A 39-year-old woman with a 9-week abdominal pregnancy noted pain in her lower abdomen and left leg. Since successive thrombi were observed extending from the left common iliac vein to the popliteal ...vein along with a thrombus in the left pulmonary artery, we diagnosed her with pulmonary thromboembolism with deep venous thrombosis (DVT). May-Thurner syndrome may have contributed to DVT in the left leg when the left iliac vein was compressed by the right iliac artery. She underwent anticoagulant therapy with heparin, followed by the subcutaneous injection of heparin at home after discharge. We herein report the case of a pregnant woman with May-Thurner syndrome who safely gave birth.
We present a case of osteogenesis imperfecta (OI) type 2A in which a natural course in utero was observed from 23 weeks’ gestation to term. At 23 weeks’ gestation, a sonographic examination showed a ...cloverleaf skull-like head, a narrow thorax, and marked shortening of the long bones with bowing of the femurs and humeri. Follow-up examinations showed that the cloverleaf skull-like head was not evident at 28 weeks’ gestation. Discontinuity of the ribs and femurs was observed at 26 and 30 weeks’ gestation, respectively. This finding suggested bone fractures, which were confirmed by three-dimensional computed tomography at 32 weeks’ gestation. Ultrasonographic findings of bones, including the long bones and calvarium, changed with advancing gestation during the second trimester. Characteristic features of OI type 2A were evident during the late second to early third trimesters. Repeated ultrasonographic examinations together with three-dimensional computed tomography are necessary for the definitive diagnosis of OI type 2A in the second trimester.
Purpose
To observe age-related changes in the anterior lower uterine segment (LUS) thickness in normal pregnancy from 20 to 35 weeks’ gestation.
Methods
Subjects were 235 uncomplicated singleton ...cases that underwent single ultrasound examination at 4-week intervals during 20–35 weeks’ gestation. Sagittal LUS sections were evaluated with transvaginal ultrasonography. Anterior LUS thickness (Th) was measured every centimeter from the lowest bladder point (Th
0cm
) to 4 cm from that point (Th
4cm
). Th values were standardized by dividing by the Th
0cm
value. Intragroup comparisons of standardized Th values and intergroup comparisons of actual Th values were made according to gestational age. Statistical analyses were performed with the Kruskal–Wallis and Tukey honest standard deviation tests; significance was set at
p
< 0.05.
Results
In the 20–23-, 24–27- and 32–35-week groups, standardized Th decreased from Th
0cm
to Th
2cm
; in the 28–31-week group standardized Th decreased from Th
0cm
to Th
3cm
. Median Th
3cm
values decreased from 5.0 mm at 20–23 weeks to 3.0 mm at 28–31 weeks, but remained unchanged thereafter.
Conclusions
The anterior LUS gradually thinned from Th
0cm
to Th
3cm
at 20–35 weeks’ gestation. Th
3cm
became increasingly thin between 20–23 and 28–31 weeks’ gestation.
Introduction
Assessing dysarthria features in patients with neurodegenerative diseases helps diagnose underlying pathologies. Although deep neural network (DNN) techniques have been widely adopted in ...various audio processing tasks, few studies have tested whether DNNs can help differentiate neurodegenerative diseases using patients’ speech data. This study evaluated whether a DNN model using a transformer architecture could differentiate patients with Parkinson’s disease (PD) from patients with spinocerebellar degeneration (SCD) using speech data.
Methods
Speech data were obtained from 251 and 101 patients with PD and SCD, respectively, while they read a passage. We fine-tuned a pre-trained DNN model using log-mel spectrograms generated from speech data. The DNN model was trained to predict whether the input spectrogram was generated from patients with PD or SCD. We used fivefold cross-validation to evaluate the predictive performance using the area under the receiver operating characteristic curve (AUC) and accuracy, sensitivity, and specificity.
Results
Average ± standard deviation of the AUC, accuracy, sensitivity, and specificity of the trained model for the fivefold cross-validation were 0.93 ± 0.04, 0.87 ± 0.03, 0.83 ± 0.05, and 0.89 ± 0.05, respectively.
Conclusion
The DNN model can differentiate speech data of patients with PD from that of patients with SCD with relatively high accuracy and AUC. The proposed method can be used as a non-invasive, easy-to-perform screening method to differentiate PD from SCD using patient speech and is expected to be applied to telemedicine.
Purpose
To evaluate the association between axial length and crystalline lens biometry with and without accommodation using the CASIA2 swept-source (SS) optical coherence tomography (OCT) system on ...the anterior segment.
Study design
Intervention study.
Methods
Individuals aged 20 to 39 years were enrolled for SS-OCT imaging at 2 separate visits within 1 week. Each eye was imaged under accommodation stimuli with different amplitudes (0 D, -1 D, -3 D, -5 D, and -7 D). The anterior and posterior lens curvature radii and lens thicknesses were measured. The participants were divided into 4 groups according to axial length.
Results
Forty-eight participants (96 eyes) were initially enrolled. All 96 eyes were included in the analyses, as they met the eligibility criteria and each had proper OCT images. The mean participant age was 25.9 ± 4.3 years, and the mean spherical error was -3.5 ± 2.5 D. The mean axial length was 25.1 ± 1.2 mm. Multivariate analysis revealed that the anterior curvature radius became flatter and the lens thickness became thicker as the axial length increased (all
P
< .01). Furthermore, axial length independently contributed to the shape of the lens after adjusting for the effects of age and accommodation stimuli.
Conclusion
Axial length was associated with lens shape after adjusting for age and accommodation stimuli. These measurements can provide a glimpse of dynamic lens biometry changes, which may help us better understand the role of lenses in various physiologic changes, including accommodation and myopia.
We have developed amphiphilic polydepsipeptide micelle “lactosome” as a novel nanocarrier with tumor accumulation properties for cancer imaging probes. In this study, radioiodine-labeled lactosomes ...were synthesized and evaluated to develop diagnostic radiotracers for in vivo imaging utilizing single photon emission computed tomography (SPECT). The 125I-labeled lactosome was obtained in sufficient yields for biodistribution studies. Radioactivity in the blood circulation was maintained at a high level between 2–48 h post-injection of 125I-labeled lactosome into BALB/c mice. Radioactivity uptake by the Colon-26 tumor implanted in the femur gradually increased. The uptake ratio of subcutaneous tumor/muscle increased to 16.7 at 48 h post-injection. Additionally, tumor SPECT imaging of 123I-labeled lactosome in mice was achieved. Radioactivity uptake of turpentine-induced inflamed tissue reached a maximum at 24 h and then decreased at 48 h post-injection. The mean uptake ratio of inflammatory tissue/muscle increased to 14.4 at 24 h. In conclusion, radioiodine-labeled lactosomes as nanocarriers may serve as potential candidates in facile and generic tumor or inflammation imaging techniques.
The prognostic impact of tumor-infiltrating lymphocytes (TILs) has been determined in non-small cell lung carcinoma; however, there is no standardized method for counting TILs. In this report, we ...applied the method proposed by the International Immuno-Oncology Biomarkers Working Group for the assessment of TILs to count the number of tumor-infiltrating neutrophils (TINs). We then analyzed the association between TIL counts, TIN counts, and clinicopathological factors in lung cancer. We retrospectively analyzed a series of 1191 Japanese patients with resected lung adenocarcinoma and squamous cell carcinoma, which were restaged according to the eighth edition of the TNM staging system. Tumors were classified according to the 2015 WHO classification of lung carcinoma. Recurrence-free probability (RFP) and overall survival (OS) were analyzed using the log-rank test and Cox proportional hazard model. Using multivariate analysis for patient outcome in patients with adenocarcinoma, high TIN counts were an independent prognostic factor for worse RFP (hazard ratio HR: 1.94, p < 0.001) and worse OS (hazard ratio HR: 1.75, p = 0.006). On the other hand, TIL counts were not related to patient outcome. We have demonstrated that high TINs are unfavorable prognostic markers for resected lung adenocarcinoma. In resected lung squamous cell carcinoma, TIL and TIN counts were not related to patient prognosis. It has been suggested that the immune response to cancer cells may differ depending on the histological type. An understanding of how neutrophils are programmed to perform protumor activities is necessary for the future design of targeted immunotherapies.
The aim of this study was to establish a new preparation method for solid dispersion formulation (SDF) of tacrolimus, a poorly water-soluble drug, without dichloromethane, because no use of ...dichloromethane is recommended by ICH harmonized tripartite guideline. To select the appropriate carrier, three different SDFs with polyethylene glycol 6000 (PEG 6000), polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC) were prepared by the conventional solvent method, in which tacrolimus and the carrier were completely dissolved in the mixture of dichloromethane and ethanol. Powder X-ray diffraction (XRD) and differential scanning calorimetry (DSC) patterns indicated that tacrolimus exists in an amorphous state in all three SDFs. The supersaturated dissolution profiles of tacrolimus were observed in all SDFs, and the highest level of supersaturation for tacrolimus was obtained and maintained for 24
h from SDF with HPMC. On the other hand, the supersaturated level from SDF with PEG 6000 or PVP decreased rapidly. The in vivo oral absorption study in dogs showed that bioavailability of tacrolimus from SDF with HPMC was remarkably improved compared with the crystalline powder. It was clarified that HPMC is the most appropriate carrier for SDF of tacrolimus. Then, SDF of tacrolimus was prepared by the new method, which allows us to make SDF of tacrolimus by swelling HPMC with ethanol, in which tacrolimus was completely dissolved. This new method does not need dichloromethane. The physicochemical properties of SDF with HPMC prepared by the new method were the same as those of SDF prepared by the conventional solvent method. Furthermore, SDF with HPMC prepared by the new method was still stable after stored at 40
°C for 3 months. The pharmacokinetic parameters after oral administration in monkeys showed no significant difference (
P>0.01) between SDFs with HPMC prepared by the two methods. In conclusion, we have established the new preparation method for SDF of tacrolimus with HPMC and the new method makes it possible to prepare SDF of tacroliumus without dichloromethane.
Previous studies suggested that high consumption of saturated fatty acid (SFA) is a risk factor for liver cancer. However, it remains unclear how dietary SFA affects liver tumorigenesis. This study ...aimed to investigate the impact of a SFA-rich diet on hepatic tumorigenesis using hepatitis C virus core gene transgenic (HCVcpTg) mice that spontaneously developed hepatic steatosis and tumors with aging. Male HCVcpTg mice were treated for 15 months with a purified control diet or SFA-rich diet prepared by replacing soybean oil in the control diet with hydrogenated coconut oil, and phenotypic changes were assessed. In this special diet, almost all dietary fatty acids were SFA. Long-term feeding of SFA-rich diet to HCVcpTg mice increased hepatic steatosis, liver dysfunction, and the prevalence of liver tumors, likely due to stimulation of de novo lipogenesis, activation of the pro-inflammatory and pro-oncogenic transcription factor nuclear factor-kappa B (NF-κB), enhanced c-Jun N-terminal kinase/activator protein 1 (JNK/AP-1) signaling and induction of the oncogenes cyclin D1 and p62/sequestosome 1. The SFA-rich diet did not affect liver fibrosis or autophagy. Collectively, long-term SFA-rich diet consumption promoted hepatic tumorigenesis mainly through activation of lipogenesis, NF-κB, and JNK/AP-1 signaling. We therefore propose that HCV-infected patients should avoid excessive intake of SFA-rich foods to prevent liver cancer.
Neoadjuvant therapy is commonly used for invasive pancreatic ductal carcinoma (PDAC). Tumor budding and high podoplanin expression in cancer-associated fibroblasts (CAFs) are prognostic factors in ...patients with various carcinomas including PDAC who have not received neoadjuvant therapy. In this study, we investigated whether tumor budding and podoplanin-positive CAFs are associated with outcomes in Japanese PDAC patients with neoadjuvant therapy. Histopathological findings of surgically resected PDACs with neoadjuvant therapy from 2005 to 2018 were reviewed (n = 97). With reference to International Tumor Budding Consensus Conference recommendations, tumors were evaluated for budding at 20 × magnification (/0.785 mm2) and at 40 × magnification (/0.237 mm2; mean number of fields: 3) for podoplanin expression in CAFs (%). Overall survival, disease-free survival, and disease-specific survival (DSS) were analyzed using the log-rank test and Cox proportional hazards model. After adjusting for T category, N category, resection margin, and adjuvant therapy, multivariate analyses demonstrated that tumor budding at 40 × magnification was an independent prognostic factor for worse DSS (hazard ratio: 2.41, p = 0.022). Tumor budding at 20 × magnification and podoplanin-positive CAFs tended to be associated with worse DSS; however, these findings were not statistically significant. Our findings indicate that tumor budding is an independent prognostic factor in PDAC patients with neoadjuvant therapy.
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