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Most infectious diseases are unequally distributed between male and female subjects. This sex dimorphism is confirmed by epidemiologic studies which suggest an increased number of male septic patients, while, due to the class age of septic patients, an overrepresentation of female patients would be expected. Lifestyle, recreational activities, professional exposition and access to care are plausible reasons for this dimorphism. However, biological differences should be carefully considered, particularly the weight of X-linked variability and the role of sex hormones. Animal models clearly show that clinical response to infection is more exuberant in males than in females. This is partly explained by an attenuation of the inflammatory response by female sex hormones. However, the translation from experimental studies to the bedside remains challenging as a result of confounding factors like age, hormone changes and response to treatment. Keywords: Bacteria, estradiol, gender, infection, sex

BackgroundIntellectual ability may be an endophenotypic marker for bipolar disorder.AimsWithin a large birth cohort, we aimed to assess whether childhood IQ (including both verbal IQ (VIQ) and performance IQ (PIQ) subscales) was predictive of lifetime features of bipolar disorder assessed in young adulthood.MethodWe used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a large UK birth cohort, to test for an association between measures of childhood IQ at age 8 years and lifetime manic features assessed at age 22–23 years using the Hypomania Checklist-32 (HCL-32; n=1881 individuals). An ordinary least squares linear regression model was used, with normal childhood IQ (range 90–109) as the referent group. We adjusted analyses for confounding factors, including gender, ethnicity, handedness, maternal social class at recruitment, maternal age, maternal history of depression and maternal education.ResultsThere was a positive association between IQ at age 8 years and lifetime manic features at age 22–23 years (Pearson's correlation coefficient 0.159 (95% CI 0.120–0.198), P>0.001). Individuals in the lowest decile of manic features had a mean full-scale IQ (FSIQ) which was almost 10 points lower than those in the highest decile of manic features: mean FSIQ 100.71 (95% CI 98.74–102.6) v. 110.14 (95% CI 107.79–112.50), P>0.001. The association between IQ and manic features was present for FSIQ, VIQ and for PIQ but was strongest for VIQ.ConclusionsA higher childhood IQ score, and high VIQ in particular, may represent a marker of risk for the later development of bipolar disorder. This finding has implications for understanding of how liability to bipolar disorder may have been selected through generations. It will also inform future genetic studies at the interface of intelligence, creativity and bipolar disorder and is relevant to the developmental trajectory of bipolar disorder. It may also improve approaches to earlier detection and treatment of bipolar disorder in adolescents and young adults.

Objectives To describe lung function in correlation with information on exposure to dust and fibers in soft tissue paper-producing factories in Germany. Methods Ambient monitoring was performed for inhalable, respirable dust and fibers in nine soft tissue paper-producing factories. In a study group of 1,047 workers (189 control subjects, 240 workers with moderate exposure, and 618 workers with high exposure), spirometry (FVC, FEV 1 ) was performed. Information on occupational history, duration of exposure, workshop within the company, former occupational exposures, and smoking habits were collected. By employing multiple linear regression modeling, the potentially confounding effects of age, sex, body mass index, smoking habits, and factory were incorporated into the analysis of FVC, FEV 1 , and FEV 1 in percent of FVC (FEV 1 %FVC). By employing a logistic regression model, odds ratios were calculated for FVC Results The mean concentrations for inhalable, respirable, and fibrous dusts were 12.4 mg/m 3 , 0.28 mg/m 3 , and 420,000 fibers per cubic meter. With relation to cumulative dust and fiber exposure, a decrease of FVC from 105.4% predicted to 96.9% predicted (dust) and 97.1% predicted (fibers) in the subgroup with highest cumulative exposure was observed. For FEV 1 , a decrease from 107.3% predicted to 103.0% predicted (dust) and 102.8% predicted (fibers) was found. The parameter estimates show dose-response relationships that are more pronounced for FVC compared to FEV 1 . FEV 1 %FVC did not change significantly with increasing cumulative exposure, indicating a restrictive pattern of the findings. Conclusions Due to high ambient dust concentrations and the observed adverse effects on lung function, a reduction of dust exposure and secondary preventive measures is advised.

ObjectiveOvarian cancer is primarily a disease of the industrialized world. However, few factors associated with industrialization that contribute to the etiology of ovarian cancer have been identified. We sought to explore factors potentially associated with ovarian cancer by correlating ovarian cancer incidence rates in US states with the distribution of US manufacturing.MethodsData on age-adjusted incidence rates for ovarian cancer per state in the United States and manufacturing rates per state were analyzed using multiple linear regression controlling for access to ovarian cancer care, fertility rate, and other potential confounders.ResultsIn univariate analyses, ovarian cancer incidence rates were positively correlated with the extent of manufacturing, with dairy production, and with the manufacturing of pulp and paper. Using multiple linear regression, only the correlation of ovarian cancer with pulp and paper manufacturing industry was significant. The correlation of ovarian cancer with pulp and paper manufacturing industry remained significant after adjusting for access to ovarian cancer care, fertility rates, and other potential confounders (P< 0.05).ConclusionsPulp and paper mills are associated with exposures to known ovarian carcinogens. Further epidemiological study of exposures involved in the manufacturing of pulp and paper in relation to risk of ovarian cancer is warranted.

Background and objectives: Whether the association between mild hyperhomocysteinaemia and ischaemic stroke is the consequence of a predisposing genetic background or is due to the confounding influence of established predisposing factors remains to be determined. Methods: Plasma total homocysteine (tHcy) concentration and the distribution of the C 677 T genotypes of the methylenetetrahydrofolate reductase gene ( MTHFR ) were compared in 174 consecutive patients with stroke aged Results: tHcy concentrations were markedly higher in patients with ischaemic stroke (median 11.9 μmol/l, range 2.0–94.0) than in controls (median 9.8 μmol/l, range 4.7–49.6). An increased risk was also associated with the TT 677 genotype (odds ratio (OR) 1.98; 95% confidence interval (CI) 1.04 to 3.78) and with the T allele (1.40; 95% 1.03 to 1.92) of the MTHFR gene. A differential effect of Hcy levels on risk of stroke was observed according to the distribution of environmental–behavioural risk factors, with a stronger influence in the subcategory of people with hypertension and smokers (OR 24.8; 95% CI 3.15 to 196). A comparable environmental-dependent TT 677 MTHFR genotype–stroke association was observed in the genotype-disease analysis. Conclusions: A consistency of phenotype-disease analysis and genotype-disease analysis is indicated by analysing specific subcategories of patients, defined by the distribution of established risk factors. The assumption that the Hcy–stroke relationship is unlikely due to a reverse-causality bias is indirectly supported by our data.

OBJECTIVES: Studies in traditional paper mills have indicated an excess cancer risk, and mutagenic compounds have been identified in the industry. No studies have reported on risk of cancer in paper recycling. Therefore the cancer incidence in Danish paper recycling mills was investigated. METHODS: 5377 employees in five paper recycling plants were included in a historical cohort study. The workers had been employed in paper recycling in 1965-90, and the cohort was followed up until 31 December 1993. The expected number of cancer cases was calculated from national rates. RESULTS: There was significantly more pharyngeal cancer among male workers (seven observed (standardised incidence ratio (SIR) 3.33, 95% confidence interval (95% CI) 1.34 to 6.87)). There was slightly more lung cancer among male workers in production (39 observed, SIR 1.21, 95% CI 0.86 to 1.65). Risk of Hodgkin9s disease was doubled in male production worker (four observed, SIR 1.90, 95% CI 0.51 to 4.85). CONCLUSIONS: The increased risk of pharyngeal cancer found in this study is interesting but may be influenced by confounders such as smoking and alcohol intake. This study also indicates an excess risk of Hodgkin9s disease, which is in accordance with some studies in the traditional paper mills. As this is the first report on risk of cancer in paper recycling, further studies are needed.

The possible confounding caused by smoking was studied in connection with a mortality and cancer incidence study of 3,520 workers in the pulp and paper industry. A group 1,290 sawmill workers was used for comparison in addition to the expected numbers based on national statistics. A total of 801 questionnaires was sent to a representative sample of the workers, 537 to people still alive and 264 to the next-of-kin of decedents. The reply percentage was 86.6 for the former and 80.9 for the latter. The prevalence of smoking was determined for 1956 and 1981. The proportions of moderate and heavy smokers were assessed for 1981, and smoking indices were calculated for each occupational group. The estimated rate ratios for lung cancer in relation to smoking categories and the corresponding smoking-adjusted standardized incidence ratios were calculated for 1981, and they were compared with the observed standardized incidence ratios for lung cancer. The smoking habits could not explain the observed excess of lung cancer, nor the increased mortality from coronary heart disease found among the pulp and paper workers. Postal questionnaires may be a feasible tool for assessing smoking habits in retrospective cohort studies.