Fine mapping of 11q13.5 identifies regions associated with prostate cancer and prostate cancer death

BackgroundChromosomal region 11q13–14 associates with prostate cancer (PrCa). Previously, we identified a rare intronic mutation on EMSY (11q13.5) that increases the risk of aggressive PrCa and associates with familial PrCa. Here, we further study the genetic structure and variants of the PrCa susceptibility region 11q13.5.MethodsThis study included 2716 unselected hospital-based PrCa cases, 1318 cases of a screening trial and 908 controls of Finnish origin. We imputed single nucleotide polymorphisms (SNPs) and structural variants from the 1000 Genomes Project and validated the associations of the variants in two PrCa patient sets by genotyping. Genetic structure was studied with haplotype analysis.ResultsTwo independent regions at 11q13.5 were associated with PrCa risk. The most significant association was at EMSY (rs10899221, odds ratio (OR) 1.29–1.40, P = 3.5 × 10^?4–0.002) near the previously identified mutation. Correlated intronic SNPs rs10899221 and rs72944758 formed with other EMSY variants common and rare haplotypes that were associated with increased risk (P = 4.0 × 10^?4) and decreased risk (P = 0.01) of PrCa, respectively. The other associated region was intergenic. Among the six validated variants, rs12277366 was significant in both patient sets (OR 1.15–1.17, P = 0.01). Haplotypes associated with an increased risk (P = 0.02) and a decreased risk (P = 0.02) were identified. In addition, the intergenic region was strongly associated with PrCa death, with the most significant association at rs12277366 (OR = 0.72, P = 4.8 × 10^?5).ConclusionsThese findings indicate that 11q13.5 contributes to PrCa predisposition with complex genetic structure and is associated with PrCa death.     

Monoterpene and wood dust exposures: work-related symptoms among Finnish sawmill workers.

BACKGROUND: Monoterpenes and wood dust are released into the work environment during sawing of fresh wood. Symptoms related to exposure to monoterpenes and wood dust include irritation of the eyes, mucous membrane, and skin. METHODS: We studied 22 sawhouse workers who process pine and spruce in 1997-99. Exposure to monoterpenes was assessed by determining monoterpenes in air and verbenols in urine by gas chromatography using flame ionization detection. Wood dust was determined gravimetrically. A questionnaire was used to evaluate work-related subjective symptoms. RESULTS: Exposures to monoterpenes (geometric mean, GM) among sawhouse workers were 61-138 mg/m(3) and 2.0-13 mg/m(3) during processing of pine and spruce, respectively. Urinary verbenol correlated well with worker exposure to the alpha-pinene fraction of monoterpenes. The inhalable dust concentration in the breathing zone was 0.5- 2.2 mg/m(3) during pine processing and 0.4-1.9 mg/m(3) during spruce processing. The prevalence of symptoms, in the eyes or respiratory tract, was high during both seasons and in connection with either tree species. CONCLUSIONS: The highest monoterpene concentration (GM), in the breathing zone, measured during processing of pine, was less than one-fourth of the Finnish occupational exposure limit (OEL, 570 mg/m(3)). Verbenol concentrations in postshift urine samples reflected accurately the exposure to monoterpenes. The concentrations of inhalable dust (GM) were less than one-half the Finnish OEL (5 mg/m(3)). No significant differences in dust exposure were observed among tree species processed. Work-related symptoms appeared to correlate with monoterpene exposure during processing of pine and with wood dust exposure during processing of spruce.     

Oncolytic adenoviruses: a game changer approach in the battle between cancer and the immune system.

Introduction: Oncolytic adenoviruses are among the most studied oncolytic viruses because of their tumor selectivity, safety, and transgene-delivery capability. With a growing number of different immunotherapies against cancer, the extraordinary immunogenicity of the adenovirus has emerged as a differentiating strength. Enabling T-cell related therapies with oncolytic adenoviruses appears a promising approach due to its inherent ability to elicit responses from the adaptive immune compartment.

Areas covered: These viruses have successfully enhanced both adoptive T-cell therapies and immune-checkpoint therapies. Oncolytic viruses induce several effects at the tumor and on the systemic level that help to circumvent current limitations of T-cells and related therapies, such as T-cell trafficking, tumor immune suppressivity and antigen spreading.

Expert opinion: Taking into account the multitude of possibilities of treating cancer with immunotherapies, learning to optimize the combinations and administration strategies of these drugs, could lead to durable responses in patients with currently incurable cancers.     

Termination of early pregnancy using flexible, low-dose mifepristone-misoprostol regimens

BACKGROUND: Various regimens of mifepristone and misoprostol are used in medical abortion. We examined the effect of a change in protocol from a fixed mifepristone-misoprostol interval to a flexible one on the efficacy and uptake of medical abortion. In addition, risk factors of incomplete abortions were evaluated. STUDY DESIGN: Altogether, 1289 medical abortions were carried out between August 2000 and December 2002. Between August 2000 and August 2001, a fixed protocol of 200 mg of oral mifepristone followed by 0.4 mg of vaginally administered misoprostol 2 days later was used. From September 2001, a flexible dosing interval of 1, 2 or 3 days between mifepristone and misoprostol was adopted. At the same time, the upper limit of gestational age was increased from 56 to 63 days. RESULTS: The uptake of medical abortion increased during the study period and was 45.8% during the use of fixed protocol versus 54.6% during flexible protocol (p<.0001). The rates of complete abortion were 94.9% and 94.4% (n.s.), respectively. Continuing pregnancy was rare (0.7%). Among all subjects, a history of abortion was associated with a significantly lower rate of complete abortion (90.9 vs. 96.3%, p<.002). The other parameters analyzed (age, parity, duration of pregnancy, smoking, mifepristone-misoprostol interval) did not have a significant effect on the rate of complete abortion. CONCLUSIONS: A flexible dosing protocol of mifepristone and misoprostol is effective; thus, its use is encouraged. Previous abortion is a significant risk factor of incomplete medical abortion. Thus, special attention should be paid to the follow-up of these women.     

Tackling community integration in mental health home visit integration in Finland

Integration – and its synonym inclusion – is emphasised in the western welfare states and in the European Union in particular. Integration is also a central topic in the social sciences and in current mental health and homelessness research and practice. As mental healthcare has shifted from psychiatric hospitals to the community, it has inevitably become involved with housing and integration issues. This article explores how community integration is understood and tackled in mental health floating support services (FSSs) and, more precisely, in service user–practitioner home visit interaction. The aim, through shedding light on how the idea of integration is present and discussed in front‐line mental health practices, is to offer a ‘template’ on how we might, in a systematic and reflective way, develop community integration research and practice. The analysis is based on ethnomethodological and micro‐sociological interaction research. The research settings are two FSSs located in a large Finnish city. The data contain 24 audio‐recorded and transcribed home visits conducted in 2011 and 2012 with 16 different service users. The study shows how the participants in service user–practitioner interaction give meaning to community integration and make decisions about how it should (or should not) be enhanced in each individual case. This activity is called community integration work in action. Community integration work in action is based on various dimensions of integration: getting out of the house, participating in group activities and getting along with those involved in one's life and working life. Additionally, the analysis demonstrates how community integration work is accomplished by discursive devices (resistance, positioning, excuses and justifications, delicacy and advice‐giving). The article concludes that community integration is about interaction: it is not only service users' individual challenge but also a social challenge, our challenge.     

Plant stanol esters in low-fat milk products lower serum total and LDL cholesterol

Background Oil-based matrices enriched with plant stanol esters lower serum LDL cholesterol. The effects of low-fat milk products have been less thoroughly examined. Aim of the study To evaluate the effect of three less explored low-fat milk products enriched with plant stanol esters on serum lipid concentrations in subjects with mild or moderate hypercholesterolemia. Methods A meta-analysis of four unpublished sub-studies (yoghurt, yoghurt single-shot drink: Studies I and II, or milk). All the sub-studies were randomized, placebo-controlled, double-blind and had a parallel-group design. They were carried out in order to evaluate the effect of low-fat milk products enriched with plant stanol esters on serum lipid concentration. Each stanol-ester-enriched milk product provided 2 g of stanols per day, and in each study the intervention period was 5 weeks. A total of 199 hypercholesterolemic subjects completed the studies. Results The pooled treatment difference in total cholesterol was −3.8% (95% CI −6.0 to −1.7, p < 0.001) when stanol was compared to placebo. In LDL cholesterol, the pooled treatment difference was −4.9% (95% CI −7.8 to −1.8, p = 0.002). There were no significant differences between the groups in pooled HDL cholesterol or triacylglycerol concentrations. The results tended to be more pronounced when we were certain that the yoghurt single-shot drink was ingested with lunch, and when the baseline LDL-cholesterol concentration was ≥3.5 mmol/l. Conclusions These results imply that low-fat milk products enriched with plant stanol esters lower both total cholesterol and LDL cholesterol statistically significantly in subjects with mild or moderate hypercholesterolemia. The changes tended to relate to the baseline LDL-cholesterol concentration.