Hypothalamic γ-melanocyte stimulating hormone gene delivery reduces fat mass in male mice

γ-Melanocyte stimulating hormone (γ-MSH) is an endogenous agonist of the melanocortin 3-receptor (MC3R). Genetic disruption of MC3Rs increases adiposity and blunts responses to fasting, suggesting that increased MC3R signaling could be physiologically beneficial in the long term. Interestingly, several studies have concluded that activation of MC3Rs is orexigenic in the short term. Therefore, we aimed to examine the short- and long-term effects of γ-MSH in the hypothalamic arcuate nucleus (ARC) on energy homeostasis and hypothesized that the effect of MC3R agonism is dependent on the state of energy balance and nutrition. Lentiviral gene delivery was used to induce a continuous expression of γ-Msh only in the ARC of male C57Bl/6N mice. Parameters of body energy homeostasis were monitored as food was changed from chow (6 weeks) to Western diet (13 weeks) and back to chow (7 weeks). The γ-MSH treatment decreased the fat mass to lean mass ratio on chow, but the effect was attenuated on Western diet. After the switch back to chow, an enhanced loss in weight (−15% vs −6%) and fat mass (−37% vs −12%) and reduced cumulative food intake were observed in γ-MSH-treated animals. Fasting-induced feeding was increased on chow diet only; however, voluntary running wheel activity on Western diet was increased. The γ-MSH treatment also modulated the expression of key neuropeptides in the ARC favoring weight loss. We have shown that a chronic treatment intended to target ARC MC3Rs modulates energy balance in nutritional state-dependent manner. Enhancement of diet-induced weight loss could be beneficial in treatment of obesity.

Vitamin D and probiotics supplement use in young children with genetic risk for type 1 diabetes.

BACKGROUND/OBJECTIVES: Vitamin D and probiotics are nutrients of interest in the context of type 1 diabetes (T1D). We assessed the prevalence of and factors associated with vitamin D and probiotic supplementations among young children with genetic risk of T1D. SUBJECTS/METHODS: Use of supplements during the first 2 years of life was collected prospectively from 8674 children in The Environmental Determinants of Diabetes in the Young (TEDDY) study. RESULTS: Single and/or multivitamin/mineral (MVM) supplements were reported by 81% of the children. The majority of participants in Finland, Germany and Sweden (97-99%) and 50% in the United States received vitamin D supplements that were mostly MVMs. Probiotics use varied from 6% in the United States to 60% in Finland and was primarily from probiotics-only preparations. More than 80% of the vitamin D and probiotics supplementation was initiated during infancy, and more than half of the uses lasted longer than a year. Being the first child, longer duration of breastfeeding, born in a later year, older maternal age and higher maternal education level were associated with both vitamin D and probiotics use. Shorter gestational age and mother not smoking during pregnancy were associated with a higher likelihood of probiotics supplementation only. CONCLUSIONS: Vitamin D and probiotics supplementations are popular in children 0-2 years old and are associated with common factors. Data documented here will allow evaluation of the relationship between early childhood dietary intake and the development of islet autoimmunity and progression to T1D.

Risks of Adverse Perinatal Outcomes after Repeat Terminations of Pregnancy by their Methods: a Nationwide Register-based Cohort Study in Finland 1996-2013.

BACKGROUND: Repeat terminations of pregnancy (TOPs) are associated with an increased risk of adverse outcomes in the subsequent birth. The perinatal outcomes after repeat TOPs by their methods have not yet been properly studied. This study aimed to examine perinatal outcomes in subsequent pregnancy among the women with a singleton birth and a history of TOPs. METHODS: All the first-time mothers (n = 419 879) with a singleton birth during 1996-2013 in Finland were identified from the Medical Birth Register and linked to the Abortion Register. Adjusted multivariable logistic regression analysis was used to estimate risks of adverse perinatal outcomes. RESULTS: The increased incidence of adverse perinatal outcomes was found with increasing number of surgical TOPs. After adjusting for confounders, the women with one surgical TOP had slightly increased but significant odds of 1.07 (95% CI 1.02, 1.13) for being small for gestational age compared with the women having no TOP. A significantly high risk for extremely preterm birth (OR 1.51, 95% CI 1.03, 2.23) was found among the women having had repeat surgical TOPs when compared to the women with no TOP. Non-significant risks were found for adverse perinatal outcomes after women's repeat surgical TOPs than repeat medical TOPs. CONCLUSION: Information regarding the consequences of repeat induced TOPs will be significant in sexual health education as well as counselling women after first termination.

Serum carotenoid and tocopherol concentrations and risk of asthma in childhood: a nested case-control study.

BACKGROUND: The antioxidant hypothesis regarding the risk of asthma in childhood has resulted in inconsistent findings. Some data indicate that the role of antioxidants in childhood asthma risk may have a critical time window of effect, but only a well-designed longitudinal cohort study can clarify this hypothesis. OBJECTIVE: To study the longitudinal associations between serum carotenoid and tocopherol concentrations during the first 4 years of life and asthma risk by the age of 5 years. METHODS: Based on a case-control design nested within a Finnish birth cohort, 146 asthma cases were matched to 270 controls on birth time, sex, genetic risk, and birth place. Non-fasting blood samples were collected at the ages of 1, 1.5, 2, 3, and 4 years and serum carotenoids and tocopherols were analysed. Parents reported the presence and age at start of persistent doctor-diagnosed asthma in the child at the age of 5 years. Data analyses were conducted using generalized estimating equations. RESULTS: We did not find strong associations between serum carotenoids and tocopherols and the risk of asthma based on age-specific and longitudinal analyses. Both lower and higher quarters of α-carotene and γ-tocopherol increased the risk of asthma. CONCLUSIONS: The current findings do not support the suggestion that the increased prevalence of asthma may be a consequence of decreased intake of antioxidant nutrients. Moreover, we did not confirm any critical time window of impact of antioxidants on asthma risk. Replication of these findings in similar longitudinal settings will strengthen this evidence base.

Maternal fatty acid intake during pregnancy and the development of childhood overweight: a birth cohort study.

BACKGROUND: Maternal diet during pregnancy may contribute to the risk of offspring adiposity. OBJECTIVES: The objective of the study is to explore the associations between maternal antenatal dietary fatty acid intake and the risk of offspring overweight and obesity at the ages of 2 to 7 years. METHODS: In a prospective Finnish birth cohort with 3807 mother-child pairs, maternal diet in late pregnancy was assessed with a food frequency questionnaire. Intakes of total fatty acids and individual saturated, monounsaturated and polyunsaturated fatty acids (PUFAs) were calculated. Generalized estimating equation models were used to study the associations of maternal dietary variables with repeatedly measured offspring overweight and obesity. RESULTS: In girls, maternal intake ratio of n-6:n-3 PUFAs had a U-shaped association with obesity (adjusted OR for the lowest 2.0 [95% CI 1.27-3.20] and the highest 1.7 [1.03-2.73] vs. the two middle quartiles of n-6:n-3 PUFAs, p = 0.01). In boys, arachidonic acid (20:4n-6): docosahexaenoic acid + eicosapentaenoic acid ratio was associated with obesity (adjusted OR for the lowest 1.0 [0.60-1.57] and the highest 0.5 [0.26-0.88] vs. the two middle quartiles, p = 0.02). Saturated fatty acids and monounsaturated fatty acids were not associated with overweight or obesity in either sex. CONCLUSIONS: Maternal intakes of PUFAs in late pregnancy were associated with risk of later obesity differently in girls and boys.

The specific sorption of Np(V) on the corundum (α-Al2O3) surface in the presence of trivalent lanthanides Eu(III) and Gd(III): A batch sorption and XAS study.

The sorption of pentavalent neptunium, Np(V), on corundum (α-Al2O3) was investigated in the absence and presence of trivalent europium or gadolinium as a competing element under CO2-free conditions. The objective of this study was to investigate how a trivalent metal ion with a higher charge than that of the neptunyl(V) ion would affect the sorption of Np(V) when allowed to adsorb on the mineral surface before the addition of Np(V). Batch sorption experiments conducted as a function of pH (pH-edges) and as a function of Np(V) concentration (isotherms) in the absence and presence of 1×10(-5)M Eu(III) showed no sign of Eu being able to block Np sorption sites. Surface complexation modelling using the diffuse double layer model was applied to the batch data to obtain surface complexation constants for the formed Np(V) complexes on corundum. To account for potential changes occurring in the coordination environment of the neptunium ion in the presence of a trivalent lanthanide, X-ray absorption spectroscopy (XAS) measurements were carried out on the samples containing only Np(V) and Np(V)+Gd(III). The results reveal the presence of a bidentate Np(V) edge-sharing complex on the corundum surface in the absence of Gd(III), while the coordination environment of Np(V) on the corundum surface could be changed when Gd(III) is added to the sample before the sorption of Np(V).

Protective layer formation on magnesium in cell culture medium.

In the past, different studies showed that hydroxyapatite (HA) or similar calcium phosphates can be precipitated on Mg during immersion in simulated body fluids. However, at the same time, in most cases a dark grey or black layer is built under the white HA crystals. This layer seems to consist as well of calcium phosphates. Until now, neither the morphology nor its influence on Mg corrosion have been investigated in detail. In this work commercially pure magnesium (cp) was immersed in cell culture medium for one, three and five days at room temperature and in the incubator (37 °C, 5% CO2). In addition, the influence of proteins on the formation of a corrosion layer was investigated by adding 20% of fetal calf serum (FCS) to the cell culture medium in the incubator. In order to analyze the formed layers, SEM images of cross sections, X-ray Photoelectron Spectroscopy (XPS), X-ray diffraction (XRD), Energy Dispersive X-ray Spectroscopy (EDX) and Fourier Transformed Infrared Spectroscopy (FTIR) measurements were carried out. Characterization of the corrosion behavior was achieved by electrochemical impedance spectroscopy (EIS) and by potentio-dynamic polarization in Dulbecco's Modified Eagle's Medium (DMEM) at 37°C. Surface analysis showed that all formed layers consist mainly of amorphous calcium phosphate compounds. For the immersion at room temperature the Ca/P ratio indicates the formation of HA, while in the incubator probably pre-stages to HA are formed. The different immersion conditions lead to a variation in layer thicknesses. However, electrochemical characterization shows that the layer thickness does not influence the corrosion resistance of magnesium. The main influencing factor for the corrosion behavior is the layer morphology. Thus, immersion at room temperature leads to the highest corrosion protection due to the formation of a compact outer layer. Layers formed in the incubator show much worse performances due to completely porous structures. The existence of proteins in DMEM seems to hinder the formation of a corrosion layer. However, protein adsorption leads to similar results as concerns corrosion protection as the formed calcium phosphate layer.

Maternal diet during pregnancy and lactation and cow's milk allergy in offspring.

BACKGROUND/OBJECTIVES: Diet during pregnancy and lactation may have a role in the development of allergic diseases. There are few human studies on the topic, especially focusing on food allergies. We sought to study the associations between maternal diet during pregnancy and lactation and cow's milk allergy (CMA) in offspring. SUBJECTS/METHODS: A population-based birth cohort with human leukocyte antigen-conferred susceptibility to type 1 diabetes was recruited in Finland between 1997 and 2004 (n=6288). Maternal diet during pregnancy and lactation was assessed by a validated, 181-item semi-quantitative food frequency questionnaire. Register-based information on diagnosed CMA was obtained from the Social Insurance Institution and completed with parental reports. The associations between maternal food consumption and CMA were assessed using logistic regression, comparing the highest and the lowest quarters to the middle half of consumption. RESULTS: Consumption of milk products in the highest quarter during pregnancy was associated with a lower risk of CMA in offspring (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.37-0.86; P<0.01). When stratified by maternal allergic rhinitis and asthma, there was evidence of an inverse association between high use of milk products and CMA in offspring of non-allergic mothers (OR 0.30, 95% CI 0.13-0.69, P<0.001). Cord blood IgA correlated positively with the consumption of milk products during pregnancy, indicating exposure to CMA and activation of antigen-specific immunity in the infant during pregnancy. CONCLUSIONS: High maternal consumption of milk products during pregnancy may protect children from developing CMA, especially in offspring of non-allergic mothers.

Bayesian Estimation of the True Prevalence and of the Diagnostic Test Sensitivity and Specificity of Enteropathogenic Yersinia in Finnish Pig Serum Samples.

Bayesian analysis was used to estimate the pig's and herd's true prevalence of enteropathogenic Yersinia in serum samples collected from Finnish pig farms. The sensitivity and specificity of the diagnostic test were also estimated for the commercially available ELISA which is used for antibody detection against enteropathogenic Yersinia. The Bayesian analysis was performed in two steps; the first step estimated the prior true prevalence of enteropathogenic Yersinia with data obtained from a systematic review of the literature. In the second step, data of the apparent prevalence (cross-sectional study data), prior true prevalence (first step), and estimated sensitivity and specificity of the diagnostic methods were used for building the Bayesian model. The true prevalence of Yersinia in slaughter-age pigs was 67.5% (95% PI 63.2-70.9). The true prevalence of Yersinia in sows was 74.0% (95% PI 57.3-82.4). The estimates of sensitivity and specificity values of the ELISA were 79.5% and 96.9%.

Electrophoretic deposition of ZnO/alginate and ZnO-bioactive glass/alginate composite coatings for antimicrobial applications.

Two organic/inorganic composite coatings based on alginate, as organic matrix, and zinc oxide nanoparticles (n-ZnO) with and without bioactive glass (BG), as inorganic components, intended for biomedical applications, were developed by electrophoretic deposition (EPD). Different n-ZnO (1-10 g/L) and BG (1-1.5 g/L) contents were studied for a fixed alginate concentration (2 g/L). The presence of n-ZnO was confirmed to impart antibacterial properties to the coatings against gram-negative bacteria Escherichia coli, while the BG induced the formation of hydroxyapatite on coating surfaces thereby imparting bioactivity, making the coating suitable for bone replacement applications. Coating composition was analyzed by thermogravimetric analysis (TG), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDS) analyses. Scanning electron microscopy (SEM) was employed to study both the surface and the cross section morphology of the coatings. Polarization curves of the coated substrates made in cell culture media at 37 °C confirmed the corrosion protection function of the novel organic/inorganic composite coatings.

Factors affecting the sorption of cesium in a nutrient-poor boreal bog.

(135)Cs is among the most important radionuclides in the long-term safety assessments of spent nuclear fuel, due to its long half-life of 2.3 My and large inventory in spent nuclear fuel. Batch sorption experiments were conducted to evaluate the sorption behavior of radiocesium ((134)Cs) in the surface moss, peat, gyttja, and clay layers of 7-m-deep profiles taken from a nutrient-poor boreal bog. The batch distribution coefficient (Kd) values of radiocesium increased as a function of sampling depth. The highest Kd values, with a geometric mean of 3200 L/kg dry weight (DW), were observed in the bottom clay layer and the lowest in the 0.5-1.0 m peat layer (50 L/kg DW). The maximum sorption in all studied layers was observed at a pH between 7 and 9.5. The in situ Kd values of (133)Cs in surface Sphagnum moss, peat and gyttja samples were one order of magnitude higher than the Kd values obtained using the batch method. The highest in situ Kd values (9040 L/kg DW) were recorded for the surface moss layer. The sterilization of fresh surface moss, peat, gyttja and clay samples decreased the sorption of radiocesium by 38%, although the difference was not statistically significant. However, bacteria belonging to the genera Pseudomonas, Paenibacillus, Rhodococcus and Burkholderia isolated from the bog were found to remove radiocesium from the solution under laboratory conditions. The highest biosorption was observed for Paenibacillus sp. V0-1-LW and Pseudomonas sp. PS-0-L isolates. When isolated bacteria were added to sterilized bog samples, the removal of radiocesium from the solution increased by an average of 50% compared to the removal recorded for pure sterilized peat. Our results demonstrate that the sorption of radiocesium in the bog environment is dependent on pH and the type of the bog layer and that common environmental bacteria prevailing in the bog can remove cesium from the solution phase.

Iron and iron-based alloys for temporary cardiovascular applications.

In the last decade, biodegradable metals have emerged as a topic of interest for particular biomedical applications which require high strength to bulk ratio, including for cardiovascular stents. The advantages of biodegradable materials are related to the reduction of long term risks associated with the presence of permanent metal implants, e.g. chronic inflammation and in-stent restenosis. From a structural point of view, the analysis of the literature reveals that iron-based alloys used as temporary biodegradable stents have several advantages over Mg-based alloys in terms of ductility and strength. Efforts on the modification and tunability of iron-based alloys design and compositions have been mainly focused on controlling the degradation rate while retaining the mechanical integrity within a reasonable period. The early pre-clinical results of many iron-based alloys seem promising for future implants developments. This review discusses the available literature focusing mainly on: (i) Fe and Fe-based alloys design and fabrication techniques; (ii) in vitro and in vivo performance; (iii) cytotoxicity and cell viability tests.

Maternal intake of fatty acids and their food sources during lactation and the risk of preclinical and clinical type 1 diabetes in the offspring.

AIMS: We examined maternal dietary intake of fatty acids and foods which are sources of fatty acids during lactation and whether they are associated with the risk of preclinical and clinical type 1 diabetes in the offspring. METHODS: The subjects comprised a cohort of 2,939 mother-child pairs from the prospective Type 1 Diabetes Prediction and Prevention Study. Composition of maternal diet during the third month of lactation was assessed by a validated food frequency questionnaire. Among the children with HLA-conferred susceptibility to type 1 diabetes, 172 developed preclinical and 81 clinical diabetes. Average follow-up for preclinical type 1 diabetes was 7.5 years (range 0.2-14.0 years) and for clinical type 1 diabetes 7.7 years (0.2-14.0 years). RESULTS: Maternal intake of fatty acids during lactation was not associated with the risk of type 1 diabetes in the offspring. After adjusting for putative confounders, maternal total consumption of red meat and meat products during lactation was associated both with increased risk for preclinical [hazard ratio (HR) 1.19, 95 % CI 1.02-1.40, p = 0.038] and clinical type 1 diabetes (HR 1.27, 95 % CI 1.06-1.52, p = 0.025). In particular, consumption of processed meat products showed an association with increased risk for type 1 diabetes (HR 1.23, 95 % CI 1.02-1.48, p = 0.045). Maternal use of vegetable oils was associated with increased risk for preclinical type 1 diabetes (HR 1.21, 95 % CI 1.03-1.41, p = 0.023). CONCLUSIONS: Maternal consumption of red meat, especially processed meat, during lactation may increase the risk of type 1 diabetes.

Bayesian modelling to identify the risk factors for Yersinia enterocolitica contamination of pork carcasses and pluck sets in slaughterhouses.

The probability of contamination by pathogenic Yersinia enterocolitica of carcasses and pluck sets at slaughterhouse was determined by means of a Bayesian analysis. Prior information of the prevalence of Y. enterocolitica in faeces and the seroprevalence of Yersinia in serum of pigs collected at farms were obtained from previous studies and introduced in the models as beta prior informative distributions. Samples of intestinal content, tonsils, and swabs of carcasses and pluck set surfaces were collected at slaughterhouses. The posterior probabilities, odds ratio (OR) and their probability interval (PI) were calculated by means of a generalized linear model constructed in WinBugs. Occurrence of Y. enterocolitica in intestinal content (OR: 35.6, 95%PI 2.8-8285), tonsils (OR: 38.4, 95%PI 5.0-854), and pluck set (OR: 16.6, 95%PI 1.9-1111) was a risk for the contamination of pork carcasses, and an increased risk of contaminated pluck set was observed when Y. enterocolitica was isolated in intestinal content (OR: 40.6, 95%PI 2.1-10510) and tonsils (OR: 17.6, 95%PI 3.4-230.6). This increased risk indicated a potential cross-contamination at the slaughterhouse.

Prenatal and post-natal exposure to antibiotics and risk of asthma in childhood.

BACKGROUND: Evidence on the association between post-natal exposure to antibiotics and the development of asthma is extensive, but inconsistent and even less is known about prenatal exposure. OBJECTIVE: The aim of this study was to examine the associations between prenatal and post-natal exposure to different antibiotics and the risk of childhood asthma in a population- and register-based nested case-control study. METHODS: All children who were born in 1996-2004 in Finland and diagnosed with asthma by 2006 were identified from a national health register. For each case, one matched control was selected. Information on asthma diagnoses, purchased anti-asthmatic drugs and antibiotics as well as putative confounders was obtained from national health registries. The associations were analysed using conditional logistic regression for children diagnosed at the age of 3 years or later (n = 6 690 case-control pairs). RESULTS: Maternal use of any antibiotics during pregnancy was associated with an increased risk of asthma in the offspring [adjusted odds ratio (OR) = 1.31 (95% confidence interval (CI): 1.21-1.42)]. Several maternal specific antibiotics were associated with the risk of asthma, and the strongest association was observed for cephalosporins [OR = 1.46 (95% CI 1.30-1.64)]. Child's use of antibiotics during the first year of life was associated with an increased risk of asthma [OR = 1.60 (95% CI 1.48-1.73)]. Child's use of cephalosporins [OR = 1.79 (95% CI 1.59-2.01)], sulphonamides and trimethoprim [OR = 1.65 (95% CI 1.34-2.02)], macrolides [OR = 1.61 (95% CI 1.46-1.78)] and amoxicillin [OR = 1.46 (95% CI 1.35-1.58)] was associated with an increased risk of asthma. CONCLUSIONS AND CLINICAL RELEVANCE: Both prenatal and post-natal exposure to antibiotics was associated with an increased risk of asthma. The potential role of adverse effects of antibiotics on the gut microbiota and the development of asthma should be further explored.

Isolation and characterization of Yersinia-specific bacteriophages from pig stools in Finland.

AIMS: Bacteriophages infect bacteria, and they are present everywhere in the world including the intestinal tracts of animals. Yersiniosis is a common foodborne infection caused by Yersinia enterocolitica and Yersinia pseudotuberculosis. As these bacteria are frequently isolated from pigs, we wanted to know whether Yersinia-specific bacteriophages are also present in the pig stools and, if so, whether there is a positive or negative association between the prevalence of the Yersinia phages and the pathogenic Yersinia in the stool samples. METHODS AND RESULTS: Altogether 793 pig stool samples collected between November 2010 and March 2012 from 14 Finnish pig farms were screened for the presence of bacteriophages able to infect Y. enterocolitica serotype O:3, O:5,27 or O:9 strains, or Y. pseudotuberculosis serotype O:1a, O:1b or O:3 strains. Yersinia phages were isolated from 90 samples from eight farms. Yersinia enterocolitica O:3 was infected by 59 phages, 28 phages infected serotypes O:3 and O:5,27, and eight phages infected serotypes O:3, O:5,27 and O:9, and Y. pseudotuberculosis O:1a by eight phages. Many phages originating from pigs in the same farm were identical based on their restriction enzyme digestion patterns; 20 clearly different phages were selected for further characterization. Host ranges of these phages were tested with 94 Yersinia strains. Six of the phages infected eight strains, 13 phages infected three strains, and one phage infected only one strain, indicating that the phages had a relatively narrow host range. CONCLUSIONS: There was a clear association between the presence of the host bacteria and specific phages in the stools. SIGNIFICANCE AND IMPACT OF THE STUDY: The isolated bacteriophages may have potential as biocontrol agents for yersiniosis in both humans and pigs in future, and as alternatives or in addition to antibiotics. To our knowledge, this is the first reported isolation of Yersinia-specific phages from pig stool samples.

White matter damage of the brain is associated with poor outcome in vascular surgery patients with claudication: a pilot study.

OBJECTIVE: Peripheral arterial disease (PAD) is a systemic atherosclerotic syndrome with high post-operative morbidity and mortality. Fractional anisotropy (FA), an index measured by magnetic resonance diffusion tensor imaging (DTI), has been shown to be exceedingly sensitive to microstructural damage in brain white matter tracts. It is hypothesized that pre-operative white matter damage is more extensive in PAD patients scheduled for vascular surgery who experience an adverse long-term outcome. METHODS: Preoperative FA values were obtained in 24 consecutive PAD patients (age >40 years) scheduled for elective infrainguinal revascularization surgery and in 15 healthy age matched participants. All patients had their clinical history taken and underwent physical examination and laboratory tests. After surgery, patients were followed for a median of 52 months (range 40-63) and major adverse cardiovascular and cerebrovascular events (MACCE) were recorded. RESULTS: There were no statistically significant differences in baseline demographic or clinical variables between the MACCE group and the non-MACCE group. During follow up, eight PAD patients suffered a MACCE and they had lower FA values than patients without MACCE or healthy controls (mean ± SD 0.370 ± 0.017 vs. 0.392 ± 0.023 vs. 0.412 ± 0.018, p = .036 and p = .00007, respectively). Voxelwise analysis of the FA data revealed diffuse spatial distribution of white matter damage in PAD patients. There was no statistically significant association between the FA values and other clinical variables. CONCLUSION: Microstructural white matter damage was associated with poor outcome in PAD patients with claudication requiring surgical revascularization, and its extent may have clinical value in risk stratification.

No association between vitamin D and ß-cell autoimmunity in Finnish and Estonian children.

BACKGROUND: Vitamin D has immunomodulatory properties, such as regulation of FOXP3 expression and regulatory T-cell activity. Our aim was to investigate whether plasma 25-hydroxyvitamin D [25(OH)D] concentrations associate with the development of ß-cell autoimmunity and the transcriptional activity of FOXP3 or vitamin D3 convertase gene (CYP27B1) in CD4+ memory T cells. METHODS: We studied 83 Finnish and 32 Estonian children participating in the DIABIMMUNE and DIPP studies. Twenty-nine Finnish and six Estonian children tested positive for at least one diabetes-associated autoantibody. The plasma concentrations of 25(OH)D and 1,25(OH)2D were analysed with an enzyme immunoassay. Gene expression of FOXP3 and CYP27B1 in the isolated CD4+ memory T cells was studied with reverse transcription quantitative polymerase chain reaction. RESULTS: Vitamin D status did not differ between subjects positive and negative for ß-cell autoantibodies. Finnish children had higher vitamin D status than Estonian children (p < 0.001). FOXP3 expression was higher in Estonian CD4+ memory T-cell samples than in Finnish samples (p < 0.01) even when including in both groups only children with serum 25(OH)D concentrations in the range of 50-80 nmol/L (p < 0.001). CONCLUSIONS: These findings do not support a crucial role of circulating 25(OH)D as a regulator of ß-cell autoimmunity or FOXP3 expression.

Introduction of infected animals to herds is an important route for the spread of Yersinia enterocolitica infection between pig farms.

Altogether, 369 pathogenic Yersinia enterocolitica isolates from 1,118 fecal samples collected from 22 pig farms of different production types were characterized by biotyping, serotyping, and genotyping using multiple-locus variable-number tandem repeats analysis. We investigated the distribution of the different genotypes at the farm level and their association with different farm conditions. Pigs were found to carry and transmit Y. enterocolitica between farms, because the same genotypes were found on farms that had previously transported the pigs between them. The purchase of new animals for the farms associated significantly with the number of different multiple-locus variable-number tandem repeats analysis types of Y. enterocolitica found within a farm. Some genotypes seemed to persist on farms for years. The results of this study show that pigs purchased from infected herds transmit Y. enterocolitica infection between farms. Certain pig farms may act as long-term sources of infection.

Serum vitamin E concentrations at 1 year and risk of atopy, atopic dermatitis, wheezing, and asthma in childhood: the PASTURE study.

BACKGROUND: Prospective studies investigating the role of serum vitamin E concentrations during early life in the development of childhood allergies and asthma are limited. OBJECTIVE: To study the associations between serum vitamin E concentrations at first year of life and longitudinal development of atopy, atopic dermatitis, wheeze, and asthma up to 6 years of age. METHODS: The setting was the PASTURE study, a multicenter prospective birth cohort study in five European rural settings. Children of 1133 mothers recruited during pregnancy were followed from birth with measurement of serum vitamin E levels at year 1 and repeated assessments of serum immunoglobulin E antibodies (year 1, 4.5, 6), atopic dermatitis, wheezing symptoms, and asthma (year 1, 1.5, 2, 3, 4, 5, 6). RESULTS: At 6 years of age, 66% and 82% of the original 1133 subjects underwent blood test for IgE and answered the questionnaire, respectively. We did not observe any statistically significant associations between serum vitamin E concentrations at year 1 and the endpoints, but borderline inverse associations between alpha tocopherol and wheezing without cold (OR 0.45, 95% CI 0.19-1.09) and any wheezing symptom (OR 0.52, 95% CI 0.27-1.02). CONCLUSIONS: Serum vitamin E concentrations at year 1 were not associated with allergies or asthma by 6 years of age. While further prospective studies with repeated assessments of vitamin E during early life may clarify its putative role in the development of the diseases, it is also possible that the antioxidant hypothesis in the development of allergies and asthma does not hold.