The concentration of fatty acids in follicular fluid reflect the physical condition of donors, and palmitic acid (PA) is a major component of follicular fluid. The present study examined the effect ...of PA on in vitro oocyte growth and investigated the molecular backgrounds of the PA induced-low quality oocytes. Oocyte-granulosa cell complexes (OGCs) were collected from early antral follicles of gilts. The OGCs were cultured for 14 days in a medium containing 0.5 mM PA or vehicle (BSA). PA was found to reduce granulosa cell (GCs) proliferation (0.73 fold) and viability (93.9% vs. 85.8%) and increase lipid content in oocytes and GCs. Oocytes developed in the presence of PA had low developmental ability to the blastocyst stage. In addition, PA affected developmental and epigenetic markers of histone modifications in oocytes; levels of H4K12 acetylation and H3K9 demethylation. PA affected cellular proliferation, apoptosis and endoplasmic reticulum stress markers along with reducing the phosphor-AKT/AKT levels and increasing the expression levels of caspase-3 and CHOP in GCs. Incubation of OGCs with PA increased ceramide content in the GC, and addition of ceramide to the culture medium inhibited GC proliferation. In conclusion, it is suggested that high PA content in the medium reduces viability and proliferation through ceramide accumulation, and PA impaires the developmental ability of oocytes grown in vitro. In addition, high-fat conditions induce changes in the histone modifications of oocytes grown in vitro.
•Palmitic acid (PA) is a major component of follicular fluid. When oocyte granulomas cell complexes derived from early antral follicles of gilt ovaries were cultured with 0.5 mM of PA, granulosa cells accumulated lipid content and showed low proliferation and viability compared with those cultured with BSA control.•Oocytes developed in the presence of PA had low developmental ability and showed differential histone modifications.•This PA-induced deterioration of granulosa cells was attributed to ceramide accumulation.
Summary
Pemphigus is a potentially fatal blistering skin disease. It is an autoimmune disease, meaning that the body's immune system, which normally fights off disease, in this case attacks healthy ...cells. The main treatments for pemphigus are with drugs called corticosteroids or immunosuppressive agents. The goal of treatment is to reach remission, a point where there are no new lesions (affected areas of skin) with minimal or no therapy (medication). However, many patients experience several relapses, meaning that after a period of improvement, the disease then worsens again, and it is often difficult for them to achieve remission. This study, from Japan, aimed to learn more about the risk factors and clinical features (signs) of pemphigus relapse. The authors retrospectively reviewed the medical records of 42 pemphigus patients. 61.9% of cases experienced relapse, usually when a medicine called oral prednisolone was tapered to around 0.1mg/kg. In a type of pemphigus called mucocutaneous pemphigus vulgaris (mcPV), the initial doses of prednisolone were lower in cases with relapse than without relapse. At relapse, mcPV shifted to subtypes (phenotypes) called mucosal dominant PV (mPV, which mainly affects the mouth and not the skin) (40%), pemphigus foliaceus (PF, affecting the skin) (20%) or others (20%). In contrast, the relapsing mPV and PF had the same clinical phenotypes as the initial phenotypes. Looking at antibodies, which are produced by the immune system to help fight off disease, patients with both anti‐Dsg1 and anti‐Dsg3 antibodies to begin with, had recurrence with anti‐Dsg3 antibodies alone (40%), with both anti‐Dsg1 and Dsg3 antibodies (30%) or with anti‐Dsg1 antibody alone (20%). In conclusion, when a patient with mcPV relapses, there can be changes in the phenotype of their disease, and the antibodies being produced. At least 1mg/kg/day of prednisolone, especially for mcPV cases, and prudent tapering around 0.1mg/kg may lead to better outcomes.
Linked Article: Ujiie et al. Br J Dermatol 2019; 180:1498–1505
Eribulin mesylate is a non-taxane microtubule dynamics inhibitor that recently gained Food and Drug Administration approval for late-line metastatic breast cancer (MBC).
In this single-arm, ...multicentre open-label phase II trial Japanese patients pretreated with an anthracycline and a taxane received 1.4 mg/m2 eribulin mesylate (2- to 5-min i.v. infusion on days 1 and 8 of a 21-day cycle). The primary efficacy end point was overall response rate (ORR) by independent review.
Patients (N = 80) had received a median of three prior chemotherapy regimens (range 1–5). ORR was 21.3% 95% confidence interval (CI) 12.9–31.8; all partial responses (PRs), stable disease (SD) occurred in 30 patients (37.5%) and the clinical benefit rate (complete response + PR + SD ≥6 months) was 27.5% (95% CI 18.1–38.6). Median duration of response was 3.9 months (95% CI 2.8–4.9), progression-free survival was 3.7 months (95% CI 2.0–4.4) and overall survival was 11.1 months (95% CI 7.9–15.8). The most frequent treatment-related grade 3/4 adverse events were neutropenia (95.1%), leukopenia (74.1%) and febrile neutropenia (13.6%). Grade 3 peripheral neuropathy occurred in 3.7% of patients (no grade 4).
Eribulin exhibited efficacy and tolerability in Japanese patients with heavily pretreated MBC.
This study addresses the hypothesis that SIRT1 upregulation prior to cryopreservation helps in recuperation from cryoinjury and improves the embryo quality. Bovine blastocysts were produced in vitro, ...and at Day 6 or 7 after fertilization, the blastocysts were cultured with 0 or 1 μM resveratrol for 6 or 24 h. This short duration of resveratrol treatment did not affect the embryo development or the grade of the blastocysts. However, both the durations of resveratrol treatment (6 h or 24 h) significantly increased the expression levels of SIRT1. When embryos pre-treated with resveratrol (0 or 1 μM) were cryopreserved and subsequently thawed, the hatching rates following 48 h of incubation were significantly higher for the resveratrol-treated embryos than for vehicle-treated embryos. Moreover, the resveratrol pretreatment significantly increased the copy number of mitochondrial DNA in the embryos, irrespective of the treatment durations. The in vitro-produced embryos at 6 days of insemination and the in vivo-developed embryos, which were collected from the donor cows at 6.5 days of insemination, were treated with resveratrol for 6 or 24 h prior to cryopreservation, respectively. The resveratrol pretreatment (for 6 or 24 h) resulted in high conception rate after thawing and transfer to the recipients, in both the in vivo and in vitro-produced embryos. In conclusion, our results suggest that pretreatment of bovine embryos with resveratrol improves the quality of embryos after cryopreservation and thawing probably through mitochondrial synthesis.
•Cryoinjury of embryos comes from mitochondrial damage.•Treatment of embryos with resveratrol prior to cryopreservation enhances SIRT1 and protects embryos against cryoinjury and results in high conception rate after transfer.
In this paper, we propose a method for designing an identification system for human-robot contact states based on tactile recognition. The following ideas are incorporated: experimentation for ...human-robot contact, verbalization of contact states, extraction of characteristic parameters from acquired tactile information, quantification of the recipient's tactile recognition incorporating its redundancy (identification confusability among contact states), evaluation of the identification confusability with a new criterion, and identification of contact states based on the received tactile stimulation. The proposed method allows a robot to quantify tactile recognition of a human (recipient) touched by other people (touch initiator), in which the verbal response by the recipient is matched with tactile stimulation acquired during physical contact utilizing a tactile interface. In addition, the method enables a robot that comes into contact with a human to identify contact states nearly similar to that of the recipient, based on the features of the received tactile stimulation. At this point, the reproduction of the identification confusability of the recipient's tactile recognition is also accomplished by using a neural network called modified counterpropagation (MCP). Once a tactile stimulation is induced on the robot body, the probability of corresponding contact states is calculated and outputted by the system, based on the degree of similarity of the characteristics between the newly received and previously stored tactile stimulation. Experimental results indicate that the constructed system allows a successful quantification of the recipient's contact-state recognition incorporating the identification confusability and the accomplishment of a high level of accuracy in contact-state identification. These results confirm that the proposed method is useful for identifying human-robot contact states based on tactile recognition.
To evaluate how computed tomography (CT) and magnetic resonance imaging (MRI) characteristics can be used to differentiate immunohistochemically confirmed mediastinal Müllerian cysts (MMCs) from ...bronchogenic cysts (BCs).
Sixteen patients with histopathologically and immunohistochemically confirmed mediastinal cysts (four with MMCs and 12 with BCs) were included in this study. CT and MRI images were reviewed retrospectively and the location, size, CT attenuation, and MRI signal intensity of the two pathologies were compared.
On review of CT images, cysts could be located to the anterior mediastinum in four BCs, middle mediastinum in three MMCs and seven BCs, and posterior mediastinum in one MMC and one BC. Contact with a vertebral body was observed in 4/4 MMCs (100%) and 6/12 BCs (50%). The ratios of minimum-to-maximum diameter (0.57±0.09 versus 0.74±0.11, p<0.01), CT attenuation (7.8±6 versus 44.3±12 HU, p<0.01), and cyst-to-spinal cord signal intensity ratios (SIRs) on T1-weighted images (0.56±0.2 versus 1.31±0.4, p<0.01) were significantly lower for MMCs than BCs. No significant differences in maximum diameter, minimum diameter, and SIRs on T2-weighted images were found between MMCs and BCs.
In characterising mediastinal cysts in a middle-aged female patient, contact with a vertebral body, flattened configuration, hypodensity on CT, and hypointensity compared to spinal cord on T1-weighted images are features that are specific to MMCs.
•Contact with a vertebral body was observed in all MMCs.•The ratios of minimum-to-maximum diameter were lower for MMCs than BCs.•CT attenuation within cysts were lower for MMCs than BCs.•Cyst-to-spinal cord SIRs on T1WI were lower for MMCs than BCs.
Primary analysis of the multicenter, open-label, single-arm, phase II DESTINY-Breast01 trial (median follow-up 11.1 months) demonstrated durable antitumor activity with trastuzumab deruxtecan (T-DXd) ...in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1). We report updated cumulative survival outcomes with a median follow-up of 26.5 months (data cut-off 26 March 2021).
Patients with HER2-positive mBC resistant or refractory to T-DM1 received T-DXd 5.4 mg/kg intravenously every 3 weeks until disease progression, unacceptable adverse events, or withdrawal of consent. The primary endpoint was confirmed objective response rate (ORR) by independent central review (ICR). Secondary endpoints included overall survival (OS), duration of response (DoR), progression-free survival (PFS), and safety.
The ORR by ICR was 62.0% 95% confidence interval (CI) 54.5% to 69.0% in patients who received T-DXd 5.4 mg/kg every 3 weeks (n = 184). Median OS was 29.1 months (95% CI 24.6-36.1 months). Median PFS and DoR were 19.4 months (95% CI 14.1-25.0 months) and 18.2 months (95% CI 15.0 months-not evaluable), respectively. Drug-related treatment-emergent adverse events (TEAEs) were observed in 183 patients (99.5%), and 99 patients (53.8%) had one or more grade ≥3 TEAEs. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 15.8% of patients (n = 29), of which 2.7% (n = 5) were grade 5.
These updated results provide further evidence of sustained antitumor activity of T-DXd with a consistent safety profile in heavily pretreated patients with HER2-positive mBC.
•T-DXd was investigated in patients with HER2-positive mBC who had prior T-DM1 treatment in DESTINY-Breast01.•Primary analysis showed a confirmed ORR of 60.9%; median OS was not reached.•This updated analysis showed a confirmed ORR of 62.0% and median OS of 29.1 months.•Safety was consistent with the primary analysis and the established safety profile of T-DXd.•These updated results further support T-DXd for the treatment of patients with heavily pretreated HER2-positive mBC.
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