The International Hereditary Thrombotic Thrombocytopenic Purpura Registry: key findings at enrollment until 2017.

Congenital thrombotic thrombocytopenic purpura is an autosomal recessive inherited disease with a clinically heterogeneous course and an incompletely understood genotype-phenotype correlation. In 2006, the Hereditary TTP Registry started recruitment for a study which aimed to improve the understanding of this ultra-rare disease. The objective of this study is to present characteristics of the cohort until the end of 2017 and to explore the relationship between overt disease onset and ADAMTS13 activity with emphasis on the recurring ADAMTS13 c.4143_4144dupA mutation. Diagnosis of congenital thrombotic thrombocytopenic purpura was confirmed by severely deficient ADAMTS13 activity (≤10% of normal) in the absence of a functional inhibitor and the presence of ADAMTS13 mutations on both alleles. By the end of 2017, 123 confirmed patients had been enrolled from Europe (n=55), Asia (n=52, 90% from Japan), the Americas (n=14), and Africa (n=2). First recognized disease manifestation occurred from around birth up to the age of 70 years. Of the 98 different ADAMTS13 mutations detected, c.4143_4144dupA (exon 29; p.Glu1382Argfs*6) was the most frequent mutation, present on 60 of 246 alleles. We found a larger proportion of compound heterozygous than homozygous carriers of ADAMTS13 c.4143_4144dupA with overt disease onset at < 3 months of age (50% vs 37%), despite the fact that ADAMTS13 activity was <1% in 18 of 20 homozygous, but in only 8 of 14 compound heterozygous carriers. An evaluation of overt disease onset in all patients with an available sensitive ADAMTS13 activity assay (n=97) shows that residual ADAMTS13 activity is not the only determinant of age at first disease manifestation. Registered at clinicaltrials.gov identifier NCT01257269.

Cellular Factor XIII, a Transglutaminase in Human Corneal Keratocytes.

Cellular factor XIII (cFXIII, FXIII-A2), a transglutaminase, has been demonstrated in a few cell types. Its main function is to cross-link proteins by isopeptide bonds. Here, we investigated the presence of cFXIII in cells of human cornea. Tissue sections of the cornea were immunostained for FXIII-A in combination with staining for CD34 antigen or isopeptide cross-links. Isolated corneal keratocytes were also evaluated by immunofluorescent microscopy and flow cytometry. FXIII-A in the corneal stroma was quantified by Western blotting. FXIII-A mRNA was detected by RT-qPCR. The cornea of FXIII-A-deficient patients was evaluated by cornea topography. FXIII-A was detected in 68 ± 13% of CD34+ keratocytes. Their distribution in the corneal stroma was unequal; they were most abundant in the subepithelial tertile. cFXIII was of cytoplasmic localization. In the stroma, 3.64 ng cFXIII/mg protein was measured. The synthesis of cFXIII by keratocytes was confirmed by RT-qPCR. Isopeptide cross-links were detected above, but not within the corneal stroma. Slight abnormality of the cornea was detected in six out of nine FXIII-A-deficient patients. The presence of cFXIII in human keratocytes was established for the first time. cFXIII might be involved in maintaining the stability of the cornea and in the corneal wound healing process.

Milk fatty acid profile related to energy balance in dairy cows.

Milk fatty acid (FA) profile is a dynamic pattern influenced by lactational stage, energy balance and dietary composition. In the first part of this study, effects of the energy balance during the proceeding lactation [weeks 1-21 post partum (pp)] on milk FA profile of 30 dairy cows were evaluated under a constant feeding regimen. In the second part, effects of a negative energy balance (NEB) induced by feed restriction on milk FA profile were studied in 40 multiparous dairy cows (20 feed-restricted and 20 control). Feed restriction (energy balance of -63 MJ NEL/d, restriction of 49 % of energy requirements) lasted 3 weeks starting at around 100 days in milk. Milk FA profile changed markedly from week 1 pp up to week 12 pp and remained unchanged thereafter. The proportion of saturated FA (predominantly 10:0, 12:0, 14:0 and 16:0) increased from week 1 pp up to week 12 pp, whereas monounsaturated FA, predominantly the proportion of 18:1,9c decreased as NEB in early lactation became less severe. During the induced NEB, milk FA profile showed a similarly directed pattern as during the NEB in early lactation, although changes were less marked for most FA. Milk FA composition changed rapidly within one week after initiation of feed restriction and tended to adjust to the initial composition despite maintenance of a high NEB. C18:1,9c was increased significantly during the induced NEB indicating mobilization of a considerable amount of adipose tissue. Besides 18:1,9c, changes in saturated FA, monounsaturated FA, de-novo synthesized and preformed FA (sum of FA >C16) reflected energy status in dairy cows and indicated the NEB in early lactation as well as the induced NEB by feed restriction.

Antibody response to Influenza booster vaccination in Franches-Montagnes stallions supplemented with Equi-Strath® : a randomized trial.

Bio-Strath® is a plasmolyzed yeast product enriched with herbs, malt, honey and orange juice. In this study, the effect of Equi-Strath® , the adapted product for horses, on the equine immune system was evaluated. A routine influenza booster vaccination was used as a model to study the effects of Equi-Strath® supplementation on the immune response. Twenty healthy Franches-Montagnes stallions with pre-existing antibody levels were randomly divided into a study group (SG, n = 10) receiving 0.06 mL/kg bodyweight of Equi-Strath® , and a control group (CG, n = 10), receiving the same amount of placebo, daily. The supplement and placebo were given from week 1 until week 14 of the trial. After 10 weeks, the horses were vaccinated with a commercial vaccine containing equine influenza strains of the H3N8 subtype. Antibody titres in blood were measured at day 0 before vaccination, and 14 and 32 days after vaccination. In addition, a complete blood count (CBC) was performed on day 0 and day 32. A linear increase of haemagglutination inhibition titres in both groups was observed after vaccination, but with no difference between treatment groups. CBC components remained unaffected by treatment. In conclusion, daily Equi-Strath® supplementation did not affect the adaptive immune response in stallions after a routine commercial H3N8 influenza booster vaccination.