The global endemic of cardiovascular diseases calls for improved risk assessment and treatment. Here, we describe an association between myocardial infarction (MI) and a common sequence variant on chromosome 9p21. This study included a total of 4587 cases and 12,767 controls. The identified variant, adjacent to the tumor suppressor genes CDKN2A and CDKN2B, was associated with the disease with high significance. Approximately 21% of individuals in the population are homozygous for this variant, and their estimated risk of suffering myocardial infarction is 1.64 times as great as that of noncarriers. The corresponding risk is 2.02 times as great for early-onset cases. The population attributable risk is 21% for MI in general and 31% for early-onset cases.

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Key Points Antibodies causing FNAIT have decreased Fc fucosylation, unlike in refractory thrombocytopenia. Decreased Fc fucose increases affinity to FcγRIIIa/b, enhances platelet phagocytosis, and correlates with increased disease severity.

Infliximab treatment was not effective in refractory inflammatory myopathies. In view of radiological and clinical worsening, and activation of the type I IFN system in several cases, infliximab is not an alternative treatment in patients with treatment-resistant myositis.

The purpose of this study was to evaluate the clinical utility of a multi-shot spin-echo echo-planar (SE-EPI) diffusion-weighted sequence in the diagnostic work-up of soft tissue tumours. There were 29 patients, 16 with a benign lesion and 13 with a sarcoma. Four of the sarcomas were examined both before and after radiation therapy. Diffusion-weighted imaging was performed with a multi-shot SE-EPI sequence. The b values were 0 and 600 s/mm(2). Phase navigation and pulse trigging were applied. The apparent diffusion constant (ADC) value of a large region of interest (ROI) representing the lesion was measured and compared to diagnosis and treatment. The ADC values of the benign lesions (mean 1.8 x 10(-3) mm(2)/s) overlapped with non-treated sarcomas (mean 1.7 x 10(-3) mm(2)/s). The ADC value increased in all radiated sarcomas. A multi-shot SE-EPI diffusion imaging sequence of less than 2-min duration is technically feasible in soft tissue tumours of the extremities and the trunk. The ADC values of benign soft tissue tumours and sarcomas overlapped and could not be used to differentiate between the bulk of benign and malignant tumours. However, the increase in ADC values of soft tissue sarcomas after radiotherapy warrants further studies of diffusion imaging for evaluating therapy response.

Human immunoglobulin G (IgG) molecules are composed of two Fab portions and one Fc portion. The glycans attached to the Fc portions of IgG are known to modulate its biological activity as they influence interaction with both complement and various cellular Fc receptors. IgG glycosylation changes significantly with pregnancy, showing a vast increase in galactosylation and sialylation and a concomitant decrease in the incidence of bisecting GlcNAc. Maternal IgGs are actively transported to the fetus by the neonatal Fc receptor (FcRn) expressed in syncytiotrophoblasts in the placenta, providing the fetus and newborn with immunological protection. Two earlier reports described significant differences in total glycosylation between fetal and maternal IgG, suggesting a possible glycosylation-selective transport via the placenta. These results might suggest an alternative maternal transport pathway, since FcRn binding to IgG does not depend on Fc-glycosylation. These early studies were performed by releasing N-glycans from total IgG. Here, we chose for an alternative approach analyzing IgG Fc glycosylation at the glycopeptide level in an Fc-specific manner, providing glycosylation profiles for IgG1 and IgG4 as well as combined Fc glycosylation profiles of IgG2 and 3. The analysis of ten pairs of fetal and maternal IgG samples revealed largely comparable Fc glycosylation for all the analyzed subclasses. Average levels of galactosylation, sialylation, bisecting GlcNAc and fucosylation were very similar for the fetal and maternal IgGs. Our data suggest that the placental IgG transport is not Fc glycosylation selective.

The neonatal Fc receptor, FcRn, is best known for its role in transporting IgG in various tissues, providing newborns with humoral immunity, and for prolonging the half-life of IgG. Recent findings implicate the involvement of FcRn in a far wider range of biological and immunological processes, as FcRn has been found to bind and extend the half-life of albumin; to be involved in IgG transport and antigen sampling at mucosal surfaces; and to be crucial for efficient IgG-mediated phagocytosis. Herein, the function of FcRn will be reviewed, with emphasis on its recently documented significance for IgG polymorphisms affecting the half-life and biodistribution of IgG3, on its role in phagocyte biology, and the subsequent role for the presentation of antigens to lymphocytes.

Visceral adipose tissue (VAT) is associated with abnormal cardiovascular and metabolic profiles. Total VAT volume of the abdominal compartment by MRI is the gold standard measurement for VAT but is costly and time consuming. Prior studies suggest VAT area on a single slice MR image may serve as a surrogate for total VAT volume but it is unknown if this relationship is maintained in overweight and obese males and females. Untreated sleep apnea subjects enrolled into the Icelandic Sleep Apnea Cohort underwent abdominal MRI. VAT area and subcutaneous adipose tissue (SAT) area at the L2-L3 and L4-L5 interspaces and total VAT and SAT volumes were determined by manual examination using image analysis software. N=539 males and N=129 females with mean ages of 54.1 and 58.8 years and mean body mass index of 32.2 kg/m2 and 33.7 kg/m2, respectively, were studied. Mean total VAT volume was 40% smaller and mean total subcutaneous adipose tissue (SAT) was 25% larger among females compared to males. The correlation with VAT volume was significantly larger for L2-L3 VAT area (r=0.96) compared to L4-L5 VAT area (r=0.83). The difference in correlation coefficients was statistically significant (non-parametric bootstrap p<0.001 with 95% CI for the difference from 0.11 to 0.15. VAT area at L2-L3 was also significantly better correlated with VAT volume than traditional anthropometric variables. Linear regression analyses demonstrated that L2-L3 area alone was sufficient for predicting total VAT volume and that the nature of the linear association was maintained across all levels of obesity and in both genders.