Association of sugar intake from different sources with cardiovascular disease incidence in the prospective cohort of UK Biobank participants.

BACKGROUND: The relation between incident cardiovascular disease (CVD) and sugar might not only depend on the quantity consumed but also on its source. This study aims to assess the association between various sources of dietary sugars and CVD incidence in the prospective population-based UK Biobank cohort. METHODS: A total of 176,352 participants from the UK Biobank with at least one web-based dietary questionnaire (Oxford WebQ) for assessment of sugar intake were included in this study. Mean follow-up lasted 10.9 years (standard deviation 2.0), with 12,355 incident cases of CVD. To determine the association of free sugar (FS) and intrinsic sugar intake with incident CVD, hazard ratios (HR) were calculated using Cox proportional hazard regression models. FS intake from beverages and beverage subtypes, i.e., soda/fruit drinks, juice, milk-based drinks, and tea/coffee, as well as from solid foods and solids subtypes, i.e., treats, cereals, toppings, and sauces, was included as penalised cubic splines. RESULTS: FS intake showed a J-shaped relationship with CVD risk, reaching the lowest HR (HR-nadir) at 9 %E, while intrinsic sugars displayed a non-linear descending association, with the HR-nadir at 14 %E. FS in beverages demonstrated a significant linear relationship with CVD with the HR-nadir at 3 %E, while FS in solids exhibited a significant non-linear U-shaped relationship with the HR-nadir at 7 %E. Within the beverage subtypes, soda/fruit drinks displayed a linear relationship, as did to a lesser extent FS in milk-based drinks and tea/coffee. Juice, however, showed a significant U-shaped relationship with CVD risk. Among solid foods subtypes, FS in treats had a J-shaped relation with the HR-nadir at 5 %E, and FS in cereals showed a linear association. In comparison, FS in toppings and sauces exhibited a U-shaped pattern with HR-nadir at 3 %E and 0.5 %E, respectively. All major results remained similar in various sensitivity analyses and were more robust for ischemic heart disease compared to stroke. CONCLUSIONS: Only some sources of FS exhibit a robust positive association with CVD incidence. Public health efforts aiming at the reduction of CVD risk should prioritise the reduction of sugary beverages with an emphasis on soda/fruit drinks.

Flavour, emulsifiers and colour are the most frequent markers to detect food ultra-processing in a UK food market analysis.

OBJECTIVE: To elucidate which markers of ultra-processing (MUP) and their combinations are best suited to detect ultra-processed food (UPF). DESIGN: The study was based on the 206 food and 32 beverage items of the Oxford WebQ which encompass all major foods consumed in the UK. For each Oxford WebQ question, ingredient lists of up to ten matching different commercial products (n 2146) were researched online using data from the two market leaders of groceries in the UK sorted by relevance (Tesco) and by top sellers (Sainsbury's), respectively. According to the NOVA classification, sixty-five MUP were defined, and if the ingredient list of a food product was positive for at least one MUP, it was regarded as UPF. The percentage of UPF items containing specific MUP was calculated. In addition, all combinations of two to six different MUP were assessed concerning the percentage of identified UPF items. SETTING: Cross-sectional analysis. PARTICIPANTS: None. RESULTS: A total of 990 products contained at least one MUP and were, therefore, regarded as UPF. The most frequent MUP were flavour (578 items, 58·4 % of all UPF), emulsifiers (353 items, 35·7 % of all UPF) and colour (262 items, 26·5 % of all UPF). Combined, these three MUP detected 79·2 % of all UPF products. Detection rate increased to 88·4 % of all UPF if ingredient lists were analysed concerning three additional MUP, that is, fibre, dextrose and firming agent. CONCLUSIONS: Almost 90 % of all UPF items can be detected by six MUP.

Association of sugar intake from different sources with incident dementia in the prospective cohort of UK Biobank participants.

BACKGROUND: Dementia is a common disease with around 55 million cases worldwide. Therefore, dietary changes and lifestyle interventions are important approaches to delay the progress of a decline in cognitive function. The study aims to explore the association of various sources of free sugars (FS) and intrinsic sugars with dementia risk in the prospective population-based UK Biobank cohort. METHODS: Sugar consumption was assessed in 186,622 UK Biobank participants with at least one web-based dietary questionnaire (Oxford WebQ). Over a mean follow-up of 10.6 (standard deviation 1.1) years, 1498 incident dementia cases occurred. The hazard ratios (HR) for incident dementia were assessed with Cox proportional hazard regression models including sugar intake from different sources as penalized cubic splines to allow for non-linear predictor effects. RESULTS: The intake of FS and intrinsic sugar was significantly associated with dementia risk in a J-shaped fashion with the HR-nadir observed at 9% and 8% total energy (%E), respectively. FS in beverages were significantly associated with dementia risk in an ascending approximately linear way, whereas no significant association was found for FS in solids. Assessing beverage subtypes, FS in soda/fruit drinks, milk-based drinks and to a lesser extent in juice were significantly and positively related to dementia risk, whereas no association was found for FS in tea/coffee. The association between sugar subtype consumption and dementia risk remained consistent in most sensitivity analyses but changed from a J-shape to a more linear shape when the analysis was restricted to participants with at least two Oxford WebQs. CONCLUSIONS: A linear-shaped association between sugar subtype intake and dementia risk is most consistently found for FS in beverages and more specifically for FS in soda/fruit drinks, as well as in milk-based drinks.

Association of alcohol types, coffee and tea intake with mortality: prospective cohort study of UK Biobank participants.

The present study examines how alcohol intake from wine and non-wine alcoholic beverages (non-wine) in g/d, as well as cups of coffee and tea included as continuous covariates and mutually adjusted are associated with all-cause, cancer, non-cancer and CVD mortality. Consumption was assessed in 354 386 participants of the UK Biobank cohort who drank alcohol at least occasionally and survived at least 2 years after baseline with 20 201 deaths occurring over 4·2 million person-years. Hazard ratios (HR) for mortality were assessed with Cox proportional hazard regression models and beverage intake fitted as penalised cubic splines. A significant U-shaped association was detected between wine consumption and all-cause, non-cancer and CVD mortality. Wine consumption with lowest risk of death (nadir) ranged from 19 to 23 g alcohol/d in all participants and both sexes separately. In contrast, non-wine intake was significantly and positively associated in a dose-dependent manner with all mortality types studied except for CVD in females and with the nadir between 0 and 12 g alcohol/d. In all participants, the nadir for all-cause mortality was 2 cups coffee/d with non-coffee drinkers showing a slightly increased risk of death. Tea consumption was significantly and negatively associated with all mortality types in both sexes. Taken together, light to moderate consumption of wine but not non-wine is associated with decreased all-cause and non-cancer mortality. A minor negative association of coffee consumption with mortality cannot be excluded whereas tea intake is associated with a consistently decreased risk of all mortality types studied.

Association of all-cause mortality with sugar intake from different sources in the prospective cohort of UK Biobank participants.

The present study elucidates the association of intrinsic sugars and free sugars (FS) from all relevant sources with all-cause mortality in the prospective UK Biobank cohort. Sugar intake was assessed in 186 811 UK Biobank participants who completed at least one web-based 24-h dietary recall (Oxford WebQ). Cox proportional hazard regression models for all-cause mortality were used with sugar intake from different sources included as penalised cubic splines to allow non-linear predictor effects. Over a mean follow-up of 12·3 years, 8576 (4·6 %) deaths occurred. FS but not intrinsic sugars were significantly and dose-dependently associated with hazard ratio (HR) for all-cause mortality. The association with all-cause mortality was significant and dose dependent for FS in beverages, but not in solids with the mean (CI) HR at 50 g/d v. 0 g/d consumption at 1·10, 95 % CI (1·07, 1·14) and 1·01, 95 % CI (0·98, 1·03), respectively. Within the beverages subcategories, a significant dose-dependent association with mortality was detected for FS in soda/fruit drinks and milk-based drinks whereas this relation was NS for FS in pure juice and tea/coffee. FS in four different subtypes of solids, i.e. treats, cereals, toppings and sauces, were not positively associated with all-cause mortality. Major findings were robust in sensitivity analyses. In conclusion, only some FS sources were associated with all-cause mortality. Interventions targeting FS subtypes might be most effective concerning mortality if focused on the reduction of soda/fruit drinks and milk-based sugary drinks; however, the present results need to be confirmed by independent studies.

Association of sugar intake from different sources with incident depression in the prospective cohort of UK Biobank participants.

PURPOSE: To elucidate the association of different sources of free sugars (FS) and intrinsic sugars with depression risk in the prospective population-based UK Biobank cohort. METHODS: Sugar consumption was assessed in 188,426 participants (age range: 39-72 years, 54.4% female) with at least one web-based dietary questionnaire (Oxford WebQ). The hazard ratios (HR) for incident depression were assessed with Cox proportional hazard regression models including sugar intake from different sources as penalized cubic splines to allow non-linear predictor effects. Over a mean follow-up of 12.3 (standard deviation 1.8) years, 5410 incident depression cases occurred. RESULTS: FS intake was significantly associated with depression risk in an ascending approximately linear way with the lowest HR observed at 9% total energy (%E). In contrast, consumption of intrinsic sugars was not significantly related with incident depression. FS in beverages were significantly associated with depression risk in an ascending approximately linear way with the lowest HR at 4%E whereas no association was found for FS in solids. Concerning beverage types, FS in soda/fruit drinks, milk-based drinks, and tea/coffee were significantly and positively related to depression risk whereas the association was U-shaped for juice. Major findings were robust in sensitivity analyses. CONCLUSION: Only some sources of FS are positively associated with incident depression. Public health initiatives targeting FS subtypes might be most effective concerning depression risk if focused on the reduction of sugary beverages and more specifically soda/fruit drinks, milk-based drinks, and tea/coffee.

Bacterial Species Associated with Highly Allergenic Plant Pollen Yield a High Level of Endotoxins and Induce Chemokine and Cytokine Release from Human A549 Cells.

Sensitization to pollen allergens has been increasing in Europe every year. Most studies in this field are related to climate change, phenology, allergens associated with different pollens, and allergic disorders. As a plant microhabitat, pollen is colonized by diverse microorganisms, including endotoxin-producing bacteria which may contribute to pollen allergy (pollinosis). Therefore, bacteria isolated from high allergenic and low allergenic plant pollen, as well as the pollen itself with all microbial inhabitants, were used to assess the effect of the pollen by measuring the endotoxins lipopolysaccharides (LPS) and lipoteichoic acid (LTA) concentrations and their effect on chemokine and cytokine release from transwell cultured epithelial A549 cells as a model of epithelial lung barrier. High allergenic pollen showed a significantly higher level of bacterial endotoxins; interestingly, the endotoxin level found in the bacterial isolates from high allergenic pollen was significantly higher compared to that of bacteria from low allergenic pollen. Moreover, bacterial LPS concentrations across different pollen species positively correlated with the LPS concentration across their corresponding bacterial isolates. Selected bacterial isolates from hazel pollen (HA5, HA13, and HA7) co-cultured with A549 cells induced a potent concentration-dependent release of the chemokine interleukin-8 and monocyte chemotactic protein-1 as well as the cytokine TNF-alpha and interleukin-2 to both apical and basal compartments of the transwell model. This study clearly shows the role of bacteria and bacterial endotoxins in the pollen allergy as well as seasonal allergic rhinitis.

Association of Alcohol Types, Coffee, and Tea Intake with Risk of Dementia: Prospective Cohort Study of UK Biobank Participants.

The prevalence of dementia is increasing globally and is linked to obesity and unfavorable dietary habits. The present study analyses the association of alcohol intake from wine and non-wine alcoholic beverages (non-wine) in g/d, as well as coffee and tea in cups/d, with incident dementia. Over 4.2 million person-years, 4270 dementia cases occurred in 351,436 UK Biobank participants. Hazard ratios (HRs) for incident dementia were defined with Cox proportional hazard regression models in which beverage intake was fitted as penalized cubic splines. Wine intake showed a significant U-shaped association with the lowest risk for incident dementia (nadir) ranging from 21 to 23 g alcohol/d in all participants and in males. In contrast, non-wine consumption was significantly and dose-dependently associated with incident dementia, and the nadir was found at 0 g alcohol/d. Coffee consumption was not related to dementia risk, while moderate-to-high tea intake was negatively associated with incident dementia. Taken together, the current study shows on a population level that moderate consumption of wine and moderate-to-high tea intake is associated with a decreased risk of incident dementia. In contrast, non-wine is positively related to dementia risk in a linear fashion, and no clear association is found for coffee.

Interleukin-1 Induces the Release of Lubricating Phospholipids from Human Osteoarthritic Fibroblast-like Synoviocytes.

(1) Background: Synovial fluid (SF) from knee joints with osteoarthritis (OA) has increased levels of phospholipids (PL). We have reported earlier that TGF-ß and IGF-1 stimulate fibroblast-like synoviocytes (FLS) to synthesize increased amounts of PLs. The current study examined whether IL-1ß induces the release of PLs in FLS and the underlying mechanism. (2) Methods: Cultured human OA FLS were treated with IL-1ß alone and with pathway inhibitors or with synthetic liver X receptor (LXR) agonists. Cholesterol hydroxylases, ABC transporters, apolipoproteins (APO), LXR, sterol regulatory binding proteins (SREBPs), and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) were analyzed by RT-PCR, Western blot, and ELISA. The release of radiolabeled PLs from FLS was determined, and statistical analysis was performed using R (N = 5-9). (3) Results: Like synthetic LXR agonists, IL-1ß induced a 1.4-fold greater release of PLs from FLS. Simultaneously, IL-1ß upregulated the level of the PL transporter ABCA1 and of cholesterol hydroxylases CH25H and CYP7B1. IL-1ß and T0901317 stimulated the expression of SREBP1c, whereas only T0901317 enhanced SREBP2, HMGCR, APOE, LXRα, and ABCG1 additionally. (4) Conclusions: IL-1ß partially controls PL levels in OA-SF by affecting the release of PLs from FLS. Our data show that IL-1ß upregulates cholesterol hydroxylases and thus the formation of oxysterols, which, as natural agonists of LXR, increase the level of active ABCA1, in turn enhancing the release of PLs.

A comparative study on the lipidome of normal knee synovial fluid from humans and horses.

The current limitations in evaluating synovial fluid (SF) components in health and disease and between species are due in part to the lack of data on normal SF, because of low availability of SF from healthy articular joints. Our study aimed to quantify species-dependent differences in phospholipid (PL) profiles of normal knee SF obtained from equine and human donors. Knee SF was obtained during autopsy by arthrocentesis from 15 and 13 joint-healthy human and equine donors, respectively. PL species extracted from SF were quantitated by mass spectrometry whereas ELISA determined apolipoprotein (Apo) B-100. Wilcoxon's rank sum test with adjustment of scores for tied values was applied followed by Holm´s method to account for multiple testing. Six lipid classes with 89 PL species were quantified, namely phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, phosphatidylethanolamine, plasmalogen, and ceramide. Importantly, equine SF contains about half of the PL content determined in human SF with some characteristic changes in PL composition. Nutritional habits, decreased apolipoprotein levels and altered enzymatic activities may have caused the observed different PL profiles. Our study provides comprehensive quantitative data on PL species levels in normal human and equine knee SF so that research in joint diseases and articular lubrication can be facilitated.

Honeybee colonies compensate for pesticide-induced effects on royal jelly composition and brood survival with increased brood production.

Sublethal doses of pesticides affect individual honeybees, but colony-level effects are less well understood and it is unclear how the two levels integrate. We studied the effect of the neonicotinoid pesticide clothianidin at field realistic concentrations on small colonies. We found that exposure to clothianidin affected worker jelly production of individual workers and created a strong dose-dependent increase in mortality of individual larvae, but strikingly the population size of capped brood remained stable. Thus, hives exhibited short-term resilience. Using a demographic matrix model, we found that the basis of resilience in dosed colonies was a substantive increase in brood initiation rate to compensate for increased brood mortality. However, computer simulation of full size colonies revealed that the increase in brood initiation led to severe reductions in colony reproduction (swarming) and long-term survival. This experiment reveals social regulatory mechanisms on colony-level that enable honeybees to partly compensate for effects on individual level.

Gluten intake and metabolic health: conflicting findings from the UK Biobank.

PURPOSE: The impact of gluten intake on metabolic health in subjects without celiac disease is unclear. The present study aimed to assess the association between gluten intake and body fat percentage (primary objective), as well as a broad set of metabolic health markers. METHODS: Gluten intake was estimated in 39,927 participants of the UK Biobank who completed a dietary questionnaire for assessment of previous 24-h dietary intakes. Multiple linear regression analyses were performed between gluten intake and markers of metabolic health with Holm adjustment for multiple comparisons. RESULTS: Median gluten intake was 9.7 g/day (male: 11.7 g/day; female: 8.2 g/day; p < 0.0001). In multiple linear regression analysis, association between gluten intake and percentage body fat was negative in males (ß = - 0.028, p = 0.0020) and positive in females (ß = 0.025, p = 0.0028). Furthermore, gluten intake was a negative predictor of total cholesterol (male: ß = - 0.031, p = 0.0154; female: ß = - 0.050, p < 0.0001), high-density lipoprotein cholesterol (male: ß = - 0.052, p < 0.0001; female: ß = - 0.068, p < 0.0001), and glomerular filtration rate (sexes combined: ß = - 0.031, p < 0.0001) in both sexes. In females only, gluten intake was positively associated with waist circumference (ß = 0.041, p < 0.0001), waist-to-height ratio (ß = 0.040, p < 0.0001), as well as body mass index (ß = 0.043, p < 0.0001), and negatively related to low-density lipoprotein cholesterol (ß = - 0.035, p = 0.0011). A positive association between gluten intake and triglycerides was observed in males only (ß = 0.043, p = 0.0001). CONCLUSION: This study indicates that gluten intake is associated with markers of metabolic health. However, all associations are weak and not clinically meaningful. Limiting gluten intake is unlikely to provide metabolic health benefits for a population in total.

Gluten Intake and All-Cause and Cause-Specific Mortality: Prospective Findings from the UK Biobank.

BACKGROUND: Gluten has been linked to adverse effects on metabolic and vascular health. OBJECTIVES: The present study determines the association between dietary gluten intake and all-cause (primary objective), as well as cause-specific, mortality in people without celiac disease. METHODS: Gluten intake was estimated in 159,265 participants of the UK Biobank which is a large multicenter, prospective cohort study initiated in 2006. Cox proportional hazard regression models were used and HRs were determined for all-cause and cause-specific mortality. All models were adjusted for confounders and multiple testing. RESULTS: Median (IQR) age was 57 (49-62) y with 52.1% of participants being female. Gluten intake was 8.5 (5.1-12.4) g/d with significantly higher consumption in males [10.0 (6.3-14.1) g/d] than in females [7.2 (4.6-10.7) g/d] (P < 0.0001). During a median follow-up of 11.1 (10.6-11.9) y and 1.8 million person-years, 6259 deaths occurred. Gluten intake was not significantly associated with all-cause mortality after adjusting for confounders (HR: 1.00; 95% CI: 1.00, 1.01; P = 0.59). Dietary gluten was not significantly associated with cancer (HR: 1.00; 95% CI: 1.00, 1.01; raw P = 0.24) or noncancer (HR: 1.00; 95% CI: 0.99, 1.01; raw P = 0.56) mortality. However, gluten intake was positively associated with ischemic heart disease mortality (HR: 1.02; 95% CI: 1.01, 1.04; raw P = 0.003, Holm-adjusted P = 0.04). CONCLUSIONS: Gluten intake is not significantly associated with all-cause and cancer mortality in adults without celiac disease. The findings support the hypothesis that limiting gluten intake is unlikely to provide significant overall survival benefits on a population level. The positive association between gluten intake and ischemic heart disease mortality requires further study.

Evaluation of Hydrogen Peroxide Fumigation and Heat Treatment for Standard Emergency Arthropod Inactivation in BSL-3 Insectaries.

Climate change and global movements of people and goods have accelerated the spread of invasive species, including insects that vector infectious diseases, which threaten the health of more than half of the world's population. Increasing research efforts to control these diseases include the study of vector - pathogen interactions, involving the handling of pathogen-infected vector insects under biosafety level (BSL) 2 and 3 conditions. Like microbiology BSL-3 laboratories, BSL-3 insectaries are usually subjected to fixed-term or emergency room decontamination using recognized methods such as hydrogen peroxide (H2O2) or formaldehyde fumigation. While these procedures have been standardized and approved for the inactivation of diverse pathogens on surfaces, to date, there are no current standards for effective room-wide inactivation of insects in BSL-3 facilities in case of an emergency such as the accidental release of a large number of infected vectors. As H2O2 is often used for standard room decontamination in BSL-3 facilities, we evaluated H2O2 fumigation as a potential standard method for the safe, room-wide deactivation of insects in BSL-3 insectaries in comparison to heat treatment. To account for physiological diversity in vector insect species, six species from three different orders were tested. For the H2O2 fumigation we observed a strong but also varying resilience across all species. Lethal exposure time for the tested dipterans ranged from nine to more than 24 h. Furthermore, the coleopteran, Tribolium castaneum, did not respond to continuous H2O2 exposure for 48 h under standard room decontamination conditions. In contrast, temperatures of 50°C effectively killed all the tested species within 2 to 10 min. The response to lower temperatures (40-48°C) again showed a strong variation between species. In summary, results suggest that H2O2 fumigation, especially in cases where a gas generator is part of the laboratory equipment, may be used for the inactivation of selected species but is not suitable as a general emergency insect inactivation method under normal room decontamination conditions. In contrast, heat treatment at 48 to 50°C has the potential to be developed as an approved standard procedure for the effective inactivation of insects in BSL-3 facilities.

Association of Antioxidants Use with All-Cause and Cause-Specific Mortality: A Prospective Study of the UK Biobank.

Prospective studies and randomized controlled trials elucidating the impact of antioxidants supplementation on mortality risk are inconclusive. The present analysis determined association between regular antioxidants use and all-cause (primary objective), as well as cause-specific, mortality in 345,626 participants of the UK Biobank cohort using Cox proportional hazard models. All models were adjusted for confounders and multiple testing. Antioxidants users were defined as participants who indicated to regularly use at least one of the following: multivitamins, vitamin C, vitamin E, selenium, and zinc. Median age of antioxidants users (n = 101,159) and non-users (n = 244,467) at baseline was 57 years. During 3.9 million person-years and a median follow-up of 11.5 years, 19,491 deaths occurred. Antioxidants use was not significantly associated with all-cause, cancer, and non-cancer mortality including several cancer and non-cancer subtypes. Interestingly, mortality risk from respiratory disease was significantly 21% lower among antioxidants users as compared to non-users (hazard ratio: 0.79; 95% confidence interval: 0.67, 0.92). In conclusion, the present study findings do not support recommendations for antioxidants supplementation to prevent all-cause, cancer, or non-cancer mortality on a population level. The significant inverse association between antioxidants use and respiratory disease mortality needs further study.

Trajectories of Body Composition during Advanced Aging in Consideration of Diet and Physical Activity: A 20-Year Longitudinal Study.

This prospective study investigates age-dependent changes in anthropometric data and body composition over a period of two decades in consideration of physical activity and diet in community-dwelling subjects ≥60 years. Overall, 401 subjects with median follow-up time of 12 years were examined. Fat-free mass (FFM) and fat mass (FM) were analyzed using bioelectrical impedance analysis. Physical activity was assessed via a self-administered questionnaire. Dietary intake was examined by 3-day dietary records. Linear mixed-effects models were used to analyze the influence of age, sex, physical activity and energy/protein intake on anthropometric data and body composition by considering year of entry, use of diuretics and diagnosis of selected diseases. At baseline, median values for daily energy and protein intakes were 8.5 megajoule and 81 g and physical activity index was 1.7. After adjusting for covariates, advancing age was associated with parabolic changes indicating overall changes from age 60 to 90 years in women and men in body mass: -4.7 kg, -5.0 kg; body mass index: +0.04 kg/m2, -0.33 kg/m2; absolute FFM: -2.8 kg, -3.5 kg; absolute FM: -1.8 kg, -1.2 kg and waist circumference: +16 cm, +12 cm, respectively. No age-dependent changes were found for upper arm circumference and relative (%) FFM. Dietary and lifestyle factors were not associated with changes in anthropometric or body composition parameters. In summary, the results indicate non-linear age-dependent changes in anthropometric data and body composition, which are largely unaffected by the degree of habitual physical activity and dietary protein intake in well-nourished community-dwelling subjects.

Biomarkers of Hand Osteoarthritis Are Detectable after Mechanical Exercise.

BACKGROUND: Hand osteoarthritis (OA) is one of the most common joint diseases, but studies on biomarkers are rare. The aim of this explorative study was (a) to evaluate potential biomarkers of hand OA, (b) to identify an optimal time point to sample venous blood, and (c) to correlate biomarker levels with radiological and clinical scores. METHODS: Four female cohorts were investigated. One with a more Heberden-accentuated OA and one with a more Bouchard-accentuated hand OA, and two symptom-free control groups aged 20-30 or 50-75 years. The venous blood was sampled before and at eight time points after mechanical exercise of the OA hand. X-rays of OA hands were assessed using the Kellgren and Lawrence as well as Kallman scores. Participants were evaluated clinically using the AUSCAN™ Index, visual analog scale (VAS), and Health Assessment Questionnaire (HAQ). Serum levels of seven biomarkers were measured by ELISA. RESULTS: The concentrations of CPII, COMP, IL-15, sVCAM-1, NGAL, and PIIANP were significantly increased within 15 min after exercise. PIIANP was markedly elevated in the Heberden-accentuated OA group as compared to both control groups, but did not correlate with any radiological or clinical score. Analysis of the probabilistic index further revealed that CPII can distinguish between Bouchard's OA and premenopausal controls whereas COMP can discriminate between Bouchard's and Heberden's OA. CONCLUSIONS: This study demonstrates that even previously undetectable biomarkers can be quantified in serum after mechanical exercise. Future larger studies are needed to determine specificity and sensitivity of these markers and their ability to diagnose even pre-radiological OA.

Low testosterone in ApoE/LDL receptor double-knockout mice is associated with rarefied testicular capillaries together with fewer and smaller Leydig cells.

The testis as a site for atherosclerotic changes has so far attracted little attention. We used the apolipoprotein E (ApoE)/low density lipoprotein (LDL) receptor deficient mouse model (KO) for atherosclerosis (20, 40, 60 and 87-week-old) to investigate whether Leydig cells or the capillary network are responsible for reduced serum testosterone levels previously observed in extreme ages of this model. In KO mice, overall testosterone levels were reduced whereas the adrenal gland-specific corticosterone was increased excluding a general defect of steroid hormone production. In addition to micro-CT investigations for bigger vessels, stereology revealed a reduction of capillary length, volume and surface area suggesting capillary rarefaction as a factor for diminished testosterone. Stereological analyses of interstitial cells demonstrated significantly reduced Leydig cell numbers and size. These structural changes in the testis occurred on an inflammatory background revealed by qPCR. Reduced litter size of the KO mice suggests hypo- or infertility as a consequence of the testicular defects. Our data suggest reduced testosterone levels in this atherosclerosis model might be explained by both, rarefication of the capillary network and reduced Leydig cell number and size. Thus, this study calls for specific treatment of male infertility induced by microvascular damage through hypercholesterolemia and atherosclerosis.

Dielectric Spectroscopy and Optical Density Measurement for the Online Monitoring and Control of Recombinant Protein Production in Stably Transformed Drosophila melanogaster S2 Cells.

The production of recombinant proteins in bioreactors requires real-time process monitoring and control to increase process efficiency and to meet the requirements for a comprehensive audit trail. The combination of optical near-infrared turbidity sensors and dielectric spectroscopy provides diverse system information because different measurement principles are exploited. We used this combination of techniques to monitor and control the growth and protein production of stably transformed Drosophila melanogaster S2 cells expressing antimicrobial proteins. The in situ monitoring system was suitable in batch, fed-batch and perfusion modes, and was particularly useful for the online determination of cell concentration, specific growth rate (µ) and cell viability. These data were used to pinpoint the optimal timing of the key transitional events (induction and harvest) during batch and fed-batch cultivation, achieving a total protein yield of ~25 mg at the 1-L scale. During cultivation in perfusion mode, the OD880 signal was used to control the bleed line in order to maintain a constant cell concentration of 5 × 107 cells/mL, thus establishing a turbidostat/permittistat culture. With this setup, a five-fold increase in productivity was achieved and 130 mg of protein was recovered after 2 days of induced perfusion. Our results demonstrate that both sensors are suitable for advanced monitoring and integration into online control strategies.

Temporal dynamics of whole body residues of the neonicotinoid insecticide imidacloprid in live or dead honeybees.

In cases of acute intoxication, honeybees often lay in front of their hives for several days, exposed to sunlight and weather, before a beekeeper can take a sample. Beekeepers send samples to analytical laboratories, but sometimes no residues can be detected. Temperature and sun light could influence the decrease of pesticides in bee samples and thereby residues left for analysis. Moreover, samples are usually sent via normal postal services without cooling. We investigated the temporal dynamics of whole-body residues of imidacloprid in live or dead honeybees following a single-meal dietary exposure of 41 ng/bee under various environmental conditions, such as freezing, exposure to UV light or transfer of individuals through the mail system. Immobile, "dead" looking honeybees recovered from paralysis after 48 hours. The decrease of residues in living but paralysed bees was stopped by freezing (= killing). UV light significantly reduced residues, but the mode of transport did not affect residue levels. Group feeding increased the variance of residues, which is relevant for acute oral toxicity tests. In conclusion, elapsed time after poisoning is key for detection of neonicotinoids. Freezing before mailing significantly reduced the decrease of imidacloprid residues and may increase the accuracy of laboratory analysis for pesticides.