Municipal distribution of breast cancer mortality among women in Spain

<p>Abstract</p> <p>Background</p> <p>Spain has one of the lowest rates of breast cancer in Europe, though estimated incidence has risen substantially in recent decades. Some years ago, the Spanish Cancer Mortality Atlas showed Spain as having a heterogeneous distribution of breast cancer mortality at a provincial level. This paper describes the municipal distribution of breast cancer mortality in Spain and its relationship with socio-economic indicators.</p> <p>Methods</p> <p>Breast cancer mortality was modelled using the Besag-York-Molliè autoregressive spatial model, including socio-economic level, rurality and percentage of population over 64 years of age as surrogates of reproductive and lifestyle risk factors. Municipal relative risks (RRs) were independently estimated for women aged under 50 years and for those aged 50 years and over. Maps were plotted depicting smoothed RR estimates and the distribution of the posterior probability of RR>1.</p> <p>Results</p> <p>In women aged 50 years and over, mortality increased with socio-economic level, and was lower in rural areas and municipalities with higher proportion of old persons. Among women aged under 50 years, rurality was the only statistically significant explanatory variable.</p> <p>For women older than 49 years, the highest relative risks were mainly registered for municipalities located in the Canary Islands, Balearic Islands, the Mediterranean coast of Catalonia and Valencia, plus others around the Ebro River. In premenopausal women, the pattern was similar but tended to be more homogeneous. In mainland Spain, a group of municipalities with high RRs were located in Andalusia, near the left bank of the Guadalquivir River.</p> <p>Conclusion</p> <p>As previously observed in other contexts, mortality rates are positively related with socio-economic status and negatively associated with rurality and the presence of a higher proportion of people over age 64 years. Taken together, these variables represent the influence of lifestyle factors which have determined the increase in breast cancer frequency over recent decades. The results for the younger group of women suggest an attenuation of the socio-economic gradient in breast cancer mortality in Spain. The geographical variation essentially suggests the influence of other environmental variables, yet the descriptive nature of this study does not allow for the main determinants to be established.</p

Inhibitory Effect of TNF-α on Malaria Pre-Erythrocytic Stage Development: Influence of Host Hepatocyte/Parasite Combinations

BACKGROUND: The liver stages of malaria parasites are inhibited by cytokines such as interferon-gamma or Interleukin (IL)-6. Binding of these cytokines to their receptors at the surface of the infected hepatocytes leads to the production of nitric oxide (NO) and radical oxygen intermediates (ROI), which kill hepatic parasites. However, conflicting results were obtained with TNF-alpha possibly because of differences in the models used. We have reassessed the role of TNF-alpha in the different cellular systems used to study the Plasmodium pre-erythrocytic stages. METHODS AND FINDINGS: Human or mouse TNF-alpha were tested against human and rodent malaria parasites grown in vitro in human or rodent primary hepatocytes, or in hepatoma cell lines. Our data demonstrated that TNF-alpha treatment prevents the development of malaria pre-erythrocytic stages. This inhibitory effect however varies with the infecting parasite species and with the nature and origin of the cytokine and hepatocytes. Inhibition was only observed for all parasite species tested when hepatocytes were pre-incubated 24 or 48 hrs before infection and activity was directed only against early hepatic parasite. We further showed that TNF-alpha inhibition was mediated by a soluble factor present in the supernatant of TNF-alpha stimulated hepatocytes but it was not related to NO or ROI. Treatment TNF-alpha prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified. CONCLUSIONS: Treatment TNF-alpha prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified. However, the nature of the cytokine-host cell-parasite combination must be carefully considered for extrapolation to the human infection

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Assisted oocyte activation overcomes fertilization failure in globozoospermic patients regardless of the DPY19L2 status

study question: Does DPY19L2 status influence intracytoplasmic sperm injection (ICSI) outcomes with or without assisted oocyte activation (AOA)? summary answer: DPY19L2 mutations have no major impact on ICSI outcomes in globozoospermic patients. what is known already: Globozoospermia is a rare and severe teratozoospermia characterized by round-headed spermatozoa lacking an acrosome. Recently, it has been shown that DPY19L2 mutations can be found in a vast majority of, but not all, globozoospermic patients (66.7%). These patients suffer from primary infertility due to a sperm-related oocyte activation deficiency secondary to the absence of an acrosome that can be overcome by the application of AOA. study design, size, duration: Cohort study, retrospective, 34 patients, 83 cycles. materials, setting, methods: Clinical and biologic data were collected from 29 patients mutated for DPY19L2 and 5 nonmutated patients. In total, 35 ICSI cycles using AOA and 48 conventional ICSI cycles were included in the analysis. Patients were divided into groups according to whether or not they were mutated for DPY19L2 and whether or not they received AOA. main results and the role of chance: Regardless of the presence of a DPY19L2 mutation, the fertilization rates with AOA are restored to normal when compared with conventional ICSI in our cohort of globozoospermic patients. Also, when performing ICSI plus AOA, both mutated and non-mutated cases have similar positive hCG rates, ongoing pregnancy rates and live birth rates per transfer. On the contrary, the fertilization rate in globozoospermic patients using conventional ICSI is correlated with the presence of a DPY19L2 mutation, with slightly better, although still very low, fertilization rates in patients carrying a DPY19L2 mutation. Nevertheless, when performing conventional ICSI, both mutated and non-mutated cases have similar very low positive hCG rates, ongoing pregnancy rates and live birth rates per transfer. limitations: A limitation of this study is the low number of included non-mutated cases. wider implications of the findings: We propose a pathway for the clinical management of globozoospermic patients depending on the phenotype that includes several diagnostic and therapeutic steps. study funding/competing interest(s): None