Metformin ameliorates mitochondrial damage induced by C9orf72 poly(GR) via upregulating AKT phosphorylation.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative diseases with no effective cure. GGGGCC repeat expansion in C9orf72 is the most common genetic cause of both ALS and FTD. A key pathological feature of C9orf72 related ALS/FTD is the presence of abnormal dipeptide repeat proteins translated from GGGGCC repeat expansion, including poly Glycine-Arginine (GR). In this study, we observed that (GR)50 conferred significant mitochondria damage and cytotoxicity. Metformin, the most widely used clinical drug, successfully relieved (GR)50 induced mitochondrial damage and inhibited (GR)50 related cytotoxicity. Further research revealed metformin effectively restored mitochondrial function by upregulating AKT phosphorylation in (GR)50 expressed cells. Taken together, our results indicated restoring mitochondrial function with metformin may be a rational therapeutic strategy to reduce poly(GR) toxicity in C9orf72 ALS/FTD patients.

Tandem "One-Shot" Measurement of Residual Chemical Shift Anisotropy and Residual Dipolar Coupling using Biphasic Supramolecular Peptide Liquid Crystals.

Both solitary and tandem applications of residual chemical shift anisotropy (RCSA) and residual dipolar coupling (RDC) show great potential for the structural and configurational determination of organic molecules. A critical component of both RDC and RCSA methodologies is the alignment medium, whose availability is limited, especially for RCSA measurement. Moreover, reported RDC and RCSA acquisitions mainly rely on two experiments conducted under two different conditions, which are relatively time-consuming and easily cause experimental errors. Herein, a biphasic supramolecular lyotropic liquid crystalline (LLC) system was developed through the self-assembly of C21H43-CONH-V4K3-CONH2, which could act as an alignment medium for not only RDC but also RCSA extraction in DMSO-d6. Notably, the RCSA extraction was easily achieved via one-shot measurement from a single one-dimensional 13C NMR experiment, with no need for special instruments, devices, and correction. Relying on the biphasic LLC medium, meanwhile, RDC data were simply extracted from a single F1-coupled HSQC experiment, different from the standard protocol that requires two spectral acquisitions corresponding to the isotropic and anisotropic conditions. Collectively, the biphasic LLC medium is applicable for tandem RCSA and RDC measurements in one single sample, advancing the stereochemical elucidation of molecules of interest.

The prognostic role of 18F-FDG PET/CT-based response evaluation in children with stage 4 neuroblastoma.

OBJECTIVES: To evaluate the association between metabolic response on 18F-FDG PET/CT and long-term survival in children with neuroblastoma (NB). METHODS: A total of 39 consecutive children with newly diagnosed stage 4 NB undergoing both 18F-FDG PET/CT imaging at baseline and after chemotherapy were retrospectively analyzed. The associations between metabolic parameters, including SUVmax of the lesion with the most intense 18F-FDG uptake at baseline (SUVb), after chemotherapy (SUVe), and the percentage change between SUVb and SUVe, and long-term survival were evaluated. RESULTS: With a median follow-up of 56 months, 22 patients who had achieved complete resolution on PET (no residual 18F-FDG uptake higher than the surrounding backgrounds) after chemotherapy had superior 5-year overall survival (OS) (73.6% vs. 39.0%, p = 0.044). SUVb > 6.9 indicated significantly poorer 5-year event-free survival (EFS) (12.5% vs. 59.3%, p = 0.005), as did SUVe > 1.2 (18.8% vs. 41.7%, p = 0.041). Children with SUVe > 1.2 had shorter 5-year OS (33.9% vs. 75.0%, p = 0.018). Multivariate analysis identified SUVe > 1.2 as an independent predictor for both EFS [hazard ratio (HR), 3.479, 95% CI, 1.381-8.761, p = 0.008] and OS (HR, 6.948, 95% CI, 1.663-29.025, p = 0.008), while SUVb > 6.9 was a predictor for EFS (HR, 2.889, 95% CI, 1.064-7.842, p = 0.037). Among 11 children with both SUVb > 6.9 and SUVe > 1.2, all experienced disease progression or relapse within 2 years since diagnosis. CONCLUSION: 18F-FDG PET/CT could be of useful to evaluate treatment response in children with stage 4 NB. CLINICAL RELEVANCE STATEMENT: 18F-FDG PET/CT after chemotherapy exhibits prognostic significance in neuroblastoma and holds potential as an alternative imaging modality for response evaluation, especially in cases with metaiodobenzylguanidine-nonavid or persistent avid disease. KEY POINTS: The prognostic value of chemotherapy response on 18F-FDG PET/CT in advanced neuroblastoma is unknown. Higher 18F-FDG uptake after chemotherapy was associated with worse long-term event-free survival and overall survival. 18F-FDG PET/CT after chemotherapy holds prognostic significance in children with stage 4 neuroblastoma.

Effects of the COVID-19 pandemic on maternal-fetal outcomes in a nonepidemic designated hospital: a retrospective study and clinical experience summary.

OBJECTIVE: To assess the changes in maternal-fetal outcomes in a nonepidemic designated hospital during the COVID-19 pandemic. METHODS: This retrospective cohort study was conducted between January 1, 2019, and December 31, 2021 on pregnant patients. The fixed-effects regression model was used to determine changes in birth outcomes and pregnancy-related complications between three periods with the pre-epidemic cohort as the control group. Logistic regression was applied to determine the odds ratio (OR) for binary outcomes. RESULTS: There were 15,261 births during the pre-epidemic period, and this number decreased by 15% and 23% to 12,980 and 11,736 in the first and second epidemic cohorts, respectively. The mean birth weight during the pre-epidemic period was 3319 which decreased to 3309 and 3272 g in the following periods. Excluding stillbirth and preterm, all other outcomes differed significantly between the three periods. Gestational diabetes mellitus (GDM) (17-19%) and maternal hypertension (9.2-11%) appeared to increase. Compared to the pre-epidemic period, the odds of macrosomia and LGA significantly decreased in the second epidemic cohort (adjusted ORs: 0.76 and 0.8), while the odds of low birth weight (LBW) and small gestation age (SGA) increased (ORs: 1.25 and 1.16). The odds of neonatal asphyxia (OR: 1.4), and hypertension (OR: 1.29) appeared to increase in the second epidemic cohort, while GDM decreased in the first cohort (OR: 0.88) and increased in the second cohort (OR: 1.15). Vaginal delivery underwent a marginal decrease in both the first and second epidemic cohorts (ORs: 0.89 and 0.92). CONCLUSION: The COVID-19 pandemic may have had a substantial and long-term impact on non-infected pregnant women and newborns. Our research results provided precious research information and clinical experience summary for population health research in the future.

Association of maternal serum uric acid levels with LBW/SGA: a large retrospective cohort study.

BACKGROUND: Elevated maternal serum uric acid (UA) levels were associated with adverse perinatal outcomes. This study aimed to examine the association between UA and the risk of low birth weight (LBW) / small for gestational age (SGA). METHODS: A cohort study of women delivered in Shanghai maternity hospital was included between 2017 and 2021. Electronic medical records were utilized to extract information and antenatal care records. The cut-off value of UA was 360 µmol/L. The outcome was LBW/SGA, with LBW defined as birth weight below 2500 g and SGA indicating birth weight below the 10th percentile of average weight for gestational age. The assessment of SGA was based on the Chinese standard curve for birth weight at various gestational ages. Univariate, multivariate logistic regression models, restricted cubic spline were used in this study, with adjustments made for confounding factors. RESULTS: Sixty-nine thousand six hundred seventy-four live births and singleton pregnancies were included. The ratio of LBW/SGA was 3.3%/9%. Maternal UA levels were significantly negatively correlated with birth weight. High UA levels were associated with high risk of LBW/SGA, especially in third trimester. In BMI < 25 group, the risk of LBW increased to 2.35-fold (95%CI, 1.66-3.31) in hyperuricemic group (UA > 360 µmol/L). The SGA risk was 1.66-fold (95%CI, 1.37-2.00). Gestational hypertension (GH) with hyperuricemica increased the risk of LBW (aOR = 4.00, 95%CI, 2.01-7.93) and SGA (aOR = 2.63, 95%CI, 1.83-3.78). Preeclampsia (PE) with hyperuricemia increased the risk of LBW (aOR = 1.38, 95%CI, 0.63-3.03) and SGA (aOR = 1.81, 95%CI, 1.18-2.78). In delivery gestational week (DGW) ≥ 37 group, if UA > 360 µmol/L, the incidence of LBW increased to 2.46-fold (95%CI, 1.62, 3.73) and the incidence of SGA increased to 1.52-fold (95%CI, 1.24, 1.87). In DGW < 37 group, if UA > 360 µmol/L, the incidence of LBW increased to 2.70-fold (95%CI, 1.92, 3.80) and the incidence of SGA increased to 2.13-fold(95%CI, 1.50, 3.02). CONCLUSIONS: The study found an inverse correlation between UA levels and birth weight. High UA levels were associated with increased risk of LBW/SGA, particularly in third trimester. GH or PE complicated by hyperuricemia were found to have significantly higher risk of developing LBW/SGA. This relationship also existed in pregnant women with BMI < 25.

Clinical Outcome of Monochorionic Diamniotic Twins with Intrauterine Growth Restriction.

OBJECTIVE: This study investigated the clinical outcome of monochorionic diamniotic (MCDA) twins with selective intrauterine growth restriction (sIUGR). STUDY DESIGN: International Peace Maternal and Child Health Hospital of Shanghai ultrasound database was investigated to identify all MCDA delivered from January 2013 to December 2017. After identifying 43 pairs of MCDA twins with sIUGR and 282 pairs of normal MCDA twins, we compared clinical outcomes between the two groups. RESULTS: Compared with normal twins, sIUGR fetuses had significantly shorter gestational age at delivery, smaller average birth weight of both twins, more significant intertwin difference in birth weight, lower Apgar scores, and higher intrauterine fetal demise (IUFD) rate, and smaller placental weight. The rate of abnormal umbilical cord insertions and abnormal blood flow in the ductus venosus (DV) and middle cerebral artery (MCA) is significantly higher in the sIUGR group. In addition, the subtype analysis of sIUGR groups indicated the poorest outcomes in type II with no significant difference between type I and III. CONCLUSION: MCDA twins with sIUGR generally exhibited limited clinical outcomes than normal MCDA twins. These limitations are mainly associated with abnormal umbilical cord insertions and blood flow in the DV and MCA. Clinical outcomes differed among the three types of sIUGR, with type II having the worst prognosis and the highest IUFD rate. KEY POINTS: · sIUGR generally exhibited limited clinical outcomes than normal MCDA twins.. · These limitations are mainly associated with blood flow of the DV and MCA.. · sIUGR with type II has the worst prognosis and the highest IUFD rate..

Soil Marginal Effect and LSTM Model in Chinese Solar Greenhouse.

The food crisis has increased demand for agricultural resources due to various factors such as extreme weather, energy crises, and conflicts. A solar greenhouse enables counter-seasonal winter cultivation due to its thermal insulation, thus alleviating the food crisis. The root temperature is of critical importance, although the mechanism of soil thermal environment change remains uncertain. This paper presents a comprehensive study of the soil thermal environment of a solar greenhouse in Jinzhong City, Shanxi Province, employing a variety of analytical techniques, including theoretical, experimental, and numerical simulation, and deep learning modelling. The results of this study demonstrate the following: During the overwintering period, the thermal environment of the solar greenhouse floor was divided into a low-temperature zone, a constant-temperature zone, and a high-temperature zone; the distance between the low-temperature boundary and the southern foot was 2.6 m. The lowest temperature in the low-temperature zone was 11.06 °C and the highest was 19.05 °C. The floor in the low-temperature zone had to be heated; the lowest value of the constant-temperature zone was 18.29 °C, without heating. The minimum distance between the area of high temperature and the southern foot of the solar greenhouse was 8 m and the lowest temperature reading was 19.29 °C. The indoor soil temperature tended to stabilise at a depth of 45 cm, and the lowest temperature reading at a horizontal distance of 1400 mm from the south foot was 19.5 °C. The Fluent and LSTM models fitted well and the models can be used to help control soil temperature during overwintering in extreme climates. The research can provide theoretical and data support for the crop areas and the heating of pipelines in the solar greenhouse.

Probing Coordination Number of Single-Atom Catalysts by d-Band Center-Regulated Luminescence.

It is essential to probe the coordination number (CN) because it is a crucial factor to ensure the catalytic capability of single-atom catalysts (SACs). Currently, synchrotron X-ray absorption spectroscopy (XAS) is widely used to measure the CN. However, the scarcity of synchrotron X-ray source and complicated data analysis restrict its wide applications in determining the CN of SACs. In this contribution, we have developed a d-band center-regulated acetone cataluminescence (CTL) probe for a rapid screening of the CN of Pt-SACs. It is disclosed that the CN-triggered CTL is attributed to the fact that the increased CN could induce the downward shift of d-band center position, which assists the acetone adsorption and promotes the subsequent catalytic reaction. In addition, the universality of the proposed acetone-CTL probe is verified by determining the CN of Fe-SACs. This work has opened a new avenue for exploring an alternative to synchrotron XAS for the determination of CN of SACs and even conventional metal catalysts through d-band center-regulated CTL.

Delayed cutaneous hypersensitivity reactions following the use of infliximab or adalimumab in patients with coronavirus disease 2019.

Recent evidence has emerged concerning delayed cutaneous hypersensitivity reactions after infliximab or adalimumab applications in patients with coronavirus disease 2019 (COVID-19). A few real-world studies compared the events, clinical features, and prognosis of infliximab- or adalimumab-related delayed cutaneous hypersensitivity reactions in COVID-19 patients. Disproportionality analysis and Bayesian analysis were utilized to determine the suspected adverse events of delayed cutaneous hypersensitivity reactions after infliximab or adalimumab use based on the Food and Drug Administration's Adverse Event Reporting Systems (FAERS) from May 2020 to December 2021. Additionally, the times to onset and fatality rates of delayed cutaneous hypersensitivity reactions following infliximab or adalimumab were compared. In total, 475 reports of delayed cutaneous hypersensitivity reactions were associated with infliximab or adalimumab. Females were affected almost twice more than males. Among the two therapies, infliximab had the highest association with delayed cutaneous hypersensitivity reactions based on the highest reporting odds ratio (2.14, 95% two-sided confidence interval [CI] = 1.2-3.81), proportional reporting ratio (1.95, χ2 = 7.03), and empirical Bayesian geometric mean (1.94, 95% one-sided CI = 1.2). Infliximab-related delayed cutaneous hypersensitivity reactions had earlier onset (0 [interquartile range (IQR): 0-0] days vs. 166.5 (IQR: 18-889.5) days, p < 0.05), while adalimumab-related delayed cutaneous hypersensitivity reactions have higher fatality rate (0.44% vs. 0.00%). Based on the FAERS database, we profiled delayed cutaneous hypersensitivity reactions related to infliximab or adalimumab application in patients with COVID-19 with more points of occurrences, clinical characteristics, and prognosis.

Intertwin growth discordance throughout gestation and hypertensive disorders of pregnancy.

BACKGROUND: Previous studies have established the association between intertwin birthweight discordance and hypertensive disorders of pregnancy. However, longitudinal fetal size discordance concerning gestational hypertension or preeclampsia remains unclear. OBJECTIVE: This study aimed to compare the patterns of estimated fetal weight discordance throughout gestation among normotensive women, women with gestational hypertension, and women with preeclampsia and to evaluate the association between crown-rump length discordance at 11 to 14 weeks of gestation and hypertensive disorders of pregnancy. STUDY DESIGN: This was a retrospective cohort study of women with twin pregnancies who had antenatal care visits and delivered at a tertiary hospital between January 2013 and June 2021. The crown-rump length was measured at 11 to 14 weeks of gestation. Estimated fetal weight was calculated based on ultrasound examinations of fetal biometrics at 16 to 18, 20 to 24, 28 to 32, and ≥34 weeks of gestation, respectively. Crown-rump length and estimated fetal weight discordances were calculated: (larger crown-rump length - smaller crown-rump length)/larger crown-rump length × 100% and (larger estimated fetal weight - smaller estimated fetal weight)/larger estimated fetal weight × 100%, respectively. Multiple imputation was used to handle missing data, and all models accounted for the imputation. Multilevel model analysis was used to compare the differences in estimated fetal weight discordances throughout gestation among normotensive women, women with gestational hypertension, and women with preeclampsia. Generalized linear models were used to evaluate the association between crown-rump length discordance and hypertensive disorders of pregnancy, assuming a Poisson distribution. The possible nonlinear relationship between continuous crown-rump length discordance and hypertensive disorders of pregnancy was examined by generalized additive models. All analyses were stratified by chorionicity. RESULTS: Of the 3280 women with twin pregnancies who met the inclusion criteria, 187 (5.7%) developed gestational hypertension, and 436 (13.3%) developed preeclampsia, including 125 (3.8%) early-onset preeclampsia and 311 (9.5%) late-onset preeclampsia. In women with dichorionic twin pregnancies, compared with normotensive women, a substantial progression of estimated fetal weight discordance throughout pregnancy was identified in women who developed preeclampsia, and a large progression of estimated fetal weight discordance in late pregnancy was identified in women who developed gestational hypertension. In women with monochorionic twin pregnancies, estimated fetal weight discordances were more progressive from 20 to 24 weeks of gestation onward in women who developed preeclampsia than in normotensive women. Crown-rump length discordance at 11 to 14 weeks of gestation was associated with an increased risk of preeclampsia (relative risk, 1.03; 95% confidence interval, 1.00-1.05), particularly early-onset preeclampsia (relative risk, 1.09; 95% confidence interval, 1.04-1.13). A crown-rump length discordance of ≥10% had 1.2 times the increased risk of developing early-onset preeclampsia (relative risk, 2.27; 95% confidence interval, 1.28-4.03). This association was identified in dichorionic twins, but not in monochorionic twins. CONCLUSION: Our study demonstrated distinct growth discordant patterns among normotensive women, women with gestational hypertension, and women with preeclampsia in twin pregnancies. Intertwin crown-rump length discordance at 11 to 14 weeks of gestation was associated with an increased risk of preeclampsia, especially early-onset preeclampsia in dichorionic twin pregnancies, with a dose-response pattern.

Emulsifying properties of plant-derived polypeptide and their conjugates: a self-consistent-field calculation study of the impact of hydrolysis.

By considering the hydrolysates of soy protein produced by trypsin as an example, the emulsion stabilizing properties of plant-based protein fragments have been investigated theoretically. We apply Self-Consistent-Field (SCF) calculations to determine the colloidal interactions induced between a pair of droplets stabilized by adsorbed layers of various soy protein fragments. The study is extended to conjugates of such polypeptides, formed by covalent bonding with a suitable hydrophilic sidechain (e.g. a polysaccharide). Our results show that the relatively longer fragments, with a greater number of hydrophobic amino acids, will display a stronger degree of adsorption affinity compared to the smaller hydrolysates, even where the latter may have a higher overall ratio of hydrophobic residues. This suggested that the degree of protein hydrolysis should be carefully controlled and limited to modest values to avoid the generation of a large number of short polypeptides, while still sufficient to improve solubility. While the emulsion stabilizing performance of a protein fragment type is strongly dependent on the conformation it adopts on the interface, we find this to be less critical for the conjugated polypeptides. However, we argue that with increasing degree of hydrolysis, many small fragments will not have the chance to form bonds with polysaccharides. It is demonstrated that the abundance of these unreacted polypeptides in the system severely reduces the efficiency of the conjugated longer protein fragments, preventing their presence on the surface of the droplets through competitive adsorption process.

Analysis of genetic testing in fetuses with congenital heart disease of single atria and/or single ventricle in a Chinese prenatal cohort.

OBJECTIVE: This study aimed to investigate the genetic etiologies of fetuses with single atria and/or ventricle (SA or/and SV) using different genetic detection methods in a Chinese prenatal cohort. METHODS: In this retrospective study, the various genetic results of 44 fetuses with SA and/or SV were analyzed. All 44 cases were tested by chromosomal microarray analysis (CMA) and karyotyping simultaneously, and 8 underwent whole exome sequencing (WES). Data on the pregnancy outcomes and neonatal prognoses were collected from medical records and postnatal follow-up. RESULTS: The whole cohort of 44 fetuses included 14 SA cases (31.8%), 12 SV cases (27.3%), and 18 SA and SV cases (40.9%). A total of 9 pathogenic genetic results were detected by conventional karyotyping, CMA and trio-WES, indicating an overall detection rate of 20.5% (9/44). Six pathogenic chromosomal abnormalities were identified by CMA among the 44 cases, showing a detection rate of 13.6% (6/44). Two microdeletions being missed by karyotyping were diagnosed by CMA, showing an additional diagnostic yield of 4.5% for CMA in present cohort(2/44). Three pathogenic variants in two fetuses were identified by WES, indicating an incremental diagnostic yield of 4.5%(2/44) for WES in fetuses with SA or/and SV. CONCLUSION: In this study, WES achieved an additional diagnostic yield of 4.5% in fetuses with SA or/and SV. WES is valuable for fetal prognosis assessment and could add diagnostic value for fetuses with SA and/or SV when CMA is negative. It would be a valuable technique for the identification of underlying pathogenic variants in prenatal cohorts.

Characterizing Periodic Variations of Atomic Frequency Standards via Their Frequency Stability Estimates.

The onboard atomic frequency standard (AFS) is a crucial element of Global Navigation Satellite System (GNSS) satellites. However, it is widely accepted that periodic variations can influence the onboard AFS. The presence of non-stationary random processes in AFS signals can lead to inaccurate separation of the periodic and stochastic components of satellite AFS clock data when using least squares and Fourier transform methods. In this paper, we characterize the periodic variations of AFS using Allan and Hadamard variances and demonstrate that the Allan and Hadamard variances of the periodics are independent of the variances of the stochastic component. The proposed model is tested against simulated and real clock data, revealing that our approach provides more precise characterization of periodic variations compared to the least squares method. Additionally, we observe that overfitting periodic variations can improve the precision of GPS clock bias prediction, as indicated by a comparison of fitting and prediction errors of satellite clock bias.

Gallic acid-fortified buckwheat Wantuo: characteristics of in vitro starch digestibility, antioxidant and eating quality.

Gallic acid (GA), presented in various plant sources, is increasingly used as a nutritional food ingredient due to its prominent bioactive. In this work, common buckwheat Wantuo (BWT, a Chinese traditional starch gel food) was fortified with 1,3,5% (w/w) GA and assessed for physicochemical properties of flour as well as in vitro starch digestibility, antioxidant and eating quality of BWT. The results clearly showed that the hydration, pasting properties as well as gel microstructure and texture of gel were influenced with addition of GA, while the color of flours showed no significantly change. Hydrogen bonds interaction between GA and starch, more hydrophilic groups exposure and more acid hydrolysis of the starch were thought to be main reasons. Furthermore, combined with structural analysis of starch, the significantly decreased rapidly digested starch (8.62%)/slowly digested starch (12.90%) and increased resistant starch (78.48%) in BWT with 5% addition amount can be mainly due to digestive enzymes inhibition, formation of V-type conformation and alteration in the local structure of starch-phenol-enzyme complex. Meanwhile, the antioxidant activity of BWT-GA improved, where as its texture properties softened due to suppressed starch retrogradation. This study demonstrated the potential use of polyphenol as food ingredient to improve the nutritional properties and eating qualities of starch gel food. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05614-x.

Rapid Discrimination of Adsorbed Oxygen and Lattice Oxygen in Catalysts by the Cataluminescence Method.

Adsorbed oxygen and lattice oxygen are crucial parameters for catalyst characterization and catalytic oxidation mechanism. Therefore, rapid discrimination of adsorbed oxygen and lattice oxygen is highly desired. Herein, a direct correlation between cataluminescence (CTL) kinetic curve and oxygen species was discovered. The adsorbed oxygen-catalyzed CTL only lasted for a few minutes, whereas the lattice oxygen-catalyzed CTL could exhibit hours of continuous luminescence. The long-term CTL was attributed to the slow migration of lattice oxygen in a slow and continuous catalytic oxidation reaction. In addition to the discrimination between the adsorbed oxygen and lattice oxygen by the CTL kinetic processes, the corresponding CTL intensity was positively proportional to their amounts. Accordingly, the developed catalytic oxidation-related CTL can be used as an indicator for rapid discrimination and determination of adsorbed oxygen and lattice oxygen in catalysts. Oxygen species detected by the proposed CTL method not only matched well with those obtained by conventional X-ray photoelectron spectroscopy and O2-temperature programmed methods but also offered some distinguished advantages, such as convenient operation, fast response, and low cost. It can be expected that the established oxygen-responsive CTL probe has great potential in distinguishing adsorbed oxygen and lattice oxygen in various catalysts.

Usefulness of brain FDG PET/CT imaging in pediatric patients with suspected autoimmune encephalitis from a prospective study.

PURPOSE: Early diagnosis and treatment are of paramount importance for pediatric patients with autoimmune encephalitis (AE). The aim is to evaluate the usefulness of FDG PET/CT in pediatric patients with suspected AE from a prospective study. METHODS: The prospective study was conducted over a period of 23.5 months from May 14, 2019, to April 30, 2021. All patients (< 18-year-old) were hospitalized at the department of pediatric neurology and met the criteria of clinical suspected AE. The children underwent the tests of blood samplings, CSF, EEG, MRI, and 18F-FDG PET/CT. The criteria for FDG PET/CT diagnosis of AE were large lobar hypometabolism with or without focal hypermetabolism found on PET/CT. The clinical final diagnosis of AE includes seropositive and seronegative AE based on the diagnostic criteria. RESULTS: One hundred four pediatric inpatients (57 boys, 47 girls) were included, of which 58 children were diagnosed with AE (seropositive, 16; seronegative, 42), 45 children were diagnosed with non-AE, and one boy remained indeterminate diagnosis. Large lobar hypometabolism was found in 61 children, of which 54 (88.5%) children were finally diagnosed with AE. The sensitivity, specificity, and accuracy of FDG PET/CT for diagnosis of AE were 93.1%, 84.4%, and 89.3%, respectively, with a positive predictive value of 88.5% and a negative predictive value of 90.5%. The most common involved with hypometabolism was the parietal lobe, followed by occipital and frontal lobes, finally the temporal lobe on PET/CT in children with AE. CONCLUSION: Brain FDG PET/CT imaging has high specificity, sensitivity, and accuracy for diagnosis of AE in clinical suspected AE children. CLINICAL TRIALS: gov. NCT02969213. Registered 17 October 2016.

Adjunctive azithromycin prophylaxis protects women from uterine cesarean scar defect: A randomized controlled trial.

INTRODUCTION: Cesarean scar defect (CSD) is a long-term outcome of cesarean section (CS) and associated with numerous gynecological and obstetric problems. Previous studies indicate that infection may be a risk factor for CSD. Adjunctive azithromycin was shown to reduce the risk of postoperative infection in patients undergoing non-elective primary cesarean delivery in labor or after the rupture of membranes compared with standard antibiotic prophylaxis. This study investigated the protective effect of adjunctive azithromycin in combination with single-dose cephalosporin against CSD in women undergoing non-elective cesarean delivery. MATERIAL AND METHODS: A randomized, double-blind, controlled clinical trial was conducted in a University hospital in Shanghai, China. A total of 242 women who underwent their first non-elective CS were randomly assigned to receive 1500 mg cefuroxime sodium plus 500 mg intravenous azithromycin (n = 121; experimental group) or 1500 mg cefuroxime sodium plus a placebo (n = 121; placebo group). The primary outcome was CSD prevalence, as determined by transvaginal ultrasound and saline infusion sonohysterography within 6 months of delivery. Secondary outcomes were changes in infectious indicators (eg hypersensitive C-reactive protein and procalcitonin), postoperative morbidity, and use of postoperative antibiotics. We also examined the operative procedure, pathogenic microorganism cultures, and fetal outcomes. Outcomes were compared between groups with the chi-squared test, Fisher's exact test, or Student's t test. RESULTS: Between May 2018 and May 2021, 121 women were randomized to each arm. Because the sonographic follow up was disrupted by the coronavirus disease 2019 pandemic and strict management policies, we merged the follow-up time points (6 weeks and 6 months) into a single time period (6 weeks to 6 months); 104 and 108 women in the experimental and placebo groups, respectively, completed the first sonographic follow up. CSD was diagnosed by sonography in 34/104 (32.7%) and 50/108 (46.3%) patients in the experimental and placebo groups, respectively (relative risk 0.71, 95% confidence interval 0.50-0.99; p = 0.043). Characteristics of CSD and short-term infection outcomes did not differ between groups. CONCLUSIONS: A single dose of intravenous 500 mg azithromycin adjunctive to single-dose cefuroxime prophylaxis significantly reduced the incidence of CSD in women undergoing non-elective CS.

Inositol hexakisphosphate kinase 3 promotes focal adhesion turnover via interactions with dynein intermediate chain 2.

Cells express a family of three inositol hexakisphosphate kinases (IP6Ks). Although sharing the same enzymatic activity, individual IP6Ks mediate different cellular processes. Here we report that IP6K3 is enriched at the leading edge of migrating cells where it associates with dynein intermediate chain 2 (DIC2). Using immunofluorescence microscopy and total internal reflection fluorescence microscopy, we found that DIC2 and IP6K3 are recruited interdependently to the leading edge of migrating cells, where they function coordinately to enhance the turnover of focal adhesions. Deletion of IP6K3 causes defects in cell motility and neuronal dendritic growth, eventually leading to brain malformations. Our results reveal a mechanism whereby IP6K3 functions in coordination with DIC2 in a confined intracellular microenvironment to promote focal adhesion turnover.

Association between placental implantation abnormalities and hypertensive disorders of pregnancy.

AIM: This study aimed to investigate the association between placental implantation abnormalities (PIAs) and gestational hypertension-preeclampsia (GH-PE) in pregnant women. METHODS: Patients were recruited from 2010 to 2019 into this retrospective study at the International Peace Maternity & Child Health Hospital. PIAs were classified as follows: placenta previa (PP), low-lying placenta (LP), placenta accreta, and placenta adherence (PA). Logistic regression models were constructed to analyze the associations between placental abnormalities and GH-PE. Propensity score matching (PSM) was conducted to reduce confounders. The relationship between PP with placenta accreta spectrum (PAS) and GH-PE were assessed. RESULTS: In total, 5527 women were recruited, and 2614 women had an abnormal placenta (992 with LP; 749 with PP 839 and PA; and 34 with placenta accreta). There were 296 patients with GH-PE in those groups. After adjustments for confounding factors, women with PP had a lower risk of PE (odds ratio [OR]: 0.43; 95% confidence interval [CI]: 0.19-0.86, p = 0.025) than those in the control group. Women with PA had a higher risk of GH-PE (OR: 1.45; 95% CI: 1.05-1.99, p = 0.022). In addition, we categorized PP into marginal, complete, and partial PP and investigated these associations. We found a lower risk of PE in complete PP (OR: 0.09, 95% CI: 0.01-0.44, p = 0.020) than in marginal or partial PP. There was no significant difference regarding GH-PE in the PP with PAS group (OR = 0.67, 95% CI: 0.82-2.34, p = 0.525). CONCLUSION: PP, especially complete PP, is associated with a lower risk of PE. PA is associated with higher risks of GH-PE.

NRP1 and MMP9 are dual targets of RNA-binding protein QKI5 to alter VEGF-R/ NRP1 signalling in trophoblasts in preeclampsia.

Preeclampsia (PE) is characterized by placental ischemia and hypoxia, resulting in abnormal casting of the uterine spiral artery, which is mainly caused by insufficient trophoblastic cell infiltration. A reduction in levels of growth factor-based signalling via Neuropilin-1 (NRP1) has been shown to contribute to dysfunctional trophoblast development. In this study, we showed that the RNA-binding protein, QKI5, regulated NRP1 expression and significantly improved trophoblast proliferation in vitro and in vivo. QKI5 and NRP1 expressions were significantly reduced in human PE placentas and in trophoblasts during hypoxia. Overexpression of these factors significantly improved cell proliferation and migration in vitro, in contrast to a decrease upon siRNA knockdown of QKI5 and NRP1 in HTR-8/SVneo cells. Using RIP and RNA pull-down assays, we further showed that QKI5 directly interacted with the 3'-UTR region of NRP1, to mediate cell proliferation and migration via matrix metalloprotease-9. Further, similar to NRP1, QKI5 also targets matrix metalloproteinase 9 (MMP9) involved in secretion of growth factors and its effects can be counteracted by NRP1 overexpression. In vivo studies using a PE mouse model revealed that QKI5 overexpression alleviated PE-related symptoms such as elevated blood pressure and proteinuria. Taken together, we found that QKI5 was a novel regulator, of VEGF-R/NRP1 signalling pathway functioning in trophoblast proliferation and migration, resulting in major contributors to the pathogenesis of PE. While careful evaluation of the broad implications of QKI5 expression is still necessary, this study identified QKI5 as a promising target for treatment strategies in acute PE patients.