Mesenchymal stem cells (MSCs) from human adult bone marrow (haMSCs) represent a promising source for bone tissue engineering. However, their low frequencies and limited proliferation restrict their clinical utility. Alternative postnatal, perinatal, and fetal sources of MSCs appear to have different osteogenic capacities, but have not been systematically compared with haMSCs. We investigated the proliferative and osteogenic potential of MSCs from human fetal bone marrow (hfMSCs), human umbilical cord (hUCMSCs), and human adult adipose tissue (hATMSCs), and haMSCs, both in monolayer cultures and after loading into three-dimensional polycaprolactone-tricalcium-phosphate scaffolds.Although all MSCs had comparable immunophenotypes, only hfMSCs and hUCMSCs were positive for the embryonic pluripotency markers Oct-4 and Nanog. hfMSCs expressed the lowest HLA-I level (55% versus 95%–99%) and the highest Stro-1 level (51% versus 10%–27%), and had the greatest colony-forming unit–fibroblast capacity (1.6×–2.0×; p < .01) and fastest doubling time (32 versus 54–111 hours; p < .01). hfMSCs had the greatest osteogenic capacity, as assessed by von-Kossa staining, alkaline phosphatase activity (5.1×–12.4×; p < .01), calcium deposition (1.6×–2.7× in monolayer and 1.6×–5.0× in scaffold culture; p < .01), calcium visualized on micro-computed tomography (3.9×17.6×; p < .01) and scanning electron microscopy, and osteogenic gene induction. Two months after implantation of cellular scaffolds in immunodeficient mice, hfMSCs resulted in the most robust mineralization (1.8×–13.3×; p < .01).The ontological and anatomical origins of MSCs have profound influences on the proliferative and osteogenic capacity of MSCs. hfMSCs had the most proliferative and osteogenic capacity of the MSC sources, as well as being the least immunogenic, suggesting they are superior candidates for bone tissue engineering.
22 April 2023 in American Journal of Obstetrics and Gynecology
Natural language processing is a form of artificial intelligence that allows human users to interface with a machine without using complex code. The ability of natural language processing systems such as ChatGPT to successfully engage with healthcare systems requiring fluid reasoning, specialist data interpretation, and empathetic communication in an unfamiliar and evolving environment is poorly studied. We tested whether the ChatGPT interface could engage with and complete a mock Objective Structured Clinical Examination simulating assessment for Membership of the Royal College of Obstetricians and Gynaecologists. We hypothesized that, without additional training, ChatGPT would achieve a score at least equivalent to that achieved by human candidates who sat for a virtual Objective Structured Clinical Examinations in Singapore. The study was conducted in two phases. In the first, a total of seven structured discussion questions were selected from two historical cohorts (Cohorts A and B) of objective structured clinical examination questions. ChatGPT was examined using these questions and responses recorded in a script. Two human candidates (acting as anonymizers) were then examined on the same questions using videoconferencing, and their responses were transcribed verbatim into written scripts. The three sets of response scripts were then mixed, and each set allocated to one of three human actors. In the second stage, actors were used to present these scripts to examiners in response to the same examination questions. These responses were blind-scored by fourteen qualified examiners. ChatGPT scores were then unblinded and compared to historical human candidate performances. The average ChatGPT score given to ChatGPT by 14 examiners was 77.2 %. The average historical human score (n=26 candidates) was 73.7 %. ChatGPT demonstrated sizable performance improvements over the average human candidate in several subject domains. The median time taken for ChatGPT to complete each station was 2.54 minutes, well before the ten-minutes allowed. ChatGPT generated factually accsturate and contextually relevant structured discussion answers to complex and evolving clinical questions based on unfamiliar settings within a very short period. ChatGPT outperformed human candidates in several knowledge areas. Not all examiners were able to discern between human and ChatGPT responses. Our data highlight the emergent ability of natural language processing models to demonstrate fluid reasoning in unfamiliar environments and successfully compete with human candidates that have undergone extensive specialist training.
Placental syncytiotrophoblast microvesicles (STBM) are shed into the maternal circulation during normal pregnancy. STBM circulate in significantly increased amounts in preeclampsia (PE) and are considered to be among contributors to the exaggerated proinflammatory, procoagulant state of PE. However, protein composition of STBM in normal pregnancy and PE remains unknown. We therefore sought to determine the protein components of STBM and whether STBM protein expressions differ in preeclamptic and normal pregnancies. Patients with PE (n = 3) and normal pregnant controls (n = 6) were recruited. STBM were prepared from placental explant culture supernatant. STBM proteins were analyzed by a combination of 1D Gel-LC-MS/MS. Protein expressions levels were quantified using spectral counts and validated by immunohistochemistry. Over 400 proteins were identified in the STBM samples. Among these, 25 proteins were found to be differentially expressed in preeclampsia compared to healthy pregnant controls, including integrins, annexins and histones. STBM proteins include those that are implicated in immune response, coagulation, oxidative stress, apoptosis as well as lipid metabolism pathways. Differential protein expressions of STBM suggest their pathophysiological relevance in PE.
This study was conducted to evaluate the prognostic significance of haptoglobin levels in the overall survival of patients presenting with various stages of epithelial ovarian cancer. We employed an in-house sandwich enzyme-linked immunosorbent assay method to determine the concentrations of preoperative haptoglobin and C-reactive protein (CRP) in sera samples obtained from 66 malignant tumors, 60 benign tumors, and 10 normal healthy women. Levels of serum haptoglobin significantly correlated with tumor type (P < .001) and International Federation of Gynecology and Obstetrics stage (P < .05). A significant correlation was observed between clinical stage and patient survival (r = 5.99, P = .026). Our data also indicated that elevated serum haptoglobin levels were associated with poor outcome for overall survival using both univariate and multivariate analyses (P = .048 and P = .036 respectively). Using Pearson's correlation, we have noted that serum CRP concentrations significantly correlated with haptoglobin levels (r(2) = 0.22, P < .001). Immunohistochemical findings and Western blot analyses were compatible with sera levels of haptoglobin in which a higher intensity of staining occurred in late-stage epithelial ovarian cancers. This study provides evidence that preoperative serum levels of haptoglobin could serve as an independent prognostic factor in patients presenting with epithelial ovarian cancer.
Background: Implementation of noninvasive prenatal testing (NIPT) as a highly accurate aneuploidy screening test has raised questions around whether the high uptake may result in more terminations of pregnancies and fewer births of children with Down syndrome (DS).Aim: The aim of the study was to investigate the impact of NIPT on termination and live birth rates for DS.Methods: Literature reporting pregnancy outcomes following NIPT was reviewed. Termination rates were calculated for women with a high‐risk NIPT result for DS. Two audits of pregnancy outcomes where NIPT indicated DS were conducted in the United Kingdom and Singapore.Results: Fourteen studies from the United States, Asia, Europe, and the United Kingdom were included in the review. Live births of children with DS were reported in 8 studies. Termination rates following NIPT were unchanged or decreased when compared to termination rates prior to the introduction of NIPT. Audits found 15 of 43 women in the United Kingdom and 2 of 6 in Singapore continued pregnancies following a high‐risk NIPT result.Conclusions: Termination rates following the detection of DS by NIPT are unchanged or decreased compared to historical termination rates. Impact on live birth rates may be minimal in settings where termination rates fall. Population‐based studies are required to determine the true impact.