Neural underpinnings of ethical decisions in life and death dilemmas in naïve and expert firefighters.

When a single choice impacts on life outcomes, faculties to make ethical judgments come into play. Here we studied decisions in a real-life setting involving life-and-death outcomes that affect others and the decision-maker as well. We chose a genuine situation where prior training and expertise play a role: firefighting in life-threatening situations. By studying the neural correlates of dilemmas involving life-saving decisions, using realistic firefighting situations, allowed us to go beyond previously used hypothetical dilemmas, while addressing the role of expertise and the use of coping strategies (n = 47). We asked the question whether the neural underpinnings of deontologically based decisions are affected by expertise. These realistic life-saving dilemmas activate the same core reward and affective processing network, in particular the ventromedial prefrontal cortex, nucleus accumbens and amygdala, irrespective of prior expertise, thereby supporting general domain theories of ethical decision-making. We found that brain activity in the hippocampus and insula parametrically increased as the risk increased. Connectivity analysis showed a larger directed influence of the insula on circuits related to action selection in non-experts, which were slower than experts in non rescuing decisions. Relative neural activity related to the decision to rescue or not, in the caudate nucleus, insula and anterior cingulate cortex was negatively associated with coping strategies, in experts (firefighters) suggesting practice-based learning. This shows an association between activity and expert-related usage of coping strategies. Expertise enables salience network activation as a function of behavioural coping dimensions, with a distinct connectivity profile when facing life-rescuing dilemmas.

Update on Melasma-Part I: Pathogenesis.

Melasma is a multifactorial dyschromia that results from exposure to external factors (such as solar radiation) and hormonal factors (such as sex hormones and pregnancy), as well as skin inflammation (such as contact dermatitis and esthetic procedures), in genetically predisposed individuals. Beyond hyperfunctional melanocytes, skin with melasma exhibits a series of structural and functional alterations in the epidermis, basement membrane, and upper dermis that interact to elicit and sustain a focal hypermelanogenic phenotype. Evolution in the knowledge of the genetic basis of melasma and the cutaneous response to solar radiation, as well as the roles of endocrine factors, antioxidant system, endothelium proliferation, fibroblast senescence, mast cell degranulation, autophagy deficits of the melanocyte, and the paracrine regulation of melanogenesis, will lead to the development of new treatments and preventive strategies. This review presents current knowledge on these aspects of the pathogenesis of melasma and discusses the effects of specific treatments and future research on these issues.

Update on Melasma-Part II: Treatment.

Melasma is a prevalent chronic relapsing pigmentary disorder that affects photoexposed areas, especially in women of childbearing age. Although there is currently no curative treatment available for melasma, this manuscript critically reviews the knowledge regarding photoprotection, topical and oral therapies, and procedures such as peelings, laser, and microneedling that represent the main strategies for control and prevention of this disease. As the pathogenesis of melasma is not entirely understood, there are prospects for the development of new therapeutic strategies that might act on the pathways that promote sustained pigmentation rather than merely decreasing melanin synthesis and removing melanin from the epidermis.

Association between dietary fiber intake and risk of incident aortic stenosis.

BACKGROUND AND AIMS: Although aortic stenosis is the most common valvular heart disease requiring intervention in Europe, the role that diet plays in development of the disease is largely unknown. The pathophysiology of aortic stenosis is however similar to other cardiovascular diseases that fiber intake has been associated with. The aim of this study was consequently to investigate the association between dietary fiber intake as well as the main food sources of fiber, i.e. fruit and vegetables and whole grains, and risk of incident aortic stenosis. METHODS AND RESULTS: The Malmö Diet and Cancer Study is a Swedish prospective population-based cohort study with baseline data collection performed between year 1991-1996. Dietary habits were recorded through seven-day food diaries, 168-item diet questionnaires, and interviews, and data on incident aortic stenosis was collected through national registers. Among the 26,063 participants, 672 cases were ascertained during a mean follow-up period of 20 years. Cox regression was used to estimate the association between dietary intakes and incident aortic stenosis. No associations were found between incident aortic stenosis and intake of dietary fiber (HR for the highest vs lowest quintile: 0.93; 95% CI: 0.72-1.24), fruit and vegetables (HR: 0.98; 95% CI: 0.76-1.28), or whole grains (HR: 1.00; 95% CI: 0.79-1.26) in the main model. CONCLUSION: The findings of this study do not indicate that consumption of dietary fiber or fiber rich foods are associated with incident aortic stenosis.

Inflammatory potential of the diet and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Background: Chronic inflammation plays a critical role in the pathogenesis of the 2 major types of gastric cancer. Several foods, nutrients, and nonnutrient food components seem to be involved in the regulation of chronic inflammation. Objective: We assessed the association between the inflammatory potential of the diet and the risk of gastric carcinoma, overall and for the 2 major subsites: cardia cancers and noncardia cancers. Design: A total of 476,160 subjects (30% men, 70% women) from the European Investigation into Cancer and Nutrition (EPIC) study were followed for 14 y, during which 913 incident cases of gastric carcinoma were identified, including 236 located in the cardia, 341 in the distal part of the stomach (noncardia), and 336 with overlapping or unknown tumor site. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated with the use of 28 dietary components and their corresponding inflammatory scores. The association between the ISD and gastric cancer risk was estimated by HRs and 95% CIs calculated by multivariate Cox regression models adjusted for confounders. Results: The inflammatory potential of the diet was associated with an increased risk of gastric cancer. The HR (95% CI) for each increase in 1 SD of the ISD were 1.25 (1.12, 1.39) for all gastric cancers, 1.30 (1.06, 1.59) for cardia cancers, and 1.07 (0.89, 1.28) for noncardia cancers. The corresponding values for the highest compared with the lowest quartiles of the ISD were 1.66 (1.26, 2.20), 1.94 (1.14, 3.30), and 1.07 (0.70, 1.70), respectively. Conclusions: Our results suggest that low-grade chronic inflammation induced by the diet may be associated with gastric cancer risk. This pattern seems to be more consistent for gastric carcinomas located in the cardia than for those located in the distal stomach. This study is listed on the ISRCTN registry as ISRCTN12136108.

Low-Grade Inflammation, Oxidative Stress and Risk of Invasive Post-Menopausal Breast Cancer - A Nested Case-Control Study from the Malmö Diet and Cancer Cohort.

OBJECTIVE: Although cancer promotes inflammation, the role of inflammation in tumor-genesis is less well established. The aim was to examine if low-grade inflammation is related to post-menopausal breast cancer risk, and if obesity modifies this association. METHODS: In the Malmö Diet and Cancer cohort, a nested case-control study was defined among 8,513 women free of cancer and aged 55-73 years at baseline (1991-96); 459 were diagnosed with invasive breast cancer during follow-up (until December 31st, 2010). In laboratory analyses of blood from 446 cases, and 885 controls (matched on age and date of blood sampling) we examined systemic inflammation markers: oxidized (ox)-LDL, interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, white blood cells, lymphocytes and neutrophils. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer risk was calculated using multivariable conditional logistic regression. RESULTS: Inverse associations with breast cancer were seen in fully-adjusted models, for 2nd and 3rd tertiles of ox-LDL, OR (95% CI): 0.65 (0.47-0.90), 0.63 (0.45-0.89) respectively, p-trend = 0.01; and for the 3rd tertile of TNF-α, 0.65 (0.43-0.99), p-trend = 0.04. In contrast, those in the highest IL-1ß category had higher risk, 1.71 (1.05-2.79), p-trend = 0.01. Obesity did not modify associations between inflammation biomarkers and breast cancer. CONCLUSION: Our study does not suggest that low-grade inflammation increase the risk of post-menopausal breast cancer.

Nutrient-wide association study of 57 foods/nutrients and epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study.

BACKGROUND: Studies of the role of dietary factors in epithelial ovarian cancer (EOC) development have been limited, and no specific dietary factors have been consistently associated with EOC risk. OBJECTIVE: We used a nutrient-wide association study approach to systematically test the association between dietary factors and invasive EOC risk while accounting for multiple hypothesis testing by using the false discovery rate and evaluated the findings in an independent cohort. DESIGN: We assessed dietary intake amounts of 28 foods/food groups and 29 nutrients estimated by using dietary questionnaires in the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 1095 cases). We selected 4 foods/nutrients that were statistically significantly associated with EOC risk when comparing the extreme quartiles of intake in the EPIC study (false discovery rate = 0.43) and evaluated these factors in the NLCS (Netherlands Cohort Study; n = 383 cases). Cox regression models were used to estimate HRs and 95% CIs. RESULTS: None of the 4 dietary factors that were associated with EOC risk in the EPIC study (cholesterol, polyunsaturated and saturated fat, and bananas) were statistically significantly associated with EOC risk in the NLCS; however, in meta-analysis of the EPIC study and the NLCS, we observed a higher risk of EOC with a high than with a low intake of saturated fat (quartile 4 compared with quartile 1; overall HR: 1.21; 95% CI: 1.04, 1.41). CONCLUSION: In the meta-analysis of both studies, there was a higher risk of EOC with a high than with a low intake of saturated fat.

Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study.

BACKGROUND: Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 521,330 total participants (approximately 370,000 women) aged 25-70 years at recruitment from 1992 to 2000. METHODS: Information on reproductive characteristics was collected at recruitment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and multivariable models were adjusted for age and year of diagnosis, body mass index, tumour stage, smoking status and stratified by study centre. RESULTS: After a mean follow-up of 3.6 years (±3.2 s.d.) following EOC diagnosis, 511 (49.9%) of the 1025 women died from EOC. We observed a suggestive survival advantage in menopausal hormone therapy (MHT) users (ever vs never use, HR=0.80, 95% CI=0.62-1.03) and a significant survival benefit in long-term MHT users (⩾5 years use vs never use, HR=0.70, 95% CI=0.50-0.99, P(trend)=0.04). We observed similar results for MHT use when restricting to serous cases. Other reproductive factors, including parity, breastfeeding, oral contraceptive use and age at menarche or menopause, were not associated with EOC-specific mortality risk. CONCLUSIONS: Further studies are warranted to investigate the possible improvement in EOC survival in MHT users.