Virus Infections in Early Childhood, Cow���s Milk Formula Exposure and Genetic Predisposition in the Development of Diabetes-Associated Autoimmunity

<B>Varhaislapsuuden virusinfektioiden, lehm��nmaitopohjaisen ��idinmaitovastikeen ja geneettisen alttiuden merkitys diabetekseen liittyv��n autoimmuniteetin kehittymisess�� </b> Tyypin 1 diabetes on autoimmuunisairaus, joka syntyy haiman insuliinia tuottavien beta-solujen tuhouduttua elimist��n oman immuunipuolustusj��rjestelm��n hy��kk��yksen seurauksena. Sek�� perim��n ett�� ymp��rist��tekij��iden arvellaan vaikuttavan tautiprosessiin, mutta taudin tarkkaa syntymekanismia ei tunneta. Tutkimuksen tarkoituksena oli selvitt���� varhaislapsuuden ymp��rist��tekij��iden vaikutusta beta-soluautoimmuniteetin syntyyn, erityispaino tutkimuksessa oli ymp��rist��tekij��iden yhteisvaikutuksessa sek�� geneettisten riskitekij��iden ja ymp��rist��tekij��iden vuorovaikutuksessa. Varhaislapsuudessa sairastettu sytomegalovirus- tai enterovirusinfektio ei lis��nnyt beta-soluautoimmuniteetin riski�� lapsilla, joilla on geneettisesti kohonnut riski sairastua tyypin 1 diabetekseen. Ennen puolen vuoden ik���� sairastettu rotavirusinfektio lis��si hieman tyypin 1 diabetekseen liittyv��n autoimmuniteetin riski��. Tarkemmassa analyysissa varhaislapsuuden enterovirusinfektio osoittautui kuitenkin autovasta-aineiden muodostumisen riskitekij��ksi niiden lasten joukossa, jotka olivat saaneet lehm��nmaitopohjaista ��idinmaidon vastiketta ensimm��isten elinkuukausien aikana. T��m�� l��yd��s viittaa enterovirusinfektion ja lehm��nmaitopohjaisen vastikkeen yhteisvaikutukseen tyypin 1 diabetekseen liittyv��n autoimmuniteetin synnyss��. L��yd��sten mukaan <i>PTPN22</i> geenin C1858T polymorfismi vaikuttaa CD4+ T solujen aktivaatioon ja proliferaatiovasteeseen, 1858T alleeliin liittyy alentunut T-soluresepto-riv��litteinen aktivaatio. 1858T alleelin kantajuuteen liittyy lis��ksi lis����ntynyt autovasta-aineiden ja kliinisen diabeteksen ilmaantuvuus. T��m�� yhteys rajoittui yksil��ihin, jotka olivat altistuneet lehm��nmaitopohjaiselle vastikkeelle ennen kuuden kuukauden ik����. Tulosten mukaan sek�� ymp��rist��tekij��iden v��liset yhteisvaikutukset ett�� perim�� vaikuttavat yksitt��isen ymp��rist��tekij��n merkitykseen tyypin 1 diabetekseen liittyv��n autoimmuniteetin synnyss��. N��m�� yhteisvaikutukset ymp��rist��tekij��iden kesken ja perim��n ja ymp��rist��tekij��iden v��lill�� selitt��v��t aiemmin julkaistujen tulosten ristiriittaisuutta tutkimuksissa, joissa on analysoitu vain yhden ymp��rist��tekij��n vaikutusta diabeteksen ilmaantuvuuteen.

Analytical challenges in breath analysis and its application to exposure monitoring

There is an increasing interest in the use of breath analysis for monitoring human physiology and exposure to toxic substances or environmental pollutants. This review focuses on the current status of the sampling procedures, collection devices and sample-enrichment methodologies used for exhaled breath-vapor analysis. We discuss the different parameters affecting each of the above steps, taking into account the requirements for breath analysis in exposure assessments and the need to analyze target compounds at sub-ppbv levels. Finally, we summarize the practical applications of exposure analysis in the past two decades

Predictors of smoking craving during virtual reality exposure

Cue exposure treatment (CET) consists of controlled and repeated exposure to drugrelated stimuli in order to reduce cue-reactivity. Virtual reality (VR) has proved to be a promising tool for exposition. However, identifying the variables that can modulate the efficacy of this technique is essential for selecting the most appropriate exposure modality. The aim of this study was to determine the relation between several individual variables and self-reported craving in smokers exposed to VR environments. Fortysix smokers were exposed to seven complex virtual environments that reproduce typical situations in which people smoke. Self-reported craving was selected as the criterion variable and three types of variables were selected as the predictor variables: related to nicotine dependence, related to anxiety and impulsivity, and related to the sense of presence in the virtual environments. Sense of presence was the only predictor of self-reported craving in all the experimental virtual environments. Nicotine dependence variables added predictive power to the model only in the virtual breakfast at home. No relation was found between anxiety or impulsivity and self-reported craving. Virtual reality technology can be very helpful for improving CET for substance use disorders. However, the use of virtual environments would make sense only insofar as the sense of presence was high. Otherwise, the effectiveness of exposure might be affected. �� 2012 by the Massachusetts Institute of Technology.

Association between Long-Term Exposure to Traffic-Related Air Pollution and Subclinical Atherosclerosis: The REGICOR Study

Background: Epidemiological evidence of the effects of long-term exposure to air pollu tion on the chronic processes of athero genesis is limited. Objective: We investigated the association of long-term exposure to traffic-related air pollu tion with subclinical atherosclerosis, measured by carotid intima media thickness (IMT) and ankle���brachial index (ABI). Methods: We performed a cross-sectional analysis using data collected during the reexamination (2007���2010) of 2,780 participants in the REGICOR (Registre Giron�� del Cor: the Gerona Heart Register) study, a population-based prospective cohort in Girona, Spain. Long-term exposure across residences was calculated as the last 10 years��� time-weighted average of residential nitrogen dioxide (NO2) estimates (based on a local-scale land-use regression model), traffic intensity in the nearest street, and traffic intensity in a 100 m buffer. Associations with IMT and ABI were estimated using linear regression and multinomial logistic regression, respectively, controlling for sex, age, smoking status, education, marital status, and several other potential confounders or intermediates. Results: Exposure contrasts between the 5th and 95th percentiles for NO2 (25 ��g/m), traffic intensity in the nearest street (15,000 vehicles/day), and traffic load within 100 m (7,200,000 vehicle-m/day) were associated with differences of 0.56% (95% CI: ���1.5, 2.6%), 2.32% (95% CI: 0.48, 4.17%), and 1.91% (95% CI: ���0.24, 4.06) percent difference in IMT, respectively. Exposures were positively associated with an ABI of > 1.3, but not an ABI of < 0.9. Stronger associations were observed among those with a high level of education and in men ��� 60 years of age. Conclusions: Long-term traffic-related exposures were associated with subclinical markers of atherosclerosis. Prospective studies are needed to confirm associations and further examine differences among population subgroups.key words: ankle���brachial index, average daily traffic, cardiovascular disease, exposure assessment, exposure to tailpipe emissions, intima media thickness, land use regression model, Mediterranean diet, nitrogen dioxide

Exposure to Tobacco Smoke and Markers of Subclinical Atherosclerosis in Children and Adolescents. The STRIP Study.

Background: Measurement of serum cotinine, a major metabolite of nicotine, provides a valid marker for quantifying exposure to tobacco smoke. Exposure to tobacco smoke causes vascular damage by multiple mechanisms, and it has been acknowledged as a risk factor for atherosclerosis. Multifactorial atherosclerosis begins in childhood, but the relationship between exposure to tobacco smoke and arterial changes related to early atherosclerosis have not been studied in children. Aims: The aim of the present study was to evaluate exposure to tobacco smoke with a biomarker, serum cotinine concentration, and its associations with markers of subclinical atherosclerosis and lipid profile in school-aged children and adolescents. Subjects and Methods: Serum cotinine concentration was measured using a gas chromatographic method annually between the ages 8 and 13 years in 538-625 children participating since infancy in a randomized, prospective atherosclerosis prevention trial STRIP (Special Turku coronary Risk factor Intervention Project). Conventional atherosclerosis risk factors were measured repeatedly. Vascular ultrasound studies were performed among 402 healthy 11-year-old children and among 494 adolescents aged 13 years. Results: According to serum cotinine measurements, a notable number of the school aged children and adolescents were exposed to tobacco smoke, but the exposure levels were only moderate. Exposure to tobacco smoke was associated with decreased endothelial function as measured with flow-mediated dilation of the brachial artery, decreased elasticity of the aorta, and increased carotid and aortic intima-media thickness. Longitudinal exposure to tobacco smoke was also related with increased apolipoprotein B and triglyceride levels in 13-year-old adolescents, whose body mass index and nutrient intakes did not differ. Conclusions: These findings suggest that exposure to tobacco smoke in childhood may play a significant role in the development of early atherosclerosis. Key Words: arterial elasticity, atherosclerosis, children, cotinine, endothelial function, environmental tobacco smoke, intima-media thickness, risk factors, ultrasound

Percutaneous access versus standard femoral exposure for endovascular abdominal aortic aneurysm repair: a randomized, controlled trial

The treatment of abdominal aortic aneurysm (AAA) has shifted from the exposure of the aorta artery in an open repair technique to a small groin cut in an endovascular repair. Recently, a percutaneous access for endovascular repair has appeared. This new technique aims to minimize the complications of the common femoral artery exposure, the patient discomfort and the length of hospitalizationObjectives: To compare the proportion of discharged patients within the first 48 postoperative hours of two common femoral artery accesses for endovascular repair of AAA: the open exposure technique and the percutaneous technique. Secondary objectives include to evaluate the total procedure time, the femoral access complications, the need for extra analgesia and the patient satisfaction and groin discomfort of the two techniquesDesign: Randomized controlled trial conducted between 2014 and 2017Participants: Patients diagnosed with abdominal aortic aneurysm with elective endovascular repair indication

Nutrimetabolomics fingerprinting to identify biomarkers of bread exposure in a free-living population from the PREDIMED study cohort

Bread is one of the most widely consumed foods. Its impact on human health is currently of special interest for researchers. We aimed to identify biomarkers of bread consumption by applying a nutrimetabolomic approach to a free-living population. An untargeted HPLC q-TOF-MS and multivariate analysis was applied to human urine from 155 subjects stratified by habitual bread consumption in three groups: non-consumers of bread (n = 56), white-bread consumers (n = 48) and whole-grain bread consumers (n = 51). The most differential metabolites (variable importance for projection ���1.5) included compounds originating from cereal plant phytochemicals such as benzoxazinoids and alkylresorcinol metabolites, and compounds produced by gut microbiota (such as enterolactones, hydroxybenzoic and dihydroferulic acid metabolites). Pyrraline, riboflavin, 3-indolecarboxylic acid glucuronide, 2,8-dihydroxyquinoline glucuronide and N-��-acetylcitrulline were also tentatively identified. In order to combine multiple metabolites in a model to predict bread consumption, a stepwise logistic regression analysis was used. Receiver operating curves were constructed to evaluate the global performance of individual metabolites and their combination. The area under the curve values [AUC (95 % CI)] of combined models ranged from 77.8 % (69.1 86.4 %) to 93.7 % (89.4 98.1 %), whereas the AUC for the metabolites included in the models had weak values when they were evaluated individually: from 58.1 % (46.6 69.7 %) to 78.4 % (69.8 87.1 %). Our study showed that a daily bread intake significantly impacted on the urinary metabolome, despite being examined under uncontrolled free-living conditions. We further concluded that a combination of several biomarkers of exposure is better than a single biomarker for the predictive ability of discriminative analysis.

Nutrimetabolomics fingerprinting to identify biomarkers of bread exposure in a free-living population from the PREDIMED study cohort

Bread is one of the most widely consumed foods. Its impact on human health is currently of special interest for researchers. We aimed to identify biomarkers of bread consumption by applying a nutrimetabolomic approach to a free-living population. An untargeted HPLC q-TOF-MS and multivariate analysis was applied to human urine from 155 subjects stratified by habitual bread consumption in three groups: non-consumers of bread (n = 56), white-bread consumers (n = 48) and whole-grain bread consumers (n = 51). The most differential metabolites (variable importance for projection ���1.5) included compounds originating from cereal plant phytochemicals such as benzoxazinoids and alkylresorcinol metabolites, and compounds produced by gut microbiota (such as enterolactones, hydroxybenzoic and dihydroferulic acid metabolites). Pyrraline, riboflavin, 3-indolecarboxylic acid glucuronide, 2,8-dihydroxyquinoline glucuronide and N-��-acetylcitrulline were also tentatively identified. In order to combine multiple metabolites in a model to predict bread consumption, a stepwise logistic regression analysis was used. Receiver operating curves were constructed to evaluate the global performance of individual metabolites and their combination. The area under the curve values [AUC (95 % CI)] of combined models ranged from 77.8 % (69.1 86.4 %) to 93.7 % (89.4 98.1 %), whereas the AUC for the metabolites included in the models had weak values when they were evaluated individually: from 58.1 % (46.6 69.7 %) to 78.4 % (69.8 87.1 %). Our study showed that a daily bread intake significantly impacted on the urinary metabolome, despite being examined under uncontrolled free-living conditions. We further concluded that a combination of several biomarkers of exposure is better than a single biomarker for the predictive ability of discriminative analysis.

Evaluation of roof slope and exposure with different roofing materials in reduced models of animal production facilities in spring and summer

The present study was conducted at the Department of Rural Engineering and the Department of Animal Morphology and Physiology of FCAV/Unesp, Jaboticabal, SP, Brazil. The objective was to verify the influence of roof slope, exposure and roofing material on the internal temperature of reduced models of animal production facilities. For the development of the research, 48 reduced and dissemble models with dimensions 1.00 �� 1.00 �� 0.50 m were used. The roof was shed-type, and the models faced to the North or South directions, with 24 models for each side of exposure. Ceramic, galvanized-steel and fibro tiles were used to build the roofs. Slopes varied between 20, 30, 40 and 50&#37; for the ceramic tile and 10, 30, 40 and 50&#37; for the other two. Inside the models, temperature readings were performed at every hour, for 12 months. The results were evaluated in a general linear model in a nested 3 �� 4 �� 2 factorial arrangement, in which the effects of roofing material and exposure were nested on the factor Slope. Means were compared by the Tukey test at 5&#37; of probability. After analyzing the data, we observed that with the increase in the slope and exposure to the South, there was a drop in the internal temperature within the model at the geographic coordinates of Jaboticabal city (SP/Brazil).

Work-related crisis exposure : psychological trauma and PTSD in news journalists

I avhandlingen unders��ktes hur journalister sj��lva reagerar efter att ha arbetat med en pl��tslig krissituation, samt vilka faktorer som kan bidra till en f��rh��jd risk f��r allvarliga l��ngsiktiga stressymptom. Temat unders��ktes (1) genom att se p�� hur journalisters tidigare erfarenheter av krisuppdrag och traumatiska upplevelser i privatlivet var relaterade till stressymptom (posttraumatiskt stressyndrom, sekund��r traumatisk stress, depression och utmattningssyndrom), och (2) genom att studera riskfaktorer i en identifierad typ av kris, de finl��ndska skolskjutningarna 2007-08. Avhandlingens resultat baserades p�� enk��tsvar fr��n finl��ndska nyhetsjournalister (N = 503) och intervjuer med personer som jobbat p�� plats vid skolskjutningar (N = 28). En klar majoritet av journalisterna hade inte allvarliga l��ngsiktiga stressymptom vid tiden f��r unders��kningen. De som varit p�� ett tidigare krisuppdrag d��r man bevittnat m��nga obehagliga detaljer hade fler allvarliga stressymptom. En annan riskfaktor var att ha ett f��rflutet med fler traumatiska h��ndelser i privatlivet. Bland de som arbetat med skolskjutningar var starka kortsiktiga reaktioner, t.ex. hj��lpl��shet och chock, relativt vanliga. Reaktionerna h��rde ��nd�� oftast till den normala ��terh��mtningsprocessen, och ledde inte till en l��ngsiktig f��rs��mring av m��endet. Journalister som i h��g grad identifierade sig med krisen, t.ex. personer med egna barn, hade st��rre risk f��r att drabbas av allvarliga symptom p�� l��ng sikt. Detsamma g��llde de som p�� plats upplevt journalistiska etiska dilemman, t.ex. att beordras av ��verordnade till uppdrag som gick emot egna principer. F��r att f��rebygga psykisk stress bland journalister ��r det viktigt att inom branschen sprida kunskap om stressreaktioner och utveckla rekommendationer f��r etisk krisjournalistik. D��rmed kan journalister f�� b��ttre verktyg f��r att minimera risken att via sitt yrkesut��vande orsaka ytterligare skada ��t krisdrabbade.

Identification and application of bile metabolites to assess the exposure of fish to pharmaceuticals in the environment

Thousands of tons of pharmaceuticals are consumed yearly worldwide. Due to the continuous and increasing consumption and their incomplete elimination in wastewater treatment plants (WWTP), pharmaceuticals and their metabolites can be detected in receiving waters, although at low concentrations (ng to low ��g/L). As bioactive molecules the presence of pharmaceuticals in the aquatic environment must be considered potentially hazardous for the aquatic organisms. In this thesis, the biotransformation and excretion of pharmaceuticals in fish was studied. The main biotransformation pathways of three anti���inflammatory drugs, diclofenac, naproxen and ibuprofen, in rainbow trout were glucuronidation and taurine conjugation of the parent compounds and their phase I metabolites. The same metabolites were present in fish bile in aquatic exposures as in fish dosed with intraperitoneal injection. Higher bioconcentration factor in bile (BCFbile) was found for ibuprofen when compared to diclofenac and naproxen. Laboratory exposure studies were followed by a study of uptake of pharmaceuticals in a wild fish population living in lake contaminated with WWTP effluents. Of the analyzed 17 pharmaceuticals and six phase I metabolites, only diclofenac, naproxen and ibuprofen was present in bream and roach bile. It was shown, that diclofenac, naproxen and ibuprofen excreted by the liver can be found in rainbow trout and in two native fish species living in the receiving waters. In the bream and roach bile, the concentrations of diclofenac, naproxen and ibuprofen were roughly 1000 times higher than those found in the lake water, while in the laboratory exposures, the bioconcentration of the compounds and their metabolites in rainbow trout bile were at the same level as in wild fish or an order of magnitude higher. Thus, the parent compounds and their metabolites in fish bile can be used as a reliable biomarker to monitor the exposure of fish to environmental pharmaceuticals present in water receiving discharges from WWTPs.

Effect of exposure to sublethal concentrations of sodium cyanide on the carbohydrate metabolism of the Indian Major Carp Labeo rohita (Hamilton, 1822)

Experiments were designed to study in-vivo effects of sodium cyanide on biochemical endpoints in the freshwater fish Labeo rohita. Fish were exposed to two sublethal concentrations (0.106 and 0.064mg/L) for a period of 15 days. Levels of glycogen, pyruvate, lactate and the enzymatic activities of lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), glucose-6-phosphate dehydrogenase (G6PDH), phosphorylase, alkaline phosphatase (ALP), acid phosphatase (AcP) were assessed in different tissues (liver, muscle and gills). Result indicated a steady decrease in glycogen, pyruvate, SDH, ALP and AcP activity with a concomitant increase in the lactate, phosphorylase, LDH and G6PD activity in all selected tissues. The alterations in all the above biochemical parameters were significantly (p<0.05) time and dose dependent. In all the above parameters, liver pointing out the intensity of cyanide intoxication compare to muscle and gills. Study revealed change in the metabolic energy by means of altered metabolic profile of the fish. Further, these observations indicated that even sublethal concentrations of sodium cyanide might not be fully devoid of deleterious influence on metabolism in L. rohita.

Developmental and behavioral effects of postnatal amitraz exposure in rats

The effects of postnatal amitraz exposure on physical and behavioral parameters were studied in Wistar rats, whose lactating dams received the pesticide (10 mg/kg) orally on days 1, 4, 7, 10, 13, 16 and 19 of lactation; control dams received distilled water (1 ml/kg) on the same days. A total of 18 different litters (9 of them control and 9 experimental) born after a 21-day gestation were used. The results showed that the median effective time (ET50) for fur development, eye opening, testis descent and onset of the startle response were increased in rats postnatally exposed to amitraz (2.7, 15.1, 21.6 and 15.3 days, respectively) compared to those of the control pups (1.8, 14.0, 19.9 and 12.9 days, respectively). The ages of incisor eruption, total unfolding of the external ears, vaginal and ear opening and the time taken to perform the grasping hindlimb reflex were not affected by amitraz exposure. Pups from dams treated with amitraz during lactation took more time (in seconds) to perform the surface righting reflex on postnatal days (PND) 3 (25.0 �� 2.0), 4 (12.3 �� 1.2) and 5 (8.7 �� 0.9) in relation to controls (10.6 �� 1.2; 4.5 �� 0.6 and 3.4 �� 0.4, respectively); the climbing response was not changed by amitraz. Postnatal amitraz exposure increased spontaneous motor activity of male and female pups in the open-field on PND 16 (140 �� 11) and 17 (124 �� 12), and 16 (104 �� 9), 17 (137 �� 9) and 18 (106 �� 8), respectively. Data on spontaneous motor activity of the control male and female pups were 59 �� 11 and 69 �� 10 for days 16 and 17 and 49 �� 9, 48 �� 7 and 56 �� 7 for days 16, 17 and 18, respectively. Some qualitative differences were also observed in spontaneous motor behavior; thus, raising the head, shoulder and pelvis matured one or two days later in the amitraz-treated offspring. Postnatal amitraz exposure did not change locomotion and rearing frequencies or immobility time in the open-field on PND 30, 60 and 90. The present findings indicate that postnatal exposure to amitraz caused transient developmental and behavioral changes in the exposed offspring and suggest that further investigation of the potential health risk of amitraz exposure to developing human and animal offsprings may be warranted.

Short duration of neutralizing antibody titers after pre-exposure rabies vaccination with suckling mouse brain vaccine

The human anti-rabies pre-exposure treatment currently used in Brazil, employing a 1-ml dose of suckling mouse brain vaccine (SMBV) administered on days 0, 2, 4 and 28, was compared to an alternative treatment with two 1 ml-doses on day 0, and one 1 ml-dose injected on days 7 and 21. The latter induced higher virus-neutralizing antibody (VNA) titers on day 21. Both Brazilian rabies vaccines produced with PV or CVS rabies virus strains were tested. Two additional volunteer vaccinee groups, receiving the pre-exposure and the abbreviated post-exposure schedules recommended by the WHO using cell-culture vaccine (CCV) produced with PM rabies virus strain, were included as reference. The VNA were measured against both PV and CVS strains on days 21, 42 and 180 by the cell-culture neutralization microtest. The PV-SMBV elicited higher seroconversion rates and VNA by day 21 than the CVS-SMBV. Both, however, failed to induce a long-term immunity, since VNA titers were &lt;0.5 IU/ml on day 180, regardless of the schedule used. Cell-culture vaccine always elicited very high VNA on all days of collection. When serum samples from people receiving mouse brain tissue were titrated against the PV and CVS strains, the VNA obtained were similar, regardless of the vaccinal strain and the virus used in the neutralization test. These results contrast with those obtained with sera from people receiving PM-CCV, whose VNA were significantly higher when tested against the CVS strain.