Evaluation of 19 years of international external proficiency testing for high-resolution HLA typing.

The international high-resolution external proficiency testing (EPT) started in 2004 with high-resolution typing of human leucocyte antigen (HLA) class I (HLA-A,B,C) and HLA class II (HLA-DRB1, DRB345, DQB1, and DPB1) alleles, since possibilities for such an EPT within Europe were limited and all existing EPTs at that time made use of the comparison of HLA typing results without a reference. This EPT was set up as a collaboration between the HLA laboratory of Leiden, providing DNA samples to the participants, and the laboratory of Maastricht, performing the high-resolution typing as the reference result and evaluating the results of all participants according to the prevailing European Federation for Immunogenetics (EFI) standards. Once a year, 12 samples were sent to the participating laboratories, and evaluation and certificates were provided at the end of that same year. During the years, the EPT was extended to low-resolution HLA class I and II typing, high-resolution typing including DQA1 and DPA1, and allelic resolution typing for HLA class I, the latter one being unique in this field. Evaluation of the high-resolution typing results of the last 19 years showed a clear increase in the number of loci tested by the participating laboratories and a clear change of method from Sanger sequencing with additional other techniques (SSO/SSP) to the nowadays widely used next-generation sequencing method. By strictly using the EFI rules for high-resolution HLA typing, the participants were made aware of the ambiguities within exons 2 and 3 for class I and exon 2 for class II and the presence of null alleles even in a two-field HLA typing. There was an impressive learning curve, resulting in >98% correctly typed samples since 2017 and a 100% fulfillment of EFI rules for all laboratories for all loci submitted in the last 2 years. Overall, this EPT meets the need of an EPT for high-resolution typing for EFI accreditation.

The Use of Antidepressants, Anxiolytics, and Hypnotics in People with Type 2 Diabetes and Patterns Associated with Use: The Hoorn Diabetes Care System Cohort.

Objective. With depression being present in approximately 20% of people with type 2 diabetes mellitus (T2DM), we expect equally frequent prescription of antidepressants, anxiolytics, and hypnotics. Nevertheless, prescription data in people with T2DM is missing and the effect of depression on glycaemic control is contradictory. The aim of this study was to assess the prevalence of antidepressants, anxiolytics, and/or hypnotics use in a large, managed, primary care system cohort of people with T2DM and to determine the sociodemographic characteristics, comorbidities, T2DM medication, and metabolic control associated with its use. Method. The prevalence of antidepressants, anxiolytics, and/or hypnotics use in the years 2007-2012 was assessed in the Hoorn Diabetes Care System Cohort from the Netherlands. Results. From the 7016 people with T2DM, 500 people (7.1%) used antidepressants only, 456 people (6.5%) used anxiolytics and/or hypnotics only, and 254 people (3.6%) used a combination. Conclusion. We conclude that in our managed, primary care system 17% of all people with T2DM used antidepressants, anxiolytics, and/or hypnotics. Users of antidepressants, anxiolytics, and/or hypnotics were more often female, non-Caucasian, lower educated, and more often treated with insulin.

Propranolol as first-line treatment in orbital infantile haemangiomas: a case series.

PURPOSE: To highlight the importance of Magnetic Resonance Imaging (MRI) and the use of propranolol as both a final diagnostic tool and adequate treatment for orbital Infantile Haemangiomas (IHs). METHODS: A retrospective study was conducted using a case series of 5 infants diagnosed with orbital IH. All patients presented with progressive unilateral proptosis and were at high risk of developing amblyopia, some had combined swelling of the eyelid, impaired eye movements or exposure keratopathy. Propranolol was administered in an initial dose of 0.6 mg/kg/day orally divided in three daily doses and increased in 4 days to 2.7 mg/kg/day. MRI was performed in all children. RESULTS: Striking MR characteristics of an IH lesion were seen in each of our 5 cases, including the presence of flow voids, high contrast enhancement, hypo-intense T1W signal, iso- to hyper intense T2W signal, and lobulated appearance. All patients showed a quick clinical response to treatment, resulting in significant reduction in tumour size within a range of 1-3 weeks and almost complete regression of the lesion at the end of the treatment schedule. CONCLUSIONS: Our study adds another 5 cases to the growing body of reports confirming the efficacy and safety - under controlled circumstances - of propranolol therapy in orbital IH management, in which we highlight the use of propranolol as both a final diagnostic tool and as an adequate treatment.

Molecular tools and analytical approaches for the characterization of farm animal genetic diversity.

Genetic studies of livestock populations focus on questions of domestication, within- and among-breed diversity, breed history and adaptive variation. In this review, we describe the use of different molecular markers and methods for data analysis used to address these questions. There is a clear trend towards the use of single nucleotide polymorphisms and whole-genome sequence information, the application of Bayesian or Approximate Bayesian analysis and the use of adaptive next to neutral diversity to support decisions on conservation.

Genetic diversity and conservation of South African indigenous chicken populations.

In this study, we compare the level and distribution of genetic variation between South African conserved and village chicken populations using microsatellite markers. In addition, diversity in South African chickens was compared to that of a reference data set consisting of other African and purebred commercial lines. Three chicken populations Venda, Ovambo and Eastern Cape and four conserved flocks of the Venda, Ovambo, Naked Neck and Potchefstroom Koekoek from the Poultry Breeding Resource Unit of the Agricultural Research Council were genotyped at 29 autosomal microsatellite loci. All markers were polymorphic. Village chicken populations were more diverse than conservation flocks. structure software was used to cluster individuals to a predefined number of 2 ≤ K ≤ 6 clusters. The most probable clustering was found at K = 5 (95% identical runs). At this level of differentiation, the four conservation flocks separated as four independent clusters, while the three village chicken populations together formed another cluster. Thus, cluster analysis indicated a clear subdivision of each of the conservation flocks that were different from the three village chicken populations. The contribution of each South African chicken populations to the total diversity of the chickens studied was determined by calculating the optimal core set contributions based on Marker estimated kinship. Safe set analysis was carried out using bootstrapped kinship values calculated to relate the added genetic diversity of seven South African chicken populations to a set of reference populations consisting of other African and purebred commercial broiler and layer chickens. In both core set and the safe set analyses, village chicken populations scored slightly higher to the reference set compared to conservation flocks. Overall, the present study demonstrated that the conservation flocks of South African chickens displayed considerable genetic variability that is different from that of the assumed founder populations (village chickens).

Genetic diversity in farm animals--a review.

Domestication of livestock species and a long history of migrations, selection and adaptation have created an enormous variety of breeds. Conservation of these genetic resources relies on demographic characterization, recording of production environments and effective data management. In addition, molecular genetic studies allow a comparison of genetic diversity within and across breeds and a reconstruction of the history of breeds and ancestral populations. This has been summarized for cattle, yak, water buffalo, sheep, goats, camelids, pigs, horses, and chickens. Further progress is expected to benefit from advances in molecular technology.

Assessing genetic diversity of Vietnamese local chicken breeds using microsatellites.

This study aimed to assess genetic diversity within and between nine Vietnamese local chicken breeds and two Chinese breeds included for comparison. Genotyping 29 microsatellites revealed high diversity of both Vietnamese and Chinese breeds. Cluster analysis using the STRUCTURE software suggested six clusters as the most likely grouping of the 11 breeds studied. These groups encompassed four homogeneous clusters, one formed by the two Chinese breeds and the other three representing a single breed each: the Mekong Delta breed Ac, the South Central Coast breed Choi, and the Red River Delta breed Dong Tao. The six remaining breeds formed two additional admixed clusters.

Introgressive hybridization in southern African baboons shapes patterns of mtDNA variation.

Species, as main evolutionary units have long been considered to be morphological entities with limited hybridization potential. The occurrence of taxa which maintain morphological distinctness despite extensive hybridization is an interesting phenomenon. To understand the evolution of these taxa, descriptions of contemporary morphological and genetic variation are essential, also to reconstruct sound phylogenies. Baboons, with their wide geographic range, variant morphotypes, and extensive hybridization offer an intriguing model for those studies. We focus on the complex situation in southern Africa that, in contrast to east Africa, has been neglected in terms of baboon hybridization history. We aim to clarify the distribution and identify possible overlapping zones between different, previously described mitochondrial (mt) DNA clades of baboons that do not match with the ranges of traditionally recognized species. On the basis of the widespread sampling and mitochondrial cytochrome b gene sequencing, we constructed a phylogenetic tree that separates representatives of the two southern African baboon species, yellow and chacma baboons, into six clades: southern, northern and eastern chacmas, Kinda baboons and southern and Luangwa yellow baboons. The ranges of the chacma clades come into close contact or overlap in two regions in the Republic of South Africa and Namibia. Our phylogenetic reconstruction reveals mitochondrial paraphyly for chacma and yellow baboons, which is probably caused by introgressive hybridization and subsequent nuclear swamping, whereby males of the chacma morphotype population from the south invaded the yellow morphotype population in the north bringing their morphotype into a population that maintained its yellow baboon mtDNA.

HLA class II amino acid epitopes as susceptibility markers of sarcoidosis.

Sarcoidosis is a multisystemic disorder of unknown etiology, affecting primarily the lung and characterized by epithelioid granulomas. Disease association studies showed human leukocyte antigen (HLA) class II to be related to sarcoidosis. Initially, we studied the association of sarcoidosis with DQB1, and in the present study, we evaluated all amino acid variants of the HLA-DPB1, -DQB1, -DRB1, -DRB3, -DRB4 and -DRB5 genes to identify possible polymorphisms associated with the disease. Patients and controls were typed for class II genes to the allele level by sequence-based typing. Multiple logistic regression models showed DRAla71 and DQPhe9 to be independently associated with the disease. Subdivision of patients according to their radiographic stage resulted in identification of DRArg74 as independent associated residue in the RS I group, whereas DRAla71 and DQTyr30 were associated with RS II-IV groups. Polymorphic residues specifically associated with sarcoidosis shed new light on the characteristics of sarcoidosis-triggered peptides. Overall, pocket 9 of DQ and pocket 4 of DR seem to be the most important areas involved in the association with sarcoidosis.