Intermanufacturer assessment of diagnostic performance of angiogenic ratio vs glycosylated fibronectin in women with suspected pre-eclampsia.

OBJECTIVE: To compare the diagnostic performance of different manufacturers' immunoassays for the soluble fms-like tyrosine kinase-1 (sFlt-1)-to-placental growth factor (PlGF) ratio with that of a point-of-care test for glycosylated fibronectin (GlyFn) in women with suspected pre-eclampsia (PE). METHODS: This was a prospective, single-center, double-blinded, non-interventional study of East Asian women with a singleton pregnancy who presented with hypertension with or without clinical features of PE after 20 weeks' gestation between January 2020 and March 2022. Maternal serum samples were collected at the time of presentation, and subsequent management followed the departmental protocol, based on gestational age, severity of hypertension, fetal condition and presence of severe PE features. Women diagnosed with PE at presentation were excluded. PE was diagnosed according to the 2018 International Society for the Study of Hypertension in Pregnancy classification. Levels of sFlt-1 and PlGF were measured using the Cobas e411 (Roche Diagnostics), BRAHMS KRYPTOR (ThermoFisher Scientific) and iMAGIN 1800 (Ningbo-Aucheer) platforms. GlyFn levels were measured using the Lumella™ GlyFn PoC test (Diabetomics). The predictive performance of each test to rule out PE within 7 days and rule in PE within 28 days from the date of presentation was assessed. Based on the PROGNOSIS study, a sFlt-1/PlGF ratio of ≤ 38 on the Roche platform was used to predict the absence of PE within 7 days. The sFlt-1/PlGF ratio was classified as high or low using platform-specific thresholds equivalent to a Roche sFlt-1/PlGF ratio of 38, which were derived using Passing-Bablok regression. GlyFn was categorized as high or low using two reported clinical management thresholds (263 µg/mL and 510 µg/mL). RESULTS: Overall, 236 women with suspected PE were included, of whom 70 (29.7%) were diagnosed with PE; 36 (51.4%) and 70 (100%) developed PE within 7 days and 28 days, respectively. Eighty-eight (37.3%) women had a sFlt-1/PlGF ratio of > 38 on the Roche platform, 79 (33.5%) women had a sFlt-1/PlGF ratio of > 55 on the KRYPTOR platform and 96 (40.7%) women had a sFlt-1/PlGF ratio of > 40 on the iMAGIN 1800 platform. Furthermore, 62 (26.3%) and four (1.7%) women had a GlyFn level of > 263 µg/mL and > 510 µg/mL, respectively. The negative predictive value (NPV) of the sFlt-1/PlGF ratio measured on the Roche, KRYPTOR and iMAGIN 1800 platforms to rule out PE within 7 days after presentation was 83.3%, 82.0% and 82.9%, respectively, while that for GlyFn > 263 µg/mL and > 510 µg/mL was 82.6% and 70.4%, respectively. The corresponding positive predictive values (PPV) to rule in PE within 28 days after presentation were 50.5%, 52.3% and 46.7%, respectively, for the sFlt-1/PlGF ratio, and 35.4% and 50.0%, respectively, for GlyFn > 263 µg/mL and > 510 µg/mL. CONCLUSIONS: The predictive performance of different manufacturers' assays for the sFlt-1/PlGF ratio to rule in and rule out PE were similar once standardized to a common threshold. Our findings suggest that the sFlt-1/PlGF ratio and GlyFn using a cut-off of 263 µg/mL can both be utilized to rule out PE within 7 days after assessment, with a moderate NPV. The PPV for ruling in PE within 28 days remains poor. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Implementation of sonopartogram: multicenter feasibility study.

OBJECTIVES: Well-established clinical practice for assessing progress in labor involves routine abdominal palpation and vaginal examination (VE). However, VE is subjective, poorly reproducible and painful for most women. In this study, our aim was to evaluate the feasibility of systematically integrating transabdominal and transperineal ultrasound assessment of fetal position, parasagittal angle of progression (psAOP), head-perineum distance (HPD) and sonographic cervical dilatation (SCD) to monitor the progress of labor in women undergoing induction of labor (IOL). We also aimed to determine if ultrasound can reduce women's pain during such examinations. METHODS: Women were recruited as they presented for IOL in three maternity units. Ultrasound assessments were performed in 100 women between 37 + 0 and 41 + 6 weeks' gestation. A baseline combined transabdominal and transperineal scan was performed, including assessment of fetal biometry, umbilical artery and fetal middle cerebral artery Doppler, amniotic fluid index, fetal spine and occiput positions, psAOP, HPD, SCD and cervical length. Intrapartum scans were performed instead of VE, unless there was a clinical indication to perform a VE, according to protocol. Participants were asked to indicate their level of pain by verbally giving a pain score between 0 and 10 (with 0 representing no pain) during assessment. Repeated measures data were analyzed using mixed-effect models to identify significant factors that affected the relationship between psAOP, HPD, SCD and mode of delivery. RESULTS: A total of 100 women were included in the study. Of these, 20% delivered by Cesarean section, 65% vaginally and 15% by instrumental delivery. There were no adverse fetal or maternal outcomes. A total of 223 intrapartum ultrasound scans were performed in 87 participants (13 women delivered before intrapartum ultrasound was performed), with a median of two scans per participant (interquartile range (IQR), 1-3). Of these, 76 women underwent a total of 151 VEs with a median of one VE per participant (IQR, 0-2), with no significant difference between vaginal- or Cesarean-delivery groups. After excluding those with epidural anesthesia during examination, the median pain score for intrapartum scans was 0 (IQR, 0-1) and for VE it was 3 (IQR, 0-6). Cesarean delivery was significantly associated with a slower rate of change in psAOP, HPD and SCD. CONCLUSIONS: Comprehensive transabdominal and transperineal ultrasound assessment can be used to assess progress in labor and can reduce the level of pain experienced during examination. Ultrasound assessment may be able to replace some transabdominal and vaginal examinations during labor. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Glycosylated fibronectin improves first-trimester prediction of pre-eclampsia.

OBJECTIVE: To determine whether maternal serum glycosylated fibronectin (GlyFn) level in the first trimester increases the sensitivity of the Fetal Medicine Foundation (FMF) triple test, which incorporates mean arterial pressure, uterine artery pulsatility index and placental growth factor, when screening for pre-eclampsia (PE) in an Asian population. METHODS: This was a nested case-control study of Chinese women with a singleton pregnancy who were screened for PE at 11-13 weeks' gestation as part of a non-intervention study between December 2016 and June 2018. GlyFn levels were measured retrospectively in archived serum from 1685 pregnancies, including 101 with PE, using an enzyme-linked immunosorbent assay (ELISA), and from 448 pregnancies, including 101 with PE, using a point-of-care (POC) device. Concordance between ELISA and POC tests was assessed using Lin's correlation coefficient and Passing-Bablok and Bland-Altman analyses. GlyFn was transformed into multiples of the median (MoM) to adjust for maternal and pregnancy characteristics. GlyFn MoM was compared between PE and non-PE pregnancies, and the association between GlyFn MoM and gestational age at delivery with PE was assessed. Risk for developing PE was estimated using the FMF competing-risks model. Screening performance for preterm and any-onset PE using different biomarker combinations was quantified by area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% fixed false-positive rate (FPR). Differences in AUC between biomarker combinations were compared using the DeLong test. RESULTS: The concordance correlation coefficient between ELISA and POC measurements was 0.86 (95% CI, 0.83-0.88). Passing-Bablok analysis indicated proportional bias (slope, 1.08 (95% CI, 1.04-1.14)), with POC GlyFn being significantly higher compared with ELISA GlyFn. ELISA GlyFn in non-PE pregnancies was independent of gestational age at screening (P = 0.11), but significantly dependent on maternal age (P < 0.003), weight (P < 0.0002), height (P = 0.001), parity (P < 0.02) and smoking status (P = 0.002). Compared with non-PE pregnancies, median GlyFn MoM using ELISA and POC testing was elevated significantly in those with preterm PE (1.23 vs 1.00; P < 0.0001 and 1.18 vs 1.00; P < 0.0001, respectively) and those with term PE (1.26 vs 1.00; P < 0.0001 and 1.22 vs 1.00; P < 0.0001, respectively). GlyFn MoM was not correlated with gestational age at delivery with PE (P = 0.989). Adding GlyFn to the FMF triple test for preterm PE increased significantly the AUC from 0.859 to 0.896 (P = 0.012) and increased the DR at 10% FPR from 64.9% (95% CI, 48.7-81.1%) to 82.9% (95% CI, 66.4-93.4%). The corresponding DRs at 10% FPR for any-onset PE were 52.5% (95% CI, 42.3-62.5%) and 65.4% (95% CI, 55.2-74.5%), respectively. CONCLUSIONS: Adding GlyFn to the FMF triple test increased the screening sensitivity for both preterm and any-onset PE in an Asian population. Prospective non-intervention studies are needed to confirm these initial findings. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Characterization of microbial communities in exhaust air treatment systems of large-scale pig housing facilities.

Exhaust air treatment has gained importance as an essential factor in intensive livestock areas due to the rising emissions in the environment. Wet filter walls of multi-stage exhaust air treatment systems precipitate gaseous ammonia and dust particles from exhaust air in washing water. Microbial communities in the biomass developed in the washing water of five large-scale exhaust air treatment units of pig housing facilities, were investigated by fluorescence in situ hybridization (FISH) and 16S rDNA sequence analyses. No "standard" nitrifying bacteria were found in the washing water. Instead mainly α-Proteobacteria, aggregating ß- and χ-Proteobacteria, a large number of Actinobacteria, as well as individual Planctomycetales and Crenarchaeota were detected after more than twelve months' operation. The main Proteobacteria species present were affiliated to the families Alcaligenaceae, Comamonadaceae and Xanthomonadaceae. Furthermore, we investigated the consumption of inorganic nitrogen compounds in the washing water of one exhaust air treatment unit during a fattening period with and without pH control. Maintaining the pH at 6.0 resulted in a ca. fivefold higher ammonium concentration and a ca. fourfold lower concentration of oxidized nitrogen compounds after the fattening period was finished.

Morphine tolerance in mice is independent of polymorphisms in opioid receptor sequences.

Pharmacogenomics links individual drug response variation to genetic differences, such as single nucleotide polymorphisms (SNPs). In particular, pharmacogenomics will allow clinicians to use genetic diagnostics to predict the response of a patient to a drug. We investigated whether SNPs in opioid receptors correlated with the development of morphine tolerance in mouse strains that showed either high or low tolerance to morphine. Sequencing identified five silent SNPs in the delta opioid receptor that varied from the published sequence in some strains, but which were found in both high and low tolerance strains. The mu and kappa opioid receptor sequences had no SNPs. Taken together, these data definitively demonstrate that morphine tolerance development in mice is independent of opioid receptor sequence.

The downregulation of Bcl-2 expression is necessary for theophylline-induced apoptosis of eosinophil.

Apoptosis of eosinophils is of increasingly important value in modulating allergic inflammatory airway diseases, such as asthma, and is suppressed by interleukin-5 (IL-5) in in vitro culture. In this study, we examined the effects of theophylline on survival/apoptosis, intracellular cAMP concentration, and Bcl-2 protein expression. Treatment with theophylline protected eosinophils against IL-5-mediated inhibition of apoptosis with a simultaneous suppression of survival in a dose-dependent manner. Theophylline caused an increase in the intracellular cAMP levels of IL-5-stimulated eosinophils. Enhancement of eosinophil apoptosis was consistent with an increase in DNA fragmentation in eosinophils treated with theophylline. On the other hand, the Bcl-2 protein appeared to be expressed constitutively in freshly isolated eosinophils. Bcl-2 expression was augmented by IL-5 stimulation, yet it was considerably inhibited by theophylline treatment. These data suggest that intracellular cAMP levels and Bcl-2 expression are involved in the suppression of eosinophil survival by theophylline.

[The introduction of the western psychiatry into Korea: from the mid seventeenth century to 1911, the time of Japanese forced annexation of Korea].

The object of this study is to investigate the routes of the introduction of the western psychiatric knowledges and practices in Korea. The historical documents including newspapers and governmental bulletins as well as articles and books on the history of the Korean medicine were examined and the results are as follows: The western knowledge about the brain anatomy and physiology were introduced from China by the enlightened Confucian and Taoistic scholars of Korea in the mid seventeenth century through the Chinese translations of the western science and medicine. Due to the lack of support for the scholars and even persecution by the ruling power to those who had great interests in the western thoughts including sciences, the western medical knowledges could not be actualized in practice. Thus, the active practices of western medicine were started in the late 19th century in Korea through the two routes; one, via Japanese military physicians and the other one, via the western missionary physicians. The psychiatry was lectured by Japanese psychiatrist in 1910 at the medical school of Tai-Han Unwon, the Korean governmental clinic and 1913 at the Severance medical school of Tai-Han Uiwon, the Korean governmental clinic and in 1913 at the Severance medical school by the Australian psychiatrist, McLaren. As the independent department with the psychiatric ward, the first Dept. of Psychiatry was established in 1913 at the colonial governmental clinic, Chosun Chondokbu-Uiwon, the former Tai-Han Ui-won. Medicine as well as psychiatry was introduced into Korea under the political atmosphere of one sided admiration for the western science. The attempts to combine the western medicine with the traditional Korean medicine could not be tolerated by both missionary physicians and the colonial regime.

Pregnancy augments nitric oxide-dependent dilator response to acetylcholine in the human uterine artery.

The influence of pregnancy on the dilator effects of acetylcholine in the isolated human uterine artery was investigated. Acetylcholine (0.1 nM to 0.1 microM) produced concentration- and endothelium-dependent relaxation of norepinephrine (3 microM)-induced contraction. The relaxation was greater in arteries from pregnant patients (P arteries) than from non-pregnant patients (NP arteries). The maximal relaxation was 53.5+/-3.4% (n=21) in P arteries and 23.5+/-2.5% (n=35) in NP arteries. In both P and NP arteries the cholinergic relaxation was increased in the presence of superoxide dismutase and greatly reduced in the presence of the nitric oxide synthase inhibitors, NG-mono-methyl L-arginine (L-NMMA) and L-nitro-arginine-methylester (L-NAME). The effect of these nitric oxide synthase inhibitors was reversed by L-arginine. We conclude that pregnancy enhances acetylcholine-induced nitric oxide synthesis and release in the human uterine artery.

Delta opioid receptor enhancement of mu opioid receptor-induced antinociception in spinal cord.

Although the mu selective agonist [D-Ala2-MePhe4-Gly-ol5]enkephalin (DAMGO) and the delta selective agonist [D-Pen2,D-Pen5]enkephalin (DPDPE) are both antinociceptive when administered directly into the spinal cord of mice, 50% of antinociceptive dose (AD50) of DAMGO is about 2 orders of magnitude lower than the AD50 of DPDPE. In contrast, the two ligands show similar affinities for their respective receptors in in vitro binding assays. One possible explanation for this discrepancy is that DPDPE antinociception in the spinal cord is mediated through not delta but mu receptors, for which it has an several hundred-fold lower affinity than DAMGO. In support of this, we found that DPDPE-mediated antinociception was blocked by the mu selective antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP). The pA2 value of CTAP for DPDPE was virtually identical with that for DAMGO. However, because its action also was blocked by naltrindole, an antagonist selective for delta receptors, the latter must also play a role in antinociception. When DAMGO and DPDPE were administered i.t. together at ratios ranging from 1:200 to 1:500, the AD50 of DAMGO was lowered as much as 10-fold relative to its AD50 when given alone. Thus DPDPE had a potentiating effect on DAMGO, although the reverse was not observed. This potentiation was lost in animals made tolerant to systemic morphine. The loss of potentiation seemed to be caused by changes in the delta receptors, because a) the AD50 of DAMGO (i.t.) given alone to tolerant animals was virtually the same as for naive animals, whereas the AD50 of DPDPE given alone increased by 4-fold; and b) the AD50 of DPDPE given alone in the tolerant animal was increased only slightly by naltrindole, whereas CTAP was still a very potent antagonist. We conclude that DPDPE, a selective delta agonist, mediates antinociception in the spinal cord through mu receptors, consistent with results of recent studies of "knock-out" mice lacking mu receptors. At the same time, however, the delta agonist acting through delta receptors can potentiate the mu receptor-mediated antinociceptive action of either mu or delta agonists. This potentiating effect, like the synergistic effect observed between mu receptors at spinal and supraspinal sites, is lost during tolerance.