A common approach for ranking of microbiological and chemical hazards in foods based on risk assessment - useful but is it possible?

This article compares and contrasts microbial and chemical risk assessment methodologies in order to evaluate the potential for a common framework for ranking of risk of chemical and microbiological hazards, and developments needed for such a framework. An overview of microbial (MRA) and chemical (CRA) risk assessment is presented and important differences are highlighted. Two microbiological and two chemical hazard-food combinations were ranked based on both a margin of exposure and a risk assessment approach. The comparisons illustrated that it is possible to rank chemical and microbiological hazard-food combinations with traditional approaches from each domain and indicated that the rank order but not the absolute measures is similar using either approach. Including severity in the assessment using DALY reduced differences between hazards and affected the outcome more than which approach was used. Ranking frameworks should include assessment of uncertainty as an integral part of the ranking, and be based on assessment of risk, not safety, and expressed in a common health metric such as disease burden. Necessary simplifications to address data gaps can involve the use of default scenarios. Challenges include comparisons of case-based vs. non-case-based health-endpoints, e.g. biomarker concentration, and integration of the severity of health effects into ranking.

Human umbilical cord blood-derived mesenchymal stromal cells display a novel interaction between P-selectin and galectin-1.

Human multipotent mesenchymal stromal/stem cells (MSCs) have been shown to exert immunomodulatory properties that have great potential in therapies for various inflammatory and autoimmune disorders. However, intravenous delivery of these cells is followed by massive cell entrapment in the lungs and insufficient homing to target tissues or organs. In targeting to tissues, MSCs and other therapeutic cells employ similar mechanisms as leucocytes, including a cascade of rolling and adhesion steps mediated by selectins, integrins and their ligands. However, the mechanisms of MSCs homing are not well understood. We discovered that P-selectin (CD62P) binds to umbilical cord blood (UCB)-derived MSCs independently of the previously known sialyl Lewis x (sLex)-containing ligands such as P-selectin glycoprotein ligand-1 (PSGL-1, CD162). By biochemical assays, we identified galectin-1 as a novel ligand for P-selectin. Galectin-1 has previously been shown to be a key mediator of the immunosuppressive effects of human MSCs. We conclude that this novel interaction is likely to play a major role in the immunomodulatory targeting of human UCB-derived MSCs.

Dietary acrylamide exposure among Finnish adults and children: the potential effect of reduction measures.

A deterministic exposure assessment using the Nusser method that adjusts for within-subject variation and for nuisance effects among Finnish children and adults was carried out. The food consumption data covered 2038 adults (25-74 years old) and 1514 children of 1, 3 and 6 years of age, with the data on foods' acrylamide content obtained from published Finnish studies. We found that acrylamide exposure was highest among the 3-year-old children (median = 1.01 µg kg(-1) bw day(-1), 97.5th percentile = 1.95 µg kg(-1) bw day(-1)) and lowest among 65-74-year-old women (median = 0.31 µg kg(-1) bw day(-1), 97.5th percentile = 0.69 µg kg(-1) bw day(-1)). Among adults, the most important source of acrylamide exposure was coffee, followed by casseroles rich in starch, then rye bread. Among children, the most important sources were casseroles rich in starch and then biscuits and, finally, chips and other fried potatoes. Replacing lightly roasted coffee with dark-roasted, swapping sweet wheat buns for biscuits, and decreasing the acrylamide content of starch-based casseroles and rye bread by 50% would result in a 50% decrease in acrylamide exposure in adults. Among children, substituting boiled potatoes for chips and other friend potatoes and replacing biscuits with sweet wheat buns while lowering the acrylamide content of starch-based casseroles by 50% would lead to acrylamide exposure that is only half of the original exposure. In conclusions, dietary modifications could have a large impact in decreasing acrylamide exposure.

Harmonisation of food categorisation systems for dietary exposure assessments among European children.

Within the European project called EXPOCHI (Individual Food Consumption Data and Exposure Assessment Studies for Children), 14 different European individual food consumption databases of children were used to conduct harmonised dietary exposure assessments for lead, chromium, selenium and food colours. For this, two food categorisation systems were developed to classify the food consumption data in such a way that these could be linked to occurrence data of the considered compounds. One system served for the exposure calculations of lead, chromium and selenium. The second system was developed for the exposure assessment of food colours. The food categories defined for the lead, chromium and selenium exposure calculations were used as a basis for the food colour categorisation, with adaptations to optimise the linkage with the food colour occurrence data. With this work, an initial impetus was given to make user-friendly food categorisation systems for contaminants and food colours applicable on a pan-European level. However, a set of difficulties were encountered in creating a common food categorisation system for 14 individual food consumption databases that differ in the type and number of foods coded and in level of detail provided about the consumed foods. The work done and the problems encountered in this project can be of interest for future projects in which food consumption data will be collected on a pan-European level and used for common exposure assessments.

Dietary acrylamide intake and the risk of cancer among Finnish male smokers.

OBJECTIVE: To assess the association between dietary acrylamide intake and the risk of cancer among male smokers. METHODS: The study consisted of 27,111 male smokers, aged 50-69 years, without history of cancer. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire and a questionnaire on general background characteristics (including smoking habits) at baseline. Incident cases of cancer were identified through the national Finnish Cancer Registry. RESULTS: During an average 10.2 year follow-up, 1,703 lung cancers, 799 prostate cancers, 365 urothelial cancers, 316 colorectal cancers, 224 stomach cancers, 192 pancreatic cancers, 184 renal cell cancers, and 175 lymphomas were diagnosed. Dietary acrylamide intake was positively associated with the risk of lung cancer; relative risk (RR) in the highest versus the lowest quintile in the multivariable-adjusted model was 1.18 ((95% confidence interval (CI) 1.01-1.38, p for trend 0.11). Other cancers were not associated with acrylamide intake. CONCLUSIONS: High acrylamide intake is associated with increased risk of lung cancer but not with other cancers in male smokers.

Acyl chain-dependent effect of lysophosphatidylcholine on human neutrophils.

Lysophosphatidylcholine (LPC) is the most abundant lysophospholipid in plasma and tissues, and its level increases in ischemia and inflammation. LPC induces various proinflammatory actions in leukocytes, endothelial cells, and smooth muscle cells, but its effects may vary, depending on the acyl chain. In the present study, we identified the molecular species of LPC in human plasma and studied their effects on human neutrophils. Unsaturated LPC species over a wide concentration range (5-200 microM) induced long-lasting superoxide production in neutrophils. The response was preceded by a >10-min lag time and lasted for 60-90 min. Superoxide production was prevented when albumin was added together with LPC at a molar ratio of 1:2 or higher, and significant inhibition was observed even when albumin was added 4-8 min after LPC. Saturation of albumin by fivefold molar excess of stearic acid reduced the inhibitory effect significantly. Saturated LPCs, particularly the most abundant 16:0 species, induced significantly less superoxide production than the unsaturated species and only at 5-10 microM concentrations. Saturated LPC species elicited a several-fold higher increase in cytoplasmic calcium and at >20 microM, increased plasma membrane permeability. A mixture of LPCs mimicking the plasma LPC composition induced nearly similar superoxide production as the most active LPC18:1 alone. These results indicate remarkable acyl chain-dependent differences in the cellular effects of LPC. Elevation of LPC level may increase inflammation through activation of neutrophil NADPH oxidase, particularly when the simultaneous increase of free fatty acids diminishes the ability of albumin to scavenge LPCs.

Consumption of black, green and herbal tea and iron status in French adults.

OBJECTIVE: A number of potential health effects have lately been accorded to tea consumption. It is, however, not clear whether an increase in tea consumption increases the risk of iron depletion in a normal apparently healthy adult population. We have therefore evaluated this. DESIGN: Cross-sectional study. SUBJECTS: A total of 954 men (aged 52-68 years) and 1639 women (aged 42-68 years), who were participants of SU.VI.MAX Study, completed a detailed questionnaire on tea consumption. To determine the iron status of the participants, a venous blood sample was drawn and serum-ferritin was measured. Iron depletion was defined as a serum ferritin concentration <16 microg/l. Three 1-day food records were used to estimate the intake of other dietary enhancing or inhibiting factors of iron absorption, which were included in the logistic regression models. RESULTS: The mean serum-ferritin concentration was not related to black, green and herbal tea consumption in men, pre- or postmenopausal women. Also the risk of iron depletion was in the multivariate model not related to any kind of tea drinking or to the strength of tea, the infusion time or the time of tea drinking. CONCLUSIONS: The data suggest that normal apparently healthy adults are not at risk of iron depletion owing to any kind of tea drinking.

Preoperative postural control of patients with vestibular schwannoma assessed by visual feedback posturography.

BACKGROUND: The need for an objective method to describe the functional postural control of patients with vestibular schwannoma in agreement with their subjective sensation of balance. OBJECTIVES: The objective was to compare the postural control of 49 patients with unilateral vestibular schwannoma (VS) with that of healthy subjects by using visual feedback posturography (VFP). We aimed to find out if preoperative postural control of the patients correlates with their subjective sensation of balance. METHODS: In the VFP, while standing on the platform, patients were instructed to move their center of gravity (COG) marker to the targets as fast and accurately as possible. Hit delay (HD) to the targets, hold percentage (HP) within the targets, COG marker velocity (CMV) to the targets, and balance index (BI) were calculated. We rated intensity of balance disturbance using a 5-point qualitative scale. RESULTS: Twenty-two (45%) patients had at least one abnormal VFP parameter, and 49% of patients were simultaneously symptomatic. Mean hit delay (HD), hold percentage (HP), and balance index (BI) were significantly worsened in patients with VS (p < 0.05). Increased HD and BI correlated significantly with subjective sensation of imbalance (p = 0.02). CONCLUSIONS: The overall deficit in preoperative postural control of the VS patients was not severe, and this finding agreed well with their subjective sensations.

Is small-fenestra stapedotomy a safer outpatient procedure than total stapedectomy?

We compared two stapedoplasty techniques to evaluate whether one technique is safer than the other as an outpatient procedure and to demonstrate possible reasons for outpatient failures. We performed a retrospective study of patient records of 94 operated adult patients who were all initially scheduled for outpatient surgery for otosclerosis (47 total stapedectomies and 47 small-fenestra stapedotomies). Six patients (13%) with stapedectomy and 1 patient (2%) with stapedotomy had to stay overnight at the hospital due to postoperative vertigo and nausea. The number of outpatient failures was statistically significantly different between the stapedoplasty techniques (p = 0.05). Five patients (11%) with stapedectomy and 2 patients (4%) with stapedotomy had a drop in bone conduction threshold between 5 and 8 dB pre- to postoperatively (n.s.). The short-term hearing improvement did not differ statistically significantly between the techniques when compared to the preoperative values. Small-fenestra stapedotomy is the safer procedure to be performed as outpatient setting than total stapedectomy.

Abnormal response to physical activity in femurs after heterozygous inactivation of one allele of the Col2a1 gene for type II collagen in mice.

The objective of this study was to evaluate the influence of heterozygous inactivation of one allele of the type II collagen gene (Col2a1) on biomechanical properties and mineral density of bone under physical loading conditions. C57BL/6-TGN mice with heterozygous knockout (HZK) inactivation of Col2a1 gene and their nontransgenic littermate controls were housed in individual cages with running wheels for 9 and 15 months. The running activity of each mouse was monitored continuously throughout the experiment. Bone mineral density (BMD) of mice femora was measured using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT). Biomechanical properties were determined using three-point bending tests. Vertebral bone samples were prepared for quantitative polarized light microscopy and digital densitometry of proteoglycans. The concentration of total collagen and collagen cross-links were analyzed using high-performance liquid chromatograpy (HPLC). The average daily running distance was shorter for the HZK mice between the age of 4 and 15 months as compared with normal runners (P < 0.05). The ultimate breaking force was 14.8% and 23.6% (9 vs. 15 months) lower in HZK-runners than in wild-type runners. BMD of the femur was 6.1% lower in HZK-runners at the age of 9 months (P < 0.05). Physical activity increased cortical BMD in wild-type runners but not in the HZK runners at the age of 9 months. The collagen network of the HZK mice was less organized. There were only minor changes in BMD and mechanical and structural properties between sedentary HZK mice and their wild-type controls. Increased physical activity induced significantly lower bone density, mechanical properties, and organization of collagen fibers in male HZK mice. However, there were no major differences in biomechanical parameters between sedentary HZK and wild-type male mice. This suggests an important guiding role of collagen type II in bone remodelling and maturation.

Subclinical vestibulocerebellar dysfunction in migraine with and without aura.

OBJECTIVE: In patients with migraine, neurotologic symptoms and signs occur commonly. The authors' aim was to determine whether neurotologic findings are in accordance with the type of migraine and whether test findings differ from those of healthy controls. METHODS: The authors examined 36 patients with various types of migraine classified by International Headache Society criteria. Comprehensive neurotologic tests were performed between attacks: video-oculography (VOG), electronystagmography, static posturography, and audiometry on 12 patients with migraine with aura (MA) and 24 patients with migraine without aura (MO). Results were compared to those of test-specific nonmigrainous control groups. Only eight migraineurs (six with MA and two with MO) had vertigo or dizziness. RESULTS: Despite the absence of clinical neurotologic symptoms, most of the patients with migraine (83%) showed abnormalities in at least one of these tests. Both migraine types differed significantly from the control group (in VOG, in saccadic accuracy, and in static posturography). Vestibular findings tended to be more severe in MA than in MO. CONCLUSIONS: These data suggest that interictal neurotologic dysfunction in MA and MO share similar features and that the defective oculomotor function is mostly of vestibulocerebellar origin.

Three-dimensional respiratory-gated coronary MR angiography with reference to X-ray coronary angiography.

PURPOSE: To assess the clinical value of three-dimensional coronary MR angiography (CMRA) in the detection of significant coronary artery stenosis using conventional X-ray angiography as the standard reference. MATERIAL AND METHODS: Sixty-nine patients underwent X-ray coronary angiography and CMRA because of suspected or previously diagnosed coronary artery disease. MRI was performed with a 1.5-T whole body imaging system using ECG-triggered 3D gradient echo sequence with retrospective navigator echo respiratory gating and fat suppression. RESULTS: A total of 276 coronary artery segments were analyzed. The X-ray coronary angiography was normal in 22 patients. Significant proximal stenoses (exceeding 50%) or occlusions were present in 102 coronary artery segments. In all, 120 stenoses or occlusions were identified in CMRA. Sixteen percent of the coronary artery segments had to be excluded because of poor image quality. The overall sensitivity and specificity for MRA for identification of significant stenosis were 75% and 62%, respectively. CMRA correctly detected 89% of patients with at least one vessel disease, but 6 patients with coronary artery disease would have been missed. CONCLUSIONS: Because of the high data exclusion and false- negative case rate, CMRA with retrospective navigator echo triggering is at present not suitable as a clinical screening method in coronary artery disease.

Motorized head impulse stimulator to determine angular horizontal vestibulo-ocular reflex.

The objective of the current study was to develop a computer-controlled mechanical system for the generation of impulsive head rotations to measure eye movements induced by angular horizontal vestibulo-ocular reflex. This is a clinical eye movement test recently introduced for the usage of otoneurological balance laboratories. We built the system and modified our prior computer software developed for other types of eye movement tests. Motor controlled stimulation has fulfilled the requirement of more uniform and constant acceleration stimulation than obtained with manually administrated impulses. After having executed preliminary experiments at our balance laboratory we found the system to be efficient, reliable and secure.

Superior canal dehiscence: mechanisms of pressure sensitivity in a chinchilla model.

BACKGROUND: Patients with superior canal dehiscence syndrome may experience vertigo and nystagmus when pressure changes occur in the external auditory canal, the middle ear, or the intracranial space. The cause is a defect in the bone of the superior canal. OBJECTIVE: To study the mechanisms of pressure sensitivity of the labyrinth in superior canal dehiscence syndrome and its surgical repair in a chinchilla model. METHODS: We investigated the changes in firing rates of vestibular nerve afferents in the chinchilla in response to changes in external auditory canal pressure before and after fenestration of the superior canal, and after repair of the fenestra. RESULTS: Before superior canal fenestration, external auditory canal pressure changes caused no responses in horizontal canal or otolith afferents, and only 1 of 9 superior canal afferents responded to pressure. After fenestration, all superior canal afferents were excited by positive pressure and inhibited by negative pressure. Half of 18 otolith and most (21 of 33) horizontal canal afferents were unaffected by pressure. The superior canal afferents had higher pressure gain than the horizontal canal afferents (P =.03). Pressure responses could be abolished only by applying a rigid seal to the fenestra. CONCLUSIONS: Fenestration of the superior canal rendered all superior canal afferents sensitive to pressure, whereas less than half of the other afferents became pressure sensitive. The direction of the superior canal afferent responses agreed with the predictions of our model of endolymph flow within the superior canal. A rigid seal applied to the fenestra abolished pressure sensitivity while maintaining physiologic rotational sensitivity.

Premature vertebral endplate ossification and mild disc degeneration in mice after inactivation of one allele belonging to the Col2a1 gene for Type II collagen.

STUDY DESIGN: Skeletal tissues of mice with an inactivated allele of the Col2a1 gene for Type II collagen ("heterozygous knockout") were studied. OBJECTIVE: To determine whether a heterozygous inactivation of the Col2a1 gene has a role in the etiology of spine disorders such as disc degeneration. SUMMARY OF BACKGROUND DATA: Mutations in the COL2A1, COL11A1, COL11A2, and COL9A2 genes have been linked to spine disorders. However, the mechanism by which genetic factors lead to disc degeneration still are largely unknown. METHODS: Spine tissues were studied using radiograph analyses; conventional, quantitative, and polarized light microscopy; immunohistochemistry for the major extracellular components, and in situ hybridization for procollagens alpha1(I) and alpha1(II). Voluntary running activity also was monitored in half of the mice. RESULTS: As the findings showed, 1-month-old heterozygous knockout mice had shorter limb bones, skulls, and spines, as well as thicker and more irregular vertebral endplates, which calcified earlier than in the control mice. They also had a lower concentration of glycosaminoglycans in the anulus fibrosus, in the endplates, and in the vertebral bone than the controls. These features in the heterozygous knockout mice were compensated by the age of 15 months. However, the long bones and skulls of the mature heterozygous mice remained shorter than those of the controls. Gene-deficient mice used the running wheel less. However, physical exercise did not induce any marked structural changes in the skeleton. CONCLUSION: Mice with heterozygous knockout of Col2a1 show subtle early skeletal manifestations that bear some resemblance to those of human spine disorders.

Flavonol and flavone intake and the risk of cancer in male smokers (Finland).

OBJECTIVE: To study the associations between the intake of flavonols and flavones and the risk of cancer. METHODS: The study cohort consisted of 27,110 male smokers, aged 50-69 years, without history of cancer. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire at baseline. Incident cases of cancers were identified through national registers. During an average 6.1-year follow-up, 791 lung cancers, 226 prostate cancers, 156 urothelial cancers, 133 colorectal cancers, 111 stomach cancers, and 92 renal cell cancers were diagnosed. RESULTS: Intake of flavonols and flavones was inversely associated with the risk of lung cancer; multivariate relative risk in the highest vs. the lowest quartile 0.56, 95% confidence interval 0.45-0.69, p for trend 0.0001. The risk was similar in all histological types of lung cancer. No association was found between flavonol and flavone intake and the risk of other cancers. CONCLUSIONS: Intake of flavonols and flavones seemed to be inversely associated with the risk of lung cancer, but not with that of other cancers.