Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk: a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. METHODS: In a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk. FINDINGS: Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95% CI 0.47-0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95% CI 0.59-0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer. INTERPRETATION: Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations. FUNDING: World Cancer Research Fund (reference: 2013/1002); European Commission (FP7: BBMRI-LPC; reference: 313010).

Plasma Lipidomic n-6 Polyunsaturated Fatty Acids and Type 2 Diabetes Risk in the EPIC-Potsdam Prospective Cohort Study.

OBJECTIVE: Evidence on plasma n-6 polyunsaturated fatty acids (PUFAs) and type 2 diabetes risk is inconsistent. We examined the associations of lipid class-specific PUFA concentrations with type 2 diabetes risk. RESEARCH DESIGN AND METHODS: In the prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (nested case-cohort study: subcohort 1,084 participants, 536 participants with type 2 diabetes, median follow-up 6.5 years), we measured plasma 18:2, 20:3, and 20:4 concentrations in 12 lipid (sub)classes, likely reflecting the plasma concentrations of linoleic acid (18:2n-6), dihomo-γ-linolenic acid (20:3n-6), and arachidonic acid (20:4n-6). The Δ-5 desaturase (D5D) activity was estimated as the 20:4/20:3 ratio. Associations with diabetes were estimated with Cox proportional hazards models. RESULTS: Higher concentrations of 18:2 were inversely associated with type 2 diabetes risk, particularly in lysophosphatidylcholines (hazard ratio [HR] per 1 SD 0.53; 95% CI 0.23-1.26) and monoacylglycerols (HR 0.59; 0.38-0.92). Higher concentrations of 20:3 in phospholipid classes phosphatidylcholines (HR 1.63; 1.23-2.14), phosphatidylethanolamines (HR 1.87; 1.32-2.65), and phosphatidylinositol (HR 1.40; 1.05-1.87); free fatty acids (HR 1.44; 1.10-1.90); and cholesteryl esters (HR 1.47; 1.09-1.98) were linked to higher type 2 diabetes incidence, and these associations remained statistically significant after correction for multiple testing. Higher 20:4 concentrations were not associated with risk. The estimated D5D activity in phospholipids and cholesteryl esters was associated with lower type 2 diabetes risk. Single nucleotide polymorphisms in the D5D-encoding FADS genes explained relatively high proportions of variation of estimated D5D activity in those lipid classes. CONCLUSIONS: Plasma n-6 PUFAs were associated differently with type 2 diabetes, depending on fatty acid and the lipid class.

Deep Lipidomics in Human Plasma: Cardiometabolic Disease Risk and Effect of Dietary Fat Modulation.

BACKGROUND: In blood and tissues, dietary and endogenously generated fatty acids (FAs) occur in free form or as part of complex lipid molecules that collectively represent the lipidome of the respective tissue. We assessed associations of plasma lipids derived from high-resolution lipidomics with incident cardiometabolic diseases and subsequently tested if the identified risk-associated lipids were sensitive to dietary fat modification. METHODS: The EPIC Potsdam cohort study (European Prospective Investigation into Cancer and Nutrition) comprises 27 548 participants recruited within an age range of 35 to 65 years from the general population around Potsdam, Germany. We generated 2 disease-specific case cohorts on the basis of a fixed random subsample (n=1262) and all respective cohort-wide identified incident primary cardiovascular disease (composite of fatal and nonfatal myocardial infarction and stroke; n=551) and type 2 diabetes (n=775) cases. We estimated the associations of baseline plasma concentrations of 282 class-specific FA abundances (calculated from 940 distinct molecular species across 15 lipid classes) with the outcomes in multivariable-adjusted Cox models. We tested the effect of an isoenergetic dietary fat modification on risk-associated lipids in the DIVAS randomized controlled trial (Dietary Intervention and Vascular Function; n=113). Participants consumed either a diet rich in saturated FAs (control), monounsaturated FAs, or a mixture of monounsaturated and n-6 polyunsaturated FAs for 16 weeks. RESULTS: Sixty-nine lipids associated (false discovery rate<0.05) with at least 1 outcome (both, 8; only cardiovascular disease, 49; only type 2 diabetes, 12). In brief, several monoacylglycerols and FA16:0 and FA18:0 in diacylglycerols were associated with both outcomes; cholesteryl esters, free fatty acids, and sphingolipids were largely cardiovascular disease specific; and several (glycero)phospholipids were type 2 diabetes specific. In addition, 19 risk-associated lipids were affected (false discovery rate<0.05) by the diets rich in unsaturated dietary FAs compared with the saturated fat diet (17 in a direction consistent with a potential beneficial effect on long-term cardiometabolic risk). For example, the monounsaturated FA-rich diet decreased diacylglycerol(FA16:0) by 0.4 (95% CI, 0.5-0.3) SD units and increased triacylglycerol(FA22:1) by 0.5 (95% CI, 0.4-0.7) SD units. CONCLUSIONS: We identified several lipids associated with cardiometabolic disease risk. A subset was beneficially altered by a dietary fat intervention that supports the substitution of dietary saturated FAs with unsaturated FAs as a potential tool for primary disease prevention.

Plasma Industrial and Ruminant Trans Fatty Acids and Incident Type 2 Diabetes in the EPIC-Potsdam Cohort.

OBJECTIVE: Although dietary intake of trans fatty acid (TFA) is a major public health concern because of the associated increase in the risk of cardiovascular events, it remains unclear whether TFAs also influence risk of type 2 diabetes (T2D) and whether industrial TFAs (iTFAs) and ruminant TFAs (rTFAs) exert the same effect on health. RESEARCH DESIGN AND METHODS: To investigate the relationship of 7 rTFAs and iTFAs, including 2 conjugated linoleic acids (CLAs), plasma phospholipid TFAs were measured in a case-cohort study nested within the European Prospective Investigation Into Cancer and Nutrition-Potsdam cohort. The analytical sample was a random subsample (n = 1,248) and incident cases of T2D (n = 801) over a median follow-up of 6.5 years. Using multivariable Cox regression models, we examined associations of TFAs with incident T2D. RESULTS: The TFA subtypes were intercorrelated with each other, with other fatty acids, and with different food sources. After controlling for other TFAs, the iTFAs (18:1n-6t, 18:1n-9t, 18:2n-6,9t) were not associated with diabetes risk. Some rTFA subtypes were inversely associated with diabetes risk: vaccenic acid (18:1n-7t; hazard ratio [HR] per SD 0.72; 95% CI 0.58-0.89) and t10c12-CLA (HR per SD 0.81; 95% CI 0.70-0.94), whereas c9t11-CLA was positively associated (HR per SD 1.39; 95% CI 1.19-1.62). Trans-palmitoleic acid (16:1n-7t) was not associated with diabetes risk when adjusting for the other TFAs (HR per SD 1.08; 95% CI 0.88-1.31). CONCLUSIONS: The TFAs' conformation plays an essential role in their relationship to diabetes risk. rTFA subtypes may have opposing relationships to diabetes risk. Previous observations for reduced diabetes risk with higher levels of circulating trans-palmitoleic acid are likely due to confounding.

Association of the odd-chain fatty acid content in lipid groups with type 2 diabetes risk: A targeted analysis of lipidomics data in the EPIC-Potsdam cohort.

BACKGROUND: Plasma odd-chain saturated fatty acids (OCFA) are inversely associated with type 2 diabetes (T2D) risk and may serve as biomarkers for dairy fat intake. Their distribution across different lipid classes and consequences for diabetes risk remain unknown. AIM: To investigate the prospective associations of OCFA-containing lipid species with T2D risk and their dietary determinants. METHODS: Within the European Prospective Investigation into Cancer and Nutrition-Potsdam study (n = 27,548), we applied a nested case-cohort design (subcohort: n = 1,248; T2D cases: n = 820; median follow-up 6.5 years). OCFA-containing lipids included triacylglycerols, free fatty acids (FFA), cholesteryl esters (CE), phosphatidylcholines, phosphatidylethanolamines, lysophosphatidylcholines, lysophosphatidylethanolamines, monoacylglycerols, and diacylglycerols. We estimated lipid class-specific associations between OCFA-containing lipids and T2D in sex-stratified Cox proportional-hazards models. We investigated correlations between lipids and dietary intakes derived from food-frequency questionnaires. RESULTS: We observed heterogeneous integration of OCFA in different lipid classes: triacylglycerols, FFA, CE, and phosphatidylcholines contributed most to the total OCFA-plasma abundance. The relative concentration of OCFA was particularly high in monoacylglycerols, and the contribution of C15:0 versus C17:0 to the total OCFA-abundance differed across lipid classes. In women, several OCFA-containing phospholipids were inversely associated with T2D risk [phosphatidylcholine(C15:0), HR Q5 vs Q1: 0.56, 95% CI 0.32-0.97; phosphatidylcholine(C17:0), HR per SD: 0.59, 95% CI 0.48-0.71; lysophosphatidylcholine(C17:0), HR Q5 vs Q1: 0.42, 95% CI 0.23-0.76]. In men, we did not detect statistically significant inverse associations in phospholipids, and lysophosphatidylcholine(C15:0) was associated with higher T2D risk (HR Q5 vs. Q1: 1.96, 95% CI 1.06-3.63). Besides, CE(C17:0), monoacylglycerols(C15:0), and diacylglycerols(C15:0) were inversely associated with T2D risk; FFA(C17:0) was positively associated with T2D risk in women. Consumption of fat-rich dairy and fiber-rich foods were positively and red meat inversely correlated to OCFA-containing lipid plasma levels. CONCLUSIONS: OCFA-containing lipids are linked to T2D risk in a lipid class and sex-specific manner, and they are correlated with several foods.

New solutions to reduce greenhouse gas emissions through energy efficiency of buildings of special importance - Hospitals.

Saving energy has an important role in the concerted actions to protect the planet from the effects of global warming, particularly the energy consumed by the existing buildings (with various energy consuming functions, inefficient energy), by implementing environmentally friendly solutions. The present paper emphasizes the need to include elements to stimulate the renovation of the existing buildings and of their energy efficiency in the national strategies, these constructions being important energy consumers. The research started with two case studies (2 hospital buildings) dating from 70-80s, with the aim to be energy efficient and modern constructions in Eastern Europe. In the presented best practice model, significant reductions in greenhouse gas emissions, primary energy consumption along with the use of renewable energy have been achieved by transforming some energy-inefficient buildings into intelligent buildings. Thus, the authors propose a new stake: "70-70-70" for similar buildings.

Sintomas mentais em homeopatia versus neurociência em medicina veterinária / Mental symptoms in homeopathy versus neuroscience in veterinary medicine

O objetivo deste estudo foi o de conhecer a devida correspondência entre os sintomas mentais considerados na homeopatia e as várias regiões e estruturas identificáveis no encéfalo dos animais. Os resultados obtidos mostraram que as sensações e emoções muito primitivas, como medos e fobias, interagem pontualmente com regiões evolutivamente também muito primitivas do cérebro (como amígdala e núcleos septais), enquanto sentimentos “nobres” como afeto e lealdade interagem holisticamente com várias estruturas cerebrais evolutivamente mais recentes, tais como as áreas neocorticais terciárias associativas (área pré-frontal e temporal). No primeiro caso, as manifestações orgânicas são mediadas pelo sistema nervoso autônomo com sinais fisiológicos de taquicardia, elevação da pressão arterial, vasoconstrição periférica, eriçamento de pelos, midríase e secreção de hormônios como adrenalina e cortisol (disfluência comportamental), enquanto na outra situação apontada, eventuais manifestações orgânicas são harmoniosas e serenas (fluência comportamental). O conteúdo de todo o texto do trabalho é indicativo do interesse prático dos dados obtidos para o clínico veterinário homeopata, ressaltando-se nesse contexto a validação do uso de repertórios homeopáticos humanos na clínica veterinária, evidentemente com as devidas precauções sempre balizadas pelo bom senso do profissional.

This study was motivated by the need to determine the relationship between mental symptoms considered in homeopathy and several regions and structures identified in animal’s brain. Obtained results showed that very primitive sensations (what “it feels like”) and emotions (what is “put out” in behavioral terms), such as fears and phobias, interact punctually with also very primitive brain regions (from the evolutionary point of view, such as amygdala and septal nuclei), while “noble” feelings, such as affection and loyalty, interact holistically with newer brain structures (also from the evolutionary point of view), such as the tertiary associative neocortical areas (prefrontal and temporal). In the first case, the symptoms are expressed in organic manifestations, mediated by the autonomic nervous system, with physiological signs of tachycardia, elevated blood pressure, peripheral vasoconstriction, bristling hair, mydriasis and secretion of hormones, such as adrenaline and cortisol (behavioral disfluency), while, in the second case, eventual organic manifestations are harmonious and serene (behavioral fluency). Overall results are highly suggestive about the influence of mental conditions over health and disease of the physical body, through the process of somatization. The overall content of this work is indicative of the practical interest in the results by homeopathic veterinary practitioners, and in this context emphasizes the validity of using human homeopathic repertories in veterinary clinics, obviously with suitable precaution and, always directed by good professional judgment.