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Amatoxins and phallotoxins are toxic cyclopeptides found in the genus Amanita and are among the predominant causes of foodborne sickness and poisoning-related fatalities in China. This study introduces and validates a simple, rapid and cost-effective ultra-performance liquid chromatography–mass spectrometry method for the simultaneous determination and quantification of α-amanitin, β-amanitin, γ-amanitin, phallisacin, phallacidin and phalloidin in human blood and urine. Quick therapeutic decision-making is supported by a 9 min chromatographic separation performed on a Waters Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 µm) using a gradient of high-performance liquid chromatography (HPLC)-grade water and methanol:0.005% formic acid. The analyte limit of quantification was 1–3 ng/mL in blood and 0.5–2 ng/mL in urine. Calibrations curves, prepared by spiking drug-free blood and urine, demonstrated acceptable linearity with mean correlation coefficients (r) greater than 0.99 for all phallotoxins and amatoxins. Acceptable intraday and interday precision (relative standard deviation <15%) and accuracy (bias, −4.8% to 13.0% for blood and—9.0% to 14.7% for urine) were achieved. The validated method was successfully applied to analyze 9 blood samples and 2 urine samples testing positive for amatoxins and/or phallotoxins. Amatoxins and/or phallotoxins were identified in each whole blood sample at a range of 1.12–5.63 ng/mL and in two urine samples from 1.01–9.27 ng/mL. The method has the benefits of simple sample preparation (protein precipitation) and wide analyte coverage, making it suitable for emergency quantitative surveillance toxicological analysis in clinics and forensic poisoning practice. [ABSTRACT FROM AUTHOR]

Background Antiphospholipid syndrome (APS) is an autoimmune disorder that is characterized by venous or arterial thrombosis and/or obstetric morbidity in the constant presence of persistent antiphospholipid antibodies (aPLs). In patients with APS, the relationship between production of immunoglobulin (Ig)A antiphospholipid antibodies and adverse events in pregnancy is still unclear. As a result of massive trials, the clinical efficiency of IgA-aPLs is used to evaluate pregnancy outcomes in patients with APS. Methods We enrolled 381 female patients with APS and 93 healthy pregnant women. Silica clotting time ratio, dilute Russell viper venom time (dRVVT) ratio, and 6 aPLs, including IgA/IgG/IgM isotypes aβ2GPI and IgA/IgG/IgM isotypes anticardiolipin (aCL), were detected using commercial kits. Results We found no significant differences in laboratory parameters between patients with APS and the control group. The total prevalence of aCL IgA was 2.9%; the prevalence of aβ2GPI IgA was 3.4%. Only 1.3% of the individuals who tested aCL-positive (5/381) had isolated aCL IgA. Similarly, isolated aβ2GPI IgA was present in only 0.8% (3/381) of the aβ2GPI-positive subjects. Meanwhile, aCL IgA showed the maximum area under the curve (AUC) of 0.666 (95% CI, 0.60–0.73; P <.001), followed by dRVVT ratio (AUC = 0.649; 0.58–0.72; P <.001). Conclusion Positive aCL IgA and aβ2GPI IgA ratios were extremely low for each isolated isotype of aPLs. For patients with APS who experienced fetal loss, aCL IgA may be utilized as a risk factor for pregnancy loss among patients with APS. Establishing a standardized diagnosis of IgA aPLs is also important for these patients. [ABSTRACT FROM AUTHOR]

Study Question: Does in vitro maturation (IVM) result in non-inferior cumulative live birth rates compared to those after standard in vitro fertilization (IVF) in infertile women with polycystic ovary syndrome (PCOS)?Summary Answer: One cycle of IVM, without any stimulation, was inferior to one cycle of standard IVF in women with PCOS in terms of 6-month cumulative live birth rates, when choosing single vitrified-warmed blastocyst transfer.What Is Known Already: IVM is an emerging alternative treatment for women with PCOS who need assisted reproductive technology. Since a minimal or even zero dose of gonadotropins are required in the IVM procedure, the occurrence of ovarian hyperstimulation syndrome (OHSS) is eliminated. Only one clinical trial comparing the pregnancy outcome between IVM with FSH priming and IVF has been reported. However, it is still unknown whether IVM treatment without any stimulation can offer a similar live birth outcome in women with PCOS as compared to that in women receiving the standard IVF procedure with ovarian stimulation.Study Design, Size, Duration: This single-centre, open-label randomized controlled non-inferiority trial in an academic infertility centre in China was performed between March 2018 and July 2019.Participants/materials, Setting, Methods: Women aged 20-38 years with PCOS and infertility scheduled for their first IVF attempt were eligible. In total, 351 women were randomly allocated to receive one cycle of unstimulated IVM (n = 175) or one cycle of standard IVF with a flexible GnRH antagonist protocol and hCG as ovulatory trigger (n = 176). A freeze-all and single blastocyst transfer strategy was used in both groups. The primary outcome was ongoing pregnancy (leading to live birth) within 6 months after randomization. A non-inferiority margin of 15% was considered.Main Results and the Role Of Chance: The IVM procedure without additional gonadotropin resulted in a lower ongoing pregnancy (leading to live birth) within 6 months after randomization compared to standard IVF treatment (22.3% vs. 50.6%; rate difference -28.3%; 95% confidence interval [CI]: -37.9% to -18.7%). Moderate-severe OHSS did not occur in the IVM group, while in the IVF group, ten women (5.7%) had moderate OHSS and one woman (0.6%) had severe OHSS. There was no statistically significant difference in the occurrence of obstetric and perinatal complications.Limitations, Reasons For Caution: The trial was conducted using an IVM protocol without additional stimulation in a single centre, which may limit its generalizability. In addition, a GnRH agonist trigger rather than hCG for IVF stimulation in women with PCOS would be more consistent with current clinical practice.Wider Implications Of the Findings: Although IVM is considered to be a convenient, inexpensive and safe alternative to IVF for women with PCOS, our results indicated that one cycle of IVM without any stimulation was inferior to one cycle of standard IVF in terms of the cumulative live birth rate. The inferiority of IVM without ovarian stimulation could be mainly due to the limitations in the developmental potential of embryos. Further IVM development should be tested and validated in a freeze-only and blastocyst transfer setting. Further RCTs are needed to evaluate the effectiveness and safety of other IVM protocols or multiple cycles of IVM compared to IVF.Study Funding/competing Interest(s): This study was supported by the National Key Research and Development Program of China (2016YFC1000201 and 2018YFC1002104) and the National Science Foundation of China (81730038). B.W.M. is supported by a NHMRC Investigator grant (GNT1176437). All other authors declare no competing interests.Trial Registration Number: Clinicaltrials.gov NCT03463772.Trial Registration Date: 29 January 2018.Date Of First Patient’s Enrolment: 16 March 2018. [ABSTRACT FROM AUTHOR]