In the last years numerous reports describing a possible association between administration of vaccines and development of autoimmune phenomena and overt autoimmune disease were published. Possible mechanisms of induction of autoimmune phenomena by vaccines and their excipients are probably similar to those implicated in induction by infectious agents. Here we report the case of an 11-year-old girl who developed autoimmune hepatitis type II after four weeks from vaccination against human papillomavirus. The possible relationships between the use of adjuvated vaccine against papillomavirus and autoimmune hepatitis are discussed. Although we do not provide evidence for a causal link, we suggest that the occurrence of the autoimmune hepatitis may be related to the stimulation of immune system by adjuvated-vaccine, that could have triggered the disease in a genetically predisposed individual. Therefore a monitoring of liver function test following administration of vaccine against papillomavirus may be useful in adolescent girl with signs of hepatopathy, as jaundice, dark urine or hepatomegaly, to early identify and to promptly treat autoimmune liver disorders.

Randomised controlled trials (RCT) testing the effects of antioxidant supplements on endothelial function (EF) have reported conflicting results. We aimed to investigate the effects of supplementation with antioxidant vitamins C and E on EF and to explore factors that may provide explanations for the inconsistent results. We searched four databases (MEDLINE, Embase, Cochrane Library and Scopus) from inception until May 2014 for RCT involving adult participants aged≥ 18 years who were supplemented with vitamins C and E alone or in combination for more than 2 weeks and reporting changes in EF measured using flow mediated dilation or forearm blood flow. Data were pooled as standardised mean difference (SMD) and analysed using a random-effects model. Significant improvements in EF were observed in trials supplementing with vitamin C alone (500-2000 mg/d) (SMD: 0·25, 95 % CI 0·02, 0·49, P= 0·043) and vitamin E alone (300-1800 IU/d; 1 IU vitamin E = 0·67 mg natural vitamin E) (SMD: 0·48, 95 % CI 0·23, 0·72, P= 0·0001), whereas co-administration of both vitamins was ineffective (vitamin C: 500-2000 mg/d; vitamin E: 400-1200 IU/d) (SMD: 0·12, 95 % CI - 0·18, 0·42, P= 0·428). The effect of vitamin C supplementation on EF increased significantly with age (β 0·023, 95 % CI 0·001, 0·05, P= 0·042). There was a significant negative correlation between baseline plasma vitamin E concentration and the effect of vitamin E supplementation on EF (β - 0·03, 95 % CI - 0·06, - 0·001, P= 0·029). Supplementation with either vitamin C or vitamin E alone improves EF. However, subgroup analysis emphasises the importance ofcareful characterisation and selection of a population group which may benefit from such supplementation.

BACKGROUND:High intake of fruit and vegetables as well as high plasma vitamin C concentrations have been associated with low risk of ischemic heart disease in prospective studies, but results from randomized clinical trials have been inconsistent.

OBJECTIVE:We tested the hypothesis that genetically high concentrations of plasma vitamin C, such as with high intake of fruit and vegetables, are associated with low risk of ischemic heart disease and all-cause mortality.

DESIGN:We used a Mendelian randomization approach and genotyped for solute carrier family 23 member 1 (SLC23A1) rs33972313 in the sodium-dependent vitamin C transporter 1 in 97,203 white individuals of whom 10,123 subjects had ischemic heart disease, and 8477 subjects died. We measured plasma vitamin C in 3512 individuals and included dietary information on 83,256 individuals.

RESULTS:The SLC23A1 rs33972313 G allele was associated with 11% higher plasma vitamin C. The multivariable adjusted HRs for highest compared with lowest fruit and vegetable intakes were 0.87 (95% CI: 0.78, 0.97; P = 0.01) for ischemic heart disease and 0.80 (95% CI: 0.73, 0.88; P<0.001) for all-cause mortality. Corresponding HRs for rs33972313 GG (93%) compared with AA plus AG (7%) genotypes were 0.95 (95% CI: 0.88, 1.02; P = 0.21) and 0.96 (0.88, 1.03; P = 0.29), respectively. In an instrumental variable analysis, the OR for genetically determined 25% higher plasma vitamin C concentrations was 0.90 (95% CI: 0.75, 1.08; P = 0.27) for ischemic heart disease and 0.88 (0.72, 1.08; P = 0.22) for all-cause mortality.

CONCLUSIONS:High intake of fruit and vegetables was associated with low risk of ischemic heart disease and all-cause mortality. Although the 95% CI for genetically high plasma vitamin C concentrations overlapped 1.0, which made certain statistical inferences difficult, effect sizes were comparable to those for fruit and vegetables intake. Thus, judging by the effect size, our data cannot exclude that a favorable effect of high intake of fruit and vegetables could in part be driven by high vitamin C concentrations.

BACKGROUND:Narcolepsy is a rare neurological sleep disorder especially in children who are younger than 10 years. In the beginning of 2010, an exceptionally large number of Finnish children suffered from an abrupt onset of excessive daytime sleepiness (EDS) and cataplexy. Therefore, we carried out a systematic analysis of the incidence of narcolepsy in Finland between the years 2002-2010.

METHODS:All Finnish hospitals and sleep clinics were contacted to find out the incidence of narcolepsy in 2010. The national hospital discharge register from 2002 to 2009 was used as a reference.

FINDINGS:Altogether 335 cases (all ages) of narcolepsy were diagnosed in Finland during 2002-2009 giving an annual incidence of 0.79 per 100,000 inhabitants (95% confidence interval 0.62-0.96). The average annual incidence among subjects under 17 years of age was 0.31 (0.12-0.51) per 100,000 inhabitants. In 2010, 54 children under age 17 were diagnosed with narcolepsy (5.3/100,000; 17-fold increase). Among adults≥20 years of age the incidence rate in 2010 was 0.87/100,000, which equals that in 2002-2009. Thirty-four of the 54 children were HLA-typed, and they were all positive for narcolepsy risk allele DQB1*0602/DRB1*15. 50/54 children had received Pandemrix vaccination 0 to 242 days (median 42) before onset. All 50 had EDS with abnormal multiple sleep latency test (sleep latency<8 min and≥2 sleep onset REM periods). The symptoms started abruptly. Forty-seven (94%) had cataplexy, which started at the same time or soon after the onset of EDS. Psychiatric symptoms were common. Otherwise the clinical picture was similar to that described in childhood narcolepsy.

INTERPRETATION:A sudden increase in the incidence of abrupt childhood narcolepsy was observed in Finland in 2010. We consider it likely that Pandemrix vaccination contributed, perhaps together with other environmental factors, to this increase in genetically susceptible children.

We describe a case of a 15-month-old female child admitted to our hospital because of fever, rash, neurological signs (oscillation between states of irritability and drowsiness), palpebral edema and drooping eyelid, appeared 10 days after the vaccination for measles, mumps and rubella. Brain MRI images showed multiple bilateral hyperintense lesions in the white matter typical of acute disseminated encephalomyelitis (ADEM), an autoimmune demyelinating disorder with inflammatory lesions of the central nervous system, due to viral antigens or vaccines. In the mean time, because of patient's vague phenotypic manifestations, suggestive of a genetic defect, array comparative genomic hybridization was carried out which showed the presence of a microdeletion 22q11.21, linked to the DiGeorge syndrome. Our case suggests that pediatric cases of post-vaccination ADEM, in which neurological signs persist, should be investigated for genetic phenotypical features, in order to exclude the presence of a genetic syndrome or disease.

PURPOSE:Exercise is associated with reduced risk of depressive symptoms at older ages, while recent work suggests that the apolipoprotein E type 4 allele (APOE-e4) may increase risk. There are no studies of whether APOE-e4 moderates the relationship between exercise and later life depressive symptoms. This study aimed to explore whether the prospective associations between exercise and subsequent depressive symptoms were distinct between APOE-e4 carriers and non-carriers using nationwide data.

METHODS:Data from 639 participants (mean age = 66.14, SD = 7.26) in 2000 with 6 years of follow-up were studied. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale. Exercise and the APOE genotype were also assessed at baseline. Negative binomial regression models were conducted to examine the combined effects of exercise and APOE-e4 status on subsequent depressive symptoms when controlling for baseline depressive symptoms and other covariates. Sensitivity analyses to test for confounding, reverse causality, and attrition were conducted.

RESULTS:Among APOE-e4 carriers, there was no significant difference in depressive symptoms between high active and low active groups. In contrast, high active APOE-e4 non-carriers had fewer depressive symptoms than low active APOE-e4 non-carriers. The beneficial effect of exercise on depressive symptoms is restricted to APOE-e4 non-carriers. Sensitivity analyses provided further support for the robustness of these findings.

CONCLUSIONS:This is the first prospective study investigating whether APOE-e4 moderates the association between exercise and depressive symptoms. It proposes that genetic variation in APOE may influence the effect of exercise on depressive symptoms.

BACKGROUND:Leukocyte telomere length (LTL) attrition has been associated with age-related diseases. Telomerase RNA Component (TERC) genetic variants have been associated with LTL; whereas fatty acids (FAs) can interact with genetic factors and influence in aging. We explore whether variability at the TERC gene locus interacts with FA profile and two healthy diets (low-fat diet vs Mediterranean diet [MedDiet]) modulating LTL, glucose metabolism, and inflammation status in coronary heart disease (CHD) patients.

METHODS:Inflammation status (high-sensitivity C-reactive protein [hsCRP], glucose metabolism-glucose, insulin, and glycated hemoglobin [HbA1c], and homeostasis model assessment of insulin resistance [HOMA-IR]), LTL, FAs, and single nucleotide polymorphisms (SNPs) of the TERC gene (rs12696304, rs16847897, and rs3772190) were determined in 1,002 patients from the CORDIOPREV study (NCT00924937).

RESULTS:We report an interaction of the TERC rs12696304 SNP with monounsaturated fatty acid (MUFA) affecting LTL (p interaction = .01) and hsCRP (p interaction = .03). Among individuals with MUFA levels above the median, CC individuals showed higher LTL and lower hsCRP than G-allele carriers. Moreover, MedDiet interacted with TERC rs12696304 SNP (p interaction = .03). Specifically, CC individuals displayed a greater decrease in hsCRP than G-allele carriers. These results were not adjusted for multiple statistical testing and p less than .05 was considered significant.

CONCLUSIONS:Our findings suggest that the TERC rs12696304 SNP interacts with MUFA improving inflammation status and telomere attrition related with CHD. Moreover, the MedDiet intervention improves the inflammatory profile in CC individuals compared with the G-allele carriers. These interactions could provide a right strategy for personalized nutrition in CHD patients.