ABSTRACT
OBJECTIVE: To investigate the incidence and prevalence of rheumatoid arthritis (RA) in the adult Danish population. METHOD: In this nationwide register-based cohort study, patients with incident RA between 1998 and the end of 2018 were identified using Danish administrative registries. The age- and sex-standardized incidence rate (IR), incidence proportion (IP), lifetime risk (LR), and point prevalence (PP) of RA were calculated. RA was defined as a first-time RA diagnosis registered in the Danish National Patient Registry combined with a redeemed prescription of a conventional synthetic disease-modifying anti-rheumatic drug in the following year. In addition, three different case definitions of RA were explored. RESULTS: The overall age- and sex-standardized IR of RA from 1998 to 2018 was 35.5 [95% confidence interval (CI) 35.1-35.9] per 100 000 person-years while the IP was 35.2 (95% CI 34.8-35.5) per 100 000 individuals. The IR was two-fold higher for women than for men. The LR of RA ranged from 2.3% to 3.4% for women and from 1.1% to 1.5% for men, depending on the RA case definition used. The overall PP of RA was 0.6% (95% CI 0.5-0.6%) in 2018: 0.8% (95% CI 0.7-0.8%) for women and 0.3% (95% CI 0.3-0.4%) for men. The prevalence increased about 1.5-fold from 2000 to 2018. CONCLUSION: The IR and PP were approximately two-fold higher for women than for men. The prevalence of RA in Denmark increased significantly from 2000 to 2018. The RA case definition had more impact on the results than the choice of denominator.
Subject(s)
Arthritis, Rheumatoid , Adult , Male , Humans , Female , Incidence , Prevalence , Cohort Studies , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/diagnosis , Registries , Denmark/epidemiologyABSTRACT
BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. PATIENTS AND METHODS: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. RESULTS: A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. CONCLUSIONS: In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy.
Subject(s)
Ki-1 Antigen , Lymphoma, T-Cell, Peripheral , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Brentuximab Vedotin , Humans , Ki-1 Antigen/metabolism , Ki-1 Antigen/therapeutic use , Lymphoma, T-Cell, Peripheral/drug therapy , Vincristine/adverse effectsABSTRACT
Aims: End-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine. Methods and results: The AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths. Conclusions: Our findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.
ABSTRACT
Marine sediments represent an important sink of harmful petroleum hydrocarbons after an accidental oil spill. Electrobioremediation techniques, which combine electrokinetic transport and biodegradation processes, represent an emerging technological platform for a sustainable remediation of contaminated sediments. Here, we describe the results of a long-term mesocosm-scale electrobioremediation experiment for the treatment of marine sediments contaminated by crude oil. A dimensionally stable anode and a stainless-steel mesh cathode were employed to drive seawater electrolysis at a fixed current density of 11 A/m2. This approach allowed establishing conditions conducive to contaminants biodegradation, as confirmed by the enrichment of Alcanivorax borkumensis cells harboring the alkB-gene and other aerobic hydrocarbonoclastic bacteria. Oil chemistry analyses indicated that aromatic hydrocarbons were primarily removed from the sediment via electroosmosis and low molecular weight alkanes (nC6 to nC10) via biodegradation.
Subject(s)
Petroleum Pollution , Petroleum , Biodegradation, Environmental , Geologic Sediments , Hydrocarbons , SeawaterSubject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Lymphoma, Large B-Cell, Diffuse/drug therapy , Cyclophosphamide/administration & dosage , Denmark/epidemiology , Doxorubicin/administration & dosage , Drug Administration Schedule , Female , Humans , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Prednisone/administration & dosage , Registries/statistics & numerical data , Rituximab/administration & dosage , Survival Analysis , Survival Rate , Sweden/epidemiology , Treatment Outcome , Vincristine/administration & dosageABSTRACT
OBJECTIVE: This study aimed to investigate the effects of marine n-3 polyunsaturated fatty acids (PUFAs) on disease activity, use of analgesics, and inflammatory biomarkers in patients with psoriatic arthritis (PsA). METHOD: Patients with established PsA (n = 145) were investigated in a randomized, double-blind, placebo-controlled study. The participants received a supplement of 3 g n-3 PUFA/day or 3 g olive oil/day (control) for 24 weeks. Outcome measures for disease activity, use of analgesics, and leukotriene formation from activated granulocytes were assessed at baseline and at study end. RESULTS: In total, 145 patients were included and 133 completed the study. After 24 weeks, the n-3 PUFA group showed a decrease in Disease Activity Score (DAS28-CRP), 68 tender joint count, enthesitis score, and psoriasis area and severity index, although not significantly different from the controls. There was a significant reduction in non-steroidal anti-inflammatory drug (NSAID) and paracetamol use compared with controls (p = 0.04). In addition, the participants in the n-3 PUFA group had significantly lower formation of leukotriene B4 (p = 0.004) from stimulated granulocytes and significantly higher formation of leukotriene B5 (p < 0.001) compared with controls. CONCLUSION: The n-3 PUFA-supplemented group showed improvement in outcome measures for disease activity, although the difference between the groups was not statistically significant. However, use of NSAIDs and paracetamol was significantly reduced in the n-3 PUFA group compared to the control group. Finally, there was a significant decrease in leukotriene B4 formation in the n-3 PUFA group compared with controls.
Subject(s)
Analgesics/therapeutic use , Arthritis, Psoriatic/drug therapy , Biomarkers/blood , Fatty Acids, Omega-3/therapeutic use , Inflammation/drug therapy , Adult , Double-Blind Method , Female , Humans , Inflammation/blood , Male , Middle Aged , Treatment OutcomeABSTRACT
BACKGROUND/OBJECTIVES: Cardiovascular (CV) disease is the leading cause of death after renal transplantation. Marine n-3 polyunsaturated fatty acids (PUFAs) exert potential cardio-protective metabolic effects and might reduce CV morbidity and mortality in renal transplant recipients (RTRs). SUBJECTS/METHODS: In this cross-sectional study of 1990 Norwegian RTRs, transplanted between 1999 and 2011, associations between plasma phospholipid marine n-3 PUFA levels and various CV risk markers at 10 weeks after transplant were evaluated. RESULTS: Higher plasma marine n-3 PUFA levels were associated with lower resting heart rate (rHR), lower fasting plasma glucose (fPG) levels, lower plasma triglyceride levels and higher plasma high-density lipoprotein (HDL) cholesterol levels. Plasma levels of eicosapentaenoic acid, but not docosahexaenoic acid, showed a positive association with plasma HDL cholesterol levels. Plasma marine n-3 PUFA levels were not associated with plasma low-density lipoprotein cholesterol levels, pulse wave velocity or systolic and diastolic blood pressure. A negative association between plasma marine n-3 PUFA levels and CV mortality was weakened by additional adjustment for plasma triglyceride levels and rHR. The ratio of n-6 to n-3 PUFAs showed similar associations with CV risk markers as absolute plasma marine n-3 PUFA levels. CONCLUSIONS: This is the first study in RTRs showing that marine n-3 PUFAs are negatively associated with rHR and fPG in addition to beneficial effects on plasma HDL cholesterol and triglyceride levels. Especially, effects on autonomic nervous function and triglyceride metabolism might contribute to explain the lower CV mortality risk with higher plasma marine n-3 PUFA levels previously shown in this cohort.
Subject(s)
Blood Glucose/metabolism , Cardiovascular Diseases/prevention & control , Cholesterol, HDL/blood , Fatty Acids, Omega-3/blood , Heart Rate/drug effects , Kidney Transplantation/adverse effects , Triglycerides/blood , Adult , Blood Pressure/drug effects , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Cohort Studies , Cross-Sectional Studies , Diet , Dietary Fats/blood , Dietary Fats/pharmacology , Fatty Acids, Omega-3/pharmacology , Female , Fish Oils/blood , Humans , Kidney/surgery , Male , Middle Aged , Norway , Phospholipids/metabolism , Pulse Wave Analysis , Risk Factors , SeafoodABSTRACT
The development of an appropriate extraction method for untargeted environmental metabolomic analysis of marine polychaetes could promote their use for environmental monitoring purposes. To this end, we compared four extraction methods on the marine polychaete Nereis virens both exposed to crude oil and non-exposed. XCMS was used for feature detection and preprocessing; different normalization and scaling approaches were tested; and principal component analysis (PCA) was used together with basic statistical tests to ascertain common metabolic patterns and determine the most suitable extraction method. We conclude that a two-step extraction procedure with 80:20 (v/v) methanol:water on freeze dried polychaete tissue provides the best trade-off between analysis time, and extraction efficiency and intermediate reproducibility. No definitive conclusions could be drawn about the ability of the method to discriminate controls and crude oils in actual biological replicates because the experiment was carried out by design on analytical replicates only. We show that the normalization to the sum of all the common features, and the use of a weighted least squares criterion to fit the PCA by means of scaling to the median absolute deviation (MAD) of the pooled quality control samples significantly improved the clustering of controls and crude oil exposed samples. The scaling alone led to an increase of 19% in explained variance compared to ordinary PCA.
Subject(s)
Environmental Monitoring/methods , Gas Chromatography-Mass Spectrometry/standards , Metabolomics/instrumentation , Polychaeta/chemistry , Polychaeta/metabolism , Animals , Least-Squares Analysis , Petroleum/analysis , Polychaeta/genetics , Principal Component Analysis , Reproducibility of Results , Water/chemistryABSTRACT
BACKGROUND/OBJECTIVES: The evidence regarding fatty acids and breast cancer risk is inconclusive. Adipose tissue fatty acids can be used as biomarkers of fatty acid intake and of endogenous fatty acid exposure. Fatty acids in adipose tissue are correlated owing to common dietary sources and shared metabolic pathways, which group fatty acids into naturally occurring patterns. We aimed to prospectively investigate associations between adipose tissue fatty acid patterns and long-term risk of total breast cancer and breast cancer subtypes characterised by oestrogen and progesterone receptor status (ER and PR). SUBJECTS/METHODS: This case-cohort study was based on data from the Danish cohort Diet, Cancer and Health. At baseline, a fat biopsy and information on lifestyle and reproductive factors were collected. From the 31 original fatty acids measured, patterns of fatty acids were identified using the treelet transform. During a median follow-up of 5.3 years, 474 breast cancer cases were identified. Hazard ratios and 95% confidence intervals of risk of total breast cancer and of subtypes according to quintiles of factor score were determined by weighted Cox proportional hazards regression. RESULTS: After adjustment for potential confounders, factor scores for the seven patterns identified by the treelet transform were not associated with risk of total breast cancer, nor with risk of ER+, ER-, PR+ or PR- tumours. CONCLUSIONS: No clear associations between the patterns of fatty acids at baseline and long-term risk of total breast cancer or ER+, ER-, PR+ or PR- tumours were observed.
Subject(s)
Breast Neoplasms/epidemiology , Fatty Acids/analysis , Subcutaneous Fat/chemistry , Adult , Aged , Breast Neoplasms/pathology , Cohort Studies , Denmark/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Prospective Studies , Risk , Risk FactorsABSTRACT
Even though the deleterious effects of increased reactive oxygen species (ROS) levels have been implicated in a variety of neurodegenerative disorders, the triggering events that lead to the increased ROS and successive damages are still ill-defined. Mitochondria are the key organelles controlling the ROS balance, being their main source and also counteracting them by the action of the ROS scavenging system. Mitochondria, moreover, control the presence of ROS-damaged proteins by action of the protein quality control (PQC) system. One of its components is the mitochondrial chaperone Hsp60 assisting the folding of a subset of mitochondrial matrix proteins. Mutations in Hsp60 cause a late onset form of the neurodegenerative disease hereditary spastic paraplegia (SPG13). In this study, we aimed to address the molecular consequences of Hsp60 shortage. We here demonstrate that a heterozygous knockout Hsp60 model that recapitulates features of the human disease and exhibits increased oxidative stress in neuronal tissues. Moreover, we indicate that the increase of ROS is, at least in part, due to impaired folding of the manganese superoxide dismutase (MnSOD), a key antioxidant enzyme. We observed that the Hsp60 and MnSOD proteins interact. Based on these results, we propose that MnSOD is a substrate of the Hsp60 folding machinery and that under conditions of diminished availability of Hsp60, MnSOD is impaired in reaching the native state. This suggests a possible link between Hsp60-dependent PQC and the ROS scavenging systems that may have the function to increase ROS production under conditions of folding stress.
Subject(s)
Chaperonin 60/physiology , Mitochondrial Proteins/physiology , Protein Folding , Superoxide Dismutase/metabolism , Animals , Cerebral Cortex/enzymology , Female , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondria/enzymology , Oxidative Stress , Reactive Oxygen Species/metabolism , Superoxide Dismutase/genetics , Transcription, GeneticABSTRACT
INTRODUCTION: This intervention examined whether fish-oil-supplementation in late infancy modifies free-play test scores and if this is related to blood pressure (BP) and mean RR interval. PATIENTS AND METHODS: 83 Danish 9-month-old infants were randomized to ±fish oil (FO) (3.4±1.1mL/d) for 3months and 61 of these completed the free-play-test before and after the intervention. RESULTS: Most of the free-play scores changed during the intervention, but the intervention affected only the number of looks away from the toy, which was increased in +FO and decreased in -FO (p=0.037). The increased numbers of looks away were associated with an increase in erythrocyte eicosapentaenoic acid (r=0.401, p=0.017, n=35) and were also associated with a decrease in systolic-BP (r=-0.511, p<0.001, n=52). CONCLUSIONS: The results indicate that n-3 fatty acid intake also in late infancy can influence brain development and that the cognitive and cardiovascular effects may be related.
Subject(s)
Attention/drug effects , Blood Pressure/drug effects , Cognition/drug effects , Dietary Supplements , Fish Oils/administration & dosage , Attention/physiology , Blood Pressure/physiology , Brain/drug effects , Brain/growth & development , Brain/physiology , Case-Control Studies , Cognition/physiology , Female , Humans , Infant , Male , Psychological TestsABSTRACT
This review compares the reconstruction of atmospheric Hg deposition rates and historical trends over recent decades in the Arctic, inferred from Hg profiles in natural archives such as lake and marine sediments, peat bogs and glacial firn (permanent snowpack), against those predicted by three state-of-the-art atmospheric models based on global Hg emission inventories from 1990 onwards. Model veracity was first tested against atmospheric Hg measurements. Most of the natural archive and atmospheric data came from the Canadian-Greenland sectors of the Arctic, whereas spatial coverage was poor in other regions. In general, for the Canadian-Greenland Arctic, models provided good agreement with atmospheric gaseous elemental Hg (GEM) concentrations and trends measured instrumentally. However, there are few instrumented deposition data with which to test the model estimates of Hg deposition, and these data suggest models over-estimated deposition fluxes under Arctic conditions. Reconstructed GEM data from glacial firn on Greenland Summit showed the best agreement with the known decline in global Hg emissions after about 1980, and were corroborated by archived aerosol filter data from Resolute, Nunavut. The relatively stable or slowly declining firn and model GEM trends after 1990 were also corroborated by real-time instrument measurements at Alert, Nunavut, after 1995. However, Hg fluxes and trends in northern Canadian lake sediments and a southern Greenland peat bog did not exhibit good agreement with model predictions of atmospheric deposition since 1990, the Greenland firn GEM record, direct GEM measurements, or trends in global emissions since 1980. Various explanations are proposed to account for these discrepancies between atmosphere and archives, including problems with the accuracy of archive chronologies, climate-driven changes in Hg transfer rates from air to catchments, waters and subsequently into sediments, and post-depositional diagenesis in peat bogs. However, no general consensus in the scientific community has been achieved.
Subject(s)
Environmental Monitoring/methods , Environmental Pollutants/analysis , Mercury/analysis , Models, Theoretical , Air Pollutants/analysis , Arctic Regions , Atmosphere , Canada , Greenland , NunavutABSTRACT
Familial neurohypophyseal diabetes insipidus (FNDI) typically presents with age-dependent penetrance and autosomal dominant inheritance caused by missense variations in one allele of the AVP gene encoding the arginine vasopressin (AVP) prohormone. We present the molecular genetic characteristics underlying an unusual form of FNDI occurring with very early onset and seemingly autosomal recessive inheritance. By DNA amplification and sequencing, we identified a novel variant allele of the AVP gene carrying a 10,396 base pair deletion involving the majority of the AVP gene as well as its regulatory sequences in the intergenic region between the AVP and the OXT gene, encoding the oxytocin prohormone. We found two chromosomes carrying the deletion in affected family members and one in unaffected family members suspected to transmit the deleted allele. Whole-genome array analysis confirmed the results and excluded the presence of any additional major pathogenic abnormalities. The deletion is predicted to abolish the transcription of the AVP gene, thus the fact that family members heterozygous for the deletion remain healthy argues, in general, against haploinsufficiency as the pathogenic mechanism FNDI. Accordingly, our data is strong support to the prevailing idea that dominant inheritance of FNDI is due to a dominant-negative effect exerted by variant AVP prohormone.
Subject(s)
Diabetes Insipidus, Neurogenic/genetics , Neurophysins/genetics , Protein Precursors/genetics , Sequence Deletion/genetics , Vasopressins/genetics , Age of Onset , Alleles , Diabetes Insipidus, Neurogenic/physiopathology , Female , Genes, Recessive , Heterozygote , Humans , Infant , Infant, Newborn , Male , Mutation , Pedigree , PregnancyABSTRACT
Polyfluoroalkyl phosphate surfactants (PAPS) are widely used in food contact materials (FCMs) of paper and board and have recently been detected in 57% of investigated materials. Human exposure occurs as PAPS have been measured in blood; however knowledge is lacking on the toxicology of PAPS. The aim of this study was to elucidate the effects of six fluorochemicals on sex hormone synthesis and androgen receptor (AR) activation in vitro. Four PAPS and two metabolites, perfluorooctanoic acid (PFOA) and 8:2 fluorotelomer alcohol (8:2 FTOH) were tested. Hormone profiles, including eight steroid hormones, generally showed that 8:2 diPAPS, 8:2 monoPAPS and 8:2 FTOH led to decreases in androgens (testosterone, dehydroepiandrosterone, and androstenedione) in the H295R steroidogenesis assay. Decreases were observed for progesterone and 17-OH-progesterone as well. These observations indicated that a step prior to progestagen and androgen synthesis had been affected. Gene expression analysis of StAR, Bzrp, CYP11A, CYP17, CYP21 and CYP19 mRNA showed a decrease in Bzrp mRNA levels for 8:2 monoPAPS and 8:2 FTOH indicating interference with cholesterol transport to the inner mitochondria. Cortisol, estrone and 17ß-estradiol levels were in several cases increased with exposure. In accordance with these data CYP19 gene expression increased with 8:2 diPAPS, 8:2 monoPAPS and 8:2 FTOH exposures indicating that this is a contributing factor to the decreased androgen and the increased estrogen levels. Overall, these results demonstrate that fluorochemicals present in food packaging materials and their metabolites can affect steroidogenesis through decreased Bzrp and increased CYP19 gene expression leading to lower androgen and higher estrogen levels.
Subject(s)
Fluorocarbons/metabolism , Fluorocarbons/toxicity , Food Packaging , Gonadal Steroid Hormones/antagonists & inhibitors , Gonadal Steroid Hormones/biosynthesis , Caprylates/metabolism , Caprylates/toxicity , Cell Line, Tumor , Environmental Exposure/adverse effects , Humans , Male , Progesterone/antagonists & inhibitors , Progesterone/biosynthesis , Testosterone/antagonists & inhibitors , Testosterone/biosynthesisABSTRACT
Inflammation plays a pivotal role in the pathophysiology of cardiovascular disease, (CVD) and leukotrienes may play a role in atherogenesis. Statins reduce mortality from CVD by reducing LDL cholesterol and potentially by other (pleiotropic) mechanisms. The aim of this study was to investigate if atorvastatin exerts an anti-inflammatory effect by reducing leukotriene B4 (LTB4) formation from stimulated neutrophils in patients treated with coronary artery bypass grafting. The study was a randomized, placebo-controlled, double-blinded crossover study. Patients (n=80) were allocated to 80 mg atorvastatin or placebo for 6 weeks before crossing over to the opposite treatment for another 6 weeks. There was no significant correlation between baseline LDL cholesterol levels on formation of LTB4, and atorvastatin had no effect on LTB4 formation. Hence, this study does not support any effect of atorvastatin on LTB4 formation as part of the explanation for its beneficial effect on CVD.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Coronary Artery Bypass , Coronary Disease/drug therapy , Heptanoic Acids/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Leukotriene B4/metabolism , Neutrophils/drug effects , Pyrroles/administration & dosage , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Atorvastatin , Calcimycin/pharmacology , Calcium Ionophores/pharmacology , Cholesterol, LDL/blood , Combined Modality Therapy , Coronary Disease/immunology , Coronary Disease/metabolism , Coronary Disease/surgery , Cross-Over Studies , Double-Blind Method , Female , Heptanoic Acids/therapeutic use , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypercholesterolemia/etiology , Hypercholesterolemia/prevention & control , Male , Middle Aged , Neutrophil Activation/drug effects , Neutrophils/immunology , Neutrophils/metabolism , Pyrroles/therapeutic useABSTRACT
Sudden cardiac death (SCD) is a major problem in patients with end stage renal disease (ESRD) on haemodialysis (HD) and several risk factors are recognized. A major problem may be the autonomic dysfunction which is observed in more than 50 % of ESRD patients. Autonomic dysfunction, and in particular cardiac autonomic dysfunction, is associated with a high risk of ventricular arrhythmias which may eventually lead to SCD. A non-invasive method for measuring cardiac autonomic function is by assessing heart rate variability (HRV) and this review will focus on HRV in HD patients. ESRD patients have an impaired HRV which may partly explain their high risk of SCD. Some intervention studies in HD patients using HRV as a surrogate parameter have been published and are also discussed in this review.
Subject(s)
Heart Rate , Kidney Failure, Chronic/physiopathology , Kidney Failure, Chronic/therapy , Renal Dialysis , Autonomic Nervous System/physiopathology , HumansABSTRACT
Climate change is expected to affect food and feed safety, including the occurrence of natural toxins in primary crop and seafood production; however, to date, quantitative estimates are scarce. This study aimed to estimate the impact of climate change effects on mycotoxin contamination of cereal grains cultivated in the terrestrial area of north west Europe, and on the frequency of harmful algal blooms and contamination of shellfish with marine biotoxins in the North Sea coastal zone. The study focused on contamination of wheat with deoxynivalenol, and on abundance of Dinophysis spp. and the possible relationship with diarrhetic shellfish toxins. The study used currently available data and models. Global and regional climate models were combined with models of crop phenology, mycotoxin prediction models, hydrodynamic models and ecological models, with the output of one model being used as input for the other. In addition, statistical data analyses using existing national datasets from the study area were performed to obtain information on the relationships between Dinophysis spp. cell counts and contamination of shellfish with diarrhetic shellfish toxins as well as on frequency of cereal cropping. In this paper, a summary of the study is presented, and overall conclusions and recommendations are given. Climate change projections for the years 2031-2050 were used as the starting point of the analyses relative to a preceding 20-year baseline period from which the climate change signal was calculated. Results showed that, in general, climate change effects lead to advanced flowering and harvest of wheat, and increased risk of contamination of wheat with deoxynivalenol. Blooms of dinoflagellates were estimated to occur more often. If the group of Dinophysis spp. behaves similarly to other flagellates in the future then frequency of harmful algal blooms of Dinophysis spp. may also increase, but consequences for contamination of shellfish with diarrhetic shellfish toxins are uncertain. Climate change will also have indirect effects on toxin contamination, which may be equally important. For example, the frequency of cropping of wheat and maize in north Europe was projected to increase under climate change, which will also increase the risk of contamination of the grains with deoxynivalenol. Risk managers are encouraged to consider the entire range of the predictions of climate change effects on food safety hazards, rather than median or average values only. Furthermore, it is recommended to closely monitor levels of mycotoxins and marine biotoxins in the future, in particular related to risky situations associated with favourable climatic conditions for toxin producing organisms. In particular, it is important to pay attention to the continuity of collecting the right data, and the availability and accessibility of databases. On a European level, it is important to stress the need for harmonisation of terminology and data collection.
Subject(s)
Climate Change , Crops, Agricultural/chemistry , Food Contamination , Marine Toxins/biosynthesis , Shellfish/analysis , Trichothecenes/biosynthesis , Triticum/chemistry , Animals , Crops, Agricultural/growth & development , Crops, Agricultural/microbiology , Databases, Factual , Dinoflagellida/growth & development , Dinoflagellida/metabolism , Europe , Food Industry/trends , Forecasting , Fungi/growth & development , Fungi/metabolism , Harmful Algal Bloom , Humans , Marine Toxins/analysis , Models, Biological , Mollusca/chemistry , Mollusca/growth & development , Mollusca/parasitology , North Sea , Phytoplankton/growth & development , Phytoplankton/metabolism , Seeds/chemistry , Seeds/growth & development , Seeds/microbiology , Shellfish/microbiology , Spatio-Temporal Analysis , Trichothecenes/analysis , Triticum/growth & development , Triticum/microbiologyABSTRACT
Most oil characterisation procedures are time consuming, labour intensive and utilise only part of the acquired chemical information. Oil spill fingerprinting with multivariate data processing represents a fast and objective evaluation procedure, where the entire chromatographic profile is used. Methods for oil classification should be robust towards changes imposed on the spill fingerprint by short-term weathering, i.e. dissolution and evaporation processes in the hours following a spill. We propose a methodology for the classification of petroleum products. The method consists of: chemical analysis; data clean-up by baseline removal, retention time alignment and normalisation; recognition of oil type by classification followed by initial source characterisation. A classification model based on principal components and quadratic discrimination robust towards the effect of short-term weathering was established. The method was tested successfully on real spill and source samples.
Subject(s)
Flame Ionization/methods , Petroleum/classification , Algorithms , Bayes Theorem , Calibration , Discriminant Analysis , Least-Squares Analysis , Petroleum/analysis , Petroleum Pollution , Principal Component Analysis , Reproducibility of Results , WeatherABSTRACT
The proinflammatory leukotriene B4 (LTB4) may be of importance in the progression of chronic kidney disease (CKD). We investigated whether n-3 polyunsaturated fatty acids (PUFA) decrease LTB4 and increase the formation of the less inflammatory leukotriene B5 (LTB5) in patients with CKD. Fifty-six patients with CKD stage 2-5 were randomised to 2.4 g n-3 PUFA or olive oil for 8 weeks. Compared to controls, n-3 PUFA significantly decreased release of LTB4 (p<0.001) and 5-hydroxyeicosatetraenoic acid (5-HETE) (p<0.01) and significantly increased release of LTB5 (p<0.001) and 5-hydroxyeicosapentaenoic acid (5-HEPE) (p<0.001) from stimulated neutrophil granulocytes. Kidney function evaluated by creatinine clearance and proteinuria did not improve. In conclusion, n-3 PUFA supplementation for 8 weeks in patients with CKD stage 2-5 significantly decreased LTB4 and 5-HETE and significantly increased LTB5 and 5-HEPE. No effect was seen on kidney function.
Subject(s)
Dietary Supplements , Eicosapentaenoic Acid/analogs & derivatives , Fatty Acids, Omega-3/therapeutic use , Leukotriene B4/analogs & derivatives , Leukotriene B4/metabolism , Neutrophil Activation , Neutrophils/metabolism , Renal Insufficiency, Chronic/diet therapy , Dietary Supplements/adverse effects , Double-Blind Method , Down-Regulation , Eicosapentaenoic Acid/metabolism , Fatty Acids/analysis , Fatty Acids/blood , Fatty Acids, Omega-3/adverse effects , Fatty Acids, Omega-3/analysis , Female , Fish Oils/adverse effects , Fish Oils/chemistry , Fish Oils/therapeutic use , Granulocytes/immunology , Granulocytes/metabolism , Humans , Kidney/physiopathology , Male , Middle Aged , Neutrophils/immunology , Patient Dropouts , Renal Insufficiency, Chronic/immunology , Renal Insufficiency, Chronic/physiopathology , Severity of Illness Index , Up-RegulationABSTRACT
A new method for the analysis of 25 polycyclic aromatic hydrocarbon (PAH) compounds in fish was developed, validated, and used for the quantification of PAHs in 180 industrially smoked fish products. The method included pressurized liquid extraction, gel-permeation chromatography (Bio-beads S-X3), solid-phase extraction (silica gel), and gas chromatography-mass spectrometry analysis. The sum concentration of 25 PAHs ([summation operator]PAH(25)) was highest in smoked herring (n = 3) and mackerel fillets (n = 13), with an average concentration of 320 and 235 microg kg(-1), respectively. Lowest average [summation operator]PAH(25) concentrations were obtained for indirectly smoked trout (26 microg kg(-1)). Principal component analysis was used to correlate processing parameters to PAH concentrations and to identify the effects of these parameters. The analysis showed that for salmon hot-smoking conditions lead to higher SigmaPAH(25) than cold smoking, and for other fish species direct smoking leads to higher SigmaPAH(25) than indirect smoking. Also, the usage of common alder increases the PAH contamination compared with beech. The effects of smoking time, combustion temperatures, and two types of smoke-generating material on the [summation operator]PAH(25) were also tested in a pilot plant study with smoked trout as a model fish. In addition to confirming that increased combustion temperatures and usage of common alder in comparison with beech increased [summation operator]PAH(25), it was also revealed that the PAH concentration decreased in the order fish skin >> outer layer of the fish muscle > inner part of the fish muscle.