Nafamostat mesylate decreases skin flap necrosis in a mouse model of type 2 diabetes by protecting the endothelial glycocalyx.

The success rate of flap tissue reconstruction has increased in recent years owing to advancements in microsurgical techniques. However, complications, such as necrosis, are still more prevalent in diabetic patients compared to non-diabetic individuals, presenting an ongoing challenge. To address this issue, many previous studies have examined vascular anastomoses dilation and stability, primarily concerning surgical techniques or drugs. In contrast, in the present study, we focused on microvascular damage of the peripheral microvessels in patients with diabetes mellitus and the preventative impact of nafamostat mesylate. Herein, we aimed to investigate the effects of hyperglycemia on glycocalyx (GCX) levels in mice with type 2 diabetes. We examined the endothelial GCX (eGCX) in skin flap tissue of 9-12-week-old type 2 diabetic mice (db/db mice) using a perforator skin flap and explored treatment with nafamostat mesylate. The growth rates were compared after 1 week. Heterotype (db/+) mice were used as the control group. Morphological examination of postoperative tissues was performed at 1, 3, 5, and 7 days post-surgery. In addition, db/db mice were treated with 30 mg/kg/day of nafamostat mesylate daily and were evaluated on postoperative day 7. Seven days after surgery, all db/db mice showed significant partial flap necrosis. Temporal observation of the skin flaps revealed a stasis-like discoloration and necrosis starting from the contralateral side of the remaining perforating branch. The control group did not exhibit flap necrosis, and the flap remained intact. In the quantitative assessment of endothelial glycans using lectins, intensity scoring showed that the eGCX in the db/db group was significantly thinner than that in the db/+ group. These results were consistent with the scanning electron microscopy findings. In contrast, treatment with nafamostat mesylate significantly improved the flap engraftment rate and suppressed eGCX injury. In conclusion, treatment with nafamostat mesylate improves the disrupted eGCX structure of skin flap tissue in db/db mice, potentially ameliorating the impaired capillary-to-venous return in the skin flap tissue.

Omeprazole Induces CYP3A4 mRNA Expression but Not CYP3A4 Protein Expression in HepaRG Cells.

Unknown interactions between drugs remain the limiting factor for clinical application of drugs, and the induction and inhibition of drug-metabolizing CYP enzymes are considered the key to examining the drug-drug interaction (DDI). In this study, using human HepaRG cells as an in vitro model system, we analyzed the potential DDI based on the expression levels of CYP3A4 and CYP1A2. Rifampicin and omeprazole, the potent inducers for CYP3A4 and CYP1A2, respectively, induce expression of the corresponding CYP enzymes at both the mRNA and protein levels. We noticed that, in addition to inducing CYP1A2, omeprazole induced CYP3A4 mRNA expression in HepaRG cells. However, unexpectedly, CYP3A4 protein expression levels were not increased after omeprazole treatment. Concurrent administration of rifampicin and omeprazole showed an inhibitory effect of omeprazole on the CYP3A4 protein expression induced by rifampicin, while its mRNA induction remained intact. Cycloheximide chase assay revealed increased CYP3A4 protein degradation in the cells exposed to omeprazole. The data presented here suggest the potential importance of broadening the current DDI examination beyond conventional transcriptional induction and enzyme-activity inhibition tests to include post-translational regulation analysis of CYP enzyme expression.

Temperature-Dependent Upregulation of Per2 Protein Expression Is Mediated by eIF2α Kinases PERK and PKR through PI3K Activation.

Temperature-dependent translational control of the core clock gene Per2 plays an important role in establishing entrainment of the circadian clock to physiological body temperature cycles. Previously, we found an involvement of the phosphatidylinositol 3-kinase (PI3K) in causing Per2 protein expression in response to a warm temperature shift (WTS) within a physiological range (from 35 to 38.5 °C). However, signaling pathway mediating the Per2 protein expression in response to WTS is only sparsely understood. Additional factor(s) other than PI3K remains unknown. Here we report the identification of eukaryotic initiation factor 2α (eIF2α) kinases, protein kinase R (PKR) and PKR-like endoplasmic reticulum kinase (PERK), as a novel mediator of WTS-dependent Per2 protein expression. Canonically, eIF2α has been regarded as a major downstream target of PERK and PKR. However, we found that PERK and PKR mediate WTS response of Per2 in a manner not involving eIF2α. We observed that PERK and PKR serve as an upstream regulator of PI3K rather than eIF2α in the context of WTS-dependent Per2 protein expression. There have been studies reporting PI3K activation occurring depending on PERK and PKR, while its physiological contribution has remained elusive. Our finding therefore not only helps to enrich the knowledge of how WTS affects Per2 protein expression but also extends the region of cellular biology involving the PERK/PKR-mediated PI3K activation to include entrainment-mechanism of the circadian clock.

Normal values and distribution of ventricular global longitudinal strain in 513 healthy fetuses measured by two-dimensional speckle-tracking echocardiography: a multi-institutional cohort study.

This study aimed to determine the normal reference values and distribution of global longitudinal strain (GLS) in the right and left ventricles of healthy Japanese fetuses during pregnancy. This multi-institutional cohort study included healthy Japanese fetuses during normal pregnancies without maternal or fetal complications between 18 and 40 weeks of gestation. Two-dimensional fetal echocardiographic images of the four-chamber view with a high frame rate were acquired and stored as DICOM clips. Data were collected and analyzed in a central laboratory to measure the left ventricular (LV) and right ventricular (RV) GLS using two-dimensional speckle tracking. In total, 513 fetuses were enrolled. The mean LV-GLS and RV-GLS were - 24.3% ± 3.5% and - 23.5% ± 3.7%, respectively. The magnitude of the GLS, with normal limits in both ventricles, decreased with advancing gestation. LV values were r = 0.34 (95% confidence interval, 0.27-0.42) and p < 0.0001; RV values were r = 0.33 (95% confidence interval, 0.25-0.41) and p < 0.0001. The normal values of healthy Japanese fetuses in healthy pregnancies is the first to be established by the large-scale, multi-institutional cohort study as LV-GLS of 24.3% ± 3.5% and RV-GLS of - 23.5% ± 3.7%, respectively. This can serve as a basic reference for assessing the cardiac functions in Japanese fetuses with various heart diseases.

Impact of augmented renal clearance on anticoagulant therapy in critically ill patients with coronavirus disease 2019: A retrospective cohort study.

INTRODUCTION: This study aimed to determine the impact of augmented renal clearance (ARC) on anticoagulation therapy in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: This retrospective cohort study included adult patients with severe COVID-19 with ARC who had been treated at our hospital between 2020 and 2021. We measured the estimated glomerular filtration rate calculated by the Chronic Kidney Disease Epidemiology Collaboration formula (eGFRCKD-EPI) every morning, and ARC condition was defined as eGFRCKD-EPI ≥ 130 mL/min/1.73 m2. Multivariate regression analysis with Huber-White sandwich estimator was performed to examine the association of unfractionated heparin (UH) dosage between blood test timings with activated partial thromboplastin time (APTT) compared with and without ARC. RESULTS: We identified 38 enrolled patients: seven and 31 in the ARC and non-ARC groups, respectively. In the ARC coexisting condition, a higher dose of UH, which corresponded to the total dose in 24 h from the previous day, was required to achieve the same APTT prolongation, with a significant difference (p < 0.001). CONCLUSIONS: Our study suggests that careful monitoring and consideration of higher UH doses in critically ill patients with COVID-19 is necessary because anticoagulation failure can occur during ARC.

Circadian Clock and Body Temperature.

The circadian fluctuation of body temperature is one of the most prominent and stable outputs of the circadian clock and plays an important role in maintaining optimal day-night energy homeostasis. The body temperature of homothermic animals is not strictly constant, but it shows daily oscillation within a range of 1-3 °C, which is sufficient to synchronize the clocks of peripheral tissues throughout the body. The thermal entrainment mechanisms of the clock are partly mediated by the action of the heat shock transcription factor and cold-inducible RNA-binding protein-both have the ability to affect clock gene expression. Body temperature in the poikilotherms is not completely passive to the ambient temperature change; they can travel to the place of preferred temperature in a manner depending on the time of their endogenous clock. Based on this behavior-level thermoregulation, flies exhibit a clear body temperature cycle. Noticeably, flies and mice share the same molecular circuit for the controlled body temperature; in both species, the calcitonin receptors participate in the formation of body temperature rhythms during the active phase and exhibit rather specific expression in subsets of clock neurons in the brain. We summarize knowledge on mutual relationships between body temperature regulation and the circadian clock.

Embryonic and Fetal Heart Development Before 12 Weeks of Gestation.

OBJECTIVE: To assess embryonic and fetal cardiac growth and development using transvaginal 2-dimensional sonography before 12 weeks of gestation. METHODS: Transvaginal scans for first-trimester dating were performed for 131 normal fetuses at 8-11 + 6 weeks of gestation. The basal-apical length (BAL), transverse length (TL), cardiac circumference (ECC), embryonic cardiac area (ECA), global sphericity index (GSI), and cardio-thoracic area ratio (CTAR) were able to be obtained in 105 normal embryos and fetuses. RESULTS: Nomograms for several cardiac parameters including BAL, TL, ECC, ECA, GSI, and CTAR were constructed. BAL, TL, ECC, and ECA increased curvilinearly with advancing gestation (R2 = 0.97406, 0.980396, 0.978359, and 0.920705, respectively, P < .001). GSI (mean, 1.14; SD, 0.10) and CTAR (mean, 15.7%; SD, 3.3%) values were constant at 8-11 + 6 weeks of gestation. There were significant curvilinear correlations between BAL, TL, ECC, and ECA, and crown-rump length (CRL) (R2 = 0.975976, 0.983482, 0.980673, and 0.929936, respectively, P < .001). GSI and CTAR values were not changed with the increase of CRL during this period. CONCLUSION: Our results provide nomograms for several cardiac parameters which may improve the understanding of embryonic and fetal cardiac growth and development prior to 12 weeks of gestation.

Transvaginal three-dimensional ultrasound assessment of embryonic genital tubercle at 8-10+6 weeks of gestation.

OBJECTIVES: To assess embryonic genital tubercle using transvaginal three-dimensional (3D) ultrasound at 8-10+6 weeks of gestation. METHODS: One-hundred and two transvaginal 3D ultrasound scans were performed for first-trimester dating at 8-10+6 weeks of gestation. The genital tubercle angle (GTA) and genital tubercle length (GTL) were measured with a mid-sagittal view of the embryo using the 3D ultrasound multiplanar mode. Intra- and inter-observer agreements regarding GTA and GTL were also assessed with Bland-Altman plots and intra- and inter-correlation coefficients. RESULTS: There were no significant differences in GTA between male and female embryos at 8, 9, 10 weeks, or 8-10+6 weeks of gestation, respectively. There were also no significant differences in GTL between male and female embryos at 8, 9, 10 weeks, or 8-10+6 weeks of gestation, respectively. However, GTL increased linearly with advancing gestation (r=0.8276, p<0.00001). Mean GTL (SD) values at 8, 9, and 10 weeks were 0.833 mm (0.274), 1.623 mm (0.262), and 2.152 mm (0.420), respectively (p<0.001). Intra- and inter-reproducibilities of GTA and GTL were excellent. The intra- and inter-correlation coefficients of GTA and GTL were 0.964 and 0.995, and 0.996 and 0.9933, respectively. CONCLUSIONS: The genital tubercle could be identified using transvaginal 3D ultrasound at 8-10+6 weeks of gestation. However, sex differentiation could not be performed at this age. The genital tubercle linearly developed with advancing gestation during the mid-first trimester of pregnancy.

Decreased neutrophil counts prolong inflammation in acute pancreatitis and cause inflammation spillover to distant organs.

BACKGROUND/OBJECTIVE: Acute pancreatitis is an aseptic inflammation caused by pathologically activated pancreatic enzymes and inflammatory mediators produced secondarily by neutrophils and other inflammatory cells and is one of the most difficult diseases to treat. This study aimed to investigate the role of neutrophils in pancreatitis by examining tissue dynamics. METHODS: We created a model of caerulein-induced pancreatitis in 12-week-old male granulocyte colony-stimulating factor knockout mice (G-CSF-KO) and wild-type littermate control mice (six intraperitoneal injections of caerulein [80 µg/kg body weight] at hourly intervals for 2 days). Mice were sacrificed 0, 3, 6, 12, 24, 36, 48, 72, and 168 h after caerulein administration and examined histologically. RESULTS: The survival rate after one week of caerulein administration was 100 % in the control mice, whereas it was significantly lower (10 %) in the G-CSF-KO mice. Histological examination revealed significant hemorrhage and inflammatory cell migration in the G-CSF-KO mice, indicating prolonged inflammation. CONCLUSION: Prolonged inflammation was observed in the G-CSF-KO mice. Tissue cleanup by neutrophils during the acute phase of inflammation may influence healing through the chronic phase.

Embryonic and fetal tiny pericardial fluid collections at less than 12 weeks of gestation.

OBJECTIVES: To describe embryonic and fetal tiny pericardial fluid collections (PFCs) using transvaginal sonography and HDlive Silhouette at less than 12 weeks of gestation. METHODS: During an 8-month period from November 2021 to June 2022, one-hundred and thirty transvaginal scans were performed for first-trimester dating, and eleven tiny PFCs of the embryo or fetus were identified at 8+4 - 11+3 weeks of gestation (three at 8, six at 9, and two at 11 weeks). HDlive Silhouette features of PFC were evaluated. Their clinical characteristics and outcomes were also investigated. RESULTS: The incidence of tiny PFCs was 8.5 % at less than 12 weeks of gestation. The mean gestational age at the initial examination was 9.5 weeks (SD: ± 0.9). The mean crown-rump length was 25.0 mm (SD: ± 8.5). The mean PFC dimension was 0.8 mm (range: 0.5-1.3, SD: ± 0.2). Pleural effusion was associated with 3 out of 11 PFCs (27.2 %). Ascites was noted in 2 cases (18.2 %). Skin edema was identified in only in 1 case (0.09 %). There was no arrhythmia. Tiny PFC could also be depicted using HDlive Silhouette. First-trimester fetal ultrasound scans at 11 - 13+6 weeks showed no abnormal findings. PFCs resolved until 13 weeks of gestation (Mean: 12 weeks, SD: ± 1.2). All PFC pregnancies resulted in healthy neonates. CONCLUSIONS: The incidence of tiny PFCs was relatively high in early pregnancy. HDlive Silhouette can depict tiny PFCs of the embryo. Tiny PFCs in early gestation are transient, benign findings in utero.

Fetal brain activity and the free energy principle.

OBJECTIVES: To study whether the free energy principle can explain fetal brain activity and the existence of fetal consciousness via a chaotic dimension derived using artificial intelligence. METHODS: In this observational study, we used a four-dimensional ultrasound technique obtained to collect images of fetal faces from pregnancies at 27-37 weeks of gestation, between February and December 2021. We developed an artificial intelligence classifier that recognizes fetal facial expressions, which are thought to relate to fetal brain activity. We then applied the classifier to video files of facial images to generate each expression category's probabilities. We calculated the chaotic dimensions from the probability lists, and we created and investigated the free energy principle's mathematical model that was assumed to be linked to the chaotic dimension. We used a Mann-Whitney test, linear regression test, and one-way analysis of variance for statistical analysis. RESULTS: The chaotic dimension revealed that the fetus had dense and sparse states of brain activity, which fluctuated at a statistically significant level. The chaotic dimension and free energy were larger in the sparse state than in the dense state. CONCLUSIONS: The fluctuating free energy suggests consciousness seemed to exist in the fetus after 27 weeks.

Isolated tortuous ductus arteriosus in a fetus: HDlive Flow with spatiotemporal image correlation (STIC) study.

OBJECTIVES: To describe prevalence, outcome, color Doppler, and HDlive Flow (Silhouette) with spatiotemporal image correlation (STIC) features of isolated tortuous ductus arteriosus in Japanese fetuses at 28-31 + 6 weeks of gestation. METHODS: During a 37-month period, 3,150 fetal screenings were performed at 28-31 + 6 weeks of gestation. Isolated tortuous ductus arteriosus was evaluated using color Doppler and HDlive Flow (Silhouette) with STIC. Prevalence and outcomes were also assessed. RESULTS: There were 22/3,150 fetuses (0.7%) had isolated tortuous ductus arteriosus at 28-31 + 6 weeks of gestation. According to color Doppler and HDlive Flow findings, two types of isolated tortuous ductus arteriosus (Right-angled and Loop shapes) were classified. There were 20 Right-angled and 2 Loop shapes. One fetus with a Right-angled shape was associated with aortic tortuosity. HDlive Flow with STIC revealed spatial relationships of tortuous ductus arteriosus, aortic arch, and descending aorta. All fetuses with isolated tortuous ductus arteriosus had good neonatal outcomes. CONCLUSIONS: The incidence of isolated tortuous ductus arteriosus in Japanese fetuses was low compared with those in previous reports. HDlive Flow with STIC provides precise information for spatial recognition and differentiation of isolated tortuous ductus arteriosus, resulting in two type classifications. Isolated tortuous ductus arteriosus in a fetus may be a transient, benign finding in utero.

Recombinant Antithrombin Attenuates Acute Respiratory Distress Syndrome in Experimental Endotoxemia.

Sepsis-induced endothelial acute respiratory distress syndrome is related to microvascular endothelial dysfunction caused by endothelial glycocalyx disruption. Recently, recombinant antithrombin (rAT) was reported to protect the endothelial glycocalyx from septic vasculitis; however, the underlying mechanism remains unknown. Here, we investigated the effect of rAT administration on vascular endothelial injury under endotoxemia. Lipopolysaccharide (LPS; 20 mg/kg) was injected intraperitoneally into 10-week-old male C57BL/6 mice, and saline or rAT was administered intraperitoneally at 3 and 24 hours after LPS administration. Subsequently, serum and/or pulmonary tissues were examined for inflammation and cell proliferation and differentiation by histologic, ultrastructural, and microarray analyses. The survival rate was significantly higher in rAT-treated mice than in control mice 48 hours after LPS injection (75% versus 20%; P < 0.05). Serum interleukin-1ß was increased but to a lesser extent in response to LPS injection in rAT-treated mice than in control mice. Lectin staining and ultrastructural studies showed a notable attenuation of injury to the endothelial glycocalyx after rAT treatment. Microarray analysis further showed an up-regulation of gene sets corresponding to DNA repair, such as genes involved in DNA helicase activity, regulation of telomere maintenance, DNA-dependent ATPase activity, and ciliary plasm, after rAT treatment. Thus, rAT treatment may promote DNA repair, attenuate inflammation, and promote ciliogenesis, thereby attenuating the acute respiratory distress syndrome caused by endothelial injury.

Nmu/Nms/Gpr176 Triple-Deficient Mice Show Enhanced Light-Resetting of Circadian Locomotor Activity.

The suprachiasmatic nucleus (SCN) is the master circadian clock in mammals and is properly entrained by environmental light cycle. However, the molecular mechanism(s) determining the magnitude of phase shift by light is still not fully understood. The orphan G-protein-coupled receptor Gpr176 is enriched in the SCN, controls the pace (period) of the circadian rhythm in behavior but is not apparently involved in the light entrainment; Gpr176-/- animals display a shortened circadian period in constant darkness but their phase-resetting responses to light are normal. Here, we performed microarray analysis and identified enhanced mRNA expression of neuromedin U (Nmu) and neuromedin S (Nms) in the SCN of Gpr176-/- mice. By generating C57BL/6J-backcrossed Nmu/Nms/Gpr176 triple knockout mice, we noted that the mutant mice had a greater magnitude of phase shift in response to early subjective night light than wildtype mice, while Nmu/Nms double knockout mice as well as Gpr176 knockout mice are normal in the phase shifts induced by light. At the molecular level, Nmu-/-Nms-/-Gpr176-/- mice had a reduced induction of Per1 and cFos mRNA expression in the SCN by light and mildly upregulated circadian expression of Per2, Prok2, Rgs16, and Rasl11b. These expressional changes may underlie the phenotype of the Nmu/Nms/Gpr176 knockout mice. Our data argue that there is a mechanism requiring Nmu, Nms, and Gpr176 for the proper modulation of light-induced phase shift in mice. Simultaneous modulation of Nmu/Nms/Gpr176 may provide a potential target option for modulating the circadian clock.

Natural Course of Fetal Hyaloid Artery: SlowflowHD Longitudinal Study.

OBJECTIVE: To assess the natural course of the fetal hyaloid artery (FHA) using SlowflowHD during pregnancy. METHODS: One-hundred and eighteen normal fetuses were studied longitudinally using SlowflowHD to assess the natural course of FHA at 18-21 + 6, 28-31 + 6, and after 35 weeks of gestation. Blood flow of FHA with/without its branches (BF) was evaluated using SlowflowHD, and the band of FHA without blood flow (Band) was identified in each gestational period. The natural course of FHA was classified into six types: Type A, not detected (ND) in each gestational period; Type B, Band at 18-21 + 6 weeks; Type C, Band at 18-21 + 6 and 28-31 + 6 weeks; Type D, BF at 18-21 + 6 weeks; Type E, BF at 18-21 + 6 weeks and Band at 28-31 + 6 weeks; Type F, BF at 18-21 + 6 and 28-31 + 6 weeks. RESULTS: BF, Band, and ND were 83.5, 15.5, and 1.0% at 18-21 + 6 weeks, 8.8, 15.5, and 75.7% at 28-31 + 6 weeks, and 0, 0, and 100% after 35 weeks, respectively. Type A was 1.0%, Type B was 13.6%, Type C was 1.9%, Type D was 61.2%, Type E was 13.6%, and Type F was 8.7%. CONCLUSIONS: The presence of FHA blood flow before 30 weeks of gestation should be regarded as a physiologic phenomenon in normal fetuses.

HDlive Flow Silhouette with spatiotemporal image correlation for assessment of fetal cardiac structures at 12 to 14 + 6 weeks of gestation.

OBJECTIVES: To assess fetal cardiac structures using HDlive Flow Silhouette with spatiotemporal image correlation (STIC) at 12 to 14 + 6 weeks of gestation, and verify the feasibility of obtaining five cardiac views in the late first and early second trimesters of pregnancy. The fetal cardiac shape and the aspect of the descending aorta were also evaluated. METHODS: Eighty normal fetuses at 12 to 14 + 6 weeks of gestation were studied using trans-abdominal HDlive Flow Silhouette with STIC to assess the feasibility of five fetal cardiac views (frontal, spatial three-vessel, panoramic, posterior, and right lateral views). Target structures in each cardiac view were evaluated. 'Good' was assigned when all structures were noted, 'Fair' when only one structure was missed, and 'Poor' when two and more structures could not be detected. Frequencies of an elongated heart and those of a tortuous descending aorta were counted. RESULTS: Forty-nine fetuses were effectively included in the analysis. Success rates of 'Good' and 'Fair' were significantly higher with spatial three-vessel (p<0.01) and panoramic views (p<0.05). Frequencies of "Elongated heart", "Elongated left ventricle", and "Spherical heart" were 12.2, 6.2, and 81.6%, respectively. Frequencies of "Tortuous descending aorta" and "Straight descending aorta" were 12.2 and 87.8%, respectively. CONCLUSIONS: The feasibility of obtaining fetal five cardiac views using HDlive Flow Silhouette with STIC is good, and this technique provides useful information for evaluating fetal cardiac structures in the late first and early second trimesters of pregnancy.

MrgprB4 in trigeminal neurons expressing TRPA1 modulates unpleasant sensations.

Gentle touch such as stroking of the skin produces a pleasant feeling, which is detected by a rare subset of sensory neurons that express Mas-related G protein-coupled receptor B4 (MrgprB4) in mice. We examined small populations of MrgprB4-positive neurons in the trigeminal ganglion and the dorsal root ganglion, and most of these were sensitive to transient receptor potential ankyrin 1 (TRPA1) agonist but not TRPV1, TRPM8, or TRPV4 agonists. Deficiency of MrgprB4 did not affect noxious pain or itch behaviors in the hairless plantar and hairy cheek. Although behavior related to acetone-induced cold sensing in the hind paw was not changed, unpleasant sensory behaviors in response to acetone application or sucrose splash to the cheek were significantly enhanced in Mrgprb4-knockout mice as well as in TRPA1-knockout mice. These results suggest that MrgprB4 in the trigeminal neurons produces pleasant sensations in cooperation with TRPA1, rather than noxious or cold sensations. Pleasant sensations may modulate unpleasant sensations on the cheek via MrgprB4.

Possible involvement of Syndecan-1 in the state of COVID-19 related to endothelial injury.

BACKGROUND: The coronavirus infection 2019 (COVID-19) is associated with microvascular endothelial injury. Here, we report that syndecan-1, a component of endothelial glycocalyx, may reflect the disease state of COVID-19 related to endothelial injury. CASE PRESENTATION: A patient with COVID-19 was transferred to the intensive care unit of our hospital. Computed tomography of the chest showed bilateral ground glass opacities, which was diagnosed as acute respiratory syndrome. The PaO2/FIO2 ratio gradually increased from 158 on hospitalization to 300 on Day 11, on which day the ventilator was withdrawn. However, serum syndecan-1 (SDC-1) level gradually decreased from 400.5 ng/ml at hospitalization to 165.1 ng/ml on Day 5. On Day 6, serum SDC-1 level increased to 612.9 ng/ml owing to a systemic thrombosis with an increase in D-dimer. Serum SDC-1 level then decreased until 206.0 ng/ml on Day 11 after a decrease in D-dimer. The patient was transferred to another hospital on Day 21 after hospitalization. CONCLUSIONS: In this case report, changes in serum SDC-1 level closely reflected the change in disease condition in a patient with COVID-19. Serum SDC-1 may be a useful biomarker for monitoring the disease state of critically ill patients with COVID-19.

Recognition of facial expression of fetuses by artificial intelligence (AI).

OBJECTIVES: The development of the artificial intelligence (AI) classifier to recognize fetal facial expressions that are considered as being related to the brain development of fetuses as a retrospective, non-interventional pilot study. METHODS: Images of fetal faces with sonography obtained from outpatient pregnant women with a singleton fetus were enrolled in routine conventional practice from 19 to 38 weeks of gestation from January 1, 2020, to September 30, 2020, with completely de-identified data. The images were classified into seven categories, such as eye blinking, mouthing, face without any expression, scowling, smiling, tongue expulsion, and yawning. The category in which the number of fetuses was less than 10 was eliminated before preparation. Next, we created a deep learning AI classifier with the data. Statistical values such as accuracy for the test dataset and the AI confidence score profiles for each category per image for all data were obtained. RESULTS: The number of fetuses/images in the rated categories were 14/147, 23/302, 33/320, 8/55, and 10/72 for eye blinking, mouthing, face without any expression, scowling, and yawning, respectively. The accuracy of the AI fetal facial expression for the entire test data set was 0.985. The accuracy/sensitivity/specificity values were 0.996/0.993/1.000, 0.992/0.986/1.000, 0.985/1.000/0.979, 0.996/0.888/1.000, and 1.000/1.000/1.000 for the eye blinking, mouthing, face without any expression, scowling categories, and yawning, respectively. CONCLUSIONS: The AI classifier has the potential to objectively classify fetal facial expressions. AI can advance fetal brain development research using ultrasound.

A 24-segment fractional shortening of the fetal heart using FetalHQ.

OBJECTIVES: To evaluate 24-segment fractional shortening (FS) of the fetal heart using FetalHQ by speckle-tracking regarding reproducibility and the change with advancing gestation. METHODS: Eighty-one pregnant women at 18-21+6 and 28-31+6 weeks of gestation were studied using FetalHQ with the speckle-tracking technique to calculate 24-segment FS of left and right ventricles. Intra- and inter-class correlation coefficients and intra- and inter-observer agreements of measurements for FS were assessed in each segment. RESULTS: With respect to intra-observer reproducibility, all FS values showed correlations between 0.575 and 0.862 for the left ventricle, with good intra-observer agreements except for left ventricular segments 14-24. Right ventricular FS values showed correlations between 0.334 and 0.685, with good intra-observer agreements. With respect to inter-observer reproducibility, all FS values showed correlations between 0.491 and 0.801 for the left ventricle, with good intra-observer agreements except for left ventricular segments 16-22. Right ventricular FS values showed correlations between 0.375 and 0.575, with good inter-observer agreements. There were significant differences in the mean FS values in the basal segment (segments 1-5) of the left ventricle between 18 and 21+6 and 28-31+6 weeks of gestation (p<0.05), whereas there were significant differences in all mean FS values in the right ventricle between both gestational ages (p<0.05). CONCLUSIONS: These results suggest that the reproducibility of the 24-segment FS of the fetal heart using FetalHQ is fair. However, there may be significant differences in FS values with advancing gestational age, especially for the right ventricle.