Human macrophages limit oxidation products in low density lipoprotein

This study tested the hypothesis that human macrophages have the ability to modify oxidation products in LDL and oxidized LDL (oxLDL) via a cellular antioxidant defence system. While many studies have focused on macrophage LDL oxidation in atherosclerosis development, less attention has been given to the cellular antioxidant capacity of these cells. Compared to cell-free controls (6.2 ± 0.7 nmol/mg LDL), macrophages reduced TBARS to 4.42 ± 0.4 nmol/mg LDL after 24 h incubation with LDL (P = 0.022). After 2 h incubation with oxLDL, TBARS were 3.69 ± 0.5 nmol/mg LDL in cell-free media, and 2.48 ± 0.9 nmol/mg LDL in the presence of macrophages (P = 0.034). A reduction of lipid peroxides in LDL (33.7 ± 6.6 nmol/mg LDL) was found in the presence of cells after 24 h compared to cell-free incubation (105.0 ± 14.1 nmol/mg LDL) (P = 0.005). The levels of lipid peroxides in oxLDL were 137.9 ± 59.9 nmol/mg LDL and in cell-free media 242 ± 60.0 nmol/mg LDL (P = 0.012). Similar results were obtained for hydrogen peroxide. Reactive oxygen species were detected in LDL, acetylated LDL, and oxLDL by isoluminol-enhanced chemiluminescence (CL). Interestingly, oxLDL alone gives a high CL signal. Macrophages reduced the CL response in oxLDL by 45% (P = 0.0016). The increased levels of glutathione in oxLDL-treated macrophages were accompanied by enhanced catalase and glutathione peroxidase activities. Our results suggest that macrophages respond to oxidative stress by endogenous antioxidant activity, which is sufficient to decrease reactive oxygen species both in LDL and oxLDL. This may suggest that the antioxidant activity is insufficient during atherosclerosis development. Thus, macrophages may play a dual role in atherogenesis, i.e. both by promoting and limiting LDL-oxidation. © 2005 Hultén et al; licensee BioMed Central Ltd

Adaptive and maladaptive consequences of “matching habitat choice:” lessons from a rapidly-evolving butterfly metapopulation

Relationships between biased dispersal and local adaptation are currently debated. Here, I show how prior work on wild butterflies casts a novel light on this topic. “Preference” is defined as the set of likelihoods of accepting particular resources after encountering them. So defined, butterfly oviposition preferences are heritable habitat adaptations distinct from both habitat preference and biased dispersal, but influencing both processes. When a butterfly emigrates after its oviposition preference begins to reduce realized fecundity, the resulting biased dispersal is analogous to that occurring when a fish emigrates after its morphological habitat adaptations reduce its feeding rate. I illustrate preference-biased dispersal with examples from metapopulations of Melitaea cinxia and Euphydryas editha. E. editha were feeding on a well-defended host, Pedicularis, when humans created patches in which Pedicularis was killed and a less-defended host, Collinsia, was rendered phenologically available. Patch-specific natural selection favoured oviposition on Collinsia in logged (“clearing”) patches and on Pedicularis in undisturbed open forest. Quantitative variation in post-alighting oviposition preference was heritable, and evolved to be consistently different between patch types. This difference was driven more by biased dispersal than by spatial variation of natural selection. Insects developing on Collinsia in clearings retained adaptations to Pedicularis in clutch size, geotaxis and oviposition preference, forcing them to choose between emigrating in search of forest habitats with Pedicularis or staying and failing to find their preferred host. Insects that stayed suffered reduction of realized fecundity after delayed oviposition on Collinsia. Those that emigrated suffered even greater fitness penalty from consistently low offspring survival on Pedicularis. Paradoxically, most emigrants reduced both their own fitness and that of the recipient populations by dispersing from a benign natal habitat to which they were maladapted into a more demanding habitat to which they were well-adapted. “Matching habitat choice” reduced fitness when evolutionary lag rendered traditional cues unreliable in a changing environment

Host plant range of a fruit fly community (Diptera: Tephritidae): Does fruit composition influence larval performance?

Background: Phytophagous insects differ in their degree of specialisation on host plants, and range from strictly monophagous species that can develop on only one host plant to extremely polyphagous species that can develop on hundreds of plant species in many families. Nutritional compounds in host fruits affect several larval traits that may be related to adult fitness. In this study, we determined the relationship between fruit nutrient composition and the degree of host specialisation of seven of the eight tephritid species present in La Réunion; these species are known to have very different host ranges in natura. In the laboratory, larval survival, larval developmental time, and pupal weight were assessed on 22 fruit species occurring in La Réunion. In addition, data on fruit nutritional composition were obtained from existing databases. Results: For each tephritid, the three larval traits were significantly affected by fruit species and the effects of fruits on larval traits differed among tephritids. As expected, the polyphagous species Bactrocera zonata, Ceratitis catoirii, C. rosa, and C. capitata were able to survive on a larger range of fruits than the oligophagous species Zeugodacus cucurbitae, Dacus demmerezi, and Neoceratitis cyanescens. Pupal weight was positively correlated with larval survival and was negatively correlated with developmental time for polyphagous species. Canonical correspondence analysis of the relationship between fruit nutrient composition and tephritid survival showed that polyphagous species survived better than oligophagous ones in fruits containing higher concentrations of carbohydrate, fibre, and lipid. Conclusion: Nutrient composition of host fruit at least partly explains the suitability of host fruits for larvae. Completed with female preferences experiments these results will increase our understanding of factors affecting tephritid host range. (Résumé d'auteur

Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort

BACKGROUND: Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain causal estimates, we examined the role of pubertal development in prostate cancer using genetic polymorphisms associated with Tanner stage in adolescent boys in a Mendelian randomization (MR) approach. METHODS: We derived a weighted genetic risk score for pubertal development, combining 13 SNPs associated with male Tanner stage. A higher score indicated a later puberty onset. We examined the association of this score with prostate cancer risk, stage and grade in the UK-based ProtecT case-control study (n = 2,927), and used the PRACTICAL consortium (n = 43,737) as a replication sample. RESULTS: In ProtecT, the puberty genetic score was inversely associated with prostate cancer grade (odds ratio (OR) of high- vs. low-grade cancer, per tertile of the score: 0.76; 95 % CI, 0.64-0.89). In an instrumental variable estimation of the causal OR, later physical development in adolescence (equivalent to a difference of one Tanner stage between pubertal boys of the same age) was associated with a 77 % (95 % CI, 43-91 %) reduced odds of high Gleason prostate cancer. In PRACTICAL, the puberty genetic score was associated with prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95 % CI, 0.91-1.00) and prostate cancer-specific mortality (hazard ratio amongst cases, per tertile: 0.94; 95 % CI, 0.90-0.98), but not with disease grade. CONCLUSIONS: Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

Although genome-wide association studies have identified over 100 risk loci that explain ~33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa

Associations of Serum Concentrations of Organochlorine Pesticides with Breast Cancer and Prostate Cancer in U.S. Adults

Ba c k g r o u n d: Organochlorine (OC) pesticides are a group of environmental endocrine disruptors that may be associated with an increased risk for hormone-related cancers including cancers of the breast and prostate. However, epidemiologic evidence is limited and inconsistent. Objectives a n d m e t h o d s: We used 1999–2004 National Health and Nutrition Examination Survey data to examine associations between serum concentrations of OC pesticides and prostate and breast cancers. Res u l t s: After adjustment for other covariates, serum concentrations of β-hexachlorocyclohexane (HCH) (p for trend = 0.02), trans-nonachlor (p for trend = 0.002), and dieldrin (p for trend = 0.04) were significantly associated with the risk of prevalent prostate cancer. Adjusted odds ratios for the second and third tertiles of detectable values were 1.46 [95 % confidence interval (CI), 0.52–4.13] and 3.36 (95 % CI, 1.24–9.10) for β-HCH; 5.84 (95 % CI, 1.06–32.2) and 14.1 (95 % CI, 2.55–77.9) for trans-nonachlor; and 1.06 (95 % CI, 0.30–3.73) and 2.74 (95 % CI, 1.01–7.49) for dieldrin compared with concentrations in the lowest tertile or below the limit of detection. However, there was no positive association between serum concentrations of OC pesticides and breast cancer prevalence. Con c l u s i o n: Although further study is necessary to confirm these findings, these results suggest that OC pesticide exposures may have a significant effect on cancer risk. Efforts to reduce worldwide OC use are warranted. Key w o r d s: cancer, endocrine disruptors, organochlorine pesticides, pesticide, prostate cancer. Environ Health Perspect 118:60–66 (2010). doi:10.1289/ehp.0900919 available vi

Middle Eastern mothers in Sweden, their experiences of the maternal health service and their partner's involvement

<p>Abstract</p> <p>Background</p> <p>Traditional patterns relating to how to handle pregnancy and birth are often challenged due to migration. The purpose of this study was to describe Middle Eastern mothers' experiences of the maternal health care services in Sweden and the involvement of their male partner.</p> <p>Methods</p> <p>Thirteen immigrant mothers from the Middle East who had used the maternal health services in Sweden were interviewed using focus group discussions and individual interviews. These were taped, transcribed and analysed according to Content analysis.</p> <p>Results</p> <p>The four main categories that developed were:</p> <p>• Access to the professional midwife</p> <p>• Useful counselling</p> <p>• Stable motherhood in transition</p> <p>• Being a family living in a different culture</p> <p>Conclusion</p> <p>According to the respondents in this study, understanding the woman's native language or her culture was not vital to develop a good relationship with the midwife. Instead the immigrant woman developed trust in the midwife based on the knowledge and the empathy the midwife imparted.</p> <p>Increasing the amount of first trimester antenatal visits could avoid spontaneous visits to the emergency clinic. There was a greater need for involvement and support by the father during the perinatal period, such as caring for older children and carrying out household chores since the mothers' earlier female network was often lost.</p> <p>Clinical implications</p> <p>There is a need to involve immigrant parents in the available parental education in order to prepare them for parenthood in their new country as well as to explore their altered family situation. Collecting immigrant women and their partner's, experiences of maternal health care services offers a possibility to improve the existing care, both in content, access and availability where the timing of visits and content require further evaluation.</p

Is Genetic Background Important in Lung Cancer Survival?

BACKGROUND:In lung cancer, a patient's survival is poor with a wide variation in survival within the stage of disease. The aim of this study was to investigate the familial concordance in lung cancer survival by means of analyses of pairs with different degrees of familial relationships. METHODS:Our population-based Swedish family database included three million families and over 58,100 lung cancer patients. We modelled the proband (parent, sibling, spouse) survival utilizing a multivariate proportional hazard (Cox) model adjusting for possible confounders of survival. Subsequently, the survival in proband's relative (child, sibling, spouse) was analysed with a Cox model. FINDINGS:By use of Cox modelling with 5 years follow-up, we noted a decreased hazard ratio for death in children with good parental survival (Hazard Ratio [HR] = 0.71, 95% CI = 0.51 to 0.99), compared to those with poor parental survival. Also for siblings, a very strong protective effect was seen (HR = 0.14, 95% CI = 0.030 to 0.65). Finally, in spouses no correlation in survival was found. INTERPRETATION:Our findings suggest that genetic factors are important in lung cancer survival. In a clinical setting, information on prognosis in a relative may be vital in foreseeing the survival in an individual newly diagnosed with lung cancer. Future molecular studies enhancing the understanding of the underlying mechanisms and pathways are needed

What Facilitates Return to Work? Patients Experiences 3 Years After Occupational Rehabilitation

Objective We have limited knowledge about the specific elements in an occupational rehabilitation programme that facilitate the process leading to return to work (RTW) as perceived by the patients. The aim of the study was to explore individual experiences regarding contributing factors to a successful RTW, 3 years after a resident occupational rehabilitation programme. Methods The study is based on interviews of 20 individuals who attended an occupational rehabilitation programme 3 years earlier. Ten informants had returned to work (RTW) and ten were receiving disability pension (DP). Data were analysed by systematic text condensation inspired by Giorgi’s phenomenological analysis. Results The core categories describing a successful RTW process included positive encounters, increased self-understanding and support from the surroundings. While the informants on DP emphasized being seen, heard and taken seriously by the professionals, the RTW group highlighted being challenged to increase self-understanding that promoted new acting in every-day life. Being challenged on self-understanding implied increased awareness of own identity, values and resources. Support from the surroundings included support from peer participants, employer and social welfare system. Conclusion Successful RTW processes seem to comprise positive encounters, opportunities for increased self-understanding and support from significant others. An explicit focus on topics like identity, own values and resources might improve the outcome of the rehabilitation process