Sea anemones, methylmercury, and bacterial infection: A closer look at multiple stressors.

Specimens of the Mediterranean sea anemone Anemonia viridis were exposed to methylmercury (MeHg) and bacterial infection to study their immune responses to a well-known toxic pollutant. Anemones were housed in laboratory conditions and divided into five experimental groups: 1. control (no microinjection); 2. filtered seawater + buffer injection; 3. filtered seawater + Escherichia coli injection; 4. MeHg + buffer injection; 5. MeHg + E. coli injection. Data showed an increase in antioxidant enzyme production compared to the constitutive condition, while methylmercury inhibited lysozyme production. The buffer inoculation had no statistically significant effects on the animals. In addition, electrophoretic and protease analyses revealed differences in the type of proteins produced, as well as a modulation of proteases depending on the treatment. The study demonstrated the immunomodulatory effect of the organic pollutant on A. viridis, validating its use as a model organism for marine coastal biomonitoring programmes and multiple stress studies.

Global warming-related response after bacterial challenge in Astroides calycularis, a Mediterranean thermophilic coral.

A worldwide increase in the prevalence of coral diseases and mortality has been linked to ocean warming due to changes in coral-associated bacterial communities, pathogen virulence, and immune system function. In the Mediterranean basin, the worrying upward temperature trend has already caused recurrent mass mortality events in recent decades. To evaluate how elevated seawater temperatures affect the immune response of a thermophilic coral species, colonies of Astroides calycularis were exposed to environmental (23 °C) or elevated (28 °C) temperatures, and subsequently challenged with bacterial lipopolysaccharides (LPS). Using immunolabeling with specific antibodies, we detected the production of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-kB), molecules involved in coral immune responses, and heat shock protein 70 (HSP70) activity, involved in general responses to thermal stress. A histological approach allowed us to characterize the tissue sites of activation (epithelium and/or gastroderm) under different experimental conditions. The activity patterns of the examined markers after 6 h of LPS stimulation revealed an up-modulation at environmental temperature. Under warmer conditions plus LPS-challenge, TLR4-NF-kB activation was almost completely suppressed, while constituent elevated values were recorded under thermal stress only. An HSP70 up-regulation appeared in both treatments at elevated temperature, with a significantly higher activation in LPS-challenge colonies. Such an approach is useful for further understanding the molecular pathogen-defense mechanisms in corals in order to disentangle the complex interactive effects on the health of these ecologically relevant organisms related to global climate change.

A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study.

BACKGROUND: Postmenopausal hormone replacement therapy (HRT) relieves menopausal symptoms and may decrease mortality in recently postmenopausal women, but increases breast cancer risk. Low-dose tamoxifen has shown retained activity in phase-II studies. METHODS: We conducted a phase-III trial in 1884 recently postmenopausal women on HRT who were randomly assigned to either tamoxifen, 5 mg/day, or placebo for 5 years. The primary end point was breast cancer incidence. RESULTS: After 6.2 ± 1.9 years mean follow-up, there were 24 breast cancers on placebo and 19 on tamoxifen (risk ratio, RR, 0.80; 95% CI 0.44-1.46). Tamoxifen showed favorable trends in luminal-A tumors (RR, 0.32; 95% CI 0.12-0.86), in HRT users <5 years (RR, 0.35; 95% CI 0.15-0.82) and in women completing at least 12 months of treatment (RR, 0.49; 95% CI 0.23-1.02). Serious adverse events did not differ between placebo and tamoxifen, including, respectively, coronary heart syndrome (6 versus 4), cerebrovascular events (2 versus 5), VTE (2 versus 5) and uterine cancers (3 versus 1). Vasomotor symptoms were 50% more frequent on tamoxifen. CONCLUSIONS: The addition of low-dose tamoxifen to HRT did not significantly reduce breast cancer risk and increased climacteric symptoms in recently postmenopausal women. However, we noted beneficial trends in some subgroups which may deserve a larger study.

Self-assessed health status changes in a community cohort of people with multiple sclerosis: 11 years of follow-up.

BACKGROUND AND PURPOSE: Few data are available on the health status of people with multiple sclerosis (PwMS) in the community. We assessed changes in self-perceived health status and health related quality of life of a community-based cohort of PwMS over a decade, and identified predictors of such changes. METHODS: In 1999 we started the POSMOS study (Postal Survey of Self-Assessed Health of MS Adults and their Significant Others) on a random sample of 251 adults with MS from the Milan area (mean age 42 years, range 18-71 years), and prospectively assessed changes in self-perceived health status over 11 years. Participants completed the Multiple Sclerosis Quality-of-Life-54 (MSQOL-54) and a general/clinical questionnaire. We re-assessed the cohort in 2004 and 2010, sending the same questionnaires plus the Chicago Multiscale Depression Inventory. RESULTS: There were 205 (86%) respondents in 2004, 171 (74%) in 2010; 28 (11%) died during the study. Severely impaired [self-determined Expanded Disability Status Scale (EDSS) > 6.5] increased from 19% to 32%. One-fifth remained fully ambulatory (EDSS <4.0): 25% women (median age 44 years [interquartile range, IQR 39-53], median years from diagnosis 16 [IQR 12-19]); and 17% men (median age 40 years [IQR 38-45], median years from diagnosis 14 [IQR 12-17]). Changes in MSQOL-54 composite scores were negligible; but among individual scales, change in health, cognitive function and general health worsened, and social function and emotional wellbeing improved significantly. Depressive symptoms were high and stable. CONCLUSIONS: Multiple sclerosis had a pervasive but inhomogeneous impact on the lives of our MS sufferers. Notwithstanding overall clinical deterioration and aging, hospital admissions and medical consultations decreased, suggesting reduced use of health care resources. By contrast, housing adaptations and home care increased, psychological burden was high and self-perceived cognitive functioning worsened.

Health-related quality of life and depressive symptoms in significant others of people with multiple sclerosis: a community study.

BACKGROUND AND PURPOSE: Uncertain prognosis and modest treatment efficacy make multiple sclerosis (MS) a particularly difficult disease to adjust to for both patients and their significant others (SOs). Few studies have assessed health-related quality of life (HRQOL) and depressive symptoms in SOs of people with MS in the community. We assessed, and identified predictors of, HRQOL and depression in SOs of adults with MS. METHODS: POSMOS (postal survey of self-assessed health in MS adults and SOs) is a longitudinal survey on a random sample of 251 people with MS in the Milan area. In 2010, SOs and contemporaneous controls completed the SF-36 and Chicago Multiscale Depression Inventory (CMDI). RESULTS: Overall, 142 SOs (mean age 53.1 years; 50% women, 65% partners) and 120 controls (similar to SOs for sex and education, but older) participated. By multivariable modeling of the SO plus control population, SF-36 vitality was lower in SOs (proportional odds ratio 0.45; 95% confidence interval 0.28-0.70), women (0.41; 0.27-0.64), and older subjects (0.98; 0.97-0.99). SF-36 mental health was also lower in SOs (0.62; 0.40-0.96) and women (0.43; 0.28-0.67). Regarding MS characteristics associated with HRQOL and depression in SOs, severe disability [Expanded Disability Status Scale (EDSS > 6.5)] had no effect, whilst depressive symptoms (pathologic CMDI) negatively influenced most SF-36 and all CMDI scores in SOs. CONCLUSIONS: SOs had significantly lower vitality and psychological well-being than controls, identifying a burden in being the companion of a person with MS. This burden was unrelated to physical compromise but associated with depressive symptoms in MS.

The relationship between ambient particulate matter and respiratory mortality: a multi-city study in Italy.

The association of air pollutants with natural and respiratory mortality has been consistently reported. However, several aspects of the relationship between particulate matter with a 50% cut-off aerodynamic diameter of 10 µm (PM(10)) and respiratory mortality require further investigation. The aim of the present study was to assess the PM(10)-respiratory mortality association in Italy and examine potentially susceptible groups. All deaths from natural (n=276,205) and respiratory (n=19,629) causes among subjects aged ≥ 35 yrs in 10 northern, central and southern Italian cities in 2001-2005 were included in the study. Pollution data for PM(10), nitrogen dioxide and ozone were also obtained. A time-stratified case-crossover analysis was carried out. Different cumulative lags were selected to analyse immediate, delayed, prolonged and best-time effects of air pollution. The shape of the exposure-response curve was analysed. Age, sex, chronic conditions and death site were investigated as potential effect modifiers. We found a 2.29% (95% CI 1.03-3.58%) increase in respiratory mortality at 0-3 days lag. The increase in respiratory mortality was higher in summer (7.57%). The exposure-response curve had a linear shape without any threshold. Sex and chronic diseases modified the relationship between particular matter (PM) and respiratory mortality. The effect of PM on respiratory mortality was stronger and more persistent than that on natural mortality. Females and chronic disease sufferers were more likely to die of a respiratory disease caused by air pollution than males and healthy people.

Effects of cold weather on mortality: results from 15 European cities within the PHEWE project.

Weather-related health effects have attracted renewed interest because of the observed and predicted climate change. The authors studied the short-term effects of cold weather on mortality in 15 European cities. The effects of minimum apparent temperature on cause- and age-specific daily mortality were assessed for the cold season (October-March) by using data from 1990-2000. For city-specific analysis, the authors used Poisson regression and distributed lag models, controlling for potential confounders. Meta-regression models summarized the results and explored heterogeneity. A 1 degrees C decrease in temperature was associated with a 1.35% (95% confidence interval (CI): 1.16, 1.53) increase in the daily number of total natural deaths and a 1.72% (95% CI: 1.44, 2.01), 3.30% (95% CI: 2.61, 3.99), and 1.25% (95% CI: 0.77, 1.73) increase in cardiovascular, respiratory, and cerebrovascular deaths, respectively. The increase was greater for the older age groups. The cold effect was found to be greater in warmer (southern) cities and persisted up to 23 days, with no evidence of mortality displacement. Cold-related mortality is an important public health problem across Europe. It should not be underestimated by public health authorities because of the recent focus on heat-wave episodes.

The impact of the summer 2003 heat waves on mortality in four Italian cities.

This study evaluates the impact of the 2003 heat wave on cause-specific mortality and the role of demographic characteristics and socioeconomic conditions that may have increased the risk of mortality in four Italian cities: Bologna, Milan, Rome and Turin. Daily mortality counts, for the resident population by age, sex and cause of death were considered. Daily excess mortality was calculated as the difference between the number of deaths observed and the smoothed average. The impact of heat on health is measured in terms of maximum apparent temperature. The greatest excess in mortality was observed in the north west of Italy (Turin, +23% and Milan, +23%). The old (75-84 years) and the very old (85+ years) were the age groups most affected, and when stratifying by sex, the increase in mortality seemed to be greater among females. The greatest excess in mortality was registered in those with low socioeconomic status in Rome (+17.8%) and in those with lower education levels in Turin (+43%). The analysis of cause-specific mortality not only confirms results from previous studies of an increase in heat-related mortality by respiratory and cardiovascular diseases, but also shows a significant excess in mortality for diseases of the central nervous system and for metabolic/endocrine disorders. Results from 2003 highlight the necessity of targeting future prevention programmes at the susceptible sub-groups identified. The introduction of warning systems alongside efficient preventive plans and the monitoring of mortality during heat waves may represent a valid tool for the reduction of heat-related deaths.

The impact of the summer 2003 heat waves on mortality in four Italian cities.

This study evaluates the impact of the 2003 heat wave on cause-specific mortality and the role of demographic characteristics and socioeconomic conditions that may have increased the risk of mortality in four Italian cities: Bologna, Milan, Rome and Turin. Daily mortality counts, for the resident population by age, sex and cause of death were considered. Daily excess mortality was calculated as the difference between the number of deaths observed and the smoothed average. The impact of heat on health is measured in terms of maximum apparent temperature. The greatest excess in mortality was observed in the north west of Italy (Turin, +23% and Milan, +23%). The old (75-84 years) and the very old (85+ years) were the age groups most affected, and when stratifying by sex, the increase in mortality seemed to be greater among females. The greatest excess in mortality was registered in those with low socioeconomic status in Rome (+17.8%) and in those with lower education levels in Turin (+43%). The analysis of cause-specific mortality not only confirms results from previous studies of an increase in heat-related mortality by respiratory and cardiovascular diseases, but also shows a significant excess in mortality for diseases of the central nervous system and for metabolic/endocrine disorders. Results from 2003 highlight the necessity of targeting future prevention programmes at the susceptible sub-groups identified. The introduction of warning systems alongside efficient preventive plans and the monitoring of mortality during heat waves may represent a valid tool for the reduction of heat-related deaths.

Short term effects of urban air pollution on respiratory health in Milan, Italy, 1980-89.

STUDY OBJECTIVE: To investigate the association between daily urban air pollution and acute effects on respiratory health. STUDY DESIGN: Time series analysis following the procedure defined in the APHEA protocol. SETTING: City of Milan, Italy, from 1980-89. Two air pollutants, total suspended particulates (TSP) and sulphur dioxide (SO2), and two health outcomes, deaths and hospital admissions were considered. The last was analysed according to two age groups. SUBJECTS: Daily deaths and general hospital admissions for respiratory causes in residents who died in Milan or were admitted to local hospitals in that city. MAIN RESULTS: There was an increased risk of respiratory death and of hospital admission associated with increased concentrations of SO2 and TSP. The relative risks were similar for both pollutants, and were higher for respiratory deaths than for hospital admissions. No changes in relation to season were seen in the SO2 effect on respiratory deaths, but there was a suggestion of a higher effect on hospital admissions in the cool months. The seasonal pattern of the TSP effect was inconsistent: for mortality it was higher in the warm period while for hospital admissions it seemed to be higher in the cool months. This last result might be due to chance, although some role could have been played by the hospital admission data on all general admissions for respiratory causes (ICD-9: 460-519) as these are a much less specific end point. CONCLUSION: In Milan, a positive association was found between the daily SO2 or TSP concentrations and the number of deaths or hospital admissions for respiratory causes. This confirms results from other European and North American cities.

Estimate of population coverage with the prostate specific antigen (PSA) test to screen for prostate cancer in a metropolitan area of northern Italy.

The use of the prostate specific antigen (PSA) test in the period 1999-2000 in a population of 311 822 men, aged 40 years or more, resident in Milan, Italy, was examined. Data were drawn from the outpatient database of the local health information system. A total of 139 350 PSA tests were used in 83 943 subjects. Overall, 26.9% of the male population aged 40 or older, with no history of prostate cancer, received a PSA test in the 2 year study period. For subjects older than 50 the rate rose to 34%. Results show a high coverage of the male population in northern Italy with screening using the PSA test for prostate cancer.

Time To Pregnancy and occupational lead exposure.

BACKGROUND: Lead exposure is known to be harmful to the male reproductive system, including impairment of fertility. However, it is unclear whether currently existing low levels of exposure have this effect. AIMS: To study retrospectively current workers in lead using industries (battery manufacture, smelting, etc), and in non-lead using control industries, in four European countries, with Time To Pregnancy as the outcome variable, as part of the EU funded Asclepios Project. METHODS: Exposure assessment was mainly by blood lead values, which were available from the late 1970s, supplemented by imputed values where necessary. Three exposure models were studied: (1) short term (recent) exposure; (2) total duration of work in a lead using industry; and (3) cumulative exposure. A Cox proportional hazards model with discrete ties was used for the statistical analysis, with covariates for both partners. RESULTS: A total of 1104 subjects took part, of whom 638 were occupationally exposed to lead at the relevant time. Blood lead levels were mainly less than 50 microg/dl. No consistent association of Time To Pregnancy with lead exposure was found in any of the exposure models, although reduced fertility was observed in one category each in models (2) and (3). CONCLUSIONS: This basically negative result is unlikely to be due to the misclassification of key variables, to insufficient statistical power, or to bias, for example, response bias. If any impairment of male reproductive function exists at the levels of occupational lead exposure now current, it does not appear to reduce biological fertility.

Shift work and subfecundity: a European multicenter study. European Study Group on Infertility and Subfecundity.

Shift work has been associated with various unfavorable pregnancy outcomes (ie, pregnancy loss, spontaneous abortion, low birth weight, etc). The suggested underlying mechanism is the interference of shift work with the circadian regulation of human metabolism and, in particular, with the temporal pattern of endocrine function. To analyze the effect of shift work on fecundity, the Time of Unprotected Intercourses (TUI) has been measured in couples recruited in the European Studies on Infertility and Subfecundity, which were undertaken in seven European countries. A low (odds ratio < 2.0) but consistent excess risk of subfecundity (TUI > or = 9.4 months) has been observed both in a representative sample of the general population of women in reproductive age and in a sample of pregnant women or women who had just given birth. The excess risk was also consistently evident both in the subsample of the first pregnancies and in the subsample of the most recent pregnancies. Only the exposure of women to shift work seemed to affect a couple's fecundity; men working shift work did not modify the fecundity pattern of their own couples. No specific job title among shift workers concentrated the risk of subfecundity. No association of menstrual disorders with shift work was identified. Even though residual confounding could partly account for the results and the fact that a plausible biological explanation of the claimed effect is still lacking, data from this study are in favor of an association between shift work and prolonged waiting time to pregnancy.

Time to pregnancy among male workers of the reinforced plastics industry in Denmark, Italy and The Netherlands. ASCLEPIOS.

OBJECTIVES: The relationship between occupational styrene exposure and male fecundity was examined. METHODS: Among 1560 Danish, Italian, and Dutch reinforced plastics workers, 220 styrene-exposed workers and 382 unexposed referents who had fathered a child were identified. A total of 768 historical styrene measurements conducted in 1970-1996 in the study companies formed the basis for semiquantitative exposure assessment in combination with measurements of urinary styrene metabolite levels. All the subjects were interviewed about work conditions and other factors potentially related to reduced fecundity. Fecundity was measured as the reported time to pregnancy (number of months a couple needed to conceive their youngest child). RESULTS: A statistically nonsignificantly reduced fecundity was observed for the styrene-exposed workers [fecundity ratio 0.79, 95% confidence interval (95% CI) 0.59-1.05]. But no consistent pattern of a detrimental effect on fecundity was found when time to pregnancy was related to worktasks indicating higher styrene exposure levels or semiquantitative or quantitative measures of styrene exposure. The workers with high exposure showed a fecundity ratio of 1.09 (95% CI 0.69-1.72). CONCLUSIONS: It is unlikely that styrene exposure has a strong effect on male fecundity.

Objectives, designs and populations of the European Asclepios study on occupational hazards to male reproductive capability.

The main objective of the Asclepios program was to examine occupational risk factors for the male reproductive system. The program focused on occupational exposure to fungicides (farmers, greenhouse workers, and vineyard workers), styrene (laminators in the reinforced plastics industry) and inorganic lead (battery workers, foundry workers, and lead smelters). Questionnaire studies of time to pregnancy were combined with longitudinal and cross-sectional studies of semen quality. The 8 data-collecting centers addressed 6553 male workers and contributed time-to-pregnancy values on the 3077 most recent pregnancies. Data collection was by interview or self-collection. The average response rate across all exposures and centers was 69.8%. The Asclepios project is the first international multicenter research project on environmental risks to male reproductive function. A protocol for epidemiologic research on occupational risk factors to the male reproductive system was developed, and links between epidemiologic and experimental units were established. The majority, but not all, of the studies was completed within the given time frame.

[Air pollution and daily mortality among Milan residents, 1980-89. Preliminary results]. / Inquinamento atmosferico e mortalità giornaliera nei residenti a Milano, 1980-89. Risultati preliminari.

Short term effects of air pollutant levels on daily mortality were studied, using time series approach, in Milan from the year 1980 to 1989. The Poisson regression with autocorrelated residuals was applied. This paper reports preliminary results of the analyses on the association between total daily number of deaths and the 24h mean concentrations, on the same day, for two air pollutants: sulphur dioxide and total suspended particulate. A positive and curvilinear relation (with a logarithmic shape) has been found between total daily mortality and concentration levels for each pollutant. This result confirm a steeper increase in mortality at low concentrations, lower than the international standards in use at the moment.

[An epidemiological study of the health conditions of Milan traffic police with respect to pollution from vehicular traffic]. / Indagine epidemiologica sulle condizioni di salute dei vigili urbani di Milano in rapporto all'inquinamento da traffico veicolare.

An investigation on the health effects of occupational exposure to motor vehicle exhaust and environmental pollutants was carried out on traffic wardens in Milan (Italy). Randomized samples of 292 traffic wardens (exposed group) and 60 hospital staff members (control group) underwent a physical examination and laboratory tests. No significant difference was observed between the exposed and control groups as regards general morbidity, apart from musculo-skeletal disorders in females. The mean blood lead level (PbB) among traffic wardens was 15.2 micrograms/dl compared with 11.7 in control (p less than 0.01). The carboxyhaemoglobin concentration (COHb) in traffic wardens at the beginning of the shift was 2.8% for smokers and 1.2% for non-smokers (3.0% and 0.9% respectively in controls). At the end of the shift COHb in the exposed group was 4.3% for smokers and 2.5% for non-smokers (p less than 0.01). PbB was significantly correlated (r = 0.17) with Median Nerve Motor Conduction Velocity (NCV) in the exposed but not in the control group. The same pattern was observed for the correlation of PbB and Systolic Blood Pressure (SBP) (r = -0.24). COHb was significantly correlated with HDL cholesterol (r = -0.20) in the exposed group only. It is questionable whether very low PbB levels can affect NCV and SBP directly or rather whether PbB, as well as COHb, should be regarded as tracers of exposure to those urban pollutants leading also to cardiovascular and nervous disorders.