Gut microbiota and its metabolic products in acute respiratory distress syndrome.

The prevalence rate of acute respiratory distress syndrome (ARDS) is estimated at approximately 10% in critically ill patients worldwide, with the mortality rate ranging from 17% to 39%. Currently, ARDS mortality is usually higher in patients with COVID-19, giving another challenge for ARDS treatment. However, the treatment efficacy for ARDS is far from satisfactory. The relationship between the gut microbiota and ARDS has been substantiated by relevant scientific studies. ARDS not only changes the distribution of gut microbiota, but also influences intestinal mucosal barrier through the alteration of gut microbiota. The modulation of gut microbiota can impact the onset and progression of ARDS by triggering dysfunctions in inflammatory response and immune cells, oxidative stress, cell apoptosis, autophagy, pyroptosis, and ferroptosis mechanisms. Meanwhile, ARDS may also influence the distribution of metabolic products of gut microbiota. In this review, we focus on the impact of ARDS on gut microbiota and how the alteration of gut microbiota further influences the immune function, cellular functions and related signaling pathways during ARDS. The roles of gut microbiota-derived metabolites in the development and occurrence of ARDS are also discussed.

Superstructured Optoionic Heterojunctions for Promoting Ion Pumping Inspired by Photoreceptor Cells.

Photoreceptor cells of vertebrates feature ultrastructural membranes interspersed with abundant photosensitive ion pumps to boost signal generation and realize high gain in dim light. In light of this, superstructured optoionic heterojunctions (SSOHs) with cation-selective nanochannels are developed for manipulating photo-driven ion pumping. A template-directed bottom-up strategy is adopted to sequentially assemble graphene oxide (GO) and PEDOT:PSS into heterogeneous membranes with sculptured superstructures, which feature programmable variation in membrane topography and contain a donor-acceptor interface capable of maintaining electron-hole separation upon photoillumination. Such elaborate design endows SSOHs with a much higher magnitude of photo-driven ion flux against a concentration gradient in contrast to conventional optoionic membranes with planar configuration. This can be ascribed to the buildup of an enhanced transmembrane potential owing to the effective separation of photogenerated carriers at the heterojunction interface and the increase of energy input from photoillumination due to a synergistic effect of reflection reduction, broad-angle absorption, and wide-waveband absorption. This work unlocks the significance of membrane topographies in photo-driven transmembrane transportation and proposes such a universal prototype that could be extended to other optoionic membranes to develop high-performance artificial ion pumps for energy conversion and sensing.

Effects of uterine Doppler on midbrain growth and cortical development in late onset fetal growth restricted fetuses: a prospective cross-sectional study.

OBJECTIVE: To investigate midbrain growth, including corpus callusum (CC), cerebellar vermis (CV) and cortical development in late fetal growth restriction (FGR) depending on uterine artery (UtA) Pulsatility Index (PI) values. METHODS: This was a prospective study including singleton fetuses with late FGR characterized by abnormal cerebral placental ratio (CPR). According to UtA PI values, the FGR fetuses were subdivided into normal ≤95th centile) and abnormal (>95th centile). Neurosonography was performed at 33-44 weeks of gestations to assess CC and CV lengths and the depth of Sylvian fissure (SF), parieto-occipital (POF) and calcarine fissures (CF). Neurosonographic variables were normalized for fetal head circumference size. RESULTS: The study cohort included 60 fetuses with late FGR, 39 with normal UtA PI and 21 with abnormal PI values. The latter group showed significant differences in CC (median (interquartile range) normal 35.9 (28.49-45.53) vs abnormal UtA PI 25.31(19.76-35.13) mm; p < 0.0022), CV (normal 25.78 (18.19-29.35) abnormal UtA PI 17.03 (14.07-24.16)mm; p = 0.0067); SF (normal 10.58 (8.99-11.97)vs abnormal UtA PI 7.44 (6.23-8.46) mm; p < 0.0001), POF (normal 6.85 (6.35-8.14) vs abnormal UtA PI 4.82 (3.46-7.75) mm; p < = 0.0184) and CF (normal 04.157 (2.85-5.41) vs abnormal UtA PI 2.33 (2.49-4.01)); p < 0.0382). CONCLUSIONS: Late onset FGR fetuses with abnormal UtA PI showed shorter CC and CV length and delayed cortical development compared to those with normal uterine PI. These findings support the existence of a link between abnormal brain development and changes in utero placental circulation.

Effects of umbilical vein flow on midbrain growth and cortical development in late onset fetal growth restricted fetuses: a prospective cross-sectional study.

OBJECTIVES: To investigate midbrain growth, including corpus callusum (CC) and cerebellar vermis (CV) and cortical development in late fetal growth restricted (FGR) subclassified according to the umbilical vein blood flow (UVBF) values. METHODS: This was a prospective study on singleton fetuses late FGR with abnormal placental cerebral ratio (PCR). FGR fetuses were further subdivided into normal (≥fifth centile) and abnormal (

Fetal brain development in pregnancies complicated by gestational diabetes mellitus.

OBJECTIVES: Gestational diabetes mellitus (GDM) carries an increased risk of neurocognitive impairment in offsprings. However, the contribution of maternal hyperglycemia in affecting fetal brain development is not fully elucidated yet. The aim of this study was to evaluate fetal brain and sulci development in pregnancies complicated by GDM. METHODS: Prospective observational study including 100 singleton pregnancies complicated by GDM and 100 matched controls. All fetuses underwent neurosonography at 29-34 weeks of gestation, including the assessment of the length of the corpus callosum (CC), cerebellar vermis (CV), Sylvian (SF), parieto-occipital (POF) and calcarine fissures (CF). Sub-group analysis according to the specific treatment regimen adopted (n 67 diet vs. 33 insulin therapy) was also performed. RESULTS: Fetuses from mothers with GDM under insulin therapy had a smaller CC (35.54 mm) compared to both controls (40 mm; p<0.001) and women with GDM under diet (39.26 mm; p=0.022) while there was no difference in the HC between the groups. Likewise, when corrected for HC, CV depth was smaller in fetuses with GDM both under insulin therapy (7.03 mm) and diet (7.05 mm,) compared to controls (7.36 mm; p=0.013). Finally, when assessing the sulci development of the brain SF (p≤0.0001), POF (p≤0.0001) and CF (p≤0.0001) were significantly smaller in fetuses with maternal GDM. Post-hoc analysis showed that fetuses of GDM mothers requiring insulin therapy had significantly lower values of SF (p=0.032), POF (p=0.016) and CF (p=0.001). CONCLUSIONS: Pregnancies complicated by GDM showed a peculiar pattern of fetal brain growth and cortical development and these changes, which are more evident in those requiring insulin supplementation.

Effects of gender on fetal cortical development: a secondary analysis of a prospective cross-sectional study.

OBJECTIVES: The primary objective was to evaluate the effects of fetal sex on fetal cortical development in low-risk pregnancies. Secondary objective was the evaluate the impact of gestational age. METHODS: This was a secondary analysis of a prospective cross-sectional study on low-risk fetuses undergoing fetal neurosonography between 19 and 34 weeks of gestation. The depth of Sylvian Fissure (SF), Parieto Occipital Fissure (POF) and Calcarine Fissure (CF) were evaluated and related to fetal sex. Neurosonographic variables were normalized for fetal head circumference and expressed as multiple of the median (MoM). RESULTS: A total of 344 fetuses were considered (173 male, 171 female). The baseline characteristic of the two groups were similar except a higher birthweight present in male fetuses (p=0.044). The depth SF (p=0.023) CF (p=0.014) and POF (p=0.046) showed significantly higher values in male fetuses when all the gestational age range was considered. However, when data were controlled for gestational age, these differences resulted significant only after 28 weeks. CONCLUSIONS: Differences in cortical development related to gender occur after 28 weeks of gestation with an increase depth of SF, POF and CF in male fetuses.

Validation of an automated software (Smartpelvic™) in assessing hiatal area from three dimensional transperineal pelvic volumes of pregnant women: comparison with manual analysis.

OBJECTIVES: The aim of this investigation was to evaluate the agreement between a manual and an automatic technique in assessing levator hiatus area (LHA) during pregnancy from three-dimensional (3D) pelvic floor volumes obtained by trans-perineal ultrasound (TPUS). METHODS: 3D volumes were acquired during rest, maximum pelvic floor contraction and Valsalva maneuver from 66 pregnant women. Manual selection of LHA and automatic software (Smart Pelvic™) were applied on TPUS volume starting from a C-plane view. To evaluate intra- and inter-observer variability measurements of LHA were performed twice by the same operator and once by a second sonographer. Reference hiatal contours obtained manually by the first operator were compared with the automated ones. Reproducibility was evaluated by intraclass correlation coefficients (ICC) and Bland-Altman plots. RESULTS: LHA measurement, using automatic software, achieved excellent intra-observer and inter-observer reproducibility in pregnant women both at rest and after dynamic analysis (ICC>0.9). Further, an excellent agreement resulted between manual selection of the LHA and automatic imaging (ICC>0.9). The average time taken to obtain LHA manually was significantly longer when compared to the automatic analysis (p≤0.0001). CONCLUSIONS: Smart pelvic software resulted from a reliable method for automatically measuring the LHA, showing high reproducibility and accuracy.

Modeling fetal cavum septum pellucidi width by quantile regression at 18-34 weeks of gestation: A prospective cross-sectional study.

OBJECTIVE: Develop charts for cavum septum pellucidi (CSP) following a standardized methodology and using quantile regression. The secondary objective was to assess the influence of fetal gender on the generated reference curves. METHODS: In a cross-sectional prospective study 453 low-risk singleton pregnancies were evaluated at a gestational age interval between 18 and 34 weeks. The width of CSP were measured on ultrasound images using a standardized technique and their changes were evaluated by quantile regression as a function of gestational age (GA) interval or head circumference (HC). Differences between sex were evaluated. RESULTS: The measurement of CSP significantly increased with gestation and HC. Linear models better described the changes of CSP with GA and HC. The fits of CSP width with GA and HC were not significantly different. Male fetuses showed significantly higher CSP width when compared to female fetuses (u = 2.973; p = 0.005). CONCLUSIONS: We generated prospective nomograms of fetal CSP development using quantile regression and following a strict standardized methodology. These new charts may be useful to better identify abnormal cases at higher risk of associated anomalies. Further our findings underline the potential effect of gender in developing fetal brain.

Modeling fetal cortical development by quantile regression for gestational age and head circumference: a prospective cross sectional study.

OBJECTIVES: To develop charts for fetal brain cortical structures following a proposed standardized methodology and using quantile regression. METHODS: Prospective cross-sectional study including 344 low-risk singleton pregnancies between 19 and 34 weeks of gestation. The depth of Sylvian (SF), Parieto-occipital (POF) and Calcarine fissures (CF) were measured on ultrasound images using a standardized technique and their changes were evaluated by quantile regression as a function of gestational age (GA) interval or head circumference (HC). RESULTS: The measurements of SF, POF and CF depth significantly increased with gestation. Linear models better described the changes of cortical variables with GA and HC. When the fit of sulci depth with GA and HC were compared, a close relationship was highlighted for the latter variable. CONCLUSIONS: We provided prospective charts of fetal cortical development using quantile regression and following a strict standardized methodology These new charts may help in better identifying cases at higher risk of abnormal cortical neurodevelopment.

Validation of an automatic software in assessing fetal brain volume from three dimensional ultrasonographic volumes: Comparison with manual analysis.

OBJECTIVE: This study was aimed to test the agreement between a manual and an automatic technique in measuring fetal brain volume (FBV) from three-dimensional (3D) fetal head datasets. METHODS: FBV were acquired independently by two operators from low risk singleton pregnancies at a gestational age between 19 and 34 weeks. FBV measurements were obtained using an automatic software (Smart ICV™) and manually by Virtual Organ Computer-aided AnaLysis (VOCAL™). Intraclass correlation coefficient (ICC) were calculated to assess reliability, while bias and agreement were evaluate by examining Bland-Altman plots. The time spent in measuring volumes was calculated and values obtained compared. RESULTS: Sixty-three volumes were considered for the study. In all the included volumes successful volume analysis were obtained with both techniques. Smart ICV™ showed a high intra-observer (0.996; 95% CI 0.994-0.998) and inter-observer (ICC 0.995; 95% CI 0.991-0.997). An excellent degree of reliability was found when the two techniques were compared (ICC 0.995; 95% CI 0.987-0.998). The time required to perform FBV was significantly lower for Smart ICV™ than VOCAL™ (8.2 ± 4.5 vs. 121.3 ± 19.0 s; p < 0.0001). CONCLUSIONS: The measurement of FBV is feasible with both manual and automatic techniques. Smart ICV™ showed an excellent intra- and inter-observer reliability associated with a valuable agreement with volume measurements obtained manually with VOCAL™. Volumes may be measured significantly faster with smart ICV™ than manually and this automatic software has the potential to become the preferred methods for the assessment of FBV.

CircRNA circ_0043533 facilitates cell growth in polycystic ovary syndrome by targeting miR-1179.

Increasing evidence indicates that circular RNAs (CircRNAs) have an important role in human diseases, including polycystic ovary syndrome (PCOS). Recently, circ_0043533, a novel circRNA, was proposed to be involved in the progression of PCOS. However, its role in PCOS has not been explored. In this study, the expression levels of circ_0043533 and miR-1179 in ovarian granulosa cells (OGCs) were examined by qRT-PCR analysis. Moreover, knockdown of circ_0043533 in OGC lines COV434 and KGN, respectively, the cell viability, proliferation, apoptosis, and cycle-related markers of insulin-triggered OGCs were examined by CCK-8, EdU staining, flow cytometry, and western blot assays, respectively. The interaction between circ_0043533 and miR-1179 was examined by bioinformatics, dual-luciferase assay, and RNA immunoprecipitation. Besides, effects of the miR-1179 inhibitor on cell viability and apoptosis in OGC lines with circ_0043533 knockdown were also evaluated. OGCs and insulin-treated OGCs exhibited higher circ_0043533 levels in comparison to the IOSE80 cells. Additionally, knockdown of circ_0043533 remarkably inhibited the cell viability and proliferation and promoted the apoptosis of insulin-treated COV434 and KGN cells, respectively. Meanwhile, circ_0043533 knockdown could down-regulate the Bcl-2, CDK2, and Cyclin D1 expressions, and up-regulate the Bax levels. Furthermore, we demonstrated that circ_0043533 acted as a sponge to absorb miR-1179. Interestingly, miR-1179 inhibition remarkably attenuated the effect of circ_0043533 silence on cell proliferation and apoptosis in insulin-treated COV434 and KGN cells. Taken together, this study revealed that circ_0043533 knockdown restrained the malignant progression of PCOS via targeting miR-1179. Our data suggested that circ_0043533 would serve as a novel therapeutic target for PCOS.

Effect of SARS-CoV-2 infection on fetal umbilical vein flow and cardiac function: a prospective study.

OBJECTIVES: To explore whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect umbilical vein blood flow (UVBF) and fetal cardiac function. METHODS: Prospective case-control study of consecutive pregnancies complicated by SARS-CoV-2 infection during the second half of pregnancy matched with unaffected women. Measurements of UVBF normalized for fetal abdominal circumference (UVBF/AC), atrial area (AA) and ventricular sphericity indices (SI) were compared between the two study groups. Chi-square and Mann-Whitney U tests were sued to analyze the data. RESULTS: Fifty-four consecutive pregnancies complicated and 108 not complicated by SARS-CoV-2 infection were included. The median gestational age at infection was 30.2 (interquartile range [IQR] 26.2 34.1). General baseline and pregnancy characteristics were similar between pregnant women with compared to those without SARS-CoV-2 infection. There was no difference in UVBF/AC (study groups z value -0.11 vs. 0.14 control p 0.751) values between pregnancies complicated compared to those not complicated by SARS-CoV-2 infection. Likewise, there was no difference in the left and right AA (left 1.30 vs. 1.28 p=0.221 and right 1.33 vs. 1.31 p=0.324) and SI (left 1.75 vs. 1.77 p=0.208 and right 1.51 vs. 1.54 p=0.121) between the two groups. CONCLUSIONS: SARS-CoV-2 infection does not affect UVBF and fetal cardiac function in uncomplicated pregnancies.

Maternal cardiovascular function in the prediction of fetal distress in labor: a prospective cohort study.

OBJECTIVE: To explore the strength of association and the diagnostic accuracy of maternal hemodynamic parameters detected noninvasively in predicting an adverse perinatal outcome in labor. METHODS: Prospective cohort study of singleton women undergoing antepartum care at 37-39 weeks of gestation. A noninvasive ultrasonic cardiac output monitor (USCOM®) was used for cardiovascular assessment. The study outcome was a composite score of adverse perinatal outcome, which included at least one of the following variables: Cesarean or instrumental delivery for abnormal fetal heart monitoring, umbilical artery pH <7.10 or admission to neonatal special care unit. Attending clinicians were blinded to maternal cardiovascular indices. Multivariate logistic regression and area under the curve (AUC) analyses were used to test the diagnostic accuracy of different maternal and ultrasound characteristics in predicting adverse perinatal outcome. RESULTS: A total of 133 women were recruited. The rate of adverse perinatal outcome was 25.6% (34/133). Women who delivered without abnormal perinatal outcome (controls) were more likely to be parous, compared to those who had an adverse perinatal outcome (44.4 vs. 73.5%; p = .005). Control women had significantly lower systemic vascular resistance (SVR) (median, 1166 vs. 1352 dynes × s/cm5, p = .023) and SVR index (SVRI) (median, 2168 vs. 2627 dynes × s/cm5/m2, p = .039) compared to women who had an adverse perinatal outcome. In this latter group the prevalence of SV <50 ml was significantly higher than in the control group (38.2% (13/34) vs. 11.1%, (11/99) p = .0012). At multivariable logistic regression analysis, SVR (aOR 1.307; 95% CI 1.112-2.23), SV <50 ml (aOR 4.70; 95% CI 1.336-12.006) and parity (3.90: 95% CI 1.545-10.334) were the only variables independently associated with adverse perinatal outcome. A model considering only SVR showed an AUC of 0.631. Integration of SVR with SV <50 ml and parity significantly improves the diagnostic performance of SVR alone to predict adverse outcome (AUC 0.732; p = .016). CONCLUSION: Pre-labor modifications of maternal cardiovascular variables are associated with adverse perinatal outcome. However, their predictive accuracy for perinatal compromise is low, and thus their use as standalone screening test for adverse perinatal outcome in singleton pregnancies at term is not supported.

Simultaneous determination of twelve paralytic shellfish poisoning toxins in bivalve molluscs by UPLC-MS/MS and its applications to a food poisoning incident.

In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was originally developed for simultaneously quantitative analysis of twelve paralytic shellfish poisoning toxins, referring to STX, NEO, dcSTX, GTX1, GTX2, GTX3, GTX4, GTX5, C1, C2, dcGTX2, and dcGTX3 in bivalve molluscs. Chromatographic separations were performed on a TSK-Gel Amide-80 column (5 µm, 2.0 × 150 mm, Tosoh Corporation) by gradient elution with 2 mmol L-1 ammonium formate solution-acetonitrile (containing 0.1% formic acid) as mobile phases. The samples were pretreated by extraction with acetonitrile-water (80:20, v/v; containing 0.1% formic acid), followed by cleaning up using an Oasis HLB extraction cartridge (500 mg/6 mL). The present method showed good linearity (r2 > 0.99) with the limits of detection (LODs) and limits of quantification (LOQs) ranged from 1.03 to 10.65 µg/kg and 3.43-35.46 µg/kg, respectively for these toxins. Owing to its sensitivity and rapid properties, the presented method was applied to the determination of PSP toxins in bivalve molluscs involved in a food poisoning incident occurred in Zhangzhou, China, in June 2017.