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Background The impact of racism on health and the quality of health care services for racialized patients have been the object of prior research. The experiences of racialized medical students and physicians, who operate in a field of tension between natural sciences and practical application and between a ‘medical habitus’ and exclusionary discrimination, have hardly been examined to date. The education of (future) physicians is an especially fruitful research area in the context of the study of institutional racism in the health care system, as informal everyday experiences come together with formal knowledge and normative learning. Methods Based on expert consultations and preliminary interviews with civic stakeholders, teaching and learning materials in German medical studies were randomly sampled and used as a starting point for qualitative guided interviews with physicians and medical students in Germany who are themselves affected by racism. The first steps of the thematic analysis of these interviews are reflected upon and further developed in focus group discussions with the interviewees. Results The study is particularly concerned with the question of how certain dimensions of racism in the health care sector are related, and how racist normativity appears in this context. This is concretized in the relationship between formal and informal medical curricula as well as in the interweaving of everyday experiences and teaching materials. Conclusions There are different dimensions of relation between a hegemonic normativity in the medical curriculum and the everyday experiences of racialized medical students and physicians in Germany. Politics, faculties, publishers, and civic society may be the target of several recommendations for action regarding those diverse dimensions, e.g. the line between omission and stereotyping of several patient groups. Key messages • Hegemonic normativity in German medical education is an important and challenging issue. There are several institutional levels of medical knowledge reproducing racism in the health care sector. • Both racialized physicians and racialized patients are affected by symbolic and material forms of racism in the German health care system, which are interweaving and crucial on diverse levels.

The increasing demand for resource-efficient production methods is driving the development of new technologies. Sheet bulk metal forming (SBMF) offers the possibility to combine sheet metal and bulk forming operations. This allows the production of complex functional components with secondary forming elements from sheet metal. Compared to other production techniques such as machining, a more efficient use of material can be achieved. Further advantages are a near net shape production and increased strain hardening. SBMF processes are limited by forming technology boundaries. These include high forming forces, incomplete mould fillings and limited surface qualities. In this research, the possibility of enhancing the material flow, improving surface quality and reducing the tool loads in SBMF-processes is investigated by using a superimposed oscillation. The focus here is on achieving a high surface quality of components produced by forming technology and an enhanced material flow during forming. For this purpose, a forming process for ironing an axial gear geometry is superimposed with an oscillation in the main force flow.

Frauen mit Varianten der Geschlechtsentwicklung haben das Risiko einer malignen Entartung der Keimzellen in ihren dysgenetischen Gonaden, wenn diese ein Y‑Chromosom enthalten. Vermutliche Ursache ist die unkontrollierte Expression der 3 Y‑Gene DDX3Y, TSPY und UTY im Gonadoblastom-Y(GBY)-Locus. Ihre Funktion in der mannlichen Keimbahn ist die Kontrolle der Proliferation fetaler und prameiotischer Spermatogonien. Gonadoblastomzellen entstehen aus Keimzellen, wenn eine Veranderung in der geschlechtsspezifischen Gonadenentwicklung bereits sehr fruh in der Entwicklung eines 46,XY-Embryos stattgefunden hat und dessen fetale, eigentlich mannliche Keimzellen von Granulosazellen – spezifisch fur die weiblichen Gonaden – umgeben sind. Eine 2. klinische Entitat mit Varianten der Geschlechtsentwicklung findet sich bei Frauen mit 46,XY-Chromosomensatz und einer kompletten, oder partiellen Storung der Bindung von Testosteron und Dihydrotestosteron an den Androgenrezeptor durch Exonmutationen („Complete/Partial Androgen Insensitivity syndrome“ [CAIS/PAIS]). Histologisch sind in diesen Fallen die aberranten mannlichen Keimzellen von Sertoli-Zellen umgeben. Die beiden Patientengruppen unterscheiden sich deutlich in ihrem Risiko einer malignen Entartung der aberranten Keimzellen; nur bei kompletter Gonadendysgenesie ist es hoch (22–66 %). Bei CAIS-Patienten ist es vor der Pubertat relativ niedrig (2–4 %). Zur Abschatzung des Risikos einer Tumorentwicklung ist neben der Diagnostik des GBY-Locus die immunhistochemische Diagnostik von OCT3/4 zu empfehlen. Eine nichtinvasive Risikoabschatzung bezuglich der malignen Entartung der Keimzellen durch Expressionsanalysen spezifischer Mikro-RNA-Populationen in einer Blutprobe konnte eine diagnostische Gonadenbiopsie in Zukunft uberflussig machen.

Translational control is a major level of gene expression regulation in the male germ line. DDX3Y located in the AZFa region of the human Y chromosome encodes a conserved RNA helicase important for translational control at the G1-S phase of the cell cycle. In human, DDX3Y protein is expressed only in premeiotic male germ cells. In primates, DDX3Y evolved a second promoter producing novel testis-specific transcripts. Here, we show primate species-specific use of alternative polyadenylation (APA) sites for these testis-specific DDX3Y transcript variants. They have evolved subsequently in the 3´UTRs of the primates´ DDX3Y transcripts. Whereas a distal APA site (PAS4) is still used for polyadenylation of most DDX3Y testis transcripts in Callithrix jacchus; two proximal APAs (PAS1; PAS2) are used predominantly in Macaca mulatta, in Pan trogloydates and in human. This shift corresponds with a significant increase of DDX3Y protein expression in the macaque testis tissue. In chimpanzee and human, shift to predominant use of the most proximal APA site (PAS1) is associated with translation of these DDX3Y transcripts in only premeiotic male germ cells. We therefore assume evolution of a positive selection process for functional DDX3Y testis transcripts in these primates which increase their stability and translation efficiency to promote its cell cycle balancing function in the human male germ line.

Als Varianten der Geschlechtsentwicklung („differences of sex development“ [DSD]) werden Abweichungen von der normalen weiblichen oder mannlichen Entwicklung mit genitalen Fehlbildungen bezeichnet. DSD konnen durch chromosomale Aberrationen oder Genmutationen bedingt sein, die zu Entwicklungsstorungen der Gonaden fuhren. Hervorgerufen werden sie aber auch durch endokrine Storungen mit Veranderung der Hormonsynthese bzw. -wirkung oder durch sonstige Ursachen. In der Gynakologie trifft man auf weibliche Individuen mit bereits im Kindesalter diagnostizierter DSD oder mit bisher unentdeckter DSD bei Leitsymptom einer primaren Amenorrho. Zu den haufigsten DSD in der Gynakologie gehoren das Ullrich-Turner-Syndrom und die 46,XX-Gonadendysgenesie (GD), jeweils mit Stranggonaden und hypergonadotroper primarer Amenorrho. Es folgen die gemischte GD, die 46,XY-GD (Swyer-Syndrom), die komplette Androgenresistenz und das Mayer-Rokitansky-Kuster-Hauser-Syndrom. Bei einem Y‑Anteil im Karyotyp ist die Biopsie oder Entfernung der Gonaden abhangig vom individuellen Malignitatsrisiko zu diskutieren. Therapeutisch geht es je nach Diagnose um Pubertatsinduktion, individualisierte Hormontherapie und gegebenenfalls plastische Korrekturen am auseren Genitale. Ein interdisziplinares Management, um assoziierte Fehlbildungen behandeln zu konnen und die Moglichkeit einer psychologischen Begleitung sicherzustellen, ist essenziell.

We aimed to determine whether a functional link with impact on female ovarian reserve exists between FMR1 expression and expression ratios of AKT/mTOR signaling genes in human granulosa cells in vivo, as suggested from prior in vitro data. Three hundred and nine women, who were classified as normal (NOR, n = 225) and poor (POR, n = 84) responders based on their ovarian reserve, were recruited during stimulation for assisted reproductive techniques. Expressions of FMR1 and of key genes of the AKT/mTOR and AKT/FOXO1/3 signaling pathways were comparatively analyzed in their granulosa cells. FMR1 expression in granulosa cells of NOR and POR correlated significantly with AKT1, TSC2, mTOR, and S6K expression. No correlation was found between FMR1 and FOXO1 in all, and FOXO3 expression in POR, patients. AKT1 expression was significantly higher and FOXO1 expression lower in POR samples, whereas AKT1 expression was lower and FOXO1 expression was higher in NOR samples. In human native granulosa cells, FMR1 expression significantly correlated with the expression of key genes of the AKT/mTOR signaling pathway, but not with the FOXO1/3 signaling pathway. Our data point to a functional link between FMR1 expression and expression of the AKT/mTOR signaling pathway genes controlling human follicular maturation.

R. cingulata (listed on EPPO A2 list) is a severe pest of cherries. It is closely connected to its host plants Prunus avium, P. cerasi, P. serotina, P. mahaleb and P. emarginata. Prunus mahaleb is native in warm locations of Southern and Central Europe. It is used as rootstock for tart cherries and as ornamental plant. In Germany R. cingulata appears 3-4 weeks later than the native species R. cerasi, and due to this attacks late cherry varieties, mainly tart cherries, e.g. the economic important variety "Schattenmorellen". This has been proven by fruit samples, from which pupae were obtained and in the following year R. cingulata adults emerged (species confirmed by Dr. Allen Norrbom, Systematic Entomology Laboratory, USDA). Infestation levels in tart cherries amounted to more than 20%.

Genomic AZFb deletions in Yq11 coined “classical” (i.e. length of Y DNA deletion: 6.23 Mb) are associated with meiotic arrest (MA) of patient spermatogenesis, i.e., absence of any postmeiotic germ cells. These AZFb deletions are caused by non-allelic homologous recombination (NAHR) events between identical sequence blocks located in the proximal arm of the P5 palindrome and within P1.2, a 92 kb long sequence block located in the P1 palindrome structure of AZFc in Yq11. This large genomic Y region includes deletion of 6 protein encoding Y genes, EIFA1Y, HSFY, PRY, RBMY1, RPS4Y, SMCY. Additionally, one copy of CDY2 and XKRY located in the proximal P5 palindrome and one copy of BPY1, two copies of DAZ located in the P2 palindrome, and one copy of CDY1 located proximal to P1.2 are included within this AZFb microdeletion. It overlaps thus distally along 2.3 Mb with the proximal part of the genomic AZFc deletion. However, AZFb deletions have been also reported with distinct break sites in the proximal and/or distal AZFb breakpoint intervals on the Y chromosome of infertile men. These so called “non-classical” AZFb deletions are associated with variable testicular pathologies, including meiotic arrest, cryptozoospermia, severe oligozoospermia, or oligoasthenoteratozoospermia (OAT syndrome), respectively. This raised the question whether there are any specific length(s) of the AZFb deletion interval along Yq11 required to cause meiotic arrest of the patient’s spermatogenesis, respectively, whether there is any single AZFb Y gene deletion also able to cause this “classical” AZFb testicular pathology? Review of the literature and more cases with “classical” and “non-classical” AZFb deletions analysed in our lab since the last 20 years suggests that the composition of the genomic Y sequence in AZFb is variable in men with distinct Y haplogroups especially in the distal AZFb region overlapping with the proximal AZFc deletion interval and that its extension can be “polymorphic” in the P3 palindrome. That means this AZFb subinterval can be rearranged or deleted also on the Y chromosome of fertile men. Any AZFb deletion observed in infertile men with azoospermia should therefore be confirmed as “de novo” mutation event, i.e., not present on the Y chromosome of the patient’s father or fertile brother before it is considered as causative agent for man’s infertility. Moreover, its molecular length in Yq11 should be comparable to that of the “classical” AZFb deletion, before meiotic arrest is prognosed as the patient’s testicular pathology.

In humans, FMR1 (fragile X mental retardation 1) is strongly expressed in granulosa cells (GCs) of the female germline and apparently controls efficiency of folliculogenesis. Major control mechanism(s) of the gene transcription rate seem to be based on the rate of CpG-methylation along the CpG island promoter. Conducting CpG-methylation-specific bisulfite-treated PCR assays and subsequent sequence analyses of both gene alleles, revealed three variably methylated CpG domains (FMR1-VMR (variably methylated region) 1, -2, -3) and one completely unmethylated CpG-region (FMR1-UMR) in this extended FMR1-promoter-region. FMR1-UMR in the core promoter was exclusively present only in female GCs, suggesting expression from both gene alleles, i.e., escaping the female-specific X-inactivation mechanism for the second gene allele. Screening for putative target sites of transcription factors binding with CpG methylation dependence, we identified a target site for the transcriptional activator E2F1 in FMR1-VMR3. Using specific electrophoretic mobility shift assays, we found E2F1 binding efficiency to be dependent on CpG-site methylation in its target sequence. Comparative analysis of these CpGs revealed that CpG 94-methylation in primary GCs of women with normal and reduced efficiency of folliculogenesis statistically significant differences. We therefore conclude that E2F1 binding to FMR1-VMR3 in human GCs is part of an epigenetic mechanism regulating the efficiency of human folliculogenesis. Our data indicate that epigenetic mechanisms may control GC FMR1-expression rates.

Due to the low density and high tensile strength, the aluminium alloy EN AW-7075 offers a high lightweight potential for structural components. In recent years, 7xxx-aluminium alloys have been the subject of numerous investigations in the field of warm and hot forming and suitable heat treatments to fully use their potential for applications in automotive bodies. Alternatively, forming blanks of these alloys at room temperature in the W-temper state is favourable since conventional tools can be used. However, this condition is unstable. As the ageing duration after quenching increases, the formability decreases due to natural ageing. Hence, the objective of this investigation was to determine the formability of EN AW-7075 as a function of the ageing time. Furthermore, since the quenching rate after solution heat treatment influences the resulting mechanical properties, an adapted process route to manufacture components with tailored properties was explored. For this purpose, samples were partially quenched after solution heat treatment and then artificially aged. To determine the influence of the quenching rate, hardness tests were carried out.

A superimposed oscillation in the main force flow of a forming process is investigated. Therefore a tool system was developed. The oscillation in this system is generated by pulsating oil streams. As part of this research, the oscillation device is equipped with additional storage tanks, to generate a higher oil volume flow. The upgraded oscillation system is installed in a forming process. In this research, the influence of the superimposed oscillation on the necessary plastic work to form a complex gear geometry is examined. An analysis of the influence of higher forming forces, higher operating pressures and longer process times on the operating behavior of the oscillating device also takes place. The identified optimal process parameters are used in a model process based on the industrial forming process of the company Felss Systems GmbH. Furthermore, an experimental test setup to carry out these investigations is developed in this research. Forming experiments to iron an external gear geometry oscillation-free and superimposed oscillated are conducted with the new test stand.

STUDY OBJECTIVES: REM sleep behavior disorder (RBD) is characterized by dream enactment behavior and is a premotoric sign associated with parkinsonism and dementia. We previously found contrast sensitivity visual acuity (CSVA) deficiencies in earliest stages of Parkinson disease (PD), plausibly associated with alpha-synuclein deposits in the inner retinal layers. We speculated that individuals with REM sleep behavior without clinical signs of parkinsonism might also show similar deficiencies. METHODS: Twenty-three patients with RBD and 28 healthy control patients. Eleven with PD and 12 with idiopathic RBD (iRBD). Twelve patients with RBD were re-evaluated after 1 year. Evaluations consisted of CSVA SLOAN low contrast acuity charts, optical coherence topography, Unified Parkinson’s Disease Rating Scale (UPDRS), and general neurologic and ophthalmologic examinations. Data analyzed between groups using a one-way analysis of variance, and a paired samples t test for returning patients. RESULTS: Participants were classified into three groups: controls (n = 28), iRBD (n = 12), and RBD+PD (n = 11). Analysis of variance revealed CSVA scores were statistically significantly different between the three groups F(2, 50) = 7.037, P = .002. Longitudinal analysis of RBD group showed CSVA decreased significantly at 1 year (P = .0141). To date, PD has developed in three individuals with iRBD based on progression of their UPDRS scores. CONCLUSIONS: CSVA is reduced in individuals with RBD and declines over time. It is plausible that patients with iRBD may show early loss in dopaminergic lateral inhibition in the retina, evidenced by their progressive loss of CSVA. This may represent a global loss of dopaminergic neurons similar to PD. CITATION: Whitfield WH, Barr GQ, Khayata MJ, et al. Contrast sensitivity visual acuity in REM sleep behavior disorder: a comparison with and without Parkinson disease. J Clin Sleep Med. 2020;16(3):385–388.

Genetische Ursachen bei pramaturer Ovarialinsuffizienz („premature ovarian insufficiency“ [POI]) sind in ihrer Inzidenz und klinischen Relevanz sehr unterschiedlich. Teilweise handelt es sich bei den in der Literatur dokumentierten genetischen Ursachen um Einzelfallbeschreibungen von Genvarianten mit sehr seltenem Vorkommen. Andere genetische Faktoren wie die FMR1-Pramutation, FOXL2-Mutationen und das Turner-Syndrom sind allerdings haufig und stehen aufgrund ihrer moglichen Folgen nicht nur fur die Patienten selbst, sondern auch fur ihre Verwandte bei der klinischen Diagnostik eines POI im Vordergrund. Bei den genetisch bedingten Ursachen handelt es sich um X‑chromosomal wie auch autosomal lokalisierte molekulargenetische Veranderungen oder auch um strukturelle, ganze Chromosomen betreffende, zytogenetische Veranderungen.

Aufgrund der hohen erreichbaren Festigkeit eignen sich formgehärtete Bauteile besonders zur Reduzierung der Massen von modernen Karosseriebauteilen. Die hohe Festigkeit führt allerdings zu einer eingeschränkten Einsatzmöglichkeit von mechanischen Fügeverfahren. Daher soll die Duktilität des Blechwerkstoffs während des Formhärtens genutzt werden, um zeitgleich ein Funktionselement in das Bauteil einzubringen. Hierfür wurde ein Werkzeugsystem konstruiert sowie experimentell erprobt. Due to their high achievable strength, hot stamped components are particularly suitable for reducing the mass of modern car body parts. However, the high strength also leads to a limited application of mechanical joining processes. Therefore, the ductility of the sheet material during hot stamping should be used to simultaneously applicate a functional element into the component. A tool system was designed and put into operation for this purpose.