Cefcapene pivoxil hydrochloride is an antibiotic often used by women who are or may be pregnant. However, the safety of exposure to it during the first trimester of pregnancy has not been assessed. In this study, we aimed to clarify the effects of exposure during the first trimester of pregnancy on maternal and fetal outcomes. Data were obtained from pregnant women who were counseled on drug use during pregnancy at two Japanese facilities from April 1988 to December 2017. The incidence of major malformations in singleton pregnancy was compared between neonates born to women who took cefcapene pivoxil hydrochloride (n = 270) and control drugs (n = 1594) during their first trimester. The adjusted odds ratio of the incidence of major malformations was calculated using multivariate logistic regression analysis adjusted for smoking during pregnancy and maternal age. The incidence of major malformations was 2.6% in the cefcapene pivoxil hydrochloride group and 1.8% in the control group. There were no significant differences in the incidence between the cefcapene pivoxil hydrochloride and control groups (adjusted odds ratio: 1.48 [95% confidence interval: 0.64-3.42], p = 0.36). This prospective cohort study showed that exposure to cefcapene pivoxil hydrochloride during the first trimester of pregnancy was not associated with increased risk of major malformations in infants. Our findings will help healthcare providers in choosing appropriate medicines.

OBJECTIVE: Extrapulmonary sequestration (EPS) within the diaphragm (ID-EPS) is rare and requires additional procedures such as incision or detachment of the diaphragm from the lesion for diagnosis. This study aimed to describe the imaging findings and evaluate the diagnostic accuracy of ultrasonography and computed tomography (CT) for ID-EPS.
METHODS: Split diaphragm sign, shape of lesion edge, drainage vein into intra-abdomen on ultrasound and CT, and lesion characteristics on ultrasound were compared between patients with ID-EPS and with above-diaphragm EPS (AD-EPS) using Fisher\'s exact test.
RESULTS: Three and nine patients were diagnosed with ID-EPS and AD-EPS, respectively. Significant differences were observed between the two groups in the split diaphragm sign on ultrasound (presence/absence in patients with ID-EPS vs AD-EPS, 2/1 vs 0/9, P = .046), shape of lesion edge on ultrasound/CT (round/beak in patients with ID-EPS vs AD-EPS, 3/0 vs 0/9, P = .005 on both CT and ultrasound), lesion characteristics on ultrasound (presence/absence of cystic area within lesion in patients with ID-EPS vs AD-EPS, 0/3 vs 7/2, P = .046), and the drainage vein into the abdomen on CT (presence/absence in patients with ID-EPS vs AD-EPS; 2/1 vs 0/9, P = .046). No drainage veins were visualized in the abdomen on ultrasonography and no significant differences in the presence/absence of the split-diagram sign on CT (presence/absence in patients with ID-EPS vs AD-EPS and ID-EPS; 0/3 vs 0/9, P > .999; 1/2 vs 0/9, P = .250) were observed between the two groups.
CONCLUSIONS: A combination of postnatal ultrasonography and CT was useful in predicting EPS located within the diaphragm.

The endoplasmic reticulum（ER）is the largest membranous network serving as a region for protein, lipid and steroid synthesis, transport and storage. Detailed information about ER-cisternae, ER-tubules and rough endoplasmic reticulum (rER) is scarce in human blood cells. This study describes a series of giant inclusions and Auer bodies in promyeloblasts in six patients with acute promyelocytic leukemia (APL), by light microscopy, transmission electron microscopy (TEM) and cytochemical stains. TEM revealed that giant inclusions and pro-Auer bodies were associated with rER and surrounded by tubular structures composed of degenerated or redundant membrane in promyeloblasts, which corresponded with elements of the ER system. This paper reveals that in the promyeloblasts of APL, ER is the source of and transforms progressively into giant inclusions and Auer bodies.

UNASSIGNED: Developmental toxicity tests are extremely expensive, require a large number of animals, and are time-consuming. It is necessary to develop a new approach to simplify the analysis of developmental endpoints. One of these endpoints is malformation, and one group of ongoing methods for simplifying is in silico models. In this study, we aim to develop a quantitative structure-activity relationship (QSAR) model and identify the best algorithm for predicting malformations, as well as the most important and effective physicochemical properties associated with malformation.
UNASSIGNED: The dataset was extracted from a reliable database called COMPTOX. Physicochemical properties (descriptors) were calculated using Mordred and RDKit chemoinformatics software. The data were cleaned, preprocessed, and then split into training and testing sets. Machine learning algorithms, such as gradient boosting model (GBM) and logistic regression (LR), as well as deep learning models, including multilayer perceptron (MLP) and neural networks (NNs) trained with train set data and different sets of descriptors. The models were then validated with test set and various statistical parameters, such as Matthew\'s correlation coefficient (MCC) and balanced accuracy (BAC) score, were used to compare the models.
UNASSIGNED: A set of descriptors containing with 78% AUC was identified as the best set of descriptors. Gradient boosting was determined to be the best algorithm with 78% predictive power.
UNASSIGNED: The descriptors that were the most effective for developing models directly impact the mechanism of malformation, and GBM is the best model due to its MCC and BAC.

BACKGROUND: Craniosynostosis is a prevalent craniofacial malformation in Finland; however, comprehensive population-based epidemiological data are limited. This study aimed to estimate the total and birth prevalence of craniosynostosis in Finland from 1987 to 2010 and examine temporal trends.
METHODS: We collected the data from nationwide registers maintained by the Finnish Institute for Health and Welfare and Statistics Finland, as well as treating hospitals, encompassing live births, stillbirths, terminations for fetal anomalies, and infant deaths with suspected or diagnosed craniosynostosis or skull deformation. A craniofacial surgeon and a clinical geneticist reviewed 1878 medical records for diagnostic confirmation.
RESULTS: Out of 877 craniosynostosis cases, 83% were single-suture synostoses (all live births), 10% craniosynostosis syndromes, and 7% multisutural non-syndromic synostoses. Live birth prevalence from 1987 to 2010 was 6.0/10,000 live births, ranging from 5.0/10,000 in 1987 to 7.5/10,000 in 2010. Total prevalence, including live births, stillbirths, and terminations, varied from 5.0/10,000 in 1987 to 8.0/10,000 in 2010. Sagittal synostosis was the most common synostosis, with a prevalence of 3.9/10,000 live births, followed by metopic (0.6/10,000), unicoronal (0.4/10,000), and unilambdoid (0.1/10,000) synostoses.
CONCLUSIONS: The total combined prevalence of all craniosynostosis types significantly increased driven by a nonsignificant rise across all subgroups and a significant increase in the syndrome group. In live births increase was significant only within the syndrome subgroup, primarily due to an increase in Muenke syndrome patients. The rising prevalence of syndromes necessitates further investigation. Contrasting with trends in Europe, Australia, and the USA, Finland showed no significant increase in metopic craniosynostosis.

OBJECTIVE: Congenital megaprepuce (CMP) is a rare penile deformity that usually requires surgical correction. This study was performed to examine the efficacy of the modified Sugita procedure for repairing CMP in pediatric patients.
METHODS: We retrospectively analyzed the clinical data of pediatric patients with CMP treated by a surgeon using the modified Sugita procedure in our hospital from January 2019 to April 2021.
RESULTS: Twenty patients were enrolled, and their median age at surgery was 70.5 months (range, 60-96 months). All surgeries were successful, and no complications occurred during the operation. The postoperative foreskin had moderate edema in five patients, and soaking in 10% hypertonic saline resulted in disappearance of the edema within 4 to 8 weeks. The follow-up duration was 6 to 20 months (median, 10 months). No other complications occurred, such as dehiscence or hematoma.
CONCLUSIONS: The modified Sugita procedure for correction of CMP produces excellent cosmesis and a low complication rate. Our study indicates that the modified Sugita procedure is a safe and feasible treatment option.

BACKGROUND: Periapical infection of primary molars affects the development of permanent teeth (premolars). Therefore, the present study was conducted to test the null hypothesis in children aged 4-10 years with chronic apical periodontitis (CAP) of the primary molars.
METHODS: A retrospective, cross-sectional study was conducted on 185 panoramic radiographs of healthy children aged 4-10 years with CAP in the primary molars. A total of 256 infected primary molars (144 teeth in females, 112 teeth in males) were analyzed, radiographically, and compared with 245 healthy primary molars on the contralateral side. Permanent successors were evaluated for follicular damage, maturation, morphology, and deviation in the eruption path. Primary molars were evaluated for root resorption. Sixteen permanent teeth on the affected side and five teeth on the control side were excluded due to abnormal development. Student\'s t-test and the chi-square test were used to analyze the data.
RESULTS: The null hypothesis is rejected. There were significant differences in the developmental status of permanent successors on the affected side, compared to the normal side at four to seven years (p<0.05). There were no significant sex differences in the abnormalities of permanent successors on the affected side (p>0.05). As the root resorption of the primary molars increased, the follicular damage observed in the permanent successors also increased (p<0.05), which suggests that, as the infection of primary molars increases, more damage is caused to underlying permanent successors (premolars).
CONCLUSIONS: Apical periodontitis of the primary molars retards the development of permanent successors (premolars), affects their shape, causes follicular damage, and alters the eruption path.

Use of endothelin receptor antagonists (ERAs) and riociguat, approved for treatment of pulmonary hypertension (PH), is contraindicated during pregnancy due to reported teratogenicity in animals. We aimed to investigate prescribing of these drugs in girls/women of childbearing age and to explore - as a secondary aim - the occurrence of pregnancies exposed to these drugs. Using the German Pharmacoepidemiological Research Database (GePaRD, claims data from 20% of the German population) we conducted cross-sectional analyses to determine prescribing prevalence of ERAs and riociguat between 2004 and 2019 and to characterize users and prescribing patterns. In a cohort analysis, we assessed the occurrence of pregnancies exposed to these drugs in the critical time window. Overall, we identified 407 women with ≥ 1 dispensation of bosentan between 2004 and 2019; the respective number was 73 for ambrisentan, 182 for macitentan, 31 for sitaxentan, and 63 for riociguat. In nearly all years, more than 50% of the girls/women were ≤ 40 years. Age-standardized prevalence was highest for bosentan (0.04/1000) in 2012 and 2013, followed by macitentan (0.03/1000) in 2018 and 2019. We observed 10 exposed pregnancies: 5 to bosentan, 3 to ambrisentan, and 2 to macitentan. The increased prevalence of macitentan and riociguat from 2014 onwards might reflect changes in PH treatment. Even though PH is a rare disease and pregnancy should be avoided in women with PH, particularly if they use ERAs, we identified pregnancies exposed to ERAs. Multi-database studies will be needed to assess the risk of these drugs on the unborn child.

The study aims to investigate the clinical characteristics of early postnatal period in children with prenatal hydronephrosis (HN) in our single center for 8 years.
The clinical data of 1137 children with prenatal HN from 2012 to 2020 were retrospectively analyzed in our center. Variables of our study mainly included different malformations and urinary tract dilation (UTD) classification, and main outcomes were recurrent hospitalization, urinary tract infection (UTI), jaundice, and surgery.
Among the 1137 children with prenatal HN in our center, 188 cases (16.5%) were followed-up in early postnatal period, and 110 cases (58.5%) were found malformations. The incidence of recurrent hospitalization (29.8%) and UTI (72.5%) were higher in malformation, but the incidence of jaundice (46.2%) was higher in non-malformation(P < 0.001). Furthermore, UTI and jaundice were higher in vesicoureteral reflux (VUR) than those in uretero-pelvic junction obstruction (UPJO) (P < 0.05). Meanwhile, Children with UTD P2 and UTD P3 were prone to recurrent UTI, but UTD P0 was prone to jaundice (P < 0.001). In addition, 30 cases (16.0%) of surgery were all with malformations, and the surgical rates of UTD P2 and UTD P3 were higher than those of UTD P0 and UTD P1 (P < 0.001). Lastly, we concluded that the first follow-up should be less than 7 days, the first assessment should be 2 months, and the follow up should be at least once every 3 months.
Children with prenatal HN have been found many malformations in early postnatal period, and with high-grade UTD were more prone to recurrent UTI, even to surgery. So, prenatal HN with malformations and high-grade UTD should be followed up in early postnatal period regularly.

BACKGROUND: Vein of Galen malformation (VOGM) is a rare, life-threatening vascular malformation in neonates and is treated with embolization. However, even at the most experienced centers, patients face high mortality and morbidity. In utero treatment options have been limited by lack of animal models or simulations.
OBJECTIVE: To create a novel ultrasound phantom simulator for a preclinical feasibility study of in utero fetal intervention for VOGM.
METHODS: Novel phantoms were designed and built in two configurations of spherical and windsock shape from cryogel material to mimic the salient vasculature of the fetal VOGM, based on real-patient fetal MR imaging dimensions. Critical anatomy was realistically mimicked within this model and transtorcular ultrasound-guided coil deployment was simulated. Each phantom model was assessed before and after treatment to evaluate coil mass deposition within the target.
RESULTS: The two phantoms underwent pretreatment T2-weighted MR imaging assessment, ultrasound-guided embolization, post-treatment MR and fluoroscopic imaging, and visual inspection of the sliced phantoms for target embolization verification. Postoperative MR scans confirmed realistic compact deposition of the coil masses within the central cavity. Phantom embolization results were submitted as part of the institutional review board and US Food and Drug Administration investigative device exemption approval for a first-in-humans clinical trial of fetal intervention for VOGM.
CONCLUSIONS: A phantom simulator for fetal intervention of VOGM produces lifelike results during trial interventions, removing obstacles to feasibility and safety evaluations, typically precluded by non-availability of appropriate animal models. The study provides a proof of concept for potentially wider applications of medical simulation to enable novel procedural advancements in neurointerventions.