Immunogenetics in stem cell donor registry work: The DKMS example (Part 2).

DKMS is a leading stem cell donor registry with more than 9 million donors. Donor registry activities share many touch points with topics from immunogenetics or population genetics. In this two-part review article, we deal with these aspects of donor registry work by using the example of DKMS. In the second part of the review, we focus on donor typing of non-HLA genes, the impact of donor age, gender and CMV serostatus on donation probabilities, the identification of novel HLA, KIR and MIC alleles by high-throughput donor typing, the activities of the Collaborative Biobank and pharmacogenetics in the donor registry context.

Immunogenetics in stem cell donor registry work: The DKMS example (Part 1).

Currently, stem cell donor registries include more than 35 million potential donors worldwide to provide HLA-matched stem cell products for patients in need of an unrelated donor transplant. DKMS is a leading stem cell donor registry with more than 9 million donors from Germany, Poland, the United States, the United Kingdom, India and Chile. DKMS donors have donated hematopoietic stem cells more than 80,000 times. Many aspects of donor registry work are closely related to topics from immunogenetics or population genetics. In this two-part review article, we describe, analyse and discuss these areas of donor registry work by using the example of DKMS. Part 1 of the review gives a general overview on DKMS and includes typical donor registry activities with special focus on the HLA system: high-throughput HLA typing of potential stem cell donors, HLA haplotype frequencies and resulting matching probabilities, and donor file optimization with regard to HLA diversity.

Improving the improvisational pelvic circumferential compression technique for open-book pelvic fractures using a simulation model and a sphygmomanometer.

BACKGROUND: Open-book pelvic fractures are associated with significant mortality. Emergency management may require a commercial pelvic circumferential compression device to reduce the fracture and compress haemorrhaging pelvic vasculature. Standard, commercial, twin-sized bedsheets are acceptable should commercial devices be unavailable. However, obese victims or personnel with insufficient body strength may impede successful reduction. OBJECTIVE: To demonstrate the value of an improvisational windlass (intravenous pole) in improving the ability to reduce an open-book pelvic fracture. METHODS: The Institutional Review Board-approved study involved 28 diverse healthcare students and emergency medicine residents. Each participant's demographic information and physical characteristics were recorded. A METIman was prepared with knee and ankle binding and a sphygmomanometer set at 40 mm Hg placed over the symphysis pubis. Two-person teams were randomly selected to place a bedsheet at greater trochanter level and atop the sphygmomanometer. The bedsheet was secured with maximum effort by the pairs and the pressure recorded. Following this, the pairs inserted an intravenous pole in the knot and torqued the pole to maximum effort and a repeat pressure recorded. RESULTS: The mean increase in pressure using only the bedsheet was 106.43 mm Hg per team. With bedsheet and intravenous pole, the mean pressure increase was 351.79 mm Hg per team. The difference was statistically significant (independent samples t-test: t = 17.177, p < 0.001, 95% CI (216.65 to 274.07 mm Hg). There was no correlation between pressure increases and the individual physical characteristics of the subjects (r = - 0.183, p = 0.352). CONCLUSIONS: Regardless of personnel's physical attributes, the addition of an improvisational windlass to a pelvic circumferential compression bedsheet can improve the ability to reduce an open-book fracture, especially in obese victims.

Beyond bread and beer: whole cell protein extracts from baker's yeast as a bulk source for 3D cell culture matrices.

Here, we present a novel approach to form hydrogels from yeast whole cell protein. Countless hydrogels are available for sophisticated research, but their fabrication is often difficult to reproduce, with the gels being complicated to handle or simply too expensive. The yeast hydrogels presented here are polymerized using a four-armed, amine reactive crosslinker and show a high chemical and thermal resistance. The free water content was determined by measuring swelling ratios for different protein concentrations, and in a freeze-drying approach, pore sizes of up to 100 µm in the gel could be created without destabilizing the 3D network. Elasticity was proofed to be adjustable with the help of atomic force microscopy by merely changing the amount of used protein. Furthermore, the material was tested for possible cell culture applications; diffusion rates in the network are high enough for sufficient supply of human breast cancer cells and adenocarcinomic human alveolar basal epithelial cells with nutrition, and cells showed high viabilities when tested for compatibility with the material. Furthermore, hydrogels could be functionalized with RGD peptide and the optimal concentration for sufficient cell adhesion was determined to be 150 µM. Given that yeast protein is one of the cheapest and easiest available protein sources and that hydrogels are extremely easy to handle, the developed material has highly promising potential for both sophisticated cell culture techniques as well as for larger scale industrial applications.

Objective assessment of symptomatic vitreous floaters using optical coherence tomography: a case report.

BACKGROUND: Vitrectomy for symptomatic vitreous floaters carries significant risks. Justification of surgery is difficult, particularly in healthy eyes with normal visual acuity and without a posterior vitreous detachment. This is the first reported case of optical coherence tomography being utilized to objectively assess the impact of a vitreous opacity on the macula. CASE PRESENTATION: A 37-year-old Caucasian female complained of the sudden onset of a ring-like floater in the central visual field of her left eye. Visual acuity was 20/20, there was no intraocular inflammation and the posterior vitreous was not detached. Complete blood count with differential, serology screen (including cysticercosis and echinococcus), chest x-ray and abdominal ultrasound found no evidence of systemic infective or cystic disease. A color photograph and B-scan ultrasound confirmed a 4.31 mm free-floating semi-translucent vitreous cyst with a hyperechogenic, pigmented surface and faint internal strands suspended in the mid-vitreous cavity, in the visual axis. The cyst moved with ocular movements, but only within the vitreous lacuna it resided in. Humphrey and Goldmann visual fields were normal. However, spectral domain optical coherence tomography (OCT) demonstrated shadowing on either side of the fovea, consistent with the ring-like scotoma described by the patient. Removing the retinal layers from the 3D-reconstructed macular cube OCT revealed a circular shadow on the macula. The patient elected for conservative management and at 3-month follow-up her symptoms had almost fully resolved as the cyst migrated to the inferior vitreous cavity, no longer casting a shadow on the macula. CONCLUSION: To our knowledge, this is the first description of using OCT as an objective, qualitative assessment of symptoms caused by large vitreous opacities and may provide a simple yet useful adjunctive tool in evaluating the risk-benefit ratio of vitrectomy in patients with large symptomatic vitreous floaters.

Sortase A induces Th17-mediated and antibody-independent immunity to heterologous serotypes of group A streptococci.

Group A streptococci (GAS) are associated with a variety of mucosal and invasive human infections. Recurrent infections by highly heterologous serotypes indicate that cross-serotype immunity is critical for prevention of GAS infections; however, mechanisms underlying serotype-independent protection are poorly understood. Here we report that intranasal vaccination of mice with Sortase A (SrtA), a conserved cell wall bound protein, reduced colonization of nasal-associated lymphoid tissue (NALT) by heterologous serotypes of GAS. Vaccination significantly increased CD4+ IL-17A+ cells in NALT and depletion of IL-17A by neutralizing antibody prevented GAS clearance from NALT which was dependent on immunization with SrtA. Vaccination also induced high levels of SrtA-specific antibodies; however, immunized, B cell-deficient mice cleared streptococcal challenges as efficiently as wild type mice, indicating that the cross-serotype protection is Th17-biased and antibody-independent. Furthermore, efficient GAS clearance from NALT was associated with a rapid neutrophil influx into NALT of immunized mice. These results suggest that serotype independent immune protection against GAS mucosal infection can be achieved by intranasal vaccination with SrtA and enhanced neutrophil function is critical for anti-GAS defense and might be a target for prevention of GAS infections.

Cost-efficient high-throughput HLA typing by MiSeq amplicon sequencing.

BACKGROUND: A close match of the HLA alleles between donor and recipient is an important prerequisite for successful unrelated hematopoietic stem cell transplantation. To increase the chances of finding an unrelated donor, registries recruit many hundred thousands of volunteers each year. Many registries with limited resources have had to find a trade-off between cost and resolution and extent of typing for newly recruited donors in the past. Therefore, we have taken advantage of recent improvements in NGS to develop a workflow for low-cost, high-resolution HLA typing. RESULTS: We have established a straightforward three-step workflow for high-throughput HLA typing: Exons 2 and 3 of HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 are amplified by PCR on Fluidigm Access Array microfluidic chips. Illumina sequencing adapters and sample specific tags are directly incorporated during PCR. Upon pooling and cleanup, 384 samples are sequenced in a single Illumina MiSeq run. We developed "neXtype" for streamlined data analysis and HLA allele assignment. The workflow was validated with 1140 samples typed at 6 loci. All neXtype results were concordant with the Sanger sequences, demonstrating error-free typing of more than 6000 HLA loci. Current capacity in routine operation is 12,000 samples per week. CONCLUSIONS: The workflow presented proved to be a cost-efficient alternative to Sanger sequencing for high-throughput HLA typing. Despite the focus on cost efficiency, resolution exceeds the current standards of Sanger typing for donor registration.

Transdisciplinarite et anthropoformation: leur importance dans les recherches en sante / Transdisciplinarity and antropoformation: its importance in health investigations

Au-delà des normes de référence issues des statistiques, sitôt que les comportements de la personne à soigner ou à éduquer doivent être pris en compte defaçon singulière, le positionnement des soignants devient difficile entre impératifs issus des modèles normatifs se référant à la maladie mais ne tenant nul compte des malades d’un côté et de l’autre l'évidencede devoir considérer les particularités propres à chaque sujet que l’on accompagne et qui interfèrent, nécessairement, sur la santé par les comportements mais qui sont source de complexité, donc difficile à traiter. La transdisciplinarité engage à l’impératif d’un changement paradigmatique et d’un cheminement à double face, cette bipartition ne pouvant jamais totalement se distinguer. Elle s’apparente d’une part, ce qui correspond à sa définition classique, à une épistémologie qui pointerait l’importance nouvelle des frontières disciplinaires, des zones floues, non accessibles aux clôtures classiques qui définissent les objets disciplinaires. Mais elle impose d’autre part la construction d’une nouvelle épistémologie du sujet qui participe toujours, d’une manière ou de l’autre, à l’observation par son interaction plus ou moins forte avec l’objet, ce que nous définissons par le néologisme ® d ’anthropoformation ¼. Par le changement qui s’opère elle permet d’offrir à la fois une aptitude à relier les savoirs disciplinaires entre eux et une capacité d’intégration du sujet, de son indiscipline et de ses interactions. Elle dirige vers une phénoménologie dela santé associant les modes d’être aux modes de com-prendre. Le texte vise à préciser, dans le champ de la santé, les différents points soulevés par ce changement paradigmatique.

Transdisciplinaridade e antropoformação: sua importância nas pesquisas em saúde / Transdisciplinarity and antropoformation: its importance in health investigations

Além das normas de referência provenientes das estatísticas - quando comportamentos da pessoa a ser cuidada ou educada devem ser levados em conta de maneira singular - o posicionamento dos cuidadores é dificultado entre imperativos oriundos de modelos normativos que se referem à doença e não levam em conta os doentes de um lado, e do outro lado, a evidência de dever considerar as particularidades próprias a cada sujeito que se acompanha e que interferem, necessariamente, sobre a saúde pelos comportamentos mas que são fonte de complexidade, portanto difícil de tratar. A transdiciplinaridade convida ao imperativo de mudança paradigmática e de um caminho de dupla face, com essa bipartição não podendo jamais distinguir-se totalmente. Ela se aproxima por um lado - o que corresponde a sua definição clássica - de uma epistemologia que apontaria para a importância nova das fronteiras disciplinares, das zonas imprecisas, não acessíveis aos fechamentos clássicos que definem os objetos disciplinares. Mas ela impõe, por outro lado, a construção de nova epistemologia do sujeito e que participa sempre, de uma maneira ou de outra, da observação pela sua interação mais ou menos forte com o objeto, o que definimos pelo neologismo "antropoformação". Pela mudança que opera, ela permite oferecer, ao mesmo tempo, uma atitude para religar os saberes disciplinares entre eles e uma capacidade de integração do sujeito, sua indisciplina e suas interações. Ela conduz para uma fenomenologia da saúde, os diferentes pontos levantados por essa mudança paradigmática.

A dimensão ética na educação para a saúde / The ethical dimension in health education

A ética, como julgamento de apreciação das condutas positivas e negativas, tanto no que diz respeito ao usuário como ao profissional, coloca de início a problemática do desejo e do conhecimento. A educação para a saúde, através dos três modelos classicamente referidos da saúde positiva, da saúde negativa e da saúde global, vai interrogar de variadas maneiras o posicionamento ético em função dos pontos de vista diferentes fortemente ligados às representações sociais. Além disso, o questionamento ético da saúde inscreve-se também naquele, mais largo, da filosofia da educação entre práxis e poïesis.Mas ele impõe também a aceitação do acidente como imperativo que valoriza o erro, com a introdução da complexidade vindo quebrar o dogma das certezas. Reunir as diferentes facetas da saúde e de sua educação sugere então, finalmente, que tomar cuidado é viver o mais autenticamente possível, com o educar para a saúde significando formar e formar-se para a autenticidade.(Tradutora)

La dimension éthique dans l'éducation à la santé / The ethical dimension in health education

L’éthique, comme jugement dáprréciation sur les conduites positives et négatives, tant en ce qui concerne l'usager que le professionnel, pose d'emblée a problématique du désir et de Ia connaissance. L'éducation à Ia santé, au travers des trois modeles classiquement éférencés de Ia santé positive, de Ia santé négative et de Ia santé globale, va interroger différemment e positionnement éthique en fonction des points de vue différents fortement liés aux représentations ociales. Par ailleurs, le questionnement éthique de Ia santé s'inscrit aussi dans celui, plus arge, de Ia philosophie de l'éducation entre praxis et oiesis. Mais il impose aussi l'acceptation de l'accident omme impératif donnant un prix à 'l'erreur, 'introdution de Ia complexité venant briser le dogme es certitudes. réunir les différentes facettes de Ia anté et de son éducation suggere alors, au bout du ompte, que prendre soin c'est vivre le plus authentiquement ossible, éduquer à Ia santé devenant former t se former à l'authenticité.