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.

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.

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.

In Vitro and in Silico Studies of Potential Coronavirus-Specific 3C-Like Protease Inhibitors.

We investigated similar compounds to ebselen and tideglusib, which exhibit strong activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using Molecular ACCess System (MACCS) keys. Four candidate compounds were identified. One of them, phenyl-benzothiazol-3-one, showed coronavirus-specific 3C-like (3CL) protease inhibitory activity. The results indicated that a similarity score above 0.81 is a good indicator of activity for ebselen-and-tideglusib-like compounds. Subsequently, we simulated the ring-cleavage Michael reaction of ebselen at the Se center, which is responsible for its 3CL protease inhibitory activity, and determined the activation free energy of the reaction. The results showed that reaction simulation is a useful tool for estimating the activity of inhibitory compounds that undergo Michael addition reactions with the relevant cysteine S atom of 3CL proteases.

Achievements and challenges of the Sakigake designation system in Japan.

The Sakigake designation system (Sakigake) has been launched to encourage the pioneered development of innovative new medical products for the effective treatment of severe illness in Japan, which allows leveraging the several advantages in prioritized consultation, rapid review, premium drug pricing and extended data-protection period. We retrospectively analysed the Sakigake products including drugs and regenerative medical products to clarify the achievements and the future issues in this system. From April 2015 to August 2020 (the first 5-year trial period of Sakigake), 37 products were designated, and 10 of those were approved in Japan in which 7 new active substances achieved the first-in-world approvals. Oncology, neurology and cardiovascular disease were the major therapeutic areas, and those 3 accounted for 75.7% of all products. Sakigake achieved some first-in-world approvals by the Pharmaceuticals and Medical Devices Agency/the Ministry of Health, Labor and Welfare of innovative new medical products, although in some therapeutic areas, there remains room in stimulating drug development.

Rationales of delay and difference in regulatory review by Japan, the USA and Europe among new drugs first approved in Japan.

AIMS: To clarify the rationales of delay or difference in the review of new drug applications among regulatory authorities for new drugs, those first approved in the world being in Japan. METHODS: Among 80 new drugs first approved in Japan from 2008 to 2019, we identified those subsequently approved in the USA or Europe. Significant delays in approval time (boxplot outliers) and the rationales for the delays were assessed among the Pharmaceuticals and Medical Devices Agency (PMDA), the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). RESULTS: Of the 80 Japan-first approvals, 25 and 24 were approved in the USA and Europe, respectively, and their median approval times in Japan, the USA and Europe were 285, 334 and 477 days, respectively. Significant delays were identified for pirfenidone (1806 days, FDA), alogliptin benzoate (1856 days, FDA), insulin degludec (1457 days, FDA) and romosozumab (750 days, PMDA; 994 days, FDA; 748 days, EMA). Due to concerns about cardiovascular risk, alogliptin benzoate and insulin degludec were requested for additional clinical trials by the FDA, and romosozumab required a much longer review period than the standard approval time in all three regions. CONCLUSIONS: Among the new drugs significantly delayed in approval time in Japan, the USA or Europe, there were some differences in the requirements, the participating regions and the assessment of clinical trials. The regulatory views on the cardiovascular risk also differed among the three regions. These divergences may be associated with the differences in approval histories.

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.

Success rate of five fetal cardiac views using HDlive Flow with spatiotemporal image correlation at 18-21 and 28-31 weeks of gestation.

Objective To assess the success rates of five fetal cardiac views using HDlive Flow (Silhouette) with spatiotemporal image correlation (STIC) in the second and third trimesters of pregnancy, and to verify the feasibility of obtaining five cardiac views by volumes. Methods One hundred and eighteen normal fetuses at 18-21 and 28-31 weeks of gestation were studied using HDlive Flow (Silhouette) with STIC to assess the success rates 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 been detected. Results There were no significant differences in success rates of each cardiac view between 18-21 and 28-31 weeks of gestation. The rate of "Good" with a spatial three-vessel view was significantly higher than that with other cardiac views at 18-21 and 28-31 weeks, respectively (P < 0.05). Conclusion Five cardiac views using HDlive Flow (Silhouette) with STIC may become an adjunctive and useful tool in fetal cardiac examination.

GABA, γ-Aminobutyric Acid, Protects Against Severe Liver Injury.

BACKGROUND: Acute liver failure (ALF) from severe acute liver injury is a critical condition associated with high mortality. The purpose of this study was to investigate the impact of preemptive administration of γ-aminobutyric acid (GABA) on hepatic injury and survival outcomes in mice with experimentally induced ALF. MATERIALS AND METHODS: To induce ALF, C57BL/6NHsd mice were administered GABA, saline, or nothing for 7 d, followed by intraperitoneal administration of 500 µg of tumor necrosis factor α and 20 mg of D-galactosamine. The study mice were humanely euthanized 4-5 h after ALF was induced or observed for survival. Proteins present in the blood samples and liver tissue from the euthanized mice were analyzed using Western blot and immunohistochemical and histopathologic analyses. For inhibition studies, we administered the STAT3-specific inhibitor, NSC74859, 90 min before ALF induction. RESULTS: We found that GABA-treated mice had substantial attenuation of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive hepatocytes and hepatocellular necrosis, decreased caspase-3, H2AX, and p38 MAPK protein levels and increased expressions of Jak2, STAT3, Bcl-2, and Mn-SOD, with improved mitochondrial integrity. The reduced apoptotic proteins led to a significantly prolonged survival after ALF induction in GABA-treated mice. The STAT3-specific inhibitor NSC74859 eliminated the survival advantage in GABA-treated mice with ALF, indicating the involvement of the STAT3 pathway in GABA-induced reduction in apoptosis. CONCLUSIONS: Our results showed that preemptive treatment with GABA protected against severe acute liver injury in mice via GABA-mediated STAT3 signaling. Preemptive administration of GABA may be a useful approach to optimize marginal donor livers before transplantation.

Visualization of Hepatocellular Regeneration in Mice After Partial Hepatectomy.

BACKGROUND: Although hepatocellular regeneration is the cornerstone of liver homeostasis, current techniques for assessing such regeneration are limited. A method for visualizing the regeneration process would provide a means for advanced studies. Therefore, we examined the possibility of using fluorescence ubiquination-based cell cycle indicator (Fucci) mice for direct visualization of hepatocellular regeneration. MATERIALS AND METHODS: We performed a two-thirds partial hepatectomy in conventional and Fucci mice. Fucci animals have orange Cdt1 expressed in the G1 phase and green Geminin expressed in S/G2/M phases. Regenerating livers were procured daily for 7 d. Immunohistochemical staining was performed for proliferative Ki67 and mitotic pHH3 serine 10 (pHH3) markers on formalin-fixed, paraffin-embedded tissue sections from conventional mice. The orange Cdt1 and green Geminin fluorescence indicative of the G1 and S/G2/M phases, respectively, were assessed in liver tissues, in vivo and ex vivo, with two-photon laser scanning microscopy. RESULTS: Immunostaining with Ki67 and pHH3 revealed a typical profile of hepatocellular regeneration after hepatectomy in conventional mice, although immunostaining required more than a week to process. In contrast, hepatocellular regeneration could be visualized with two-photon microscopy within a few hours in regenerating livers of the Fucci mice. Only orange G1 hepatocytes were seen in the baseline liver specimens; however, multiple bright green and yellow hepatocytes were seen 48 h after hepatectomy, indicating active hepatocytes in the S/G2/M phases of the cell cycle. CONCLUSIONS: Hepatocellular regeneration is readily visualized in regenerating livers of Fucci mice. The Fucci model is an exciting tool for advanced studies of hepatocellular and liver regeneration.

Twin fetal facial expressions at 30-33+6 weeks of gestation.

Objective To assess the characteristics of twin fetal facial expressions at 30-33 + 6 weeks of gestation using four-dimensional (4D) ultrasound to clarify twin fetal brain development and maturation. Methods Frequencies of seven fetal facial expressions were studied using 4D ultrasound for 15 minutes in 30 singleton pregnancies and 18 twin pregnancies [four monochorionic diamniotic (MD) and 14 dichorionic diamniotic (DD) twins] at 30-33 + 6 weeks of gestation. Comparison of the frequency in each facial expression was performed between singleton and twin fetuses. Results Mouthing was the most frequent facial expression at 30-33 + 6 weeks of gestation, followed by blinking in twin and singleton fetuses. Both facial expressions were significantly more frequent than other expressions (P < 0.05). The frequencies of mouthing and scowling in twin fetuses were significantly lower than those in singleton fetuses, but there were no significant differences in the frequencies of the five other facial expressions between the fetal groups. Conclusion Our results suggest that restricted twin fetal behavior before 20 weeks of gestation may still affect the frequencies of twin facial expressions early in the third trimester of pregnancy. Moreover, the frequencies of facial expressions in twins are different from those of singleton fetuses.

Neurological development may be accelerated in growth-restricted fetuses: a 4D ultrasound study.

Objective To assess whether neurological maturation and development are accelerated in fetal growth restriction (FGR) in utero using four-dimensional (4D) ultrasound. Methods The facial expressions of 50 appropriate-for-gestational-age (AGA) and 34 FGR fetuses aged between 28 and 35 gestational weeks were assessed using 4D ultrasound. Subsequently, they were differentiated into two gestational age groups (19 aged 28-31 weeks and 31 aged 32-35 weeks in AGA, and 15 aged 28-31 weeks and 19 aged 32-35 weeks in FGR). Fifteen-minute recordings were made, and the frequencies of seven facial expressions during that time were examined. Correlation analysis was conducted to assess the changing number of significant correlations with advancing gestation in each group. Results Out of 21 combinations of facial expressions at 28-31 and 32-35 gestational weeks in AGA fetuses, there was only three significant correlations. Similarly, only one was noted out of 21 combinations at 28-31 gestational weeks, but there were seven significant correlations in FGR fetuses at 32-35 weeks (P=0.018). However, there was no significant difference in the number of correlations of facial expressions between AGA (3/21) and FGR (7/21) fetuses at 32-35 weeks of gestation (P=0.147). Conclusion Our results suggest that the number of significant correlations of fetal facial expressions in FGR fetuses increases more compared with that in AGA fetuses at 32-35 weeks of gestation. Due to the acceleration of neurological maturation and development in FGR fetuses, the control of facial expressions by the brain may be more evident compared with AGA fetuses at 32-35 weeks of gestation. However, the data and their interpretation in the present study should be taken with some degree of caution because of the small number of subjects studied. Further studies involving a larger sample size are needed to obtain strong or additional evidence.

Change in fetal behavior in response to vibroacoustic stimulation.

Objective To assess fetal behavioral changes in response to vibroacoustic stimulation (VAS) in normal singleton pregnancies using four-dimensional (4D) ultrasound. Methods Ten types of fetal movements and facial expressions in 68 healthy pregnant women between 24 and 40 weeks were studied using 4D ultrasound for 3 min before and after 3-s VAS. The frequencies of mouthing, yawning, tongue expulsion, back arch, jerky arm movement, startle movement, smiling, scowling, hand-to-face movement, and blinking were evaluated. The fetuses were subdivided into four gestational age groups (24-27, 28-31, 32-35, and ≥36 weeks). Comparison of the frequencies of the fetal behaviors before and after the stimulation in each gestational age group was conducted to detect the response to stimulation with advancing gestation. Results There were no significant differences in the frequency of each fetal behavior before and after VAS at 24-27, 28-31, and 32-35 weeks of gestation. However, the frequencies of blinking and startle movements were significantly higher after VAS in the 36-40 gestational age group (P < 0.05). Conclusion The age of 36 weeks of gestation might represent an advanced stage of brain and central nervous system development and maturation as the response to stimuli is prominent at this age compared with earlier gestation.

Effect of psychotropic drugs on fetal behavior in the third trimester of pregnancy.

AIM: To assess the effect of psychotropic drugs on fetal behavior using four-dimensional (4D) ultrasound in the third trimester of pregnancy. METHODS: Fetal behavior was assessed using Kurjak's antenatal neurodevelopmental test (KANET) using 4D ultrasound between 28 and 36 weeks of gestation. Thirty healthy (control group) and 10 psychotropic-drug-administered pregnant (case group) women were studied. The total value of the KANET score and values of each parameter (eight parameters) were compared between the two groups. RESULTS: The total KANET score was normal (except for one fetus in the case group: total score of 9) in both groups, and there was no significant difference in the total KANET score. When individual KANET parameters were compared, no significant differences were noted in any of the eight parameters. CONCLUSION: Our results showed that there is no difference in fetal behavior between fetuses of normal pregnant women and those of psychotropic-drug-administered pregnant women in the third trimester of pregnancy. These results suggest that psychotropic drugs may not affect fetal behavioral development in utero. However, the data and their interpretation in the present study should be taken with some degree of caution because of the small number of subjects studied. Further studies involving a larger sample size are needed to assess the effect of psychotropic drugs on fetal neurobehavior during pregnancy.

Characteristic findings of high-grade cervical intraepithelial neoplasia or more on magnifying endoscopy with narrow band imaging.

BACKGROUND: Colposcopy, which is a standard modality for diagnosing cervical intraepithelial neoplasia (CIN), can have limited accuracy owing to poor visibility. Flexible magnifying endoscopy with narrow band imaging (ME-NBI) has excellent diagnostic accuracy for early gastrointestinal neoplasms and is expected to be highly useful for CIN diagnosis. This study aimed to determine the characteristic findings and evaluate the diagnostic ability of ME-NBI for lesions ≥ CIN 3. METHODS: A well-designed prospective diagnostic case series conducted at multiple tertiary-care centers. A total of 24 patients who underwent cervical conization with a preoperative diagnosis of high-grade squamous cell intraepithelial lesions (HSILs) or lesions ≥ CIN 3 were enrolled. Prior to conization, still images and video of ME-NBI were captured to investigate the cervical lesions. The images were reviewed based on histological examination of the resected specimens. RESULTS: The NBI-ME images revealed the following abnormal findings: (1) light white epithelium (l-WE), (2) heavy white epithelium (h-WE), and (3) atypical intra-epithelial papillary capillary loop (IPCL). Pathological examination of the resected specimens confirmed cervical lesions ≥ CIN 3 in 21 patients. The ME-NBI findings were classified into four groups: l-WE, l-WE with atypical IPCL, h-WE, and h-WE with atypical IPCL, at rates of 0, 23.8, 9.5, and 66.7%, respectively. Additionally, all 3 patients with micro-invasive carcinoma showed a strong irregularity of IPCLs. CONCLUSION: The lesions ≥ CIN 3 demonstrated characteristic ME-NBI findings of h-WE alone, or l-/h-WE with atypical micro-vessels. This study indicates that ME-NBI may have novel value for CIN diagnosis.