Serum Metabonomics of Articular Cartilage Destruction Induced by T-2 Toxin in Wistar Rats

正The molecular pathogenesis of T-2toxin-induced cartilage destruction has not been fully unraveled yet.The aim of this study was to detect changes in serum metabolites in a rat anomaly model with articular cartilage destruction.Thirty healthy male Wistar rats were fed a diet containing T-2 toxin(300 ng/kg chow)for 3 months.     

Cross-neutralization between vaccine and circulating wild-type mumps viruses in Korea

Mumps is a contagious disease caused by the mumps virus. It can be prevented using mumps vaccines, administered as a measles-mumps-rubella (MMR) vaccine. For first and second dose immunization, children aged 12–15 months and 4–6 years have been administered this vaccine since 1997 in Korea. Nevertheless, mumps outbreaks still occur in vaccinated populations worldwide. Hence, immunity against these diseases may be attenuated, or there are antigenic differences between currently available vaccine strains and circulating wild-type viruses. After the introduction of national immunization programs in Korea, mumps cases became sporadic. Viral genotypes F, H, and I have emerged since 1998 whereas the vaccine strains belong to genotype A. Here, we compared the amino acid sequences of the haemagglutinin-neuraminidase (HN) gene from wild-type viruses and the mumps vaccine and measured the cross-neutralization titers between them. We selected the F, H, and I wild-type mumps strains circulating in Korea from 1998 to 2016 and analyzed changes in the amino acid sequence of the protein encoded by the HN gene. We measured mumps virus-specific IgG and rapid focus reduction neutralization test (FRNT) titers in Korean isolates and sera obtained from 50 children aged 1–2 years who had been administered a single dose of MMR vaccine. Analysis of the HN protein sequences disclosed no changes in the glycosylation sites but did reveal 4–5 differences between the Korean isolates and the genotype A vaccine strain in terms of the neutralizing epitope sites on their HN proteins. Post-vaccination FRNT titers were significantly lower against genotypes F, H, and I than they were against genotype A. This finding highlights the possibility of a recurrence of mumps outbreaks in vaccinated populations depending on the degree of genetic conservation of the HN gene. Further research into this issue is needed to prevent the resurgence of mumps.     

An exome wide association study of pulmonary tuberculosis patients and their asymptomatic household contacts

Tuberculosis is a leading cause of death in India. To identify genetic variants associated with susceptibility or resistance to Mycobacterium tuberculosis infection, we have performed an exome-wide association study with 0.2 million exonic variants among 119 pairs of tuberculosis patients and their clinically asymptomatic household contacts. The strongest association was identified for rs61104666[A], a synonymous variant (p.E292E) of exon 5 of the gene SIGLEC15 (OR = 2.4, p = 1.49 × 10⁻⁵). We also found association of non-coding variants in the 3′UTR region of a gene encoding the class II human leukocyte antigens (HLAs), HLA-DRA. rs13209234[A] (minor allele frequency (MAF) = 13.8%) (OR = 0.35, P = 2.5 × 10⁻⁴) and rs3177928[A] (minor allele frequency (MAF) = 13.7%) (OR = 0.35, P = 3.3 × 10⁻⁴) were associated with protection from tuberculosis. These two SNPs, rs13209234 and rs3177928, are in complete linkage disequilibrium. These associations remained valid when additional data on freshly recruited individuals were jointly analyzed on 250 patient-control pairs. The identified gene, HLA-DRA, suggest involvement of immune regulation, indicating pathways associated with antigen presentation in tuberculosis infection.     

Invasive pneumococcal disease in children under 16 years of age: Incomplete rebound in incidence after the maximum effect of PCV13 in 2012/13 in Germany

ObjectiveTo identify a potential nadir of the impact of pneumococcal conjugate vaccination (PCV) in infancy on invasive pneumococcal diseases (IPD) in children under 16 in Germany.MethodsActive surveillance on IPD based on two independent data sources with capture-recapture correction for underreporting. Annual incidence rates by age group, serotypes, site of infection, and relative incidence reduction compared to pre-vaccination period (1997–2001) at nadir and for the most recent season are reported. We calculated vaccine coverage at the age of 24 months using health insurance claims data.Results96–97% of children had received at least two doses of PCV since 2009. The maximum impact on overall IPD incidence was achieved in 2012/13 (−48% [95% CI: −55%; −39%]) with a rebound to −26% [95% CI: −36%; −16%] in 2015/16. Non-PCV13 serotypes accounted for 84.1% of the IPD cases in 2015/16. The most frequent non-PCV serotypes in IPD in 2014/15 and 2015/16 were 10A, 24F, 15C, 12F, 38, 22F, 23B, and 15B. The impact at nadir was highest in children 0–1 years of age both in meningitis and non-meningitis cases, whereas the impact for other age groups was higher for meningitis cases. The rebound mainly pertained to non-meningitis cases.ConclusionThe maximum impact of pneumococcal conjugate vaccination has been attained and signs of a rebound are apparent. Sustained surveillance for IPD in children is warranted to assess whether these trends will continue. There may be a need for vaccines using antigens common to all serotypes.     

From public health genomics to precision public health: a 20-year journey

In this paper, we review the evolution of the field of public health genomics in the United States in the past two decades. Public health genomics focuses on effective and responsible translation of genomic science into population health benefits. We discuss the relationship of the field to the core public health functions and essential services, review its evidentiary foundation, and provide examples of current US public health priorities and applications. We cite examples of publications to illustrate how Genetics in Medicine reflected the evolution of the field. We also reflect on how public-health genomics is contributing to the emergence of “precision public health” with near-term opportunities offered by the US Precision Medicine (AllofUs) Initiative.     

A retrospective evaluation of heparin product reactions in patients with alpha-gal allergies

BackgroundAlpha-gal allergy, also known as red meat allergy or alpha-gal syndrome, can present after bites of certain tick species that contain galactose-alpha-1,3-galactose (alpha-gal) carbohydrate. Following this exposure, patients may develop an allergic reaction after mammalian meat consumption. Some heparin products are derived from porcine intestinal tissue, and it is therefore possible that administering these medications to a patient with an alpha-gal allergy may trigger a reaction.ObjectiveThe purpose of this study was to evaluate the incidence of reactions to porcine heparin products in patients with an alpha-gal allergy.MethodsA retrospective case series was conducted by review of electronic medical record data. Patients included were between the ages of 18 and 89 years, with a documented alpha-gal or red meat allergy and an admission to a hospital in the Sentara Healthcare system. The primary outcome was the incidence of allergic reactions upon exposure to heparin products in patients with a documented alpha-gal allergy.ResultsPatients with a documented alpha-gal allergy received a heparin product in 57 of 158 hospital visits (36.1%). Heparin products were tolerated in 56 of the 57 visits (98.3%). The incidence of an alpha-gal reaction to unfractionated heparin was 2.6% (1/39) while the incidence of an alpha-gal reaction to enoxaparin was 0% (0/22).Conclusion and RelevanceHeparin products were associated with a low incidence of alpha-gal reactions among patients with documented alpha-gal allergy. It is possible that enoxaparin poses less of a risk for reaction in these patients compared to unfractionated heparin.