaurants. The contribution of each restaurant type to intakes of energy and other dietary constituents was then assessed by age group (4–11 y and 12–19 y) and by race/ethnicity.

Results

Store-bought foods and beverages provided 64.8% of energy, 61.9% of sodium, 68.9% of added sugars, and 60.1% of solid fats. FFRs provided 14.1% of energy, 15.9% of sodium, 10.4% of added sugars and 17.9% of solid fats. Among FFR segments, burger restaurants provided 6.2% of total energy, 5.8% of sodium, 6.2% of added sugars, and 7.6% of solid fats. Less energy was provided by pizza (3.3%), sandwich (1.4%), Mexican (1.3%), and chicken restaurants (1.2%). Non-Hispanic black children obtained a greater proportion of their total energy (7.4%), sodium (7.1%), and solid fats (9.5%) from burger restaurants as compared to non-Hispanic white children (6.0% of energy, 5.5% of sodium, and 7.3% of solid fat).

Conclusions

These novel analyses, based on consumption data by fast food market segment, allow public health stakeholders to better monitor the effectiveness of industry efforts to promote healthier menu options.     

Evaluation of a Public Health Intervention to Lower Mercury Exposure from Fish Consumption in Bermuda

Objectives

To assess the efficacy of a public health intervention to reduce blood mercury (Hg) concentration levels in pregnant Bermudian women.

Methods

In 2003, we conducted a study entitled “Prenatal exposure of the Bermudian Population to Environmental Contaminants” which provided Bermuda’s first baseline data on prenatal exposure to several environmental contaminants, including Hg. The mean Hg concentration from 42 healthy newborns measured in umbilical cord blood was 41.3 nmol/L, ranging from 5–160 nmol/L. This concentration was much higher than expected, being approximately 8 times the general levels found in Canada and the U.S. Furthermore, we estimated that 85% of total Hg measured was in the form of methylmercury (MeHg), indicating that seafood consumption was the primary source of Hg exposure during pregnancy in Bermuda. Locally sourced seafood was identified as the most significant possible contributory source of Hg exposure. In 2005 the authors began a complementary research programme to study the levels of Hg in local commercial fish species. Coming out of this research were specific local fish consumption guidelines issued by the Department of Health advising pregnant women to avoid those local fish species found to be high in Hg while still encouraging consumption of fish species having lower Hg levels.

Results

In 2010, under another research initiative, we returned to Bermuda to carry out another evaluation of Hg in human blood. Hg was measured in the blood of 49 pregnant women. The arithmetic mean Hg blood concentration was 6.6 nmol/L and the geometric mean 4.2 nmol/L. The maximum concentration found was 24 nmol/L.

Conclusions

Hg exposure of Bermudian pregnant women has dropped significantly by a factor of around 5 since the foetal cord blood study in 2003.     

Multi-Scale Glycemic Variability: A Link to Gray Matter Atrophy and Cognitive Decline in Type 2 Diabetes

Objective

Type 2 diabetes mellitus (DM) accelerates brain aging and cognitive decline. Complex interactions between hyperglycemia, glycemic variability and brain aging remain unresolved. This study investigated the relationship between glycemic variability at multiple time scales, brain volumes and cognition in type 2 DM.

Research Design and Methods

Forty-three older adults with and 26 without type 2 DM completed 72-hour continuous glucose monitoring, cognitive tests and anatomical MRI. We described a new analysis of continuous glucose monitoring, termed Multi-Scale glycemic variability (Multi-Scale GV), to examine glycemic variability at multiple time scales. Specifically, Ensemble Empirical Mode Decomposition was used to identify five unique ultradian glycemic variability cycles (GVC_1–5) that modulate serum glucose with periods ranging from 0.5–12 hrs.

Results

Type 2 DM subjects demonstrated greater variability in GVC_3–5 (period 2.0–12 hrs) than controls (P<0.0001), during the day as well as during the night. Multi-Scale GV was related to conventional markers of glycemic variability (e.g. standard deviation and mean glycemic excursions), but demonstrated greater sensitivity and specificity to conventional markers, and was associated with worse long-term glycemic control (e.g. fasting glucose and HbA1c). Across all subjects, those with greater glycemic variability within higher frequency cycles (GVC_1–3; 0.5–2.0 hrs) had less gray matter within the limbic system and temporo-parietal lobes (e.g. cingulum, insular, hippocampus), and exhibited worse cognitive performance. Specifically within those with type 2 DM, greater glycemic variability in GVC_2–3 was associated with worse learning and memory scores. Greater variability in GVC₅ was associated with longer DM duration and more depression. These relationships were independent of HbA1c and hypoglycemic episodes.

Conclusions

Type 2 DM is associated with dysregulation of glycemic variability over multiple scales of time. These time-scale-dependent glycemic fluctuations might contribute to brain atrophy and cognitive outcomes within this vulnerable population.     

Maternal exposure to folic acid antagonists and placenta-mediated adverse pregnancy outcomes

Background

In previous studies, maternal exposure to folic acid antagonists was associated with increased risks of neural tube defects, cardiovascular defects, oral clefts and urinary tract defects. The objective of the current study was to assess the possible effects of using folic acid antagonists in pregnancy on placenta-mediated adverse outcomes of pregnancy.

Methods

We used data from an administrative database to retrospectively compare the occurrence of placenta-mediated adverse pregnancy outcomes between pregnant women exposed to folic acid antagonists and women without exposure to these agents.

Results

We included in the analysis a total of 14 982 women who had been exposed to folic acid antagonists and 59 825 women who had not been exposed. Sulfamethoxazole–trimethoprim was the most frequently prescribed dihydrofolate reductase inhibitor (a total of 12 546 exposures during the preconception period and all 3 trimesters), and phenobarbital was the most frequently prescribed among the other folic acid antagonists (a total of 1565 exposures). The risks of preeclampsia (adjusted odds ratio [OR] 1.52, 95% confidence interval [CI] 1.39–1.66), severe preeclampsia (OR 1.77, 95% CI 1.38–2.28), placental abruption (OR 1.32, 95% CI 1.12–1.57), fetal growth restriction defined as less than the 10th percentile (OR 1.07, 95% CI 1.01–1.13), fetal growth restriction defined as less than the 3rd percentile (OR 1.22, 95% CI 1.11–1.34) and fetal death (OR 1.35, 95% CI 1.07–1.70) were greater among mothers with exposure to folic acid antagonists. In general, the risks associated with exposure to other folic acid antagonists were higher than those associated with exposure to dihydrofolate reductase inhibitors. Supplementary analyses involving tight matching with propensity score, restriction of the analysis to women with exposure during the first and second trimesters and restriction of the analysis to specific categories of folic acid antagonists yielded similar results.

Interpretation

Maternal exposure to folic acid antagonists appears to increase the risk of placenta-mediated adverse outcomes of pregnancy.     

A Meta-Analysis on the Relationship between Exposure to ELF-EMFs and the Risk of Female Breast Cancer

Objective

To comprehensively analyze the relationship between exposure to extremely low frequency electromagnetic fields (ELF-EMFs) and the development of female breast cancer.

Methods

Reports of case-control studies published from 1990 to 2010 were analyzed. The quality effect model was chosen to calculate total odds ratio (OR) depending on the data in studies and quality scores. Subgroup analyses were also performed by the situation of menopause, estrogenic receptor and exposure assessment respectively.

Results

For all 23 studies the OR was 1.07, 95% CI = 1.02–1.13, for estrogen receptor positive subgroup,OR = 1.11, 95% CI = 1.03–1.20; for premenopausal subgroup, OR = 1.11, 95% CI = 1.00–1.23. The results of other subgroups showed no significant association between ELF-EMF and female breast cancer.

Conclusion

ELF-EMFs might be related to an increased risk for female breast cancer, especially for premenopausal and ER+ females. However, it''s necessary to undertake better epidemiologic researches to verify the association between ELF-EMF and female breast cancer due to the limits of current study, especially the one on exposure assessment.     

A surface energy spectral study on the bone heterogeneity and beam obliquity using the flattened and unflattened photon beams

Aim

Using flattened and unflattened photon beams, this study investigated the spectral variations of surface photon energy and energy fluence in the bone heterogeneity and beam obliquity.

Background

Surface dose enhancement is a dosimetric concern when using unflattened photon beam in radiotherapy. It is because the unflattened photon beam contains more low-energy photons which are removed by the flattening filter of the flattened photon beam.

Materials and methods

We used a water and bone heterogeneity phantom to study the distributions of energy, energy fluence and mean energy of the 6 MV flattened and unflattened photon beams (field size = 10 cm × 10 cm) produced by a Varian TrueBEAM linear accelerator. These elements were calculated at the phantom surfaces using Monte Carlo simulations. The photon energy and energy fluence calculations were repeated with the beam angle turned from 0° to 15°, 30° and 45° in the water and bone phantom.

Results

Spectral results at the phantom surfaces showed that the unflattened photon beams contained more photons concentrated mainly in the low-energy range (0–2 MeV) than the flattened beams associated with a flattening filter. With a bone layer of 1 cm under the phantom surface and within the build-up region of the 6 MV photon beam, it is found that both the flattened and unflattened beams had slightly less photons in the energy range <0.4 MeV compared to the water phantom. This shows that the presence of the bone decreased the low-energy photon backscatters to the phantom surface. When both the flattened and unflattened photon beams were rotated from 0° to 45°, the number of photon and mean photon energy increased. This indicates that both photon beams became more hardened or penetrate when the beam angle increased. In the presence of bone, the mean energies of both photon beams increased. This is due to the absorption of low-energy photons by the bone, resulting in more beam hardening.

Conclusions

This study explores the spectral relationships of surface photon energy and energy fluence with bone heterogeneity and beam obliquity for the flattened and unflattened photon beams. The photon spectral information is important in studies on the patient''s surface dose enhancement using unflattened photon beams in radiotherapy.     

Efficacy of Anti-VEGF and Laser Photocoagulation in the Treatment of Visual Impairment due to Diabetic Macular Edema: A Systematic Review and Network Meta-Analysis

Objective

Compare the efficacy of ranibizumab, aflibercept, laser, and sham in the first-line treatment of diabetic macular edema (DME) to inform technology assessments such as those conducted by the UK National Institute for Health and Care Excellence (NICE).

Data sources

MEDLINE, Embase, Cochrane Library, congress abstracts, ClinicalTrials.gov registry and Novartis data on file.

Inclusion criteria

Studies reporting 6- or 12-month results of randomized controlled trials (RCTs) evaluating at least two of ranibizumab 0.5 mg pro re nata, aflibercept 2.0 mg bi-monthly, laser photocoagulation or sham. Study quality was assessed based on likelihood of bias in selection, attrition, detection and performance.

Outcome measure

Improvement in best-corrected visual acuity (BCVA) measured as the proportion of patients gaining ≥10 letters on the Early Treatment Diabetic Retinopathy Study scale. The outcome was chosen following acceptance by NICE of a Markov model with 10-letter health states in the assessment of ranibizumab for DME.

Meta-analysis

Bayesian network meta-analyses with fixed and random effects adjusted for differences in baseline BCVA or central retinal thickness.

Results

The analysis included 1,978 patients from eight RCTs. The random effects model adjusting for baseline BCVA was the best model based on total residual. The efficacy of ranibizumab was numerically, but not statistically, superior to aflibercept (odds ratio [OR] 1.59; 95% credible interval [CrI], 0.61–5.37). Ranibizumab and aflibercept were statistically superior to laser monotherapy with ORs of 5.50 (2.73–13.16) and 3.45 (1.62–6.84) respectively. The probability that ranibizumab is the most efficacious treatment was 73% compared with 14% for aflibercept, 12% for ranibizumab plus laser, and 0% for laser.

Limitations

Three of the eight RCTs included are not yet published. The models did not adjust for all potential effect modifiers.

Conclusion

Ranibizumab was non-significantly superior to aflibercept and both anti-VEGF therapies had statistically superior efficacy to laser.     

Association between Farming and Chronic Energy Deficiency in Rural South India

Objective

To examine factors associated with chronic energy deficiency (CED) and anaemia in disadvantaged Indian adults who are mostly involved in subsistence farming.

Design

A cross-sectional study in which we collected information on socio-demographic factors, physical activity, anthropometry, blood haemoglobin concentration, and daily household food intake. These data were used to calculate body mass index (BMI), basal metabolic rate (BMR), daily energy expenditure, and energy and nutrient intake. Multivariable backward stepwise logistic regression was used to assess socioeconomic and lifestyle factors associated with CED (defined as BMI<18 kg/m²) and anaemia.

Setting

The study was conducted in 12 villages, in the Rishi Valley, Andhra Pradesh, India.

Subjects

Individuals aged 18 years and above, residing in the 12 villages, were eligible to participate.

Results

Data were available for 1178 individuals (45% male, median age 36 years (inter quartile range (IQR 27–50)). The prevalence of CED (38%) and anaemia (25%) was high. Farming was associated with CED in women (2.20, 95% CI: 1.39–3.49) and men (1.71, 95% CI: (1.06–2.74). Low income was also significantly associated with CED, while not completing high school was positively associated with anaemia. Median iron intake was high: 35.7 mg/day (IQR 26–46) in women and 43.4 mg/day (IQR 34–55) in men.

Conclusions

Farming is an important risk factor associated with CED in this rural Indian population and low dietary iron is not the main cause of anaemia. Better farming practice may help to reduce CED in this population.     

Longer Sleep – Slimmer Kids: The ENERGY-Project

Background

Few studies have differentiated between weekday and weekend day sleep duration in their association with indicators of weight status in children. Therefore, we examined the association of week and weekend day sleep duration with indicators of body composition in 10–12 year old European school children.

Methods and Findings

Multi-level linear regression analysis was performed to examine the association between parent-reported week and weekend day sleep duration and objectively assessed child BMI and WC, adjusting for socio-demographic variables and energy balanced related behaviours EBRBs (i.e. dietary, physical and sedentary behaviour). Compared to sleeping 10 hrs/night or more, sleeping on average less than 10 hrs/night during weekdays was associated with higher BMI (for example, B = 0.86 and CI = [0.27;1.45] when sleeping ≤7 hrs) and WC (for example, B = 1.99 and CI = [0.32;3.65] when sleeping ≤7 hrs). Sleeping 9 hrs/night during weekend days, but not ≤8 hrs, was associated with higher WC (B = 0.66; CI = [0.04;1.28]) compared to sleeping more than 10 hrs/night. Average (week and weekend) sleep duration less than 10 hrs/night was associated with higher values for BMI (B = 0.98; CI = [0.24;1.73] and WC (B = 2.35; CI = [0.08;4.31]).

Conclusions

Weekday sleep duration seems more strongly associated with body composition in European school children than weekend day sleep duration. Promoting adequate sleep duration may contribute to healthy weight in children.     

Impact of Prior Traumatic Life Events on Parental Early Stage Reactions following a Child's Cancer

Background

In pediatric oncology, effective clinic–based management of acute and long–term distress in families calls for investigation of determinants of parents'' psychological response to the child''s cancer. We examined the relationship between parents'' prior exposure to traumatic life events (TLE) and the occurrence of posttraumatic stress symptoms (PTSS) following their child''s cancer diagnosis. Factors mediating the TLE–PTSS relationship were analyzed.

Methodology

The study comprised 169 parents (97 mothers, 72 fathers) of 103 cancer diagnosed children (median age: 5,9 years; range 0.1–19.7 years). Thirty five parents were of immigrant origin (20.7%). Prior TLE were collated using a standardized questionnaire, PTSS was assessed using the Impact of Events–Revised (IES–R) questionnaire covering intrusion, avoidance and hyperarousal symptoms. The predictive significance of prior TLE on PTSS was tested in adjusted regression models.

Results

Mothers demonstrated more severe PTSS across all symptom dimensions. TLE were associated with significantly increased hyperarousal symptoms. Parents'' gender, age and immigrant status did not significantly influence the TLE–PTSS relationship.

Conclusions

Prior traumatic life–events aggravate posttraumatic hyperarousal symptoms. In clinic–based psychological care of parents of high–risk pediatric patients, attention needs to be paid to life history, and to heightened vulnerability to PTSS associated with female gender.     

Movie Smoking and Youth Initiation: Parsing Smoking Imagery and Other Adult Content

Objectives

To isolate the independent influence of exposure to smoking and other adult content in the movies on youth smoking uptake.

Methods

We used discrete time survival analysis to quantify the influence of exposure to smoking and other adult content in the movies on transitioning from (1) closed to open to smoking; (2) never to ever trying smoking; and (3) never to ever hitting, slapping, or shoving someone on two or more occasions in the past 30 days. The latter is a comparative outcome, hypothesized to have no correlation with exposure to smoking in the movies.

Results

Assessed separately, both exposure to smoking imagery and exposure to adult content were associated with increased likelihood of youth becoming open to smoking (OR = 1.09, 95% CI: 1.04–1.15 and OR = 1.10, 95% CI: 1.04–1.17) and having tried smoking (OR = 1.06, 95% CI: 1.00–1.12 and OR = 1.06, 95% CI: 1.00–1.13). Both measures were also separately associated with aggressive behavior (OR = 1.09, 95% CI: 1.04–1.14 and OR = 1.09, 95% CI: 1.04–1.15). A very high correlation between the two measures (0.995, p<0.000) prevented an assessment of their independent effects on smoking initiation.

Conclusion

Although exposure to smoking in the movies is correlated with smoking susceptibility and initiation, the high correlation between exposure to smoking in the movies and other adult content suggests that more research is needed to disentangle their independent influence on smoking.     

Occupational Exposure to Ultraviolet Radiation and Risk of Non-Melanoma Skin Cancer in a Multinational European Study

Background

Studies suggest that ambient sunlight plays an important role in the pathogenesis of non-melanoma skin cancers (NMSC). However, there is ongoing controversy regarding the relevance of occupational exposure to natural and artificial ultraviolet radiation (UV) radiation.

Objectives

We investigated potential associations between natural and artificial UV radiation exposure at work with NMSC in a case-control study conducted in Hungary, Romania, and Slovakia.

Methods

Occupational exposures were classified by expert assessment for 527 controls and 618 NMSC cases (515 basal cell carcinoma, BCC). Covariate information was collected via interview and multiple logistic regression models were used to assess associations between UV exposure and NMSC.

Results

Lifetime prevalence of occupational exposure in the participants was 13% for natural UV radiation and 7% for artificial UV radiation. Significant negative associations between occupational exposure to natural UV radiation and NMSC were detected for all who had ever been exposed (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.27–0.80); similar results were detected using a semi-quantitative metric of cumulative exposure. The effects were modified by skin complexion, with significantly decreased risks of BCC among participants with light skin complexion. No associations were observed in relation to occupational artificial UV radiation exposure.

Conclusions

The protective effect of occupational exposure to natural UV radiation was unexpected, but limited to light-skinned people, suggesting adequate sun-protection behaviors. Further investigations focusing on variations in the individual genetic susceptibility and potential interactions with environmental and other relevant factors are planned.     

Consuming More of Daily Caloric Intake at Dinner Predisposes to Obesity. A 6-Year Population-Based Prospective Cohort Study

Background/Objectives

It has been hypothesized that assuming most of the caloric intake later in the day leads to metabolic disadvantages, but few studies are available on this topic. Aim of our study was to prospectively examine whether eating more of the daily caloric intake at dinner leads to an increased risk of obesity, hyperglycemia, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD).

Subjects/Methods

1245 non-obese, non-diabetic middle-aged adults from a population-based cohort underwent a 3-day food record questionnaire at enrollment. Anthropometric values, blood pressure, blood metabolic variables, and estimated liver fat were measured at baseline and at 6-year follow-up.

Design

Prospective cohort study.

Results

Subjects were divided according to tertiles of percent daily caloric intake at dinner. A significant increase in the incidence rate of obesity (from 4.7 to 11.4%), metabolic syndrome (from 11.1 to 16.1%), and estimated NAFLD (from 16.5 to 23.8%) was observed from the lower to higher tertile. In a multiple logistic regression model adjusted for multiple covariates, subjects in the highest tertile showed an increased risk of developing obesity (OR = 2.33; 95% CI 1.17–4.65; p = 0.02), metabolic syndrome (OR = 1.52; 95% CI 1.01–2.30; p = 0.04), and NAFLD (OR = 1.56; 95% CI 1.10–2.22; p = 0.01).

Conclusions

Consuming more of the daily energy intake at dinner is associated with an increased risk of obesity, metabolic syndrome, and NAFLD.     

A Nation-Wide Study of Prevalence and Risk Factors for Fecal Impaction in Nursing Homes

Background

There are no existing studies that provide data regarding the epidemiology of, and risk factors for, fecal impaction, either in the general population or in any sub-group of people.

Objective

Estimate the prevalence of and factors associated with fecal impaction on a representative sample of the institutionalized elderly population.

Design

Two-phase study. Phase 1: pilot study validating the methodology in which all residents of a single nursing home participated. Phase 2: national multi-center cross-sectional study.

Setting

34 randomly selected nursing homes.

Measurements

The presence of fecal impaction and associated factors were evaluated using three different tools: data collected from medical records; a self-completion questionnaire filled out by the subjects or a proxy; and a rectal examination.

Subjects

Older subjects living in nursing homes.

Results

The prevalence of chronic constipation was 70.7% (95%CI: 67.3–74.1%), of which 95.9% of patients were properly diagnosed and 43.1% were properly controlled. The prevalence of FI according to patient history was 47.3% (43.6–51.0%) and 6.6% (4.7–8.5%) according to rectal examination. Controlled constipation (OR: 9.8 [5.2–18.4]) and uncontrolled constipation (OR: 37.21 [19.7–70.1]), the number of medications (OR: 1.2 [1.1–1.3]), reduced functional capacity (OR: 0.98 [0.97–0.99]) and the occasional use of NSAIDs were independent risk factors for fecal impaction.

Conclusions

Constipation affects more than 70% of people living in nursing homes. Although it is properly diagnosed in more than 95% of cases, the disease is only controlled in less than 50%. Constipation, especially when not controlled, is the most significant risk factor leading to fecal impaction, which is prevalent in almost 50% of this population.     

Association between Exposure to Environmental Tobacco Smoke and Biomarkers of Oxidative Stress Among Patients Hospitalised with Acute Myocardial Infarction

Objective

To determine whether exposure to environmental tobacco smoke was associated with oxidative stress among patients hospitalised for acute myocardial infarction.

Design

An existing cohort study of 1,261 patients hospitalised for acute myocardial infarction.

Setting

Nine acute hospitals in Scotland.

Participants

Sixty never smokers who had been exposed to environmental tobacco smoke (admission serum cotinine ≥3.0 ng/mL) were compared with 60 never smokers who had not (admission serum cotinine ≤0.1 ng/mL).

Intervention

None.

Main outcome measures

Three biomarkers of oxidative stress (protein carbonyl, malondialdehyde (MDA) and oxidised low-density lipoprotein (ox-LDL)) were measured on admission blood samples and adjusted for potential confounders.

Results

After adjusting for baseline differences in age, sex and socioeconomic status, exposure to environmental tobacco smoke was associated with serum concentrations of both protein carbonyl (beta coefficient 7.96, 95% CI 0.76, 15.17, p = 0.031) and MDA (beta coefficient 10.57, 95% CI 4.32, 16.81, p = 0.001) but not ox-LDL (beta coefficient 2.14, 95% CI −8.94, 13.21, p = 0.703).

Conclusions

Exposure to environmental tobacco smoke was associated with increased oxidative stress. Further studies are requires to explore the role of oxidative stress in the association between environmental tobacco smoke and myocardial infarction.     

Light and competition gradients fail to explain the coexistence of shade-tolerant Fagus sylvatica and shade-intermediate Quercus petraea seedlings

Background and Aims

The coexistence of forest tree species has often been linked to differences among species in terms of their response to light availability during the regeneration stage. From this perspective, species coexistence results from growth–growth or mortality–growth trade-offs along spatial light gradients. Experimental evidence of growth–growth trade-offs in natural conditions is sparse due to various confounding factors that potentially hinder the relationship. This study examined growth hierarchies along light gradients between two tree species with contrasting shade tolerance by controlling potential confounding factors such as seedling size, seedling status, seedling density and species composition.

Methods

Natural regenerated shade-tolerant Fagus sylvatica and shade-intermediate Quercus petraea seedlings were used, and growth rankings over a 4-year period were compared in 8- to 10-year-old tree seedlings.

Key results

No rank reversal occurs between the two species along the light gradient, or along the density, mixture or seedling size gradients. The shade-tolerant species was always the more competitive of the two. Pronounced effects of initial size on seedling growth were observed, whereas the effects of light and competition by neighbours were of secondary importance. The paramount effect of size, which results from the asymmetric nature of interseedling competition, gives a strong advantage to tall seedlings over the long term.

Conclusions

This study extends previous efforts to identify potential drivers of rank reversals in young tree mixtures. It does not support the classical assumption that spatial heterogeneity in canopy opening explains the coexistence of the two species studied. It suggests that spatial variation in local size hierarchies among seedlings that may be caused by seedling emergence time or seedling initial performance is the main driver of the dynamics of these mixed stands.     

Myocardial Creatine Levels Do Not Influence Response to Acute Oxidative Stress in Isolated Perfused Heart

Background

Multiple studies suggest creatine mediates anti-oxidant activity in addition to its established role in cellular energy metabolism. The functional significance for the heart has yet to be established, but antioxidant activity could contribute to the cardioprotective effect of creatine in ischaemia/reperfusion injury.

Objectives

To determine whether intracellular creatine levels influence responses to acute reactive oxygen species (ROS) exposure in the intact beating heart. We hypothesised that mice with elevated creatine due to over-expression of the creatine transporter (CrT-OE) would be relatively protected, while mice with creatine-deficiency (GAMT KO) would fare worse.

Methods and Results

CrT-OE mice were pre-selected for creatine levels 20–100% above wild-type using in vivo ¹H^–MRS. Hearts were perfused in isovolumic Langendorff mode and cardiac function monitored throughout. After 20 min equilibration, hearts were perfused with either H₂O₂ 0.5 µM (30 min), or the anti-neoplastic drug doxorubicin 15 µM (100 min). Protein carbonylation, creatine kinase isoenzyme activities and phospho-PKCδ expression were quantified in perfused hearts as markers of oxidative damage and apoptotic signalling. Wild-type hearts responded to ROS challenge with a profound decline in contractile function that was ameliorated by co-administration of catalase or dexrazoxane as positive controls. In contrast, the functional deterioration in CrT-OE and GAMT KO hearts was indistinguishable from wild-type controls, as was the extent of oxidative damage and apoptosis. Exogenous creatine supplementation also failed to protect hearts from doxorubicin-induced dysfunction.

Conclusions

Intracellular creatine levels do not influence the response to acute ROS challenge in the intact beating heart, arguing against creatine exerting (patho-)physiologically relevant anti-oxidant activity.