Immunoglobulin G1 Antibodies Against Phosphorylcholine Are Associated With Protection in Systemic Lupus Erythematosus and Atherosclerosis: Potential Underlying Mechanisms.

OBJECTIVE: Immunoglobulin M antibodies against phosphorylcholine (anti-PCs) may be protective in atherosclerosis, cardiovascular disease (CVD), and systemic lupus erythematosus (SLE). We study immunoglobulin G1 (IgG1) and immunoglobulin G2 (IgG2) anti-PCs, with a focus on atherosclerosis and SLE. METHODS: We determined anti-PCs by using the enzyme-linked immunosorbent assay in 116 patients with SLE and 110 age- and sex-matched controls. For functional studies, we used three in-house-generated, fully human monoclonal IgG1 anti-PCs (A01, D05, and E01). Apoptosis was induced in Jurkat T cells and preincubated with A01, D05, E01, or IgG1 isotype control, and effects on efferocytosis by human macrophages were studied. Anti-PC peptide/protein characterization was determined using a proteomics de novo sequencing approach. RESULTS: IgG1, but not IgG2, anti-PC levels were higher among patients with SLE (P = 0.02). IgG1 anti-PCs were negatively associated with Systemic Lupus International Collaborating Clinics (SLICC) damage index and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores (odds ratio [OR]: 2.978 [confidence interval (CI): 0.876-10.098] and OR: 5.108 [CI 1.3-20.067], respectively) and negatively associated with CVD, atherosclerotic plaques, and echolucent plaques (potentially vulnerable plaques), but the association for the two former was not significant after controlling for confounders. D05 had a maximum effect on macrophage efferocytosis efficiency, followed by A01 and E01. The monoclonal antibodies showed differential binding specificity to PC and PC-associated neoepitopes. A peptide analysis showed a difference in the complementarity-determining region 3 of the three IgG1 anti-PC clones that are crucial for recognition of PC on apoptotic cell surfaces and other neoepitopes. CONCLUSION: IgG1 anti-PCs are negatively associated with disease activity and disease damage in SLE, but the negative association with CVD is also dependent on confounding risk factors. One potential underlying mechanism could be increased clearance of dead cells.

Circulating fatty acids in relation to alcohol consumption: Cross-sectional results from a cohort of 60-year-old men and women.

BACKGROUND & AIMS: Alcohol consumption is considered to affect circulating fatty acids (FAs) but knowledge about specific associations is limited. We aimed to assess the relation between alcohol consumption and serum FAs in 60-year-old Swedish men and women. METHODS: In a random sample of 1917 men and 2058 women residing in Stockholm county, cross-sectional associations between different categories of alcohol consumption and FAs were assessed using linear regression; ß1 coefficients with 95% confidence interval (CI) were calculated. Self-reported alcohol consumption was categorized as none, low (≤9.9 g/day) (reference), moderate (10-29.9 g/day) and high (≥30 g/day). Moderate alcohol consumption was further subdivided into consumption of beer, wine, liquor and their combinations. Thirteen serum cholesterol ester FAs were measured by gas chromatography and individual FAs were expressed as percentage of total FAs. RESULTS: Increasing alcohol consumption was associated to linear increase of saturated myristic acid, monounsaturated FAs and n-6 polyunsaturated (PUFA) arachidonic acid, whereas linear decrease was noted for saturated pentadecanoic acid and for n-6 PUFA linoleic acid. With non-linear associations, increasing alcohol consumption also associated to decreased saturated stearic acid, n-6 PUFA dihomo-gamma-linolenic acid, and n-3 PUFA docosahexaenoic acid and increased saturated palmitic acid, n-6 PUFA gamma-linolenic acid and n-3 PUFA eicosapentaenoic acid. Among types of beverages, wine consumption was associated with n-6 PUFA arachidonic acid (ß1 0.59; 95% CI: 0.30;0.88) and the n-3 PUFAs eicosapentaenoic acid (ß1 0.54; 95% CI: 0.30;0.78), and docosahexaenoic acid (ß1 0.06; 95% CI: 0.00;0.12). CONCLUSIONS: These findings may give important basis for further investigations to better understand biological mechanisms behind the dose-dependent associations between alcohol consumption and health outcomes observed in many previous studies.

Cross-sectional relationships between dietary fat intake and serum cholesterol fatty acids in a Swedish cohort of 60-year-old men and women.

BACKGROUND: The present study aimed to describe the relationship between self-reported dietary intake and serum cholesterol fatty acids (FAs) in a Swedish population of 60-year-old men and women. METHODS: Cross-sectional data collected in 1997-1998 from 4232 individuals residing in Stockholm County were used. Five diet scores were created to reflect the intake of saturated fats in general, as well as fats from dairy, fish, processed meat and vegetable oils and margarines. Gas chromatography was used to assess 13 FAs in serum cholesterol esters. The association between each diet score and specific FAs was assessed by percentile differences (PD) with 95% confidence intervals (CI) at the 10th, 25th, 50th, 75th and 90th percentile of each FA across levels of diet scores using quantile regression. RESULTS: Fish intake was associated with high proportions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). For each point increase in fish score, the 50th PD in EPA and DHA was 32.78% (95% CI = 29.22% to 36.35%) and 10.63% (95% CI = 9.52% to 11.74%), respectively. Vegetable fat intake was associated with a high proportion of linoleic acid and total polyunsaturated fatty acids (PUFA) and a low proportion of total saturated fatty acids (SFA). The intake of saturated fats in general and dairy fat was slightly associated with specific SFA, although the intake of fat from meat was not. CONCLUSIONS: In the present study population, using a rather simple dietary assessment method, the intake of fish and vegetable fats was clearly associated with serum PUFA, whereas foods rich in saturated fats in general showed a weak relationship with serum SFA. Our results may contribute to increased knowledge about underlying biology in diet-cardiovascular disease associations.

Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.

Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.

The psychometric characteristics of an assessment instrument for perceived harmfulness in adolescents with musculoskeletal pain (PHODA-youth).

BACKGROUND: Cognitive-behavioural models of chronic pain predict that dysfunctional assumptions about harmfulness of activities may maintain pain-related fear and disability. To assess perceived harmfulness in adolescents, the Photograph Series of Daily Activities for youth (PHODA-youth) was developed. Information concerning its methodological quality is currently lacking. OBJECTIVE: To investigate psychometric characteristics (factor structure, test-retest reliability, construct validity) and feasibility of the PHODA-youth in adolescents with chronic musculoskeletal pain. STUDY DESIGN: Test-retest design. STUDY POPULATION: Adolescents aged 13-21 years with chronic nonspecific musculoskeletal pain. METHODS: Participants filled in an electronic version of the PHODA-youth including 89 items twice with a 4-week interval. The instrument's factor structure was determined by a factor analysis. Construct validity was studied with criterion variables: catastrophizing (Pain Catastrophizing Scale for Children), pain intensity (visual analogue scale), depression (Children's Depression Inventory) and pain-related disability (Functional Disability Inventory) using regression analysis. Test-retest reliability was evaluated based on the Pearson correlation coefficient. Feasibility was studied with self-constructed questions. RESULTS: Seventy-one adolescents participated. Results show a three-factor structure for the PHODA-youth including 51 items with subscales labelled as: 'activities of daily life', 'intensive physical activities' and 'social activities'. Total and subscale scores showed a high internal consistency. Its test-retest reliability was good (r = 0.94) and its construct validity is supported by the finding that both catastrophizing (ß = 0.25; p = 0.02) and disability (ß = 0.71; p < 0.001) were uniquely related to the PHODA-youth. In addition, feasibility appeared adequate. CONCLUSION: The findings support the PHODA-youth as a valid and reliable measure of the perceived harmfulness of activities in adolescents with musculoskeletal pain.

Protein hydrolysate co-ingestion does not modulate 24 h glycemic control in long-standing type 2 diabetes patients.

OBJECTIVE: Evaluate the efficacy of protein hydrolysate co-ingestion as a dietary strategy to improve blood glucose homeostasis under free-living conditions in long-standing type 2 diabetes patients. METHODS: A total of 13 type 2 diabetes patients were enrolled in a randomized, double-blind cross-over design and studied on two occasions for 40 h under strict dietary standardization but otherwise normal, free-living conditions. In one trial, subjects ingested a protein hydrolysate (0.4 g kg(-1) bw casein hydrolysate, PRO) with every main meal. In the other trial, a placebo was ingested (PLA). Blood glucose concentrations were assessed by continuous glucose monitoring. RESULTS: Average 24 h glucose concentrations were similar between the PLA and the PRO trials (8.9 +/- 0.8 vs 9.2 +/- 0.7 mmol l(-1), respectively). Hyperglycemia (glucose concentrations >10 mmol l(-1)) was experienced 34 +/- 9% of the time (8 +/- 2 h per 24 h) in the PLA trial. Protein hydrolysate co-ingestion with each main meal (PRO) did not reduce the prevalence of hyperglycemia (39 +/- 10%, 9 +/- 2 h per 24 h; P=0.2). CONCLUSION: Co-ingestion of a protein hydrolysate with each main meal does not improve glucose homeostasis over a 24 h period in long-standing type 2 diabetes patients.

Modelling of temperature effects on removal efficiency and dissolved oxygen concentrations in stormwater ponds.

The performance of stormwater ponds, operated under winter conditions, was modelled using the commercial software Mike21 and MOUSE. Direct and indirect effects of changing temperature were investigated. The most important effect of winter conditions is the changed hydrology, characterised by long periods with no runoff followed by snowmelt events with large runoff volumes during several days. This gives lower removal efficiencies than during a period with the same precipitation but without winter conditions. For the concentration of dissolved oxygen, wind is an important factor. Consequently the most important effect of an ice cover on the pond is that it prevents the oxygenation effects of the wind. The direct temperature effects on the removal processes are negligible compared to the indirect effects in changed hydrology and forming of ice cover.