Background
Recently, the Japan Society of Obstetrics and Gynecology initiated a clinical study of preimplantation genetic test for aneuploidy. There will be a great need for a standardized embryo ...biopsy technique in Japan. However, the gold standard trophectoderm (TE) biopsy procedure has not been established, and this review outlines the clinical use of TE biopsy.
Methods
Based on literature, the method and associated techniques for TE biopsy, a dissection method of TE cells from blastocysts, were investigated.
Main findings
Two TE biopsy methods are used, namely assisted hatching (herniating) and non‐assisted hatching (direct suction); however, it is not clear which of these methods is superior. It is critical to understand whether the flicking or pulling method is beneficial.
Conclusion
Non‐assisted hatching biopsy method may cause blastocyst collapse with a higher probability, and it may extend the biopsy time. The biopsy procedure should be performed within 3 minutes, and thus direct TE suction may have greater disadvantages. It is a fact that pulling method of TE dissection with laser pulse is simple; however, excess laser shots may induce a higher frequency of mosaicism. It is important to understand that each technique of TE biopsy has benefits and disadvantages.
The issue of copying values or references has historically been studied for managing memory objects, especially in distributed systems. In this paper, we explore a new topic on copying values v.s. ...references, for memory page compaction on virtualized systems. Memory page compaction moves target physical pages to a contiguous memory region at the operating system kernel level to create huge pages. Memory virtualization provides an opportunity to perform memory page compaction by copying the references of the physical pages. That is, instead of copying pages' values, we can move guest physical pages by changing the mappings of guest-physical to machine-physical pages. The goal of this paper is a quantitative comparison between value- and reference-based memory page compaction. To do so, we developed a software mechanism that achieves memory page compaction by appropriately updating the references of guest-physical pages. We prototyped the mechanism on Linux 4.19.29 and the experimental results show that the prototype's page compaction is up to 78% faster and achieves up to 17% higher performance on the memory-intensive real-world applications as compared to the default value-copy compaction scheme.
The present study was designed to test the hypothesis that osteoclasts appear after or at the same time as the initiation of bone mineralization in developing intramembranous bones. We examined ...mineral deposition via Von Kossa staining to determine when bone mineralization begins, tartrate-resistant acid phosphatase (TRAP) activity and cathepsin K immunoreactivity to identify the presence of osteoclasts, and their mRNA expression levels to assess osteoclastic differentiation in the embryonic mouse mandible. Cathepsin K-immunopositive cells were detected around the same time as the onset of bone mineralization, whereas TRAP-positive cells appeared prior to bone mineralization. Cathepsin K protein was expressed only in multinucleated osteoclasts, whereas TRAP activity was identified in both mono- and multinucleated cells. During bone development, TRAP-positive cells altered their morphology, which was related to the number of their nuclei. The elevated mRNA levels of TRAP and cathepsin K were consistent with the increased percentage of multinucleated osteoclasts and the progression of bone development. Our study revealed that TRAP-positive cells appear prior to bone mineralization, and TRAP- and cathepsin K-positive multinucleated osteoclasts appear at the same time as the initiation of bone mineralization in embryonic mouse mandibles, suggesting that osteoclasts contribute to bone matrix maturation during intramembranous ossification.
Abstract
The (pro)renin receptor (P)RR) is a multifunctional protein that is cleaved to generate the soluble (P)RR s(P)RR, reflecting the status of the tissue renin-angiotensin system and/or activity ...of the (P)RR. The serum s(P)RR level is associated with arteriosclerosis, independent of other risk factors, in patients undergoing hemodialysis (HD). This study was conducted to investigate whether the s(P)RR level was associated with new-onset cardiovascular events or malignant diseases and poor prognosis in patients undergoing HD. Overall, 258 patients 70 (61–76) years, 146 males undergoing maintenance HD were prospectively followed up for 60 months. We investigated the relationships between s(P)RR levels and new-onset cardiovascular events/ malignant diseases and mortality during the follow-up period using Cox proportional hazard analyses. The cumulative incidence of new-onset cardiovascular events (
P
= 0.009) and deaths (
P
< 0.001), but not of malignant diseases, was significantly greater in patients with higher serum s(P)RR level (≥ 29.8 ng/ml) than in those with lower s(P)RR level (< 29.8 ng/ml). A high serum s(P)RR level was independently correlated with cardiovascular mortality (95% CI 1.001–1.083,
P
= 0.046). The serum s(P)RR level was associated with cardiovascular events and mortality, thus qualifying as a biomarker for identifying patients requiring intensive care.
Use of clinical-grade human induced pluripotent stem cell (iPSC) lines as a starting material for the generation of cellular therapeutics requires demonstration of comparability of lines derived from ...different individuals and in different facilities. This requires agreement on the critical quality attributes of such lines and the assays that should be used. Working from established recommendations and guidance from the International Stem Cell Banking Initiative for human embryonic stem cell banking, and concentrating on those issues more relevant to iPSCs, a series of consensus workshops has made initial recommendations on the minimum dataset required to consider an iPSC line of clinical grade, which are outlined in this report. Continued evolution of this field will likely lead to revision of these guidelines on a regular basis.
This study was aimed at exploring the benefits of preimplantation genetic testing for aneuploidy (PGT-A) in ensuring a successful pregnancy in patients with recurrent pregnancy loss (RPL) caused by ...an abnormal number of chromosomes in the embryo and recurrent implantation failure (RIF). Thirty-two patients who underwent PGT-A (18 in the RIF protocol and 14 in the RPL protocol) were enrolled in the study, and 2556 patients who did not undergo PGT-A during the same in vitro fertilization (IVF) treatment period were enrolled as controls. All patients underwent minimal stimulation cycle IVF. In the RPL protocol, the live birth rate per embryo transfer (ET) and that per patient were higher with PGT-A (80.0% each) than without it (0% each; P = 0.0050), and the rate of miscarriages was lower with PGT-A than without it (20.0% vs. 100.0%, P = 0.0098). In the RIF protocol, there were no significant differences in the live birth rate per ET and in the rate of miscarriages between groups with and without PGT-A-90.0% vs. 69.2% (P = 0.2313) and 0% vs. 10.0% (P = 0.3297), respectively. None of the children whose mothers underwent PGT-A presented adverse findings at a 1.5-year developmental check-up. In conclusion, PGT-A in RPL is advantageous for improving the live birth rate per ET and that per patient in minimal stimulation cycle IVF; it reduces the rate of miscarriages. In addition, PGT-A might be more beneficial for embryo selection than the existing morphological grades of blastocysts, resulting in earlier conception.
Purpose Kinesiophobia after anterior cruciate ligament reconstruction has been identified as an inhibitor of return to sports. This study aimed to clarify the relationship between kinesiophobia and ...knee function 6 months after anterior cruciate ligament reconstruction when the patient intends to return to sports. Participants and Methods A total of 66 patients who underwent primary anterior cruciate ligament reconstruction (mean age 17.3 ± 2.6 years, 17 males and 49 females, Tegner activity score ≥7) were included in the study. The 11-item version of Tampa scale of kinesiophobia was used to evaluate kinesiophobia 6 months postoperatively. Knee function was evaluated with knee extension muscle strength, tibial anterior displacement, heel buttock distance, heel height difference, anterior knee pain score, and single-leg hop test. The relationship between Tampa scale of kinesiophobia, patient characteristics, and knee function was investigated. Results A low Anterior knee pain score and low single-leg hop test, male gender, and age were significant factors associated with kinesiophobia. Conclusion Kinesiophobia was associated with a low anterior knee pain score and low single-leg hop test 6 months after anterior cruciate ligament reconstruction. Patients with a low single-leg hop test score or severe pain may need rehabilitation to reduce kinesiophobia.
Visit-to-visit blood pressure variability (VVBPV) is an independent risk factor for cardiovascular morbidity and mortality in the general population. Hemodialysis (HD) patients have a poor prognosis ...due to an increased prevalence of cardiovascular disease. Intradialytic hypotension is associated with excess mortality, but whether VVBPV influences mortality is still unclear in HD patients. The present study aimed to investigate the characteristics of VVBPV in these patients. A total of 324 maintenance HD patients, who could be followed for 60 months, were recruited. We used variation independent of the mean (VIM) in pre-dialysis systolic blood pressure (pre-VIM-SBP) as an index of VVBPV. We investigated (1) the reproducibility of pre-VIM-SBP, (2) the relationship between pre-VIM-SBP and background factors, and (3) the association between pre-VIM-SBP and mortality. Pre-VIM-SBP showed significant reproducibility intraclass correlation, 0.45 (P < 0.001). Higher pre-VIM-SBP was associated with less physical activity and worse left ventricular diastolic function. Higher pre-VIM-SBP was associated with a higher rate of cardiovascular deaths independent of other factors. These data suggest that VVBPV in HD patients is reproducible and associated with various background factors. VVBPV is independently correlated with cardiovascular mortality (hazard ratio: 1.166, 95% confidence interval: 1.030-1.320, P = 0.015). Further studies are necessary to confirm the mechanism of increased VVBPV and to clarify whether reducing VVBPV will improve the prognosis for HD patients.
Abstract
Objectives
Understanding the miss rate and characteristics of missed pharyngeal and laryngeal cancers during upper gastrointestinal endoscopy may aid in reducing the endoscopic miss rate of ...this cancer type. However, little is known regarding the miss rate and characteristics of such cancers. Therefore, the aim of this study was to investigate the upper gastrointestinal endoscopic miss rate of oro-hypopharyngeal and laryngeal cancers, the characteristics of the missed cancers, and risk factors associated with the missed cancers.
Methods
Patients who underwent upper gastrointestinal endoscopy and were pathologically diagnosed with oro-hypopharyngeal and laryngeal squamous cell carcinoma from January 2019 to November 2020 at our institution were retrospectively evaluated. Missed cancers were defined as those diagnosed within 15 months after a negative upper gastrointestinal endoscopy.
Results
A total of 240 lesions were finally included. Eighty-five lesions were classified as missed cancers, and 155 lesions as non-missed cancers. The upper gastrointestinal endoscopic miss rate for oro-hypopharyngeal and laryngeal cancers was 35.4%. Multivariate analysis revealed that a tumor size of <13 mm (odds ratio: 1.96, P=0.026), tumors located on the anterior surface of the epiglottis/valleculae (odds ratio: 2.98, P=0.045) and inside of the pyriform sinus (odds ratio: 2.28, P=0.046) were associated with missed cancers.
Conclusions
This study revealed a high miss rate of oro-hypopharyngeal and laryngeal cancers during endoscopic observations. High-quality upper gastrointestinal endoscopic observation and awareness of missed cancer may help reduce this rate.
Tumors located on the anterior surface of the epiglottis/valleculae and inside of the pyriform sinus were associated with missed cancers during endoscopy. High-quality upper gastrointestinal endoscopy and awareness are necessary.
The clinical application of human adipose-derived mesenchymal stem cells (MSCs) as treatment for intractable diseases or traumatic tissue damage has attracted attention. To address the ability of ...reactivating injured ovaries, we prepared a rat model with damaged ovaries by using an anticancer agent, cyclophosphamide (CTX). We then investigated the restorative effects on ovarian function and the safety of adipose-derived MSCs (A-MSCs). MSCs were shown to be capable of inducing angiogenesis and restoring the number of ovarian follicles and corpus lutea in ovaries. No deformities, tumor formation or deaths were observed in F1 and F2 rats, indicating that the local injection of MSCs into the ovary did not have any obvious side effects. In addition, the localization of the Y chromosome was investigated using the fluorescent in situ hybridization method by injecting male A-MSCs into the ovaries; as a result, the Y chromosomes were localized not in the follicles, but in the thecal layers. ELISA revealed that A-MSCs secreted higher levels of vascular endothelial cell growth factor (VEGF), insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) than tail fibroblast cells. Quantitative real-time PCR and immunohistochemistry showed that higher expression levels of VEGF, IGF-1 and HGF were observed in CTX-treated ovaries after A-MSC transplantation. These findings suggest that MSCs may have a role in restoring damaged ovarian function and could be useful for regenerative medicine.
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