Evaluating Cranial Growth in Japanese Infants Using a Three-dimensional Scanner: Relationship between Growth-related Parameters and Deformational Plagiocephaly.

In this study, we aimed to evaluate the longitudinal changes in the cranial shape of healthy Japanese infants using a three-dimensional scanner and construct a normal values database for the growth process. Preterm infants (gestational age < 37 weeks), infants with neonatal asphyxia (5-minute Apgar score of <7), and patients who started helmet therapy for deformational plagiocephaly were excluded from this study. The first scan was performed at approximately 1 month of age, followed by two scans conducted at 3 and 6 months of age. The parameters considered were as follows: cranial length, width, height, circumference, volume, cranial vault asymmetry index, and cephalic index. A cranial vault asymmetry index >5% was defined as deformational plagiocephaly. Changes in each parameter were examined using repeated-measures analysis of variance classified by sex and deformational plagiocephaly status. The rate of increase in each parameter was also examined. In total, 88 infants (45 boys and 43 girls) were included in this study. All growth-related parameters were noted to increase linearly with time. Sex differences were observed in all parameters except cranial length. Deformational plagiocephaly was found to have no effect on growth-related parameters. Cranial volume increased by 60% from 1 to 6 months of age. The growth almost uniformly influenced the rate of increase in volume in each coordinate axis direction. Overall, the mean trends in three-dimensional parameters in infants up to 6 months of age were obtained using a three-dimensional scanner. These trends could be used as a guide by medical professionals involved in cranioplasty.

Natural-Course Evaluation of Infants with Positional Severe Plagiocephaly Using a Three-Dimensional Scanner in Japan: Comparison with Those Who Received Cranial Helmet Therapy.

This study aimed to clarify the natural course of positional plagiocephaly using a three-dimensional (3D) scanner and investigate the effectiveness of cranial helmet therapy (CHT). One hundred infants with severe plagiocephaly who visited our institutions between April 2020 and March 2021 were included. Cranial shape was measured using an Artec Eva 3D scanner. A cranial asymmetry (CA) >12 mm was diagnosed as severe plagiocephaly. An infant whose CA subsided to <12 mm was considered to have improved naturally or by CHT. The difference in CA between the second and initial scans was defined as the improvement value (median scan interval was two months). In the natural-course group comprising 56 infants with severe plagiocephaly, 37 (66%) with a median CA of 15.6 mm exhibited no improvement after two months. In the scan age- and evaluation interval-matched case-control study, the CA value in the CHT group improved by three times that in the natural-course group (-4.6 mm [n = 33] vs. -1.55 mm [n = 24], p < 0.001). Severe plagiocephaly did not improve naturally in 66% of the cases. Therefore, CHT should be considered if the CA is >12 mm on the initial evaluation.

An improved primer design for the loop-mediated isothermal amplification (LAMP) method to detect oxacillinase (OXA)-48 ß-lactamase genes in Gram-negative bacteria for clinical applications.

INTRODUCTION: Recently, increased frequencies of carbapenemase-producing Enterobacteriaceae have been reported worldwide. Among multiple genetic subtypes, oxacillinase (OXA)-48 ß-lactamase-producing strains have been associated with inbound infection because they have been detected predominantly in patients who traveled outside of Japan. However, a recent case report of OXA-48 ß-lactamase-producing Enterobacteriaceae suggested the latent spread of domestic infections. Due to a lack of specific inhibitors, culture-based detection of OXA-48 ß-lactamase-producing bacteria is difficult. Thus, DNA-based detection methods, including PCR, direct sequencing and loop-mediated isothermal amplification (LAMP), have been employed. Among these methods, LAMP detection is more favorable than other methods because of its technical simplicity and low cost. METHODS: We designed novel LAMP primers to detect OXA-48 ß-lactamase-producing bacteria and investigated their possible clinical applications with bacterial genome-spiked human materials (cerebrospinal fluid, blood, feces, urine, and sputum). We evaluated the specificity of the LAMP primers using 37 bacterial strains: 8 standard, 9 reference, and 20 clinical Gram-negative strains. RESULTS: Our LAMP primers detected 10 copies of the OXA-48 type ß-lactamase gene and exhibited no cross reactivity with other ß-lactamase genes. Sensitivity was not influenced in any clinical sample, in contrast to PCR detection, which was strongly inhibited by substances in fecal samples. CONCLUSIONS: These results suggest the superior performance of LAMP compared with conventional PCR for detecting the OXA-48 type ß-lactamase gene in various clinical samples.

The Epithelial-to-Mesenchymal Transition-Like Process Induced by TGF-ß1 Enhances Rubella Virus Binding and Infection in A549 Cells via the Smad Pathway.

Virus-host cell interactions in rubella virus (RuV) are of great interest in current research in the field, as their mechanism is not yet well understood. By hypothesizing that the epithelial-to-mesenchymal transition (EMT) may play a role in RuV infection, this study aimed to investigate the influence of TGF-ß1-induced EMT of human lung epithelial A549 cells on the infectivity of RuV. A549 cells were cultured and treated with TGF-ß1 for 1 to 2 days prior to virus infection (with a clinical strain). Viral infectivity was determined by flow cytometry analysis of cells harvested at 24 and 48 h post-infection (hpi) and by titration of supernatants collected at 48 hpi. The results showed that the percentages of the TGF-ß1-treated A549 cells that were positive for RuV were at least twofold higher than those of the control, and the viral progeny titers in the supernatants collected at 48 hpi were significantly higher in the treatment group than in the control group. In addition, the virus binding assay showed a strong increase (more than threefold) in the percentages of RuV-positive cells, as determined by flow cytometry analysis and further confirmed by real-time PCR. Such an enhancement effect on RuV infectivity was abolished using LY364947 or SB431542, inhibitors of the TGF-ß/Smad signaling pathway. The findings suggest that the TGF-ß1-induced EMT-like process enhances RuV binding and infection in A549 cells via the Smad pathway. Further studies are necessary to identify possible proteins that facilitate viral binding and entry into treated cells.

A legendary sumo wrestler with gigantism or acromegaly? The case of Ikezuki Geitazaemon (1827-1850).

Sumo is a traditional Japanese full-contact wrestling sport. Among sumo wrestlers, Ikezuki Geitazaemon (1827-1850) was one of the most famous wrestlers due to his large body size. Here, we hypothesize that the legendary Japanese sumo wrestler could have had gigantism or acromegaly, which are disorders caused by the hypersecretion of growth hormone (GH). GH-secreting pituitary adenoma leads to the hypersecretion of GH and insulin-like growth factor-1 (IGF-1). If GH-secreting pituitary adenoma develops during childhood/puberty, it can cause gigantism. Adenomas also occur in over 95% of patients with acromegaly. Based on his substantial height (227 cm), Geitazaemon may have had gigantism, or acromegaly considering his characteristics of mandibular prognathism, enlarged fingertips, and heel pad thickness, as shown in woodblock prints (ukiyo-e). He would thus be the first recorded patient with gigantism or acromegaly in premodern Japan.

Tectal Low-Grade Glioma with H3 K27M Mutation.

BACKGROUND: In the revised World Health Organization 2016 classification of central nervous system tumors, "diffuse midline glioma, H3 K27M-mutant" has been added as a new diagnostic entity. However, some confusion exists concerning this diagnostic entity because H3 K27M-mutant diffuse midline glioma is diagnosed with grade IV regardless of morphologic phenotype. Furthermore, the significance of H3 K27M mutation in tumors that aren't typical "diffuse midline glioma, H3 K27M-mutant," such as those with an unusual location and nontypical histology, remains unclear. CASE DESCRIPTION: To elucidate further such unusual tumors, we describe here a rare case of pediatric low-grade glioma located in the tectum, which was morphologically a pilocytic astrocytoma (PA) with genetically H3 K27M mutation but no microvascular proliferation, necrosis, mitoses, or other genetic alterations, insofar as we were able to observe. At the latest follow-up, 28 months after surgery, radiotherapy, and chemotherapy, the patient was found to be free from any neurologic deficits and MRI demonstrated that the tumor was stable without tumor regrowth. This case might be identified as "diffuse midline glioma, H3 K27M-mutant", grade IV, when applying only the current World Health Organization 2016 classification. In addition, we discuss the morphologically benign gliomas harboring the H3 K27M mutation based on the literature. CONCLUSIONS: We describe here a rare case and present a short literature review of circumscribed/nondiffuse gliomas, particularly in PA with H3 K27M mutation. However, the significance of H3 K27M mutation for PA remains unclear, so further studies and clinical data are needed to elucidate the biology and optimal treatment of such tumors.

Molecular serotype-specific identification of Streptococcus pneumoniae using loop-mediated isothermal amplification.

In children, the incidence of pneumococcal meningitis has decreased since the introduction of pneumococcal conjugate vaccine (PCV7 and PCV13). However, since the introduction of the vaccine, developed countries have seen the emergence of non-PCV13 serotypes. However, invasive pneumococcal disease (IPD) caused by PCV13-targeted serotypes still represents an important public health problem in resource-limited countries. To develop a rapid, simple, and cost-effective assay to detect serotypes of Streptococcus pneumoniae, we developed a novel loop-mediated isothermal amplification (LAMP) assay based on the sequences available for the 13 capsular types that are included in PCV13: 1, 3, 4, 5, 6 A, 6B, 7 F, 9 V, 14, 18 C, 19 A, 19 F, and 23 F. We evaluated test reactivity, specificity, sensitivity and performance, and compared the results between established LAMP and conventional PCR assays. To support its clinical use, the detection limits of the LAMP assay were evaluated using bacterial genomic DNA-spiked cerebrospinal fluid (CSF) and blood specimens. We confirmed the specificity of the LAMP assay using 41 serotypes of pneumococcal strains. The sensitivity of the LAMP assay was 10 to 100 copies per reaction, compared to 10 to 104 copies per reaction for PCR assays. The detection limits of the LAMP assay were comparable when using DNA-spiked CSF and blood specimens, as compared to using purified DNA as the template. In conclusion, a rapid and simple LAMP-based pneumococcal serotyping method has been developed. This is the first report of a LAMP method for a PCV13 serotype-specific identification assay, which could be a promising step to facilitate epidemiological studies of pneumococcal serotyping.

Lactobacillus crispatus accelerates re-epithelialization in vaginal epithelial cell line MS74.

PROBLEM: The functions of vaginal lactobacilli in susceptibility to infectious diseases as regards epithelial barrier integrity and wound healing remain incompletely understood. METHOD OF STUDY: Lactobacillus crispatus, one of the most common Lactobacillus species in the vagina and among the most protective against sexually transmitted infections, was cocultured with an immortalized human vaginal epithelial cell line (MS74), and a scratch assay was performed to evaluate re-epithelialization. The concentration of vascular endothelial growth factor A (VEGF) was measured using enzyme-linked immunosorbent assay (ELISA). An immunofluorescence assay was performed to locate the expression of VEGF and VEGF receptor (VEGFR) 1 and 2. The effects of the bacterial supernatant of L. crispatus were also evaluated. RESULTS: Lactobacillus crispatus significantly accelerated re-epithelialization of MS74 cells, accompanied by an increase in VEGF concentration. In contrast, heat-killed L. crispatus did not show this effect. The bacterial supernatant of L. crispatus also induced re-epithelialization. The immunoreactivity of VEGF was higher at the scratched edge, whereas VEGFR1 and 2 stained site-independently. Recombinant VEGF induced cell migration in a dose-dependent manner. The bacterial supernatant of L. crispatus also significantly accelerated re-epithelialization in MS74 cells and increased the concentration of VEGF in the culture 24 hours after the scratch. CONCLUSION: These results may enhance our knowledge of the importance of L. crispatus in the healing of damaged vaginal epithelium and protection against the consequent risk of pathogenic infections, such as human immunodeficiency virus (HIV), and improve our understanding of vaginal epithelial barrier integrity maintenance by this bacterium.

Unusual presentation of a skull base mass lesion in sarcoidosis mimicking malignant neoplasm: a case report.

BACKGROUND: Sarcoidosis is a multi-organ disease of unknown etiology characterised by the presence of epithelioid granulomas, without caseous necrosis. Systemic sarcoidosis is rare among children, while neurosarcoidosis in children is even rarer whether it is systemic or not. CASE PRESENTATION: We described the case of a 12-year-old boy who presented with monocular vision loss accompanied by unusual MRI features of an extensive meningeal infiltrating mass lesion. The patient underwent surgical resection (biopsy) via a frontotemporal craniotomy to establish a definitive diagnosis based on the histopathology, since neurosarcoidosis remains a very difficult diagnosis to establish from neuroradiogenic imagings. Based on the histopathology of the resected mass lesion, neurosarcoidosis was diagnosed. On follow-up after 3 months of steroid therapy, the patient displayed a good response on the imaging studies. MRI revealed that the preexisting mass lesion had regressed extremely. We also conducted a small literature review on imaging studies, manifestations, appropriate treatments, etc., in particular neurosarcoidosis including children. CONCLUSION: Although extremely rare, neurosarcoidosis, even in children, should be considered in the differential diagnosis of skull base mass lesions to avoid unnecessary aggressive surgery and delay in treatment, since surgery may have little role in the treatment of sarcoidosis.

Myelomeningocele associated with split cord malformation type I -three case reports-.

Three neonates presented with split cord malformation (SCM) associated with myelomeningocele (MMC), complicated with various coexisting anomalies. All patients were female and classified as SCM type I. All patients had a syrinx located rostral to the SCM. One patient had hydrocephalus and Chiari malformation causing serious respiratory problems. Two patients had partial hypertrichosis located close to the MMC, suggesting association with SCM. One patient had sacral hypoplasty and right kidney agenesis, suggesting that some embryologic errors may affect not only neural but also mesodermal development. All patients underwent surgical treatment for SCM after detailed evaluation and management of concomitant anomalies, and developed no new neurological deficits. Delayed surgery is an alternative treatment strategy for SCM in patients with both SCM and MMC with similar complications.

Diffusion-weighted imaging of an atypical teratoid/rhabdoid tumor of the cervical spine.

Spinal atypical teratoid/rhabdoid tumor (AT/RT) is a rare, aggressive malignant neoplasm of the central nervous system usually seen in young children and infants. We present diffusion-weighted imaging (DWI) findings for an intradural extramedullary AT/RT in the cervical spine of a 6-year-old boy. High signal on DWI and low apparent diffusion coefficients may represent high cellularity of the tumor. These findings indicated a highly malignant tumor.