Quantitative risk assessment on dietary exposure of children and

Nitraattia esiintyy luonnostaan monissa kasviksissa ja talousvedessä. Osa syödystä nitraatista muuttuu elimistössä nitriitiksi. Nitraattia ja nitriittiä käytetään myös elintarvikelisäaineina, koska ne hillitsevät haitallisten mikrobien kasvua. Toisaalta niiden suuren saannin katsotaan aiheuttavan terveyshaittoja. Esitetty probabilistinen riskinarviointi perustuu vuosina 2004 – 2012 tutkittuihin valvonta- ja tutkimusprojektinäytteisiin sekä kirjallisuustietoihin. Lisäksi käytettiin Terveyden ja hyvinvoinnin laitokselta saatuja Finravinto 2007- ja DIPP-ravintotutkimuksen tuottamia aikuisten ja lasten ruoankulutustietoja. Nitraattialtistus lisäainelähteistä on vähäistä. Valtaosa nitraattialtistuksesta saadaan luontaisista lähteistä: vihanneksista, hedelmistä ja vedestä. Kasvisten käsittely ja hyvä viljelykäytäntö vähentävät saantia. Paljon nitraattia sisältävien kasvisten suurkuluttajien altistus voi ylittää nitraatin hyväksyttävän päivittäissaannin (ADI). Nitriittialtistus elintarvikkeista ja talousvedestä voi ylittää ADI-arvon noin 14 %:lla 3-vuotiaista ja 11 %:lla 6-vuotiaista suomalaislapsista. Suurin altistuslähde ovat ruokamakkarat. Toisaalta jos nitriittipitoisuuksia alennettaisiin nykytasosta, hygieniavaatimuksia ja kylmäketjuhallintaa olisi tehostettava.Nitrat är en naturlig komponent i många grönsaker och hushållsvatten. En del av nitratet förvandlas av kroppen till nitrit. Nitrater och nitriter används också som tillsatsämnen i livsmedel för att förhindra tillväxt av skadliga mikrober. Å andra sidan kan ett stort intag av de här ämnena orsaka hälsoskador. Den här probabilistiska riskvärderingen baserar sig på nitrat- och nitrithalter i bevakningsprover samt forskningsprover som analyserades mellan 2004 och 2012 och på litteratur. Institutet för Hälsa och Välfärd tillhandahöll matanvändningsdata från Findiet 2007 studien för vuxna och DIPP-studien för barn. Exponeringen för nitrat via tillsattsämnen är låg. Nitratintaget härstammar främst från naturliga källor, dvs. vegetabilier, frukt och vatten. Behandling av grönsaker och goda odlingsrutiner minskar intaget. För dem som äter mycket vegetabilier med höga nitrathalter kan exponeringen överstiga det acceptabla dagliga intaget(ADI) för nitrat. För cirka 14 % av finska 3-åringar och 11 % av 6-åringarna kan exponeringen för nitrit från mat och vatten överstiga ADI. Den största nitritkällan är korv. Å andra sidan skulle minskade nitrithalter kräva skärpta krav på hygien och temperaturkontroll för köttprodukter.Nitrate is a natural component of many plants and tap water. A part of the ingested nitrate is transformed into nitrite in the body. Nitrate and nitrite are also used as food additives to prevent growth of dangerous microbes. On the other hand, high exposure to these compounds can cause health damage. This probabilistic risk assessment is based on monitoring and research project samples analysed during the years 2004 – 2012 as well as on literature. The National Institute for Health and Welfare supplied the Findiet 2007 and DIPP food study consumption data for adults and children. Nitrate exposure from food additives is low. Dietary nitrate exposure mainly comes from natural sources, i.e., vegetables, fruit and water. Processing of vegetables and good agricultural practices decrease the intake. High consumers of vegetables with high nitrate content may exceed the acceptable daily intake (ADI) of nitrate. Nitrite exposure from foods and tap water may exceed the ADI for approximately 14% of Finnish 3-year-olds and for 11% of 6-yearolds. The main source of exposure is sausages. If the nitrite content of processed meat were decreased from current levels, the demands on hygiene and temperature control would need to be tightened

Biallelic loss-of-function P4HTM gene variants cause hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye abnormalities (HIDEA syndrome)

Purpose: A new syndrome with hypotonia, intellectual disability, and eye abnormalities (HIDEA) was previously described in a large consanguineous family. Linkage analysis identified the recessive disease locus, and genome sequencing yielded three candidate genes with potentially pathogenic biallelic variants: transketolase (TKT), transmembrane prolyl 4-hydroxylase (P4HTM), and ubiquitin specific peptidase 4 (USP4). However, the causative gene remained elusive. Methods: International collaboration and exome sequencing were used to identify new patients with HIDEA and biallelic, potentially pathogenic, P4HTM variants. Segregation analysis was performed using Sanger sequencing. P4H-TM wild-type and variant constructs without the transmembrane region were overexpressed in insect cells and analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot. Results: Five different homozygous or compound heterozygous pathogenic P4HTM gene variants were identified in six new and six previously published patients presenting with HIDEA. Hypoventilation, obstructive and central sleep apnea, and dysautonomia were identified as novel features associated with the phenotype. Characterization of three of the P4H-TM variants demonstrated yielding insoluble protein products and, thus, loss-of-function. Conclusions: Biallelic loss-of-function P4HTM variants were shown to cause HIDEA syndrome. Our findings enable diagnosis of the condition, and highlight the importance of assessing the need for noninvasive ventilatory support in patients.Peer reviewe

Biallelic loss-of-function P4HTM gene variants cause hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye abnormalities (HIDEA syndrome)

Purpose: A new syndrome with hypotonia, intellectual disability, and eye abnormalities (HIDEA) was previously described in a large consanguineous family. Linkage analysis identified the recessive disease locus, and genome sequencing yielded three candidate genes with potentially pathogenic biallelic variants: transketolase (TKT), transmembrane prolyl 4-hydroxylase (P4HTM), and ubiquitin specific peptidase 4 (USP4). However, the causative gene remained elusive. Methods: International collaboration and exome sequencing were used to identify new patients with HIDEA and biallelic, potentially pathogenic, P4HTM variants. Segregation analysis was performed using Sanger sequencing. P4H-TM wild-type and variant constructs without the transmembrane region were overexpressed in insect cells and analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot. Results: Five different homozygous or compound heterozygous pathogenic P4HTM gene variants were identified in six new and six previously published patients presenting with HIDEA. Hypoventilation, obstructive and central sleep apnea, and dysautonomia were identified as novel features associated with the phenotype. Characterization of three of the P4H-TM variants demonstrated yielding insoluble protein products and, thus, loss-of-function. Conclusions: Biallelic loss-of-function P4HTM variants were shown to cause HIDEA syndrome. Our findings enable diagnosis of the condition, and highlight the importance of assessing the need for noninvasive ventilatory support in patients.Peer reviewe

Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients

Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, n = 625) to controls (Stage 0, n = 1582). For genotyping we used iPLEX(TM) Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in TNFA and rs1800896 in IL10 and AKI, we found no association (odds ratios 1.06 (95% CI 0.89-1.28, p = 0.51) and 0.92 (95% CI 0.80-1.05, p = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients.Peer reviewe

Heme oxygenase-1 repeat polymorphism in septic acute kidney injury

Acute kidney injury (AKI) is a syndrome that frequently affects the critically ill. Recently, an increased number of dinucleotide repeats in the HMOX1 gene were reported to associate with development of AKI in cardiac surgery. We aimed to test the replicability of this finding in a Finnish cohort of critically ill septic patients. This multicenter study was part of the national FINNAKI study. We genotyped 300 patients with severe AKI (KDIGO 2 or 3) and 353 controls without AKI (KDIGO 0) for the guanine-thymine (GTn) repeat in the promoter region of the HMOX1 gene. The allele calling was based on the number of repeats, the cut off being 27 repeats in the S-L (short to long) classification, and 27 and 34 repeats for the S-M-L2 (short to medium to very long) classification. The plasma concentrations of heme oxygenase-1 (HO-1) enzyme were measured on admission. The allele distribution in our patients was similar to that published previously, with peaks at 23 and 30 repeats. The S-allele increases AKI risk. An adjusted OR was 1.30 for each S-allele in an additive genetic model (95% CI 1.01-1.66; p = 0.041). Alleles with a repeat number greater than 34 were significantly associated with lower HO-1 concentration (p<0.001). In septic patients, we report an association between a short repeat in HMOX1 and AKI risk

Väylärakentamisen ympäristövaikutukset ja ekoindikaattorit : ehdotus arviointijärjestelmäksi

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