Age at diagnosis of Type 2 diabetes in Germany: a nationwide analysis based on claims data from 69 million people.

AIM: For many European countries, including Germany, no valid estimates are available on age at diagnosis of Type 2 diabetes. Thus, we aimed to estimate the age at diagnosis in Germany. METHODS: Age at diagnosis of Type 2 diabetes in Germany was estimated based on Type 2 diabetes prevalence and incidence and the age distribution of the German population. Age- and sex-specific incidence and prevalence in 2014/2015, based on claims data from statutory health insurance (n= 69 000 000, ~85% of the German population), and the age pyramid for Germany in 2015 were used for the calculation. Age at Type 2 diabetes diagnosis was stratified by sex. CIs were estimated using bootstrap methods. In addition, the age range in which 50% of the population received a diagnosis of Type 2 diabetes was calculated (the interquartile range). RESULTS: The mean ± sd age at Type 2 diabetes diagnosis in 2015 was 61.0 ± 13.4 years (95% CI 60.9-61.0) in men. Women were diagnosed ~2 years later than men (mean age 63.4 ± 14.9 years; 95% CI 63.4-63.5). The age range in which 50% of the population was diagnosed with diabetes was 53-72 years for men and 54-76 years for women. CONCLUSIONS: The sex differences are mainly attributable to a higher incidence of Type 2 diabetes in men than women during middle age and the higher absolute number of women in the older ages. The early age at diabetes diagnosis compared to average life expectancy means that the risk of diabetes-related complications is increased.

A Behavioral Assay to Study Effects of Retinoid Pharmacology on Nervous System Development in a Marine Annelid.

Autonomous animal locomotion, such as swimming, is modulated by neuronal networks acting on cilia or muscles. Understanding how these networks are formed and coordinated is a complex scientific problem, which requires various technical approaches. Among others, behavioral studies of developing animals treated with exogenous substances have proven to be a successful approach for studying the functions of neuronal networks. One such substance crucial for the proper development of the nervous system is the vitamin A-derived morphogen retinoic acid (RA). In the larva of the marine annelid Platynereis dumerilii , for example, RA is involved in the specification and differentiation of individual neurons and responsible for orchestrating the swimming behavior of the developing larva. Here, we report a workflow to analyze the effects of RA on the locomotion of the P. dumerilii larva. We provide a protocol for both the treatment with RA and the recording of larval swimming behavior. Additionally, we present a pipeline for the analysis of the obtained data in terms of swimming speed and movement trajectory. This chapter thus summarizes the methodology for analyzing the effects of a specific drug treatment on larval swimming behavior. We expect this approach to be readily adaptable to a wide variety of pharmacological compounds and aquatic species.

Vasa unveils a common origin of germ cells and of somatic stem cells from the posterior growth zone in the polychaete Platynereis dumerilii.

To elucidate the evolution of germ cell specification in Metazoa, recent comparative studies focus on ancestral animal groups. Here, we followed the germline throughout the life cycle of the polychaete annelid Platynereis dumerilii, by examining mRNA and protein expression of vasa and other germline-specific factors in combination with lineage tracing experiments. In the fertilised egg, maternal Vasa protein localises to the yolk-free cytoplasm at the animal pole. It then asymmetrically segregates first into the micromeres, then into the founder cells of the mesodermal posterior growth zone (MPGZ). Vasa transcripts initially show ubiquitous distribution, but then become progressively restricted to the MPGZ. The cells of the MPGZ are highly proliferative, as evidenced by BrdU pulse labelling experiments. Besides vasa, they express nanos along with the stem cell-specific genes piwi, and PL10. At 4 days of development, four primordial germ cells are singled out from within the MPGZ, and migrate into the anterior segments to colonise a newly discovered "primary gonad". Our data suggest a common origin of germ cells and of somatic stem cells, similar to the situation found in planarians and cnidarians, which may constitute the ancestral mode of germ cell specification in Metazoa.

Reconstructing the eyes of Urbilateria.

The shared roles of Pax6 and Six homologues in the eye development of various bilaterians suggest that Urbilateria, the common ancestors of all Bilateria, already possessed some simple form of eyes. Here, we re-address the homology of bilaterian cerebral eyes at the level of eye anatomy, of eye-constituting cell types and of phototransductory molecules. The most widespread eye type found in Bilateria are the larval pigment-cup eyes located to the left and right of the apical organ in primary, ciliary larvae of Protostomia and Deuterostomia. They can be as simple as comprising a single pigment cell and a single photoreceptor cell in inverse orientation. Another more elaborate type of cerebral pigment-cup eyes with an everse arrangement of photoreceptor cells is found in adult Protostomia. Both inverse larval and everse adult eyes employ rhabdomeric photoreceptor cells and thus differ from the chordate cerebral eyes with ciliary photoreceptors. This is highly significant because on the molecular level we find that for phototransduction rhabdomeric versus ciliary photoreceptor cells employ divergent rhodopsins and non-orthologous G-proteins, rhodopsin kinases and arrestins. Our comparison supports homology of cerebral eyes in Protostomia; it challenges, however, homology of chordate and non-chordate cerebral eyes that employ photoreceptor cells with non-orthologous phototransductory cascades.

Medaka eyeless is the key factor linking retinal determination and eye growth.

The complete absence of eyes in the medaka fish mutation eyeless is the result of defective optic vesicle evagination. We show that the eyeless mutation is caused by an intronic insertion in the Rx3 homeobox gene resulting in a transcriptional repression of the locus that is rescued by injection of plasmid DNA containing the wild-type locus. Functional analysis reveals that Six3- and Pax6- dependent retina determination does not require Rx3. However, gain- and loss-of-function phenotypes show that Rx3 is indispensable to initiate optic vesicle evagination and to control vesicle proliferation, by that regulating organ size. Thus, Rx3 acts at a key position coupling the determination with subsequent morphogenesis and differentiation of the developing eye.

Evolution of the bilaterian larval foregut.

Bilateria are subdivided into Protostomia and Deuterostomia. Indirect development through primary, ciliary larvae occurs in both of these branches; however, the closing blastopore develops into mouth and anus in Protostomia and into anus only in Deuterostomia. Because of this important difference in larval gut ontogeny, the tube-shaped guts in protostome and deuterostome primary larvae are thought to have evolved independently. To test this hypothesis, we have analysed the expression of brachyury, otx and goosecoid homologues in the polychaete Platynereis dumerilii, which develops by means of a trochophora larva-the primary, ciliary larva prototypic for Protostomia. Here we show that brachyury expression in the ventral portion of the developing foregut in Platynereis and also otx expression along ciliated bands in the mouth region of the trochophora larva parallels expression in primary larvae in Deuterostomia. In addition, goosecoid expression in the foregut of Platynereis mirrors the function in higher Deuterostomia. We present molecular evidence for the evolutionary conservation of larval foreguts and mouth regions of Protostomia and Deuterostomia. Our data indicate that Urbilateria, the common bilaterian ancestors, developed through a primary, ciliary larva that already possessed a tripartite tube-shaped gut.

Role of the dental team in mass fatality incidents.

The process of dental identification for a mass fatality incident has unique aspects in comparison with that of a routine dental identification, outside of the obvious increase in the number of victims and responders. The dental team is a small part of a large effort to resolve the incident. Incident command structure applies to the dental team as a unit as well as to the entire organization of the response. Teamwork and planning are essential on all levels. Discussing the casework is limited to the public information officer; only the public information officer is authorized to talk to anyone outside the medical examiner's office. For the team, communication is essential between the team members and between the team and other morgue sections. Daily meetings not only update progress, but also identify and solve problems as they arise. Redundancy and cross-checking occur each step in each section. A core team of trained individuals provides a framework for the use of less experienced members. Use of a dental identification computer program is extremely beneficial, especially as the amount of fragmentation or number of victims increases. Because of the magnitude of the response, the physical and mental stresses require critical incident stress debriefing for all responders, regardless of their experience. The past and future service of the dental profession to the victims of mass fatality incidents and their families is an excellent example of the ideal of service on which the profession is based.

Aggressive (malignant) epithelial odontogenic ghost cell tumor.

A 57-year-old man had an expanding cystic lesion of the anterior maxilla that demonstrated destruction and disruption of local structures. A cystic odontogenic neoplasm as well as various forms of odontogenic carcinoma was suspected. Incisional biopsy and microscopic examination revealed an aggressive epithelial odontogenic tumor with histologic features suggesting malignant transformation from an odontogenic cyst. The patient continues to refuse further treatment despite remaining tumor. This case further documents the malignant potential of a calcifying odontogenic cyst and the existence of at least an aggressive or possibly malignant form of epithelial odontogenic ghost cell tumor. To date, metastatic work-up has not been performed.

[The human being from the point of view of animals or, "Who knows whether the breath of men goes upwards?" (Ecclesiastes 3:21)]. / Der Mensch in animalischer Perspektive oder "Wer weiss, ob der Odem des Menschen aufwärts fahre?" (Koh. 3,21).

The question of whether animals have souls has been asked since as early as the Old Testament. Where this is believed to be true, fiction has provided interesting models in literature: The human being as seen by animals has been a popular subject since Apuleius' 'Asinus aureus' and how man appears from the perspective of a donkey or a beetle, that is to say the perspective from below, becomes controversial. Examples may be found in all languages and centuries in Jonathan Swift, Miguel Cervantes, E. T. A. Hoffmann, Ludwig Tieck, Heinrich Heine, Viktor von Scheffel, Franz Kafka and others. Résumé at the end: How does man answer this question or his own self-questioning?

Rearranging gastrulation in the name of yolk: evolution of gastrulation in yolk-rich amniote eggs.

Gastrulating birds and mammals form a primitive streak in lieu of a circular blastopore, and a conspicuous underlying tissue layer, the hypoblast. In an attempt to understand the evolution of these amniote characteristics, pregastrula and gastrulation stages in selected amniotes are compared with the more ancestral situation in amphibians. At blastula/blastoderm stages, the overall fate maps and the arrangement of tissues around the organizer are rather similar, as is exemplified by a comparison of gene expression and fate maps in the frog and chick. Compared with amphibians, however, the eggs of reptiles, birds and monotreme mammals have a disproportionately large yolk that alters gastrulation morphology. During amphibian gastrulation, the organizer moves from anterior to posterior, to lay down the dorsal axis around the vegetal hemisphere (Arendt, D., Nübler-Jung, K., 1997. Dorsal or ventral: similarities in fate maps and gastrulation patterns in annelids, arthropods and chordates. Mech. Dev. 61, 1-15). In contrast, in amniote eggs, the large yolk impedes the organizer from moving around the entire vegetal hemisphere so that axis formation begins and ends at the same side of the egg. This has apparently provoked an evolutionary transformation of an amphibian-like blastopore, first into the 'blastoporal canal' of reptiles, and then into the birds' and mammals' primitive streak. The blastopore divides into two functionally divergent parts, one as the site of mesoderm internalization ('intraembryonic blastopore') and the other as the site of ectodermal epiboly ('extraembryonic blastopore'). The hypoblast is proposed to derive from the 'endodermal wedge' that is seen already in the amphibian gastrula. Hypoblast formation would then represent a special kind of gastrulation movement that also exists in the amphibians, and for which the term 'hypoboly' is introduced.

Comparison of early nerve cord development in insects and vertebrates.

It is widely held that the insect and vertebrate CNS evolved independently. This view is now challenged by the concept of dorsoventral axis inversion, which holds that ventral in insects corresponds to dorsal in vertebrates. Here, insect and vertebrate CNS development is compared involving embryological and molecular data. In insects and vertebrates, neurons differentiate towards the body cavity. At early stages of neurogenesis, neural progenitor cells are arranged in three longitudinal columns on either side of the midline, and NK-2/NK-2.2, ind/Gsh and msh/Msx homologs specify the medial, intermediate and lateral columns, respectively. Other pairs of regional specification genes are, however, expressed in transverse stripes in insects, and in longitudinal stripes in the vertebrates. There are differences in the regional distribution of cell types in the developing neuroectoderm. However, within a given neurogenic column in insects and vertebrates some of the emerging cell types are remarkably similar and may thus be phylogenetically old: NK-2/NK-2.2-expressing medial column neuroblasts give rise to interneurons that pioneer the medial longitudinal fascicles, and to motoneurons that exit via lateral nerve roots to then project peripherally. Lateral column neuroblasts produce, among other cell types, nerve root glia and peripheral glia. Midline precursors give rise to glial cells that enwrap outgrowing commissural axons. The midline glia also express netrin homologs to attract commissural axons from a distance.

Dorsal or ventral: similarities in fate maps and gastrulation patterns in annelids, arthropods and chordates.

The idea that chordates, during their evolution, have inverted their dorsoventral body axis has recently gained substantial support. It has been shown that various dorsoventral patterning genes that are evolutionarily conserved between insects and vertebrates are expressed dorsally in insects, and ventrally in vertebrates, or vice versa. The ventral body side of insects thus seems to correspond to the dorsal body side of vertebrates, and these are nerve cord-bearing, neural body sides in both groups. In order to exclude that the inverted polarity of gene patterning activity is purely accidental, we compare here vertebrate and invertebrate blastula fate maps and their gastrulation patterns in the framework of early gene expression. From this comparison it appears that the neural body sides, 'ventral' in annelids or arthropods, and 'dorsal' in chordates, develop at similar positions with respect to the initial egg asymmetry. In addition, the formation of the neural body sides involves similar movements during gastrulation. We further suggest that the deuterostome gastrulation seen in today's chordates can be derived from a more ancestral gastrulation pattern seen in today's annelids and arthropods, and that the ventral midline cells of insects correspond to the dorsal midline cells of vertebrates.

Common ground plans in early brain development in mice and flies.

Comparing expression patterns of orthologous genes between insects and vertebrates, we have recently proposed that the ventral nerve cord in insects may correspond to the dorsal nerve cord in vertebrates. Here we show that the early development of the insect and vertebrate brain anlagen is indeed very similar. Insect and vertebrate brains express similar sets of genes in comparable areas with similar functions in the adult. In addition, early axogenesis establishes surprisingly similar patterns of axonal connectivity in both groups. We therefore propose that insect and vertebrate brains are built according to a common ground plan, and that specific areas of the insect and vertebrate brains be considered as homologous, meaning that these areas already existed, with their specific functions, in their common ancestor.

The effect of cold therapy on pain, swelling, and range of motion after anterior cruciate ligament reconstructive surgery.

This prospective study assessed the effect of cold therapy on pain, pain medication use, limb swelling, and knee range of motion in 131 patients who had an arthroscopically assisted anterior cruciate ligament reconstruction. Patients were randomized into five treatment groups. Cooling pads were incorporated into the dressing in 89 patients, and no cooling pads were used in 42 patients. There were four cooling-pad temperature groups: 40 degrees F, 45 degrees F, 55 degrees F, and 70 degrees F. The cooling pads lowered the skin temperature. There was no difference between groups with respect to hospital stay, pain medication use, pain scale, knee girth, or range of motion.

Blocked endocytotic uptake by the oocyte causes accumulation of vitellogenins in the haemolymph of the female-sterile mutants quitPX61 and stand stillPS34 of Drosophila.

The developmental lesions in two female-sterile mutants, quitPX61 (qui) and stand stillPS34 (stil), of Drosophila have been analysed. Previtellogenic development is normal in mutant qui ovarioles but, during vitellogenic stages, only small quantities of yolk accumulate in the oocyte. The nurse-cell cytoplasm does not stream into the oocyte. However, the follicle cells continue their developmental program and synthesize an excessive quantity of eggshell material. In the mutant stil, the oocyte remains small and contains only a fraction of the yolk proteins present in wild-type follicles. Histological and ultrastructural observations and the failure to incorporate trypan blue indicate that the yolk proteins present in the mutant follicles are neither derived from the fat body nor from the follicle cells. Since, in both mutants, the uptake mechanism of vitellogenin is affected, the 3 polypeptides accumulate in the haemolymph (in stil, the protein concentration is up to 4 times higher than in wild-type females) and the haemolymph volume increases. Reciprocal transplantations of ovarioles show that the developmental lesions in both mutants are ovary-autonomous. Furthermore, genetic chimeras of stil show that the activity of the stil gene is required in the germline cells and not in the somatic tissues.