Balance recovery for lower limb exoskeleton in standing posture based on orbit energy analysis.

Introduction: The need for effective balance control in lower limb rehabilitation exoskeletons is critical for ensuring stability and safety during rehabilitation training. Current research into specialized balance recovery strategies is limited, highlighting a gap in biomechanics-inspired control methods. Methods: We introduce a new metric called "Orbit Energy" (OE), which assesses the balance state of the human-exoskeleton system based on the dynamics of the overall center of mass. Our control framework utilizes OE to choose appropriate balance recovery strategies, including torque controls at the ankle and hip joints. Results: The efficacy of our control algorithm was confirmed through Matlab Simulink simulations, which analyzed the recovery of balance under various disturbance forces and conditions. Further validation came from physical experiments with human subjects wearing the exoskeleton, where a significant reduction in muscle activation was observed during balance maintenance under external disturbances. Discussion: Our findings underscore the potential of biomechanics-inspired metrics like OE in enhancing exoskeleton functionality for rehabilitation purposes. The introduction of such metrics could lead to more targeted and effective balance recovery strategies, ultimately improving the safety and stability of exoskeleton use in rehabilitation settings.

Tailored design of NHS-SS-NHS cross-linked chitosan nano-hydrogels for enhanced anti-tumor efficacy by GSH-responsive drug release.

The traditional chemotherapeutic agents' disadvantages such as high toxicity, untargeting and poor water solubility lead to disappointing chemotherapy effects, which restricts its clinical application. In this work, novel size-appropriate and glutathione (GSH)-responsive nano-hydrogels were successfully prepared via the active ester method between chitosan (containing -NH2) and cross-linker (containing NHS). Especially, the cross-linker was elaborately designed to possess a disulfide linkage (SS) as well as two terminal NHS groups, namely NHS-SS-NHS. These functionalities endowed chitosan-based cross-linked scaffolds with capabilities for drug loading and delivery, as well as a GSH-responsive mechanism for drug release. The prepared nano-hydrogels demonstrated excellent performance applicable morphology, excellent drug loading efficiency (∼22.5%), suitable size (∼100 nm) and long-term stability. The prepared nano-hydrogels released over 80% doxorubicin (DOX) after incubation in 10 mM GSH while a minimal DOX release less than 25% was tested in normal physiological buffer (pH = 7.4). The unloaded nano-hydrogels did not show any apparent cytotoxicity to A 549 cells. In contrast, DOX-loaded nano-hydrogels exhibited marked anti-tumor activity against A 549 cells, especially in high GSH environment. Finally, through fluorescent imaging and flow cytometry analysis, fluorescein isothiocyanate-labeled nano-hydrogels show obvious specific binding to the GSH high-expressing A549 cells and nonspecific binding to the GSH low-expressing A549 cells. Therefore, with this cross-linking approach, our present finding suggests that cross-linked chitosan nano-hydrogel drug carrier improves the anti-tumor effect of the A 549 cells and may serve as a potential injectable delivery carrier.

Multi-layer CNN-LSTM network with self-attention mechanism for robust estimation of nonlinear uncertain systems.

Introduction: With the help of robot technology, intelligent rehabilitation of patients with lower limb motor dysfunction caused by stroke can be realized. A key factor constraining the clinical application of rehabilitation robots is how to realize pattern recognition of human movement intentions by using the surface electromyography (sEMG) sensors to ensure unhindered human-robot interaction. Methods: A multilayer CNN-LSTM prediction network incorporating the self-attention mechanism (SAM) is proposed, in this paper, which can extract and learn the periodic and trend characteristics of the sEMG signals, and realize the accurate autoregressive prediction of the human motion information. Firstly, the multilayer CNN-LSTM network utilizes the CNN layer for initial feature extraction of data, and the LSTM network is used to improve the enhancement of the historical time-series features. Then, the SAM is used to improve the global feature extraction performance and parallel computation speed of the network. Results: In comparison with existing test is carried out using actual data from five healthy subjects as well as a clinical hemiplegic patient to verify the superiority and practicality of the proposed algorithm. The results show that most of the model's prediction R > 0.9 for different motion states of healthy subjects; in the experiments oriented to the motion characteristics of patient subjects, the angle prediction results of R > 0.99 for the untrained data on the affected side, which proves that our proposed model also has a better effect on the angle prediction of the affected side. Discussion: The main contribution of this paper is to realize continuous motion estimation of ankle joint for healthy and hemiplegic individuals under non-ideal conditions (weak sEMG signals, muscle fatigue, high muscle tension, etc.), which improves the pattern recognition accuracy and robustness of the sEMG sensor-based system.

Efficacy of Using Intermittent Theta Burst Stimulation to Treat Negative Symptoms in Patients with Schizophrenia-A Systematic Review and Meta-Analysis.

Negative symptoms in schizophrenia impose a significant burden with limited effective pharmacological treatment options. Recent trials have shown preliminary evidence for the efficacy of using intermittent theta burst stimulation (iTBS) in treating negative symptoms in schizophrenia. We aim to systematically review the current evidence of iTBS in the treatment of the negative symptoms of schizophrenia as an augmentation therapy. The study protocol was developed and registered on Prospero (registration ID: 323381). MEDLINE, EMBASE, Web of Science (Scopus), PsycINFO and Wan Fang databases were searched for sham-controlled, randomized trials of iTBS among patients with schizophrenia. The mean difference in major outcome assessments for negative symptoms was calculated. The quality of evidence was assessed using the Cochrane Risk of Bias Tool (version 1) and the GRADE system. Moreover, 12 studies including a total of 637 participants were included. Compared to sham treatment, the pooled analysis was in favor of iTBS treatment for negative symptoms (mean weight effect size: 0.59, p = 0.03) but not for positive symptoms (mean weight effect size: 0.01, p = 0.91) and depressive symptoms (mean weight effect size: 0.35, p = 0.16). A significant treatment effect was also observed on the iTBS target site left dorsal prefrontal cortex (mean weight effect size: 0.86, p = 0.007) and for stimulation with 80% motor threshold (mean weight effect size: 0.86, p = 0.02). Thus, our synthesized data support iTBS as a potential treatment for negative symptoms among patients with schizophrenia. However, the long-term efficacy and safety issues of iTBS in a larger population have yet to be examined.

Major Adverse Cardiac Events With Immune Checkpoint Inhibitors: A Pooled Analysis of Trials Sponsored by the National Cancer Institute-Cancer Therapy Evaluation Program.

PURPOSE: Major adverse cardiac events (MACEs) because of immune checkpoint inhibitors (ICIs) are infrequent immune-related adverse events (irAEs) that comprise a spectrum of cardiac toxicities with variable manifestations. ICI-related MACEs can lead to significant morbidity and mortality, hence the need to better define presentations of MACEs and their association with noncardiac irAEs in ICI-treated patients. METHODS: We conducted a retrospective pooled analysis of MACE captured in the serious adverse events reporting database of the National Cancer Institute-Cancer Therapy Evaluation Program for National Cancer Institute-sponsored investigational clinical trials between June 2015 and December 2019. Patients were eligible if they had been treated with anti-programmed cell death protein-1 (anti-PD-1)/programmed cell death-ligand 1 (anti-PD-L1) alone or with additional anticancer therapies. RESULTS: A total of 6,925 participants received anti-PD-(L)1-based therapies; 48% (n = 3,354) were treated with single-agent anti-PD-(L)1 therapy. Of 6,925 patients, 0.6% (n = 40) qualified as ICI-related MACE, with 77.5% (n = 31 of 40) being ≥ grade 3. Myocarditis accounted for 45% (n = 18 of 40) of total ICI-MACEs. Concurrent multisystem involvement with other noncardiac irAEs was seen in 65% (n = 26 of 40). Most patients with myocarditis (83%, n = 15 of 18) had one or more noncardiac irAEs associated. Incidence of MACE was higher with anti-PD-(L)1 + targeted therapies compared with anti-PD-(L)1 + anti-cytotoxic T-cell lymphocyte-4 combinations (2.1% v 0.9%, P = .08). There was a higher incidence of myocarditis with anti-PD-(L)1-based combination therapies versus single-agent anti-PD-(L)1 therapies (0.36%, n = 13 of 3,571 v 0.15%, n = 5 of 3,354, P = .08). Deaths related to myocarditis were identified in 22.5% (n = 4 of 18). All four patients who died had concurrent myositis. CONCLUSION: Increasing patient and prescriber awareness in understanding patterns of ICI-MACE and associated noncardiac irAEs should be emphasized. Better characterization of the risk of MACE with the concurrent use of non-ICI-based anticancer therapies with anti-PD-(L)1 treatments is needed.

The Impact of Electroconvulsive Therapy on Negative Symptoms in Schizophrenia and Their Association with Clinical Outcomes.

OBJECTIVE: The treatment efficacy of electroconvulsive therapy (ECT) for negative symptoms amongst patients with schizophrenia remains unclear. In this study, we aim to examine the effects of ECT on negative symptoms in schizophrenia and their association with other clinical outcomes, including cognition and function. METHODS: This is a retrospective data analysis of patients with schizophrenia/schizoaffective disorder treated with ECT at the Institute of Mental Health (IMH), Singapore, between January 2016 and December 2019. Clinical outcomes were assessed by the Brief Psychiatric Rating Scale (BPRS), the Montreal Cognitive Assessment (MoCA), and Global Assessment of Function (GAF). Changes in scores were compared with repeated measures analysis of variance. Sequential structural modelling was utilized to examine the pathway relationships between changes in negative symptoms, global functioning, and cognition functioning after ECT. RESULTS: A total of 340 patients were analysed. Hence, 196 (57.6%), 53 (15.5%), and 91 (26.7%) showed improvements, no change, and deterioration in negative symptoms, respectively. ECT-induced improvement of negative symptoms was significantly associated with improvement of global functioning (direct effect correlation coefficient (r): -0.496; se: 0.152; p = 0.001) and cognition function (indirect effect r: -0.077; se: 0.037; p = 0.035). Moreover, having capacity to consent, more severe baseline negative symptoms, lithium prescription, and an indirect effect of voluntary admission status via consent capacity predicted ECT associated negative symptoms improvement. CONCLUSION: ECT is generally associated with improvements of negative symptoms in people with schizophrenia, which correlate with improvements of overall function. Possible novel clinical predictors of negative symptom improvement have been identified and will require further research and validation.

The Religious and Spiritual Needs of Patients in the Hospital Setting Do Not Depend on Patient Level of Religious/Spiritual Observance and Should be Initiated by Healthcare Providers.

According to many studies, addressing the religious and spiritual (R/S) needs of patient's increase patient satisfaction. One area of interest is how patient self-perceived level of religiosity and spirituality (R/S) influences hospital needs. In this cross-sectional study, 195 inpatients at a non-faith-based academic hospital in Toledo, OH, USA completed surveys examining self-perceived R/S levels, as well as how those R/S levels impacted preferred services, conversations, and experiences in the hospital. Patients with no religious identity (self-identified as atheist, agnostic, or no religion) were less likely to report discussions about R/S needs than religious respondents (16.7% vs. 47.3%, p = 0.039). Nevertheless, such patients were just as likely to want a R/S conversation started by their healthcare provider (75% vs. 56%, p = 0.241). Those with no R/S identity were more likely to report presumed negative assumptions by hospital staff (25% vs. 0%, p < 0.001). Our data suggests that even for a nonreligious population, it is important to consider R/S needs.

Upregulation of fibroblast growth factor 2 contributes to endometriosis through SPRYs/DUSP6/ERK signaling pathway.

Previous studies report that fibroblast growth factor 2 (FGF2) modulates Sproutys (SPRYs)/dual specificity phosphatase 6 (DUSP6)/extracellular signal-regulated kinase (ERK) signaling pathway in endometrial glandular epithelial cells. However, its role in endometriosis remains unclear. The expression patterns and localization of related proteins in endometrium patients' samples were determined using quantitative reverse transcription PCR, Western blotting, and immunohistochemistry, respectively. Human endometrial stromal cells (HESCs) were isolated and transfected with small interfering RNA (siRNA) targeting FGF2 (FGF2-siRNA). Cell viability was determined using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. It was found that FGF2 mRNA and protein levels were increased in the ectopic endometrium, whilst the mRNA and protein levels of SPRYs/DUSP6/ERK signaling pathway related-genes were dysregulated. Spearman's rank correlation analysis revealed a negative correlation between FGF2 and SPRYs/DUSP6 signaling pathway-related proteins. In vitro study demonstrated that FGF2 silencing suppressed cell proliferation. Our results suggest that FGF2 upregulation might contribute to endometriosis via the regulation of the SPRYs/DUSP6/ERK signaling pathway.

Peripheral artery disease and clinical outcomes in patients with atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac rhythm disturbance and leads to morbidity and mortality. Peripheral artery disease (PAD) is associated with atherosclerotic risk factors and always classified as a vascular disease and deemed to be a bad complication of AF. In patients with AF, the risk and prognostic value of PAD have not been estimated comprehensively. HYPOTHESIS: PAD is associated with all-cause mortality, cardiovascular (CV) mortality, and other outcomes in patients with AF. METHODS: We searched PubMed, Embase, and Cochrane Library databases for prospective studies published before April 2021 that provided outcomes data on PAD in confirmed patients with AF. Heterogeneity was estimated using the I2 statistic. The fixed-effects model was used for low to moderate heterogeneity studies, and the random-effects model was used for high heterogeneity studies. RESULTS: Eight prospective studies (Newcastle-Ottawa score range, 7-8) with 39 654 patients were enrolled. We found a significant association between PAD and all-cause mortality (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.25-1.62; p < .001), CV mortality (HR, 1.64; 95% CI, 1.32-2.05; p < .001) and MACE (HR, 1.75; 95% CI, 1.38-2.22; p < .001) in patients with AF. No significant relationship was found in major bleeding (HR, 1.22; 95% CI, 0.95-1.57; p = 0.118), myocardial infarction (MI) (HR, 2.07; 95% CI, 1.17-3.67; p = .038), and stroke (HR, 1.14; 95% CI, 0.87-1.50, p = 0.351). CONCLUSIONS: PAD is associated with an increased risk of all-cause mortality, CV mortality, and MACE in patients with AF. However, no significant association was found with major bleeding, MI, and stroke.

Clinical characteristics and predictive value of lower CD4+T cell level in patients with moderate and severe COVID-19: a multicenter retrospective study.

BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei, China. Moreover, it has become a global pandemic. This is of great value in describing the clinical symptoms of COVID-19 patients in detail and looking for markers which are significant to predict the prognosis of COVID-19 patients. METHODS: In this multicenter, retrospective study, 476 patients with COVID-19 were enrolled from a consecutive series. After screening, a total of 395 patients were included in this study. All-cause death was the primary endpoint. All patients were followed up from admission till discharge or death. RESULTS: The main symptoms observed in the study included fever on admission, cough, fatigue, and shortness of breath. The most common comorbidities were hypertension and diabetes mellitus. Patients with lower CD4+T cell level were older and more often male compared to those with higher CD4+T cell level. Reduced CD8+T cell level was an indicator of the severity of COVID-19. Both decreased CD4+T [HR:13.659; 95%CI: 3.235-57.671] and CD8+T [HR: 10.883; 95%CI: 3.277-36.145] cell levels were associated with in-hospital death in COVID-19 patients, but only the decrease of CD4+T cell level was an independent predictor of in-hospital death in COVID-19 patients. CONCLUSIONS: Reductions in lymphocytes and lymphocyte subsets were common in COVID-19 patients, especially in severe cases of COVID-19. It was the CD8+T cell level, not the CD4+T cell level, that reflected the severity of the patient's disease. Only reduced CD4+T cell level was independently associated with increased in-hospital death in COVID-19 patients. TRIAL REGISTRATION: Prognostic Factors of Patients With COVID-19, NCT04292964 . Registered 03 March 2020. Retrospectively registered.

Prognostic value of NT-proBNP in patients with severe COVID-19.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown. METHODS: The study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records. RESULTS: The best cut-off value of NT-proBNP for predicting in-hospital death was 88.64 pg/mL with the sensitivity for 100% and the specificity for 66.67%. Patients with high NT-proBNP values (> 88.64 pg/mL) had a significantly increased risk of death during the days of following-up compared with those with low values (≤88.64 pg/mL). After adjustment for potential risk factors, NT-proBNP was independently correlated with in-hospital death. CONCLUSION: NT-proBNP might be an independent risk factor for in-hospital death in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials, NCT04292964. Registered 03 March 2020.

Inhibiting glycogen synthase kinase-3 and transforming growth factor-ß signaling to promote epithelial transition of human adipose mesenchymal stem cells.

BACKGROUND: This study was aimed to investigate the epithelial differentiation of human adipose-derived mesenchymal stem cells (ADSCs) by inhibiting glycogen synthase kinase-3 (GSK3) and transforming growth factor ß (TGFß) signaling. METHODS AND RESULTS: STEMPRO human ADSCs at passage 2 were treated with CHIR99021 (GSK3 inhibitor), E-616452 (TGFß1 receptor kinase inhibitor), A-83-01 (TGFß type 1 receptor inhibitor), valproic acid (histone deacetylase inhibitor), tranylcypromine (monoamine oxidase inhibitor) and all-trans retinoic acid for 72 h. The mesenchymal-epithelial transition was shown by down-regulation of mesenchymal genes (Slug, Zinc Finger E-box Binding Homeobox 1 ZEB1, integrin α5 ITGA5 and vimentin VIM) and up-regulation of epithelial genes (E-cadherin, Epithelial Cell Adhesion Molecule EpCAM, Zonula Occludens-1 ZO-1, occludin, deltaN p63 δNp63, Transcription Factor 4 TCF4 and Twist Family bHLH Transcription Factor TWIST), compared to untreated ADSCs. Cell morphology and stress fiber pattern were examined and the treated cells became less migratory in scratch wound closure assay. The formation of cell junction complexes was observed under transmission electron microscopy. Global gene expression using GeneChip® Human Genome U133 Array (Affymetrix) showed that the treatment up-regulated 540 genes (containing genes for cell cycle, cytoskeleton reorganization, chemotaxis, epithelium development and regulation of cell migration) and down-regulated 483 genes. CONCLUSION: Human ADSCs were transited to epithelial lineage by inhibiting GSK3 and TGFß signaling. It can be an adult stem cell source for epithelial cell-based therapy.

Osteo-odonto keratoprosthesis: systematic review of surgical outcomes and complication rates.

Case series on osteo-odonto keratoprosthesis (OOKP) published in English from 1950-June 2010 were identified in Medline/PubMed. Indications for surgery, visual acuity, anatomical survival, complication and repeat surgery rates were compared among the different studies. Our own case series is a retrospective review of all OOKP surgeries performed in our center from February 2004-July 2011. Eight case series including our own were systematically reviewed. Sample sizes ranged from 4-181 eyes. The most common indications for surgery were severe cases of Stevens-Johnson syndrome and thermal and chemical burns that were unamenable to other forms of surgery or had had previous surgical failure. Anatomical survival rate in all the studies was 87.8% (range 67-100%) at 5 years, and three studies showed survival rates of 81.0% (range 65-98%) at 20 years. Visual acuity was more than 6/18 in 52% (range 46-72%) of the eyes with OOKP surgery. The most common intraoperative complication was vitreous hemorrhage (0-52%) and the most common long-term blinding complication was glaucoma (7-47%). Endophthalmitis rates ranged from 2-8%. The most common repeat surgical procedure was mucosal trimming due to mucosal overgrowth at the optical cylinder and mucosal grafting for extrusion of the OOKP or mucosal ulceration. Of the available biological and synthetic keratoprosthesis, OOKP appears to be an excellent option for the treatment of end-stage corneal diseases.

Ex vivo expansion of conjunctival and limbal epithelial cells using cord blood serum-supplemented culture medium.

PURPOSE: Conventional cell culture methods use fetal bovine serum (FBS) as a growth supplement. The purpose of this study was to develop a xenobiotic-free culture system using umbilical cord blood serum (CBS) as an alternative growth supplement for the cultivation of human conjunctival and limbal epithelial cells. METHODS: Human conjunctival and limbal epithelial cells were cultivated in varying concentrations of CBS-supplemented medium and compared with FBS-supplemented medium. Bromodeoxyuridine (BrdU) ELISA proliferation assay, colony-forming efficiency (CFE), and a number of cell generations were analyzed. Cytokeratin expression of cultured cells was evaluated (K3, K4, K12, K13, K14, K15, K19, and PanCK). The authors compared the cytokine and growth factor levels in CBS, FBS, and adult serum using antibody array assays. RESULTS: Conjunctival and limbal cells cultivated in 0.25% CBS- and 0.5% CBS-supplemented culture media demonstrated the highest proliferative capacity in terms of BrdU proliferation assay, CFE, and number of cell generations. These results were comparable to FBS-supplemented medium. Cultured epithelial cells retained their normal cytokeratin expression. Cytokines brain-derived neurotrophic factor, growth-related oncogene, and leptin and growth factors EGF, HGF, FGF-6, IGF-1, PDGF, and IGFBP were present in higher concentrations in CBS than in FBS and adult serum. CONCLUSIONS: CBS-supplemented culture medium supported the proliferation and differentiation of conjunctival and limbal epithelial cells. CBS contained a higher concentration of growth factors and cytokines than FBS and adult serum. CBS may be a viable and safer alternative to FBS as a growth supplement in the culture medium for culturing epithelial cells, which may have important clinical implications when bioengineering tissues for clinical use.

Pregnancy-associated progenitor cells differentiate and mature into neurons in the maternal brain.

Bidirectional cell trafficking between fetus and mother during pregnancy is a well-established phenomenon observed in placental vertebrates including humans. Although studies have shown that transmigratory fetal cells, also termed pregnancy-associated progenitor cells (PAPCs), can integrate into multiple maternal organs, the integration, long-term survival, and differentiation of PAPCs in the brain has not been extensively studied. Using a murine model of fetomaternal microchimerism, we show that PAPCs integrated and persisted in several areas of the maternal brain for up to 7 months postpartum. Besides expressing neural stem cell or immature neuronal markers, PAPCs were observed to express mature neuronal markers, indicating that PAPCs adopted a neuronal fate. Further, PAPCs also displayed morphologically neuronal maturation by an increasing axonal/dendritic complexity over time. Therefore, PAPCs seem to undergo a molecular and morphological maturation program similar to that observed during adult neurogenesis. We provide evidence that neuronal gene expression of PAPCs was not a consequence of cell fusion with maternal neurons. In addition, in mothers with experimentally induced Parkinson's disease (PD), the frequency of PAPCs within the hippocampus initially increased whereas long-term presence of PAPCs was compromised. Also, the spatial distribution of PAPCs within the hippocampus was altered in mothers with PD. Thus, the disease context influenced the initial attraction, long-term survival, and spatial distribution of PAPCs, which may have wider implications on cell replacement strategies in human neurodegenerative diseases such as PD.

Fetal microchimerism in the maternal mouse brain: a novel population of fetal progenitor or stem cells able to cross the blood-brain barrier?

We investigated whether fetal cells can enter the maternal brain during pregnancy. Female wild-type C57BL/6 mice were crossed with transgenic Green Mice ubiquitously expressing enhanced green fluorescent protein (EGFP). Green Mouse fetal cells were found in the maternal brain. Quantitative real-time polymerase chain reaction (PCR) of genomic DNA for the EGFP gene showed that more fetal cells were present in the maternal brain 4 weeks postpartum than on the day of parturition. After an excitotoxic lesion to the brain, more fetal cells were detected in the injured region. The presence of fetal cells in the maternal brain was also confirmed by quantitative real-time PCR for the sex-determining region of the Y chromosome. Four weeks postpartum, EGFP-positive Green Mouse fetal cells in the maternal brain were found to adopt locations, morphologies, and expression of immunocytochemical markers indicative of perivascular macrophage-, neuron-, astrocyte-, and oligodendrocyte-like cell types. Expression of morphological and immunocytochemical characteristics of neuron- and astrocyte-like cell types was confirmed on identification of fetal cells in maternal brain by Y chromosome fluorescence in situ hybridization. Although further studies are required to determine whether such engraftment of the maternal brain has any physiological or pathophysiological functional significance, fetomaternal microchimerism provides a novel model for the experimental investigation of the properties of fetal progenitor or stem cells in the brain without prior in vitro manipulation. Characterization of the properties of these cells that allow them to cross both the placental and blood-brain barriers and to target injured brain may improve selection procedures for isolation of progenitor or stem cells for brain repair by intravenous infusion.