The Prevention of Musculoskeletal Complaints in Instrumental Musicians: A Systematic Review.

OBJECTIVE: This systematic review synthesizes the evidence of various interventions aiming to prevent muscu¬loskeletal complaints in professional musicians. METHODS: This study comprises a systematic review according to PRISMA guidelines. A database search was performed in Cochrane, Embase, and PubMed on 13 September 2022 without time and language restrictions. The search consisted of the following groups of keywords: preventive measures AND musculoskeletal AND musicians. Risk of bias was assessed with the PEDro and MINORs criteria. Two reviewers independently selected and assessed the quality of the studies. RESULTS: A total of 1,831 articles were screened and 20 articles were included in this review. There is a wide range of interventions aiming to reduce musculoskeletal complaints in musicians. Among the studied programs were interventions focused on strength, cardiovascular and general fitness, flexibility as well as educational interventions and combinations of these. On average, scientific quality was good, moderate, and low for randomized controlled trials (RCTs), comparative studies, and non-comparative studies, respectively. A significant beneficial effect of the evaluated intervention on either playing-related musculoskeletal disorders (PRMD) frequency or severity or (playing-related) pain frequency and intensity was reported in at least 12 of the 20 studies. In particular, interventions with a strength training program reported a beneficial effect on PRMD frequency and severity as well as pain intensity and interference on the short-term. CONCLUSION: This systematic review highlights the heterogeneity in interventions aiming to prevent musculoskeletal complaints in musicians. Strength training might have a positive short-term effect on reducing musculoskeletal complaints. There is a need for further research to improve the quality of evidence as well as long-term outcomes of injury prevention programs.

Ceramic-on-ceramic articulation in press-fit total hip arthroplasty as a potential reason for early failure, what about the survivors: a ten year follow-up.

PURPOSE: In press-fit total hip arthroplasty (THA), primary stability is needed to avoid micromotion and hereby aseptic loosening, the main reason for early revision. High aseptic loosening revision rates of the seleXys TH+ cup (Mathys Medical) with Ceramys ceramic-on-ceramic (CoC) bearing are seen in literature. Since CoC is presumed to overcome long-term wear-related revisions, the reason for early failure of this cup is important to clarify. The aim is to investigate its ten year outcomes and differentiate between potential causes and identify risk factors for aseptic loosening. METHODS: Retrospective screening of a prospectively documented series of 315 THAs was performed. Primary outcome was cumulative incidence of cup revision due to aseptic loosening. Secondary outcomes were component revision and reoperation. Additionally, potential predictive factors for aseptic loosening were evaluated. RESULTS: At the median follow-up of 9.7 years [IQR 4.4; 10.3], 48 TH+ (15.2%) were revised due to aseptic loosening. Competing risk analysis showed a ten year cumulative incidence of cup revision due to aseptic loosening of 15.6% (95% CI 12.0-20.2). Stabilization of early revision rates was observed, following a high rate of respectively 81.3% (n = 39) and 95.8% (n = 46) within the first two and three years. No significant predictive factors for aseptic loosening were found. CONCLUSION: The ten year results of seleXys TH+ cup with Ceramys CoC bearing showed an unacceptable high aseptic loosening rate, which stabilized over time after a high early failure incidence. This could be attributed to a problem with osseointegration during the transition of primary to definitive stability.

The application of platelet-rich plasma in the treatment of deep dermal burns: A randomized, double-blind, intra-patient controlled study.

Platelet-rich plasma (PRP) is a fraction of blood with a platelet concentration above baseline. When platelets get activated, growth factors involved in wound healing are released. The application of PRP has shown good results in wound care, however, up to date no substantial research has been performed on the effect of PRP in burn treatment. This randomized double blind intra-patient controlled study investigates the effect of autologous PRP on wound healing in burns that require surgery with a meshed split skin graft (SSG). Fifty-two patients with various areas of deep dermal to full thickness burns, receiving surgery with a SSG were included after informed consent. Comparable study areas A and B (intra-patient) were appointed, randomized and either treated with a SSG and PRP or with a SSG alone. At day 5 to 7 postoperative, the epithelialization and graft take rate were assessed. Three, six, and twelve months postoperative, follow-up measurements were performed in the form of POSAS-questionnaires, DermoSpectroMeter, and Cutometer measurements. There was no statistically significant difference between the mean take rate nor the mean epithelialization rate at day 5-7 between the PRP-treated and control areas. However, PRP-treated wound areas showed more often better or equal epithelialization and take rates at day 5-7 than the standard treated areas. Minor effects were also seen in the reoperated and early operated subgroups. At 3, 6, and 12 months postoperative, POSAS scores from the patients and the observers, Dermaspectro-, and Cutometer measurements did not depict a significant difference between the PRP and standard treated areas. Concluding, the addition of PRP in the treatment of burn wounds did not result in improved graft take and epithelialization, nor could we demonstrate better scar quality. There was, however, a considerable variation in our clinical population.

Biopsychosocial complexity in patients scheduled for elective TKA surgery: A feasibility pilot study with the INTERMED self-assessment questionnaire.

OBJECTIVE: Primary aim; to determine the feasibility of implementation of the INTERMED Self-Assessment (IM-SA) in adult patients scheduled for total knee arthroplasty (TKA). Secondary aim; to measure biopsychosocial complexity, referral to psychiatry or psychology in cases of complexity and to gain insight into the relation between biopsychosocial complexity and length of stay (LOS), method of discharge (MOD) and polypharmacy. METHODS: A feasibility study was conducted with 76 participants in a general hospital in the Netherlands. Feasibility was determined by the number of completed questionnaires, time spent completing the questionnaire and the attitude of staff and patients towards the IM-SA. A cut off point ≥19 on the IM-SA was used to determine the prevalence of biopsychosocial complexity. A case file study was performed to check if referral to psychiatry or psychology had taken place. The Spearman's Rank Correlation Coefficient or Phi was used to determine if there was a relation between biopsychosocial complexity and LOS, MOD and polypharmacy. RESULTS: All participants completed the IM-SA. The average time spent completing the questionnaire was 11.46 min (SD 5.74). The attitude towards the IM-SA was positive. The prevalence of biopsychosocial complexity was 11.84%. Referral to psychiatry or psychology did not take place. There was no relation between complexity and LOS (Spearman's rho (r) = 0.079, p = 0.499, MOD (Phi = 0.169, p = 0.173) and polypharmacy (Phi = 0.007, p = 0.953). CONCLUSION: Biopsychosocial complexity can be identified in TKA patients during the pre-operative phase by using the IM-SA. Implementation of the IM-SA in a Dutch general hospital is feasible.

Laboratory-based surveillance in the molecular era: the TYPENED model, a joint data-sharing platform for clinical and public health laboratories.

Laboratory-based surveillance, one of the pillars of monitoring infectious disease trends, relies on data produced in clinical and/or public health laboratories. Currently, diagnostic laboratories worldwide submit strains or samples to a relatively small number of reference laboratories for characterisation and typing. However, with the introduction of molecular diagnostic methods and sequencing in most of the larger diagnostic and university hospital centres in high-income countries, the distinction between diagnostic and reference/public health laboratory functions has become less clear-cut. Given these developments, new ways of networking and data sharing are needed. Assuming that clinical and public health laboratories may be able to use the same data for their own purposes when sequence-based testing and typing are used, we explored ways to develop a collaborative approach and a jointly owned database (TYPENED) in the Netherlands. The rationale was that sequence data - whether produced to support clinical care or for surveillance -can be aggregated to meet both needs. Here we describe the development of the TYPENED approach and supporting infrastructure, and the implementation of a pilot laboratory network sharing enterovirus sequences and metadata.

Preoperative PSMA-PET/CT as a predictor of biochemical persistence and early recurrence following radical prostatectomy with lymph node dissection.

BACKGROUND: This study aims to evaluate the predictive value of lymph nodes (LN) suspicious for metastases on preoperative prostate-specific membrane antigen (PSMA) PET/CT for biochemical persistence (BCP) and early biochemical recurrence (BCR) following robotic-assisted radical prostatectomy (RARP) with extended pelvic LN dissection (ePLND). METHODS: We evaluated 213 patients with intermediate and high-risk prostate cancer (PCa) who underwent clinical staging with preoperative 68Ga- or 18F-PSMA-PET/CT scan and subsequent RARP with ePLND. Patients were grouped as PSMA- or PSMA+ depending on their LN status on PSMA-PET/CT and subdivided according to histological LN status in pN0 or pN1. Diagnostic accuracy of PSMA-PET/CT for the detection of pN1 was evaluated. BCP was defined as a first postoperative serum PSA level ≥0.1 ng/mL 6-12 weeks following RP. Early BCR was defined as detectable PSA > 0.2 ng/mL within 12 months of follow-up. Univariable logistic regression analyses were used to evaluate the effect of PSMA+ on BCP and BCR. RESULTS: Forty patients (19%) were PSMA+. The overall incidence of pN1 was 23%. Sensitivity, specificity, PPV and NPV on a per patient level for the detection of pN1 was 29%, 84%, 35%, and 80% respectively. BCP was observed in 26 of 211 patients (12%) and early BCR in 23 of 110 patients (21%). The presence of PSMA+ was a significant predictor for BCP (OR 7.1, 2.9-17.1 95% CI) and BCR (OR 8.1, 2.9-22.6 95% CI). CONCLUSION: Preoperative PSMA-PET/CT may be a valuable tool for patient counseling for RARP and ePLND as it is a significant predictor for the risk of postoperative BCP and early BCR. We conclude that an ePLND should not be avoided in men with intermediate or high-risk PCa and preoperative negative PSMA-PET/CT, as 20% have microscopic LN metastasis.

The transcription factor RFX3 directs nodal cilium development and left-right asymmetry specification.

There are five members of the RFX family of transcription factors in mammals. While RFX5 plays a well-defined role in the immune system, the functions of RFX1 to RFX4 remain largely unknown. We have generated mice with a deletion of the Rfx3 gene. RFX3-deficient mice exhibit frequent left-right (LR) asymmetry defects leading to a high rate of embryonic lethality and situs inversus in surviving adults. In vertebrates, specification of the LR body axis is controlled by monocilia in the embryonic node, and defects in nodal cilia consequently result in abnormal LR patterning. Consistent with this, Rfx3 is expressed in ciliated cells of the node and RFX3-deficient mice exhibit a pronounced defect in nodal cilia. In contrast to the case for wild-type embryos, for which we document for the first time a twofold increase in the length of nodal cilia during development, the cilia are present but remain markedly stunted in mutant embryos. Finally, we show that RFX3 regulates the expression of D2lic, the mouse orthologue of a Caenorhabditis elegans gene that is implicated in intraflagellar transport, a process required for the assembly and maintenance of cilia. In conclusion, RFX3 is essential for the differentiation of nodal monocilia and hence for LR body axis determination.

A structural comparison of molybdenum cofactor-containing enzymes.

This work gives an overview of the recent achievements which have contributed to the understanding of the structure and function of molybdenum and tungsten enzymes. Known structures of molybdo-pterin cofactor-containing enzymes will be described briefly and the structural differences between representatives of the same and different families will be analyzed. This comparison will show that the molybdo-pterin cofactor-containing enzymes represent a very heterogeneous group with differences in overall enzyme structure, cofactor composition and stoichiometry, as well as differences in the immediate molybdenum environment. Two recently discovered molybdo-pterin cofactor-containing enzymes will be described with regard to molecular and EPR spectroscopic properties, pyrogallol-phloroglucinol transhydroxylase from Pelobacter acidigallici and acetylene hydratase from Pelobacter acetylenicus. On the basis of its amino acid sequence, transhydroxylase can be classified as a member of the dimethylsulfoxide reductase family, whereas classification of the tungsten/molybdenum-containing acetylene hydratase has to await the determination of its amino acid sequence.

Tissue engineering in burn scar reconstruction.

Nowadays, most patients with severe burns will survive their injury. This evolution is accompanied by the challenge to cover a large percentage of total body surface area burned. Consequently, more and more patients have to deal with the sequelae of burn scars and require (multiple) reconstructions. This review provides a gross overview of developments in the field of tissue engineering for permanent burn wound coverage and reconstructive burn surgery, focusing on usage and clinical effectiveness. Not only skin substitutes will be discussed but also the replacement of subcutaneous fat tissue and cartilage.

The subcellular localization of Otx2 is cell-type specific and developmentally regulated in the mouse retina.

Recent evidence implicates homeodomain-containing proteins in the specification of cell fates in the central nervous system. Here we report that in the embryonic mouse eye Otx2, a paired homeodomain transcription factor, was found in retinal pigment epithelial cells and a restricted subset of retinal neurons, including ganglion cells. In the postnatal and adult eye, however, both the cellular and subcellular distribution of the Otx2 protein were cell type-specific. Otx2 was detected only in the nuclei of retinal pigment epithelial and bipolar cells, but was present in the cytoplasm of rod photoreceptors. Immunohistochemical studies of retinal explants and transfected cell lines both suggested that the retention of Otx2 in the cytoplasm of immature rods is a developmentally regulated process. The differential distribution of Otx2 in the cytoplasm of rods and the nucleus of other cell types, suggests that subcellular localization of this transcription factor may participate cell fate determination during specific phases of retinal development.

Expression of alpha and beta thyroid receptors during oligodendrocyte differentiation.

To determine which thyroid receptor (TR) isoforms are expressed during oligodendrocyte differentiation, we studied the expression of the mRNAs encoding two alpha (alpha 1 and alpha 2) and one beta (beta 1) TR isoforms in a bipotential oligodendrocyte-type 2-astrocyte (O-2A) progenitor cell line (CG-4) as well as in rat O-2A progenitor cells and oligodendrocytes. O-2A progenitor cells expressed only TR alpha-mRNAs, whereas oligodendrocytes and type 2-astrocytes also expressed TR beta 1-mRNAs. The differential expression of alpha 1 and beta 1 TRs suggests specific functions for both types of TRs during oligodendrocyte differentiation. We present evidence for a possible role of TR alpha 1 in the effect of thyroid hormones on the proliferation of CG-4 cells maintained as progenitor cells.

Posttranscriptional regulation of oligodendroglial thyroid hormone (T3) receptor beta 1 by T3.

3,5,3'-triiodo-L-thyronine interacts with the genome by binding and activating nuclear 3,5,3'-triiodo-L-thyronine receptors. To determine how in secondary oligodendrocyte cultures, exogenous 3,5,3'-triiodo-L-thyronine influences the expression of different 3,5,3'-triiodo-L-thyronine receptor isoforms, we studied the regulation of alpha 1, alpha 2 and beta 1 3,5,3'-triiodo-L-thyronine receptor mRNAs. In culture, we find that beta 1, 3,5,3'-triiodo-L-thyronine receptor mRNA, but not alpha 1 and alpha 2 3,5,3'-triiodo-L-thyronine receptor mRNAs, is up-regulated by 3,5,3'-triiodo-L-thyronine in a time and dose dependent manner. In addition, we present evidence indicating that beta 1 3,5,3'-triiodo-L-thyronine receptor expression is posttranscriptionally regulated by 3,5,3'-triiodo-L-thyronine. Previous studies from our laboratory and others have shown that in the rat oligodendrocyte lineage, 3,5,3'-triiodo-L-thyronine receptors alpha 1 and alpha 2 were expressed in both early progenitor cells and mature oligodendrocytes. In contrast, beta 1 3,5,3'-triiodo-L-thyronine receptor was found to be expressed only in mature oligodendrocytes. This suggests that thyroid hormone may influence oligodendrocyte differentiation and maturation via 3,5,3'-triiodo-L-thyronine receptor beta 1, which is expressed only in oligodendrocytes and not in progenitor cells. We therefore show that this effect is indirect and is mediated by 3,5,3'-triiodo-L-thyronine which acts posttranscriptionally on the 3,5,3'-triiodo-L-thyronine receptor beta 1 gene.

Glutamine synthetase expression and activity are regulated by 3,5,3'-triodo-L-thyronine and hydrocortisone in rat oligodendrocyte cultures.

Glutamine synthetase plays a central role in the detoxification of brain ammonia. Previously, we demonstrated that in vitro glutamine synthetase is expressed by all macroglial cell types and is developmentally regulated in oligodendrocyte lineage. Furthermore, glutamine synthetase is increased in secondary cultures of oligodendrocytes following a 72 h treatment with 30 nM 3,5,3'-triodo-L-thyronine [Baas, D., Bourbeau, D., Sarliève, L. L., Ittel, M. E., Dussault, J. H. and Puymirat, J., Oligodendrocyte maturation and progenitor cell proliferation are independently regulated by thyroid hormone. Glia, 1997, 19, 324-332]. Hydrocortisone also increases glutamine synthetase activity after 72 h [Fressinaud, C., Weinrauder, H., Delaunoy, J. P., Tholey, G., Labourdette, G. and Sarliève, L. L., Glutamine synthetase expression in rat oligodendrocytes in culture: regulation by hormones and growth factors. J. Cell. Physiol., 1991, 149, 459-468]; however, it is still unknown whether these increases in glutamine synthetase expression in oligodendrocytes after 3,5,3'-triodo-L-thyronine and hydrocortisone application are dose- and time-dependent. To further investigate this issue, we measured glutamine synthetase levels by Northern analysis, immunostaining and determination of glutamine synthetase activity after 3,5,3'-triodo-L-thyronine or hydrocortisone stimulation. We find that in rat oligodendrocyte secondary cultures, 3,5,3'-triodo-L-thyronine and hydrocortisone cause a dose- and time-dependent increase in glutamine synthetase mRNA, protein and activity. However, these hormones do not exert an additive or synergistic effect. Because purines, pyrimidines, and certain amino acids necessary for the synthesis of myelin components, are, in part, provided by the glutamine synthetase pathway, 3,5,3'-triodo-L-thyronine effect on myelination development and maturation could be mediated in part, through the glutamine synthetase gene regulation.

Expression of thyroid hormone receptor isoforms in rat oligodendrocyte cultures. Effect of 3,5,3'-triiodo-L-thyronine.

3,5,3'-Triiodo-L-thyronine (T3) acts at the genomic level by interacting with nuclear T3 receptors (T3Rs). We have used double immunostaining to follow the expression of T3Rs and oligodendrocytes (OL) lineage markers in rat secondary cultures consisting of 85-90% OL. Using antibodies against different synthetic peptides of T3Rs (alpha common: alpha 1 + alpha 2 and beta 1) we find that alpha-T3R is expressed in both O-2A progenitors and in mature OL, while beta 1-T3R is expressed only in mature OL. In cultured OL, beta 1-T3R mRNA is upregulated the most by T3. OL exhibit more numerous and longer processes when treated by T3.

The alpha and beta thyroid receptors are expressed by cultured ependymal cells. Correlation with the effect of L-3,5,3'-triiodothyronine on glutamine synthetase mRNAs.

It is generally accepted that L-3,5,3'-triiodothyronine (L-T3) acts at the genomic level through an interaction with specific nuclear L-T3 receptors (NT3R). Using antibodies raised against different peptides of NT3R, we report here the immunocytochemical localization of the alpha, alpha 2, beta 1 NT3R subtypes in ependymal cell primary cultures. The alpha and beta thyroid hormone receptors are both expressed. While the alpha and alpha 2 subtypes are found in almost all cells, the beta 1 receptors are present in few cells only. The possibility that alpha and beta receptors are colocalized is discussed. We also demonstrate that ependymal cells respond to L-T3 with a marked increase of the expression of the glutamine synthetase messenger RNAs.

Effects of coffee on driving performance during prolonged simulated highway driving.

RATIONALE: Coffee is often consumed to counteract driver sleepiness. There is limited information on the effects of a single low dose of coffee on prolonged highway driving in non-sleep deprived individuals. OBJECTIVES: The aim of this study was to examine the effects of a single cup of coffee (80 mg caffeine) on simulated highway driving performance. METHODS: Non-sleep deprived healthy volunteers (n024) participated in a double-blind, placebo-controlled, crossover study. After 2 h of monotonous highway driving, subjects received caffeinated or decaffeinated coffee during a 15-min break before continuing driving for another 2 h. The primary outcome measure was the standard deviation of lateral position (SDLP), reflecting the weaving of the car. Secondary outcome measures were speed variability, subjective sleepiness, and subjective driving performance. RESULTS: The results showed that caffeinated coffee significantly reduced SDLP as compared to decaffeinated coffee, both in the first (p00.024) and second hour (p00.019) after the break. Similarly, the standard deviation of speed (p0 0.024; p00.001), mental effort (p00.003; p00.023), and subjective sleepiness (p00.001; p00.002) were reduced in both the first and second hour after consuming caffeinated coffee. Subjective driving quality was significantly improved in the first hour after consuming caffeinated coffee (p00.004). CONCLUSIONS: These findings demonstrate a positive effect of one cup of caffeinated coffee on driving performance and subjective sleepiness during monotonous simulated highway driving.

The dynamic nature of Bruch's membrane.

Bruch's membrane (BM) is a unique pentalaminar structure, which is strategically located between the retinal pigment epithelium (RPE) and the fenestrated choroidal capillaries of the eye. BM is an elastin- and collagen-rich extracellular matrix that acts as a molecular sieve. BM partly regulates the reciprocal exchange of biomolecules, nutrients, oxygen, fluids and metabolic waste products between the retina and the general circulation. Accumulating evidence suggests that the molecular, structural and functional properties of BM are dependent on age, genetic constitution, environmental factors, retinal location and disease state. As a result, part of the properties of BM are unique to each human individual at a given age, and therefore uniquely affect the development of normal vision and ocular disease. The changes occurring in BM with age include increased calcification of elastic fibres, increased cross-linkage of collagen fibres and increased turnover of glycosaminoglycans. In addition, advanced glycation end products (AGEs) and fat accumulate in BM. These age-related changes may not only influence the normal age-related health of photoreceptor cells, but also the onset and progression of diseases like retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Undoubtedly, BM is the site of drusen development. Confluent drusen and uncontrolled activation of the complement cascade are most likely the first signs of AMD. Furthermore, the nature of adhesive interactions between the RPE and BM are instrumental in the development of retinal detachments and proliferative retinal disease. Finally, BM is passively or actively involved in a range of other retinal disorders such as Pseudoxanthoma elasticum (PXE), Sorsby's Fundus Dystrophy and Malattia Leventinese. Here, we review the dynamic nature of Bruch's membrane, from molecule to man, during development, aging and disease. We propose a simple and straightforward nomenclature for BM deposits. Finally, we attempt to correlate recently published mRNA expression profiles of the RPE and choroid with molecular, structural and functional properties of BM. Our review may shed light on the complex involvement of BM in retinal pathology, notably age-related macular degeneration.

Social judgement in clinically stable patients with schizophrenia and healthy relatives: behavioural evidence of social brain dysfunction.

BACKGROUND: Patients with schizophrenia have been found to display abnormalities in social cognition. The aim of the study was to test whether patients with schizophrenia and unaffected first-degree relatives of schizophrenic patients display behavioural signs of social brain dysfunction when making social judgements. METHOD: Eighteen patients with schizophrenia, 24 first-degree unaffected relatives and 28 healthy comparison subjects completed a task which involves trustworthiness judgements of faces. A second task was completed to measure the general ability to recognize faces. RESULTS: Patients with schizophrenia rated faces as more trustworthy, especially those that were judged to be untrustworthy by healthy comparison subjects. Siblings of schizophrenia patients display the same bias, albeit to a lesser degree. CONCLUSIONS: The pattern of more positive trustworthiness judgements parallels the results from studies of patients with abnormalities in brain areas involved in social cognition. Because patients and siblings did not differ significantly from controls in their general ability to recognize faces, these findings cannot be dismissed as abnormalities in face perception by itself.

A deficiency in RFX3 causes hydrocephalus associated with abnormal differentiation of ependymal cells.

Ciliated ependymal cells play central functions in the control of cerebrospinal fluid homeostasis in the mammalian brain, and defects in their differentiation or ciliated properties can lead to hydrocephalus. Regulatory factor X (RFX) transcription factors regulate genes required for ciliogenesis in the nematode, drosophila and mammals. We show here that Rfx3-deficient mice suffer from hydrocephalus without stenosis of the aqueduct of Sylvius. RFX3 is expressed strongly in the ciliated ependymal cells of the subcommissural organ (SCO), choroid plexuses (CP) and ventricular walls during embryonic and postnatal development. Ultrastructural analysis revealed that the hydrocephalus is associated with a general defect in CP differentiation and with severe agenesis of the SCO. The specialized ependymal cells of the CP show an altered epithelial organization, and the SCO cells lose their characteristic ultrastructural features and adopt aspects more typical of classical ependymal cells. These differentiation defects are associated with changes in the number of cilia, although no obvious ultrastructural defects of these cilia can be observed in adult mice. Moreover, agenesis of the SCO is associated with downregulation of SCO-spondin expression as early as E14.5 of embryonic development. These results demonstrate that RFX3 is necessary for ciliated ependymal cell differentiation in the mouse.