Prevalence and predictors of vitamin D-deficiency in frail older hospitalized patients.

BACKGROUND: Vitamin D deficiency is known to be highly prevalent in older persons. However, the prevalence in the subgroup of frail older hospitalized patients is not clear. We sought to investigate the prevalence and predictors of vitamin D deficiency in frail older hospitalized patients. METHODS: 217 consecutively geriatric hospitalized patients with routine measurements of 25-hydroxyvitamin D [25 (OH)D] at hospital admission were analyzed retrospectively, including information of previous vitamin D supplementation and the geriatric assessment. Serum 25 (OH)D concentrations < 20 ng/ml and between 20 and 29.99 ng/ml were classified as deficient and insufficient, respectively, whereas concentrations ≥30 ng/ml were considered as desirable. A stepwise binary logistic regression model was performed to assess the simultaneous effects of age, gender and geriatric assessments on the prevalence of low vitamin D concentration. RESULTS: Mean age of the cohort was 81.6 ± 8.0 years (70.0% females). Mean serum 25(OH)D was 12.7 ± 12.9 ng/ml. Of 167 (77%) subjects without known previous vitamin D supplementation, only 21 (12.6%) had serum concentrations ≥20 ng/ml and only 8 (4.2%) had desirable serum concentrations ≥30 ng/ml. In total population, 146 (87.4%) participants were vitamin D deficient. Despite vitamin D supplementation, 22 of 50 participants (44.0%) were vitamin D deficient and only 19 (38.0%) had desirable concentrations of ≥30 ng/ml. In a stepwise logistic regression analysis, only previous intake of vitamin D supplementation and high Geriatric Depression Scale score (GDS-15) were significantly associated with vitamin D deficiency. CONCLUSIONS: In the group of frail older hospitalized patients without previous vitamin D supplementation, the prevalence of inadequate vitamin D concentrations is extremely high. Therefore, usefulness of the routine measurement of vitamin D status before initiating of supplementation appears to be questionable in this patient group.

Spatiotemporal expression of Math6 during mouse embryonic development.

The basic helix-loop-helix transcription factor Math6 was shown to have important regulatory functions during many developmental events. However, a systematic description of Math6 expression during mouse embryonic development is up to now still lacking. We carried out this study to show Math6 expression at different stages of mouse embryonic development aiming to provide a wide insight into the regulatory functions during the mouse organogenesis. Using immunohistochemistry, we could show that Math6 expression is activated in the inner cell mass at the blastocyst stage and in the neural tube as well as somatic and splanchnic mesoderm at stage E8.5. At stages E8.5 and E10.5, Math6 transcripts were detected in the myotome, neural tube, pharyngeal arches, foregut and heart. At stages E11.5 and E12.5, Math6 transcripts were accumulated in the developing brain, heart, limb buds and liver. The heterozygous transgenic mouse embryos carrying EGFP-Cre under the Math6 promoter were used to analyze Math6 expression at later stages by means of immunohistochemistry against EGFP protein. EGFP was observed in the neural tube, heart, lung, skeletal muscle, skin, cartilage, trachea and aorta. We have observed Math6 expression in various organs at early and late stages of mouse development, which illustrates the involvement of Math6 in multiple developmental events.

Commitment of chondrogenic precursors of the avian scapula takes place after epithelial-mesenchymal transition of the dermomyotome.

BACKGROUND: Cells of the epithelially organised dermomyotome are traditionally believed to give rise to skeletal muscle and dermis. We have previously shown that the dermomyotome can undergo epithelial-mesenchymal transition (EMT) and give rise to chondrogenic cells, which go on to form the scapula blade in birds. At present we have little understanding regarding the issue of when the chondrogenic fate of dermomyotomal cells is determined. Using quail-chick grafting experiments, we investigated whether scapula precursor cells are committed to a chondrogenic fate while in an epithelial state or whether commitment is established after EMT. RESULTS: We show that the hypaxial dermomyotome, which normally forms the scapula, does not generate cartilaginous tissue after it is grafted to the epaxial domain. In contrast engraftment of the epaxial dermomyotome to the hypaxial domain gives rise to scapula-like cartilage. However, the hypaxial sub-ectodermal mesenchyme (SEM), which originates from the hypaxial dermomyotome after EMT, generates cartilaginous elements in the epaxial domain, whereas in reciprocal grafting experiments, the epaxial SEM cannot form cartilage in the hypaxial domain. CONCLUSIONS: We suggest that the epithelial cells of the dermomyotome are not committed to the chondrogenic lineage. Commitment to this lineage occurs after it has undergone EMT to form the sub-ectodermal mesenchyme.

Homeobox transcription factor Prox1 in sympathetic ganglia of vertebrate embryos: correlation with human stage 4s neuroblastoma.

Previously, we observed expression of the homeobox transcription factor Prox1 in neuroectodermal embryonic tissues. Besides essential functions during embryonic development, Prox1 has been implicated in both progression and suppression of malignancies. Here, we show that Prox1 is expressed in embryonic sympathetic trunk ganglia of avian and murine embryos. Prox1 protein is localized in the nucleus of neurofilament-positive sympathetic neurons. Sympathetic progenitors represent the cell of origin of neuroblastoma (NB), the most frequent solid extracranial malignancy of children. NB may progress to life-threatening stage 4, or regress spontaneously in the special stage 4s. By qRT-PCR, we show that Prox1 is expressed at low levels in 24 human NB cell lines compared with human lymphatic endothelial cells (LECs), whereas equal immunostaining of nuclei can be seen in embryonic LECs and sympathetic neurons. In NB stages 1, 2, 3, and 4, we observed almost equal expression levels, but significantly higher amounts in stage 4s NB. By immunohistochemistry, we found variable amounts of Prox1 protein in nuclei of NB cells, showing intra and interindividual differences. Because stage 4s NB are susceptible to postnatal apoptosis, we assume that high Prox1 levels are critical for their behavior.

Intrinsic cartilage-forming potential of dermomyotomal cells requires ectodermal signals for the development of the scapula blade.

The avian scapula has a dual origin. The cranial part derives from the somatopleure of the forelimb field, while the caudal part, the scapula blade, originates from the dermomyotomes of the cervicothoracic transition zone. Thus, these dermomyotomes have, in addition to the well-known myogenic, angiogenic, and dermogenic potential, the ability to form cartilage. The scapula blade is therefore a derivative of dermomyotomal chondrogenesis. Although the mechanisms that direct the sclerotomal chondrogenesis are beginning to be understood, little is known about dermomyotomal chondrogenesis. Here, we address the mechanisms that control dermomyotomal cells to become chondrocytes. After heterotopic transplantation of dorsal epithelial somite halves from the scapula-forming level to the cervical level, the grafted tissue retains the capability to form cartilage, indicating that the dermomyotomal chondrogenic potential must be specified during anterior-to-posterior regionalization of the paraxial mesoderm. Furthermore, we show that signals from the ectoderm are required, allowing dermomyotome cells to express markers associated with the chondrogenic lineage.

Impaired angiogenesis and tumor development by inhibition of the mitotic kinesin Eg5.

Kinesin motor proteins exert essential cellular functions in all eukaryotes. They control mitosis, migration and intracellular transport through interaction with microtubules. Small molecule inhibitors of the mitotic kinesin KiF11/Eg5 are a promising new class of anti-neoplastic agents currently evaluated in clinical cancer trials for solid tumors and hematological malignancies. Here we report induction of Eg5 and four other mitotic kinesins including KIF20A/Mklp2 upon stimulation of in vivo angiogenesis with vascular endothelial growth factor-A (VEGF-A). Expression analyses indicate up-regulation of several kinesin-encoding genes predominantly in lymphoblasts and endothelial cells. Chemical blockade of Eg5 inhibits endothelial cell proliferation and migration in vitro. Mitosis-independent vascular outgrowth in aortic ring cultures is strongly impaired after Eg5 or Mklp2 protein inhibition. In vivo, interfering with KIF11/Eg5 function causes developmental and vascular defects in zebrafish and chick embryos and potent inhibition of tumor angiogenesis in experimental tumor models. Besides blocking tumor cell proliferation, impairing endothelial function is a novel mechanism of action of kinesin inhibitors.

The formation of the avian scapula blade takes place in the hypaxial domain of the somites and requires somatopleure-derived BMP signals.

The avian scapula is a long bone located dorsally on the thorax. The cranial part that articulates with the upper limb is derived from the somatopleure of the forelimb field, while the caudal part, the scapula blade, originates from the dermomyotomes of brachial and thoracic somites. In previous studies, we have shown that scapula blade formation is intrinsically controlled by segment-specific information as well as extrinsically by ectoderm-derived signals. Here, we addressed the role of signals derived from the lateral plate mesoderm on scapula development. Chick-quail chimera experiments revealed that scapula precursor cells are located within the hypaxial domain of the dermomyotome adjacent to somatopleural cells. Barrier implantation between these two cell populations inhibited scapula blade formation. Furthermore, we identified BMPs as scapula-inducing signals from the somatopleure using injection of Noggin-producing cells into the hypaxial domain of scapula-forming dermomyotomes. We found that inhibition of BMP activity interfered with scapula-specific Pax1 expression and scapula blade formation. Taken together, we demonstrate that the scapula-forming cells located within the hypaxial somitic domain require BMP signals derived from the somatopleure for their specification and differentiation.