Correlation between attention deficit hyperactivity disorder and sugar consumption, quality of diet, and dietary behavior in school children

This study investigated the correlation between consumption of sugar intake by fifth grade students in primary schools and development of Attention Deficit Hyperactivity Disorder (ADHD). A total of 107 students participated, and eight boys and one girl (8.4% of the total) categorized as high risk for ADHD according to diagnostic criteria. There were significant differences in the occupations and drinking habits of the respondents' fathers between the normal group and risk group. In a comparison of students' nutrition intake status with daily nutrition intake standards for Koreans, students consumed twice as much protein as the recommended level, whereas their calcium intake was only 60% of the recommended DRI (dietary reference intake). Regarding intake volume of vitamin C, the normal group posted 143.9% of the recommended DRI, whereas the risk group showed only 65.5% of the recommended DRI. In terms of simple sugar intake from snacks, students in the normal group consumed 58.4 g while the risk group consumed 50.2 g. These levels constituted 12.5% of their total daily volume of sugar intake from snacks, which is higher than the 10% standard recommended by the WHO. In conclusion, children who consumed less sugar from fruit snacks or whose vitamin C intake was less than RI was at increased risks for ADHD (P < 0.05). However, no significant association was observed between total volume of simple sugar intake from snacks and ADHD development

Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH: Extracolonic cancer risks for people with biallelic and monoallelicMUTYHmutations

Germline mutations in the DNA base excision repair gene MUTYH are known to increase a carrier’s risk of colorectal cancer. However, the risks of other (extracolonic) cancers for MUTYH mutation carriers are not well defined. We identified 266 probands (91% Caucasians) with a MUTYH mutation (41 biallelic and 225 monoallelic) from the Colon Cancer Family Registry. Mutation status, sex, age, and histories of cancer from their 1,903 first- and 3,255 second-degree relatives, were analysed using modified segregation analysis conditioned on the ascertainment criteria. Compared with incidences for the general population, hazard ratios (HRs) (95% confidence intervals [CIs]) for biallelic MUTYH mutation carriers were: urinary bladder cancer, 19(3.7–97); and ovarian cancer, 17(2.4–115). The HRs (95%CI) for monoallelic MUTYH mutation carriers were: gastric cancer, 9.3(6.7–13); hepatobiliary cancer, 4.5(2.7–7.5); endometrial cancer, 2.1(1.1–3.9); and breast cancer, 1.4(1.0–2.0). There was no evidence for an increased risk of cancers at the other sites examined (brain, pancreas, kidney or prostate). Based on the USA population incidences, the estimated cumulative risks (95%CI) to age 70 years for biallelic mutation carriers were: bladder cancer, 25%(5%–77%) for males and 8%(2%–33%) for females; and ovarian cancer, 14%(2%–65%). The cumulative risks (95%CI) for monoallelic mutation carriers were: gastric cancer, 5%(4%–7%) for males and 2.3%(1.7%–3.3%) for females; hepatobiliary cancer, 3%(2%–5%) for males and 1.4%(0.8%–2.3%) for females; endometrial cancer, 3%(2%–6%); and breast cancer 11%(8%–16%). These unbiased estimates of both relative and absolute risks of extracolonic cancers for people, mostly Caucasians, with MUTYH mutations will be important for their clinical management

Characterization of Mutant MUTYH Proteins Associated With Familial Colorectal Cancer

BACKGROUND & AIMS: The human mutyh gene encodes a base excision repair (BER) protein that prevents G:C to T:A transversions in DNA. Biallelic mutations in this gene are associated with recessively inherited familial colorectal cancer. The aim of this study was to characterize the functional activity of mutant-MUTYH and SNP-MUTYH proteins involving familial colorectal cancer. METHODS: MUTYH variants were cloned and assayed for their glycosylase and DNA binding activities using synthetic double-stranded oligonucleotide substrates by analyzing cleavage products by polyacrylamide gel electrophoresis. RESULTS: In this study, we have characterized nine missense/frameshift mutants, and two SNPs, for their DNA binding and repair activity in-vitro. Two missense mutants (R260Q and G382D) were found to be partially active in both glycosylase and DNA binding, while three other missense mutants (Y165C, R231H and P281L) were severely defective in both activities. All of the frameshift mutants (Y90X, Q377X, E466X and 1103delC) were completely devoid of both glycosylase and DNA binding activities. One SNP (V22M) showed the same activity as wild type MUTYH protein, but the other SNP (Q324H) was partially impaired in adenine removal. CONCLUSIONS: This study of MUTYH mutants suggests that certain SNPs may be as partially dysfunctional in BER as missense-MUTYH mutants and lead to colorectal carcinogenesis

Germline MutY Human Homologue Mutations and Colorectal Cancer:A Multisite Case-Control Study

BACKGROUND & AIMS: The MutY human homologue (MYH) gene is a member of the base-excision repair pathway involved in the repair of oxidative DNA damage. The objective of this study was to determine colorectal cancer (CRC) risk associated with mutations in the MYH gene. METHODS: A total of 3811 CRC cases and 2802 controls collected from a multisite CRC registry were screened for 9 germline MYH mutations; subjects with any mutation underwent screening of the entire MYH gene. Logistic regression was used to estimate age- and sex-adjusted odds ratios (AOR). Clinicopathologic and epidemiologic data were reviewed to describe the phenotype associated with MYH mutation status and assess for potential confounding and effect modification. RESULTS: Twenty-seven cases and 1 control subject carried homozygous or compound heterozygous MYH mutations (AOR, 18.1; 95% confidence interval, 2.5–132.7). CRC cases with homozygous/compound heterozygous mutations were younger at diagnosis (P = .01), had a higher proportion of right-sided (P = .01), synchronous cancers (P < .01), and personal history of adenomatous polyps (P = .003). Heterozygous MYH mutations were identified in 87 CRC cases and 43 controls; carriers were at increased risk of CRC (AOR, 1.48; 95% confidence interval, 1.02–2.16). There was a higher prevalence of low-frequency microsatellite instability (MSI) in tumors from heterozygous and homozygous/compound heterozygous MYH mutation carriers (P = .02); MSI status modified the CRC risk associated with heterozygous MYH mutations (P interaction < .001). CONCLUSIONS: Homozygous/compound heterozygous MYH mutations account for less than 1% of CRC cases. Heterozygous carriers are at increased risk of CRC. Further studies are needed to understand the possible interaction between the base excision repair and low-frequency MSI pathways

Cross-protection against MERS-CoV by prime-boost vaccination using viral spike DNA and Protein

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness and has a high mortality of -34%. However, since its discovery in 2012, an effective vaccine has not been developed for it. To develop a vaccine against multiple strains of MERS-CoV, we targeted spike glycoprotein (S) using prime-boost vaccination with DNA and insect cell-expressed recombinant proteins for the receptor-binding domain (RBD), S1, S2, S Delta TM, or S Delta ER. Our S subunits were generated using an S sequence derived from the MERS-CoV EMC/2012 strain. We examined humoral and cellular immune responses of various combinations with DNA plasmids and recombinant proteins in mice. Mouse sera immunized with S Delta ER DNA priming/S Delta TM protein boosting showed cross-neutralization against 15 variants of S-pseudovirions and the wild-type KOR/KNIH/002 strain. In addition, these immunizations provided full protection against the KOR/KNIH/002 strain challenge in human DPP4 knock-in mice. These findings suggest that vaccination with the S subunits derived from one viral strain can provide cross-protection against variant MERS-CoV strains with mutations in S. DNA priming/protein boosting increased gamma interferon production, while protein-alone immunization did not. The RBD subunit alone was insufficient to induce neutralizing antibodies, suggesting the importance of structural conformation. In conclusion, heterologous DNA priming with protein boosting is an effective way to induce both neutralizing antibodies and cell mediated immune responses for MERS-CoV vaccine development. This study suggests a strategy for selecting a suitable platform for developing vaccines against MERS-CoV or other emerging coronaviruses. IMPORTANCE Coronavirus is an RNA virus with a higher mutation rate than DNA viruses. Therefore, a mutation in S-protein, which mediates viral infection by binding to a human cellular receptor, is expected to cause difficulties in vaccine development. Given that DNA-protein vaccines promote stronger cell-mediated immune responses than protein-only vaccination, we immunized mice with various combinations of DNA priming and protein boosting using the S-subunit sequences of the MERS-CoV EMC/2012 strain. We demonstrated a cross-protective effect against wild type KOR/KNIH/002, a strain with two mutations in the S amino acids, including one in its RBD. The vaccine also provided cross-neutralization against 15 different S-pseudotyped viruses. These suggested that a vaccine targeting one variant of S can provide cross-protection against multiple viral strains with mutations in S. The regimen of DNA priming/Protein boosting can be applied to the development of other coronavirus vaccines.Y