Impact of Masticatory Performance and the Tongue-Lip Motor Function on Incident Adverse Health Events in Patients with Metabolic Disease.

AIM: The present study aimed to determine whether decreased masticatory performance and tongue-lip motor function are associated with an increased incidence of adverse health events in patients with metabolic disease. METHODS: One thousand patients with metabolic diseases including diabetes, dyslipidemia, hypertension, and hyperuricemia were recruited. Masticatory performance was assessed using a gummy jelly test, wherein glucose elution from chewed gummy jelly was measured. The tongue-lip motor function was measured using repeatedly pronounced syllables per second. Their association with the incidence of adverse health events (a composite of all-cause death, cardiovascular disease, bone fracture, malignant neoplasm, pneumonia, and dementia) was investigated using the generalized propensity score (GPS) method. RESULTS: During a median follow-up period of 36.6 (interquartile range, 35.0-37.7) months, adverse health events were observed in 191 patients. The GPS adjusted dose-response function demonstrated that masticatory performance was inversely associated with the incidence of adverse health events. The 3-year incidence rate was 22.8% (95% confidence interval, 19.0-26.4%) for the lower quartile versus 13.6% (10.5-16.7%) for the upper quartile (P＜0.001). Similarly, the tongue-lip motor function was inversely associated with the incidence of adverse health events, with a 3-year incidence rate of 23.6% (20.0-27.0%) for the lower quartile versus 13.2% (10.4-15.9%) for the upper quartile (P＜0.001). CONCLUSIONS: Decreased masticatory performance and tongue-lip motor function were associated with an increased incidence of adverse health events in patients with metabolic disease.

Experience-Dependent Behavioral Plasticity in Avoiding Epigallocatechin Gallate (EGCG) Requires DAF-16/FOXO in the AIY Interneurons of Caenorhabditis elegans.

Bitterness and astringency are the aversive tastes in mammals. In humans, aversion to bitterness and astringency may be reduced depending on the eating experience. However, the cellular and molecular mechanisms underlying plasticity in preference to bitter and astringent tastants remain unknown. This study aimed to investigate the preference plasticity to bitter and astringent tea polyphenols, including catechins and tannic acids, in the model animal Caenorhabditis elegans. C. elegans showed avoidance behavior against epigallocatechin gallate (EGCG), tannic acid, and theaflavin. However, they displayed diminishing avoidance against EGCG depending on their EGCG-feeding regime at larval stages. Additionally, the behavioral plasticity in avoiding EGCG required the transcription factor DAF-16/FOXO. Isoform-specific deletion mutant analysis and cell-specific rescue analysis revealed that the function of daf-16 isoform b in AIY interneurons is necessary for experience-dependent behavioral plasticity to EGCG.

A Cerebral Embolism Caused by a Malignant Peripheral Nerve Sheath Tumor in a Patient with Neurofibromatosis Type 1.

A 31-year-old man with neurofibromatosis type 1 (NF-1) had undergone resection of a malignant peripheral nerve sheath tumor (MPNST) on the buttock 3 months previously. He subsequently underwent mechanical thrombectomy for a hyperacute left middle cerebral artery embolism. Histopathologically, the emboli comprised neurofilament-positive pleomorphic tumor cells with geographic necrosis and conspicuous mitosis and were identified as MPNST. The patient died of respiratory failure due to lung MPNST metastasis on day 15 of hospitalization. To our knowledge, this is the first report of a spontaneous cerebral embolism due to MPNST in a NF-1 patient.

A child with TSC2/PKD1 contiguous gene deletion syndrome successfully treated with tolvaptan for rapidly enlarging renal cysts.

Tolvaptan, a vasopressin receptor antagonist, has been shown to be effective in the treatment of renal cysts in ADPKD. However, tolvaptan is not indicated for pediatric patients, and reports of its use are rare, making its efficacy and adverse reactions unclear. Herein, we present the case of an 11-year-old girl who had vitiligo from birth. She was diagnosed with West syndrome at 6 months of age and tuberous sclerosis at 2 years of age. At the age of 6 years, an abdominal magnetic resonance imaging (MRI) revealed multiple bilateral renal cysts, and she was diagnosed with ADPKD. Abdominal MRI scans performed at 10 years and 11 years showed rapid renal cyst enlargement, and the renal prognosis was judged to be poor. The patient was treated with tolvaptan to delay cyst exacerbation. There were no apparent adverse events after the initiation of treatment, and the MRI performed 12 months after treatment initiation showed that renal cyst enlargement was suppressed. The results suggest that tolvaptan may be effective in pediatric patients with severe ADPKD who have rapidly enlarging renal cysts, although evaluation of renal cyst enlargement and side effects should be continued.

Association between History of Vaccination and Symptoms at Diagnosis of Coronavirus Disease 2019.

Introduction: We investigated the association between history of vaccination for coronavirus disease 2019 (COVID-19) and symptoms at its diagnosis. Methods: We retrospectively analyzed 2566 consecutive individuals suspected of having COVID-19 and visited a designated clinic between January and September 2022 (1733 were diagnosed with COVID-19, and 816 tested negative for COVID-19) in Japan. The individuals were divided by vaccination history for COVID-19. Results: In the COVID-19-free individuals, the vaccination was not significantly associated with any symptoms. Contrarily, those with COVID-19 demonstrated an inverse relationship between the vaccination and body temperature; the adjusted mean value was higher by 0.01°C, 0.04°C, 0.09°C, 0.27°C, and 0.34°C and 0.48°C in individuals vaccinated 2-4, 4-6, 6-8, 8-10, and >10 months before and those unvaccinated, respectively, than in those vaccinated within 2 months (P = 0.96, 0.41, 0.081, 0.006, 0.004, and <0.001). Furthermore, among the affected population, individuals vaccinated long before or never vaccinated more frequently complained of fatigue and headache; the adjusted odds ratios of those vaccinated >10 months before and those unvaccinated compared with those vaccinated within 2 months were 2.53 and 2.45 for fatigue and 2.53 and 2.17 for headache (all P < 0.05). Contrarily, the prevalence of rhinorrhea, sore throat, and cough was higher in recently vaccinated individuals (adjusted odds ratios of those vaccinated within 2 months versus those unvaccinated, 2.40, 2.46, and 2.46; all P < 0.05). Conclusions: Symptoms at the COVID-19 diagnosis differed with the vaccination history. Information on vaccination history would be worth using when suspecting COVID-19 based on symptoms.

Familial focal segmental glomerulosclerosis with Alport-like glomerular basement changes caused by paired box protein 2 gene variant.

Paired box protein 2 (PAX2) gene variant causes renal coloboma syndrome (MIM#120330). Further, they are associated with focal segmental glomerulosclerosis and characterized by basement membrane changes similar to Alport syndrome.Herein, we report an 8-year-old boy who presented with proteinuria and decreased renal function. His paternal uncle has focal segmental glomerulosclerosis and renal failure, and his paternal grandmother has renal failure and is receiving peritoneal dialysis. Further, his father has stage 2 chronic kidney disease. At 3 years of age, his serum creatinine-estimated glomerular filtration rate was 40-50 mL/min/1.73 m2. At 8 years of age, his renal function further decreased and he had proteinuria (urinary protein/Cr 3.39 g/g Cr). Renal histopathology showed oligonephronia and focal segmental glomerulosclerosis. A partial basket-weave pattern, similar to Alport syndrome, was also observed on a transmission electron microscope, and low-vacuum scanning electron microscopy revealed coarse meshwork changes in the glomerular basement membrane. Genetic analysis revealed a PAX2 heterozygous variant (NM_003987.4:c.959C  >  G), a nonsense variant in which the serine at position 320 changes to a stop codon, in our patient and his father. PAX2 is a transcription factor that is important for the podocyte variant. However, podocytes with PAX2 gene variants may cause abnormal basement membrane production and repair, thereby resulting in Alport-like changes.

Comparison of regional cerebral oxygen saturation during one-lung ventilation under desflurane or propofol anesthesia: A randomized trial.

BACKGROUND: During one-lung ventilation (OLV), deterioration of pulmonary oxygenation reduces arterial oxygen saturation and cerebral oxygen saturation (rSO2). However, oxidative stress during OLV causes lung injury, so the fraction of inspiratory oxygen (FiO2) should be kept as low as possible. We investigated the changes in rSO2 under propofol or desflurane anesthesia while percutaneous oxygen saturation (SpO2) was kept as low as possible during OLV. METHODS: Thirty-six patients scheduled for thoracic surgery under OLV in the lateral decubitus position were randomly assigned to propofol (n = 19) or desflurane (n = 17) anesthesia. FiO2 was set to 0.4 at the start of surgery under two-lung ventilation (measurement point: T3) and then adjusted to maintain an SpO2 of 92% to 94% after the initiation of OLV. The primary outcome was the difference in the absolute value of the decrease in rSO2 from T3 to 30 minutes after the initiation of OLV (T5), which was analyzed by an analysis of covariance adjusted for the rSO2 value at T3. RESULTS: The mean rSO2 values were 61.5% ± 5.1% at T3 and 57.1% ± 5.3% at T5 in the propofol group and 62.2% ± 6.0% at T3 and 58.6% ± 5.3% at T5 in the desflurane group. The difference in the absolute value of decrease between groups (propofol group - desflurane group) was 0.95 (95% confidence interval, [-0.32, 2.2]; P = .152). CONCLUSIONS: Both propofol and desflurane anesthesia maintain comparable cerebral oxygenation and can be used safely, even when the SpO2 is kept as low as possible during OLV.

Orthodontic Management of the Edentulous Space Caused by Surgical Removal of a Large Dentigerous Cyst.

Herein, we report the orthodontic management of a patient with excessive bone and permanent tooth loss after surgical cyst removal. The patient was a 13-year-old Japanese boy who was referred to our department by an oral surgeon. He had an edentulous space with alveolar bone loss and loss of 2 permanent molars in the left mandibular region, following surgical removal of a large dentigerous cyst. We decided to close this space orthodontically. First, we moved the left mandibular second premolar into the edentulous region and autotransplanted the left maxillary lateral incisor in the adjacent distal space. We then performed comprehensive orthodontic treatment to establish stable occlusion. Following treatment, functional and stable occlusion of all permanent teeth was achieved without any spaces. The findings from this case suggest that orthodontic treatment is effective in growing patients with edentulous spaces and alveolar bone loss.

Single-Session, Internet-Based Cognitive Behavioral Therapy to Improve Parenting Skills to Help Children Cope With Anxiety During the COVID-19 Pandemic: Feasibility Study.

BACKGROUND: The COVID-19 pandemic has had a major impact on families' daily routines and psychosocial well-being, and technology has played a key role in providing socially distanced health care services. OBJECTIVE: The first objective of this paper was to describe the content and delivery of a single-session, internet-based cognitive behavioral therapy (iCBT) intervention, which has been developed to help parents cope with children's anxiety and manage daily situations with their children. The second objective was to report user adherence and satisfaction among the first participants who completed the intervention. METHODS: The Let's Cope Together intervention has been developed by our research group. It combines evidence-based CBT elements, such as psychoeducation and skills to manage anxiety, with parent training programs that strengthen how parents interact with their child and handle daily situations. A pre-post design was used to examine user satisfaction and the skills the parents learned. Participants were recruited using advertisements, media activity, day care centers, and schools and asked about background characteristics, emotional symptoms, and parenting practices before they underwent the iCBT. After they completed the 7 themes, they were asked what new parenting skills they had learned from the iCBT and how satisfied they were with the program. RESULTS: Of the 602 participants who filled in the baseline survey, 196 (32.6%) completed the program's 7 themes, and 189 (31.4%) completed the postintervention survey. Most (138/189, 73.0%) of the participants who completed the postintervention survey were satisfied with the program and had learned skills that eased both their anxiety (141/189, 74.6%) and their children's anxiety (157/189, 83.1%). The majority (157/189, 83.1%) reported that they learned how to organize their daily routines better, and just over one-half (100/189, 53.0%) reported that the program improved how they planned each day with their children. CONCLUSIONS: The single-session iCBT helped parents to face the psychological demands of the COVID-19 pandemic. Future studies should determine how the participation rate and adherence can be optimized in digital, universal interventions. This will help to determine what kinds of programs should be developed, including their content and delivery.

Zero-fluoroscopy ablation in patients with cardiac electronic implantable devices.

INTRODUCTION: Utilizing a three-dimensional (3-D) mapping system and intracardiac echocardiography (ICE) has allowed ablation procedures with less or without fluoroscopy; however, there is limited data for patients with cardiac electronic implantable device (CIED) leads regarding the suspected risk of lead injury. Therefore, we sought to explore technics to perform safe trans-septal approach and catheter manipulation technique in patients with CIED leads. METHODS AND RESULTS: This study comprised 49 consecutive patients (59% males, median 73 years old) with CIED who underwent catheter ablation for supraventricular tachycardia requiring the trans-septal approach, 15 without fluoroscopy (zero-fluoro group), and 34 with fluoroscopy (conventional-fluoro group), between July 2019 and April 2021. All procedures were performed under a 3-D mapping system and ICE guidance. We compared the differences in treatment and development of complications between the two groups. The procedures were for atrial fibrillation (82%) and atrial tachycardia (76%). Coronary sinus catheter insertion and the trans-septal procedure were successfully performed in all patients. The median time from venipuncture to trans-septal procedure (zero-fluoro vs. conventional-fluoro group: 28 [18-37] min vs. 24 [21-31] min, p = .70), total procedure time (231 [142-274] min vs. 175 [163-225] min, p = .63), and the acute procedural success rate (100% vs. 97%, p = 1.00) did not differ between both groups. No patient showed lead-related complications in both groups. CONCLUSION: This is the first study to show zero-fluoro ablation for supraventricular arrhythmia using 3-D mapping and ICE in patients with CIED leads was feasible under careful catheter manipulation.

Fascin as a useful marker for cancer-associated fibroblasts in invasive lung adenocarcinoma.

ABSTRACT: Cancer-associated fibroblasts (CAFs) have been attracting attention in recent years, but their nature has not been fully elucidated. Although CAFs have been recognized as an important therapeutic target, therapeutic agents have not been developed to date. CAFs are characterized by their high migration rate and involvement in epithelial-to-mesenchymal transition with some displaying a dendritic morphology that is reminiscent of fascin expression.The present study was designed to immunohistochemically investigate fascin expression in lung adenocarcinoma including CAFs and compare the results with existing CAF markers.We immunohistochemically investigated fascin expression in not only cancer tissue but also CAFs from 26 autopsy cases of lung adenocarcinoma. Immunohistochemistry of α-smooth muscle actin and fibroblast activation protein was also performed.Fascin-positive staining in CAFs was observed in all cases, with a strong correlation observed with existing CAF markers α-smooth muscle actin and fibroblast activation protein (P < .001). In addition, the proportion of tumor cells showing fascin-positive staining was found to correlate with its expression in CAFs (P < .05).We propose that CAFs express fascin, and that fascin may mediate crosstalk between cancer tissue and CAFs. Fascin might be a novel therapeutic target for treatments that target the cancer stroma.

Establishment of novel common marmoset embryonic stem cell lines under various conditions.

Pluripotent stem cells (PSCs), embryonic stem cells (ESCs), and induced PSCs (iPSCs) are excellent tools for studying embryonic development in organisms and classified into naïve and primed states. ESC-derived germline chimera individuals can be produced by injecting naïve ESCs/iPSCs into preimplantation embryos, and conversion of primed human ESCs/iPSCs into a naïve state provides insights into epiblast cell features. Non-human ESCs/iPSCs are alternatives to human naïve ESCs/iPSCs, which elicit ethical issues. In this study, we used the common marmoset (Callithrix jacchus) as an animal model. Since 1996, 16 marmoset ESC lines have been established. Because most of these ESC lines are female and were derived >10 years ago, new ESCs, particularly male marmoset ESC lines, are needed. Here, we successfully established 17 novel marmoset ESC lines, including six male ESC lines from in vitro-fertilized (IVF) embryos and 12 ESC lines under feeder-free conditions. This report is the first to establish ESC lines using feeder-free conditions and IVF preimplantation blastocysts in marmosets, and these novel ESC lines could potentially facilitate future non-human primate ESC studies.

Determination of Absolute Purities of Hygroscopic Substances by Quantitative NMR Analysis for the Standardization of Quantitative Reagents in the Japanese Pharmacopoeia (Part 2).

As a new absolute quantitation method for low-molecular compounds, quantitative NMR (qNMR) has emerged. In the Japanese Pharmacopoeia (JP), 15 compounds evaluated by qNMR are listed as reagents used as the HPLC reference standards in the assay of crude drug section of the JP. In a previous study, we revealed that humidity affects purity values of hygroscopic reagents and that (i) humidity control before and during weighing is important for a reproducible preparation and (ii) indication of the absolute amount (not purity value), which is not affected by water content, is important for hygroscopic products determined by qNMR. In this study, typical and optimal conditions that affect the determination of the purity of ginsenoside Rb1 (GRB1), saikosaponin a (SSA), and barbaloin (BB) (i.e., hygroscopic reagents) by qNMR were examined. First, the effect of humidity before and during weighing on the purity of commercial GRB1, with a purity value determined by qNMR, was examined. The results showed the importance afore-mentioned. The results of SSA, which is relatively unstable in the dissolved state, suggested that the standardization of humidity control before and during weighing for a specific time provides a practical approach for hygroscopic products. In regard to BB, its humidity control for a specific time, only before weighing, is enough for a reproducible purity determination.

A Comparison of the Required Bronchial Cuff Volume Obtained by 2 Cuff Inflation Methods, Capnogram Waveform-Guided Versus Pressure-Guided: A Prospective Randomized Controlled Study.

BACKGROUND: Double-lumen endobronchial tubes (DLTs) are used for one-lung ventilation (OLV) during thoracic surgery. Overinflation into the bronchial cuff causes damage to the tracheobronchial mucosa, whereas underinflation leads to an incomplete collapse of the nonventilated lung or incomplete ventilation of the ventilated lung. However, how to determine the appropriate bronchial cuff volume and pressure during OLV is unclear. The objective of this study is to compare the required bronchial cuff volume for lung separation obtained by 2 different cuff inflation methods under closed- and open-chest conditions. METHODS: A total of 64 patients scheduled to undergo elective thoracic surgery requiring OLV were recruited. Left DLTs were used for both right- and left-sided surgery. The patients were randomly assigned to 1 of 2 inflation-type groups to estimate the bronchial cuff volume. In the capnogram waveform-guided bronchial cuff inflation group (capno group, n = 27), the bronchial cuff was inflated until a capnometer sampling gas containing CO2 from the nonventilated lung displayed a flat line. The corresponding bronchial cuff volume and pressure were then recorded. In the pressure-guided bronchial cuff inflation group (pressure group, n = 29), the bronchial cuff was inflated by a cuff inflator to a pressure of 20 cm H2O. Lung separation was confirmed when a flat line of a capnometer was observed after gas sampling from the nonventilated lung. RESULTS: Under closed-chest conditions, the bronchial cuff sealing volume for the capno group was significantly lower than that for the pressure group (mean [standard deviation {SD}], 1.00 [0.65] mL vs 1.44 [0.59] mL, mean difference, -0.44; 97.5% confidence interval [CI], -0.78 to -0.11; P = .010). Under open-chest conditions, the bronchial cuff sealing volume for the capno group was also significantly lower than that for the pressure group (mean [SD], 0.65 [0.66] mL vs 1.22 [0.45] mL, mean difference, -0.58; 97.5% CI, -0.88 to -0.27; P < .001). CONCLUSIONS: The lowest cuff volume providing an air-tight bronchial seal was obtained by the capnogram waveform-guided bronchial cuff inflation method. Since the cuff volume required to achieve an air-tight seal decreases after opening the chest, readjustment of the bronchial cuff volume to prevent bronchial cuff damage to the tracheobronchial mucosa after opening the chest may be advisable.

Absolute Purity Determination of a Hygroscopic Substance, Indocyanine Green, Using Quantitative NMR (qNMR).

Quantitative NMR (qNMR) is applied to determine the absolute quantitative value of analytical standards for HPLC-based quantification. We have previously reported the optimal and reproducible sample preparation method for qNMR of hygroscopic reagents, such as saikosaponin a, which is used as an analytical standard in the assay of crude drug section of Japanese Pharmacopoeia (JP). In this study, we examined the absolute purity determination of a hygroscopic substance, indocyanine green (ICG), listed in the Japanese Pharmaceutical Codex 2002, using qNMR for standardization by focusing on the adaptation of ICG to JP. The purity of ICG, as an official non-Pharmacopoeial reference standard (non-PRS), had high variation (86.12 ± 2.70%) when preparing qNMR samples under non-controlled humidity (a conventional method). Additionally, residual ethanol (0.26 ± 0.11%) was observed in the non-PRS ICG. Next, the purity of non-PRS ICG was determined via qNMR when preparing samples under controlled humidity using a saturated sodium bromide solution. The purity was 84.19 ± 0.47% with a lower variation than that under non-controlled humidity. Moreover, ethanol signal almost disappeared. We estimated that residual ethanol in non-PRS ICG was replaced with water under controlled humidity. Subsequently, qNMR analysis was performed when preparing samples under controlled humidity in a constant temperature and humidity box. It showed excellent results with the lowest variation (82.26 ± 0.19%). As the use of a constant temperature and humidity box resulted in the lowest variability, it is recommended to use the control box if the reference ICG standard is needed for JP assays.

MDP is effective for removing residual polycarboxylate temporary cement as an adhesion inhibitor.

The effect of cleaner containing 10-methacryloyloxydecyl dihydrogen phosphate (MDP) for removing temporary cement remnants on dentin surface was evaluated. Flat dentin surfaces were wet-polished (Co) and HY-BOND temporary cement hard (Shofu) was applied to the surface. This temporary cement was removed using an air-scaler (Sc), brush (Br), or phosphoric acid and NaOCl (NC). A prototype cleaner containing MDP (Kuraray Noritake Dental, Tokyo, Japan) was used with agitation mode (MC+AG). KATANA Avencia block (Kuraray Noritake Dental) was luted with SA Cement Plus Automix (Kuraray Noritake Dental). Co showed significantly higher bond strength than Sc or Br (p<0.001 each). Bond strengths with NC (p=0.99) and MC+AG (p=0.38) did not differ significantly from that with Co. Transmission electron microscopy revealed sufficient interaction of MC+AG. Cleaner containing MDP can effectively remove temporary cement by agitation, and can be expected to improve the chemical bonding ability by binding more MDP to dentin.

Systematic Evaluation of KCNQ1 Variant Using ACMG/AMP Guidelines and Risk Stratification in Long QT Syndrome Type 1.

Background - Mutation/variant-site specific risk stratification in long-QT syndrome type 1 (LQT1) has been well investigated, but it is still challenging to adapt current enormous genomic information to clinical aspects caused by each mutation/variant. We assessed a novel variant-specific risk stratification in LQT1 patients. Methods - We classified a pathogenicity of 141 KCNQ1 variants among 927 LQT1 patients (536 probands) based on the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines and evaluated whether the ACMG/AMP-based classification was associated with arrhythmic risk in LQT1 patients. Results - Among 141 KCNQ1 variants, 61 (43.3%), 55 (39.0%), and 25 (17.7%) variants were classified into pathogenic (P), likely pathogenic (LP), and variant of unknown significance (VUS), respectively. Multivariable analysis showed that proband (HR = 2.53; 95%CI = 1.94-3.32; p <0.0001), longer QTc (≥500ms) (HR = 1.44; 95%CI = 1.13-1.83; p = 0.004), variants at membrane spanning (MS) (vs. those at N/C terminus) (HR = 1.42; 95%CI = 1.08-1.88; p = 0.01), C-loop (vs. N/C terminus) (HR = 1.52; 95%CI = 1.06-2.16; p = 0.02), and P variants [(vs. LP) (HR = 1.72; 95%CI = 1.32-2.26; p <0.0001), (vs. VUS) (HR = 1.81; 95%CI = 1.15-2.99; p = 0.009)] were significantly associated with syncopal events. The ACMG/AMP-based KCNQ1 evaluation was useful for risk stratification not only in family members but also in probands. A clinical score (0~4) based on proband, QTc (≥500ms), variant location (MS or C-loop) and P variant by ACMG/AMP guidelines allowed identification of patients more likely to have arrhythmic events. Conclusions - Comprehensive evaluation of clinical findings and pathogenicity of KCNQ1 variants based on the ACMG/AMP-based evaluation may stratify arrhythmic risk of congenital long-QT syndrome type 1.

[Determination of Absolute Purities of Hygroscopic Substances by Quantitative NMR Analysis for the Standardization of Quantitative Reagents in the Japanese Pharmacopoeia (Part 1)].

Quantitative NMR (qNMR) has been developed as an absolute quantitation method to determine the purity or content of organic compounds including marker compounds in crude drugs. The "qNMR test" has been introduced into the crude-drug section of the Japanese Pharmacopoeia (JP) for determining the purity of reagents used for the assay in the JP. In Supplement II to the JP 17th edition published in June 2019, fifteen compounds adopted qNMR test were listed as the reagents for the assay. To establish the "qNMR test" in the crude drug section of the JP, there were several problems to be solved. Previously, we reported that the handling impurity signals from reference substances and targeted marker compounds, chemical shifts of reference substances, and peak unity of signals of targeted marker compounds are important factors to conduct qNMR measurements with intended accuracy. In this study, we investigated that the hygroscopicity of reagents could cause the changes in the compounds' purity depending on increasing their water content. Twenty-one standard products used for the crude-drug test in JP were examined by water sorption-desorption analysis, and ginsenosides and saikosaponins were found to be hygroscopic. To prepare a sample solution of saikosaponin b2 for qNMR analysis, samples need to be maintained for 18 h at 25°C and 76% relative humidity; further, samples need to be weighed at the same humidity for the qNMR analysis.

Successful Treatment of Cyst Infection in an Infant With Autosomal Dominant Polycystic Kidney Disease Using Trimethoprim/Sulfamethoxazole.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease causing renal cysts. Reports on kidney cyst infection in children are rare despite cyst infections being important complications of ADPKD. Here, we report a case of a child without any medical history who had a urinary tract infection with sepsis at 7 months. Leukocyturia persisted despite antibiotic therapy because the infection was treatment-resistant. Initial ultrasound and contrast computed tomography were inconclusive because cysts could not be detected clearly, and a family history of renal cysts was not determined. Subsequently, history of paternal renal cysts, thick walls in infectious cystic lesions on diffusion-weighted magnetic resonance imaging (MRI), and multiple small lesions with high signals on T2-weighted imaging in both kidneys became apparent. Upon diagnosis of ADPKD with cyst infection, antibiotic therapy was switched from cefotaxime to trimethoprim/sulfamethoxazole to achieve better cyst penetration, which successfully resolved the infection. In this patient, MRI was effective for clear visualization and diagnosis of infectious lesions and small cysts in undiagnosed ADPKD with cyst infection. Administering antibiotics with better cyst penetration is important. Trimethoprim/sulfamethoxazole is an option for use in children. This is the first case report that describes ADPKD with cyst infection in an infant in detail.