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Polydimethylsiloxane (PDMS)-coated macroporous silica (MPSi) particles were developed for the extraction of volatile organic compounds (VOCs) from air samples in thermal desorption-gas chromatographic analysis. The gas sample was collected by a gas sampling pump at 100 mL/min. Different amounts of PDMS coating were prepared, and the fundamental extraction and desorption performances were investigated using even numbered n-alkanes of C8–C28. The extraction efficiency increased by increasing PDMS coating, and the desorption efficiency showed more than 99% at a desorption temperature of 310°C for all the investigated adsorbents. This remarkable desorption performance showed a higher peak area of the analytes than that of the Tenax TA-packed thermal desorption tube, especially for higher molecular weight compounds. Furthermore, an activated carbon particle of Carbopack X was introduced on the latter side of the PDMS-MPSi to extract low-molecular weight compounds. This double-bed-type extraction tube showed a successful determination of a wide range of VOCs. The double-bed-type extraction tube was then applied to the extraction of VOCs related to sick building syndrome (SBS). The results for the extraction and desorption performances of the SBS-related VOCs were well agreed with that of alkanes, and the applicability of the extraction tube to the determination of other types of conventional VOCs were confirmed.

Osteoid osteoma (OO) is a benign osteoblastic tumor characterized by nocturnal pain that responds well to non-steroidal anti-inflammatory drugs. This condition commonly affects adolescents and young adults, and patients between 5 and 24 years of age account for 85% of all OO cases; it occurs very rarely in patients under 5 years old. Tumors often occur in the cortical bone in the diaphysis and metaphysis of the appendicular skeleton and are more common in the lower extremities than upper extremities. Here, we present an extremely rare case of intramedullary OO that arose in the proximal metaphysis of the humerus in a 2-year-old boy, which mimicked subacute osteomyelitis on imaging studies. We also conducted a retrospective literature review and found that the intramedullary location was fairly common in very young patients (

Introduction: EGFR tyrosine kinase inhibitors are standard therapeutic agents for patients with advanced NSCLC harboring EGFR mutations. Nevertheless, some patients exhibit primary resistance to EGFR tyrosine kinase inhibitors in the first-line treatment setting. AXL, a member of the TYRO3, AXL, and MERTK family of receptor tyrosine kinases, is involved in primary resistance to EGFR tyrosine kinase inhibitors in EGFR-mutated NSCLC. Methods: We investigated spatial tumor heterogeneity using autopsy specimens and a patient-derived cell line from a patient with EGFR-mutated NSCLC having primary resistance to erlotinib plus ramucirumab. Results: Quantitative polymerase chain reaction analysis revealed that AXL mRNA expression differed at each metastatic site. In addition, AXL expression levels were likely to be negatively correlated with the effectiveness of erlotinib plus ramucirumab therapy. Analysis of a patient-derived cell line established from the left pleural effusion before initiation of treatment revealed that the combination of EGFR tyrosine kinase inhibitors and an AXL inhibitor remarkably inhibited cell viability and increased cell apoptosis in comparison with EGFR tyrosine kinase inhibitor monotherapy or combination therapy of these inhibitors with ramucirumab. Conclusions: Our observations suggest that AXL expression may play a critical role in the progression of spatial tumor heterogeneity and primary resistance to EGFR tyrosine kinase inhibitors in patients with EGFR-mutated NSCLC.

Summary: The small GTPase Rab8 plays a vital role in the vesicular trafficking of cargo proteins from the trans-Golgi network to target membranes. Upon reaching its target destination, Rab8 is released from the vesicular membrane into the cytoplasm via guanosine triphosphate (GTP) hydrolysis. The fate of GDP-bound Rab8 released from the destination membranes, however, has not been investigated adequately. In this study, we found that GDP-bound Rab8 subfamily proteins are targeted for immediate degradation, and the pre-emptive quality control machinery is responsible for eliminating these proteins in a nucleotide-specific manner. We provide evidence that components of this quality control machinery have a critical role in vesicular trafficking events, including the formation of primary cilia, a process regulated by the Rab8 subfamily. These results suggest that the protein degradation machinery plays a critical role in the integrity of membrane trafficking by limiting the excessive accumulation of GDP-bound Rab8 subfamily proteins.

Summary: Photo-isolation chemistry (PIC) enables isolation of transcriptome information from locally defined areas by photo-irradiation. Here, we present an optimized PIC protocol for formalin-fixed frozen and paraffin mouse sections and fresh-frozen mouse sections. We describe tissue section preparation and permeabilization, followed by in situ reverse transcription using photo-caged primers. We then detail immunostaining and UV-mediated uncaging to the target areas, followed by linear amplification of uncaged cDNAs, library preparation, and quantification. This protocol can be applied to various animal tissue types.For complete details on the use and execution of this protocol, please refer to Honda et al. (2021).

Background: Betaine is known to act against various biological stresses and its levels were reported to be decreased in schizophrenia patients. We aimed to test the role of betaine in schizophrenia pathophysiology, and to evaluate its potential as a novel psychotherapeutic. Methods: Using Chdh (a gene for betaine synthesis)-deficient mice and betaine-supplemented inbred mice, we assessed the role of betaine in psychiatric pathophysiology, and its potential as a novel psychotherapeutic, by leveraging metabolomics, behavioral-, transcriptomics and DNA methylation analyses. Findings: The Chdh-deficient mice revealed remnants of psychiatric behaviors along with schizophrenia-related molecular perturbations in the brain. Betaine supplementation elicited genetic background-dependent improvement in cognitive performance, and suppressed methamphetamine (MAP)-induced behavioral sensitization. Furthermore, betaine rectified the altered antioxidative and proinflammatory responses induced by MAP and in vitro phencyclidine (PCP) treatments. Betaine also showed a prophylactic effect on behavioral abnormality induced by PCP. Notably, betaine levels were decreased in the postmortem brains from schizophrenia, and a coexisting elevated carbonyl stress, a form of oxidative stress, demarcated a subset of schizophrenia with “betaine deficit-oxidative stress pathology”. We revealed the decrease of betaine levels in glyoxylase 1 (GLO1)-deficient hiPSCs, which shows elevated carbonyl stress, and the efficacy of betaine in alleviating it, thus supporting a causal link between betaine and oxidative stress conditions. Furthermore, a CHDH variant, rs35518479, was identified as a cis-expression quantitative trait locus (QTL) for CHDH expression in postmortem brains from schizophrenia, allowing genotype-based stratification of schizophrenia patients for betaine efficacy. Interpretation: The present study revealed the role of betaine in psychiatric pathophysiology and underscores the potential benefit of betaine in a subset of schizophrenia. Fund: This study was supported by the Strategic Research Program for Brain Sciences from AMED (Japan Agency for Medical Research and Development) under Grant Numbers JP18dm0107083 and JP19dm0107083 (TY), JP18dm0107129 (MM), JP18dm0107086 (YK), JP18dm0107107 (HY), JP18dm0107104 (AK) and JP19dm0107119 (KH), by the Grant-in-Aid for Scientific Research on Innovative Areas from the MEXT under Grant Numbers JP18H05435 (TY), JP18H05433 (AH.-T), JP18H05428 (AH.-T and TY), and JP16H06277 (HY), and by JSPS KAKENHI under Grant Number JP17H01574 (TY). In addition, this study was supported by the Collaborative Research Project of Brain Research Institute, Niigata University under Grant Numbers 2018–2809 (YK) and RIKEN Epigenetics Presidential Fund (100214–201801063606-340120) (TY). Keywords: Schizophrenia, Chdh, DNA methylation, Postmortem brain, Carbonyl stress, iPS cell

A 73-year-old-male patient with hypertension and grade 3B chronic kidney disease underwent radical nephrectomy in the year 2000. As the renal function gradually worsened, the patient was started on hemodialysis in 2003. Eleven years after nephrectomy, the metastases were pointed out. The patient received sunitinib as first-line therapy. Thereafter, as the metastatic lesions became larger, we initiated nivolumab therapy (3 mg/m2 every 2 weeks). After 52 weeks, the metastatic lesions continued showing complete response (CR). No adverse effects were observed during nivolumab treatment.

We investigated the mechanisms associated with projected early-summer low-temperature extremes in Japan at the end of the 21st century by means of a well-developed nonhydrostatic regional climate model under the A1B scenario provided by the Intergovernmental Panel on Climate Change-Special Report on Emission Scenario. The projected surface air temperature reveals that even in a climate warmer than that at present, extremely low daily minimum temperatures in early summer are comparable to those in the present climate at several locations. At locations where future low temperatures are remarkable, the temperature drop at night is larger in the future than at present. This temperature drop results from mainly two heat fluxes: upward longwave radiation and latent heat flux. In the future climate, upward longwave radiation increases owing to high temperature at the surface around the time of the sunset. In addition, the upward flux of latent heat increases owing to low relative humidity just above the surface. These dryer conditions are associated with lower relative humidity at 850 hPa, suggesting the effects of synoptic systems. These two fluxes act to reduce the surface temperature, and hence surface air temperature.

The biologic behavior of and optimal treatment for oral verrucous carcinoma (VC) remain controversial. We analyzed the clinicopathological characteristics of 12 patients with oral VC. Immunohistochemical techniques were used to evaluate p53 protein, CD44 variant 9, and proliferating cell nucleus antigen. The TNM classification (UICC, 1997) was T1 in 1 patient, T2 in 3, T3 in 4, and T4 in 4. All patients were classified as N0M0. Four patients were treated by surgery alone and 8 by surgery after chemotherapy, radiotherapy, or both. After surgery, two patients had primary recurrence of disease. Immunohistochemically, the proliferative activity of tumor cells as evaluated by proliferating cell nuclear antigen labeling index and p53 protein expression was similar in VC and well-differentiated squamous cell carcinoma. However, CD44 varient 9 expression was positive in 8 of 10 VC, suggesting that oral VC is associated with a low risk of lymph node metastasis. Positive CD44 variant 9 expression by most oral VCs, indicating a low risk of cervical lymph node metastasis, suggests that most cases can be controlled by surgical intervention.

This study was performed to investigate the presence of microorganisms in the epithelial cells of leukoplakia. Frozen sections of 20 specimens of leukoplakia were stained with DNA-binding bisbenzimide Hoechst 33258. As a control, 20 specimens of normal oral mucosa and five specimens of normal skin were used. In all preparations of leukoplakia, small granular fluorescing structures were observed within the cytoplasm of the epithelial cells, predominantly within the cytoplasm of prickle cells, although the amount of the granular structures varied between specimens, layers of the epithelium and even areas of the epithelium within a single section. Less granular structures were observed, or none at all, in the cytoplasm of the epithelial cells of normal mucosa. No structures were observed in the cytoplasm of the epithelium of skin. The results in this study strongly suggest that microorganisms are present in the epithelial cells of oral mucosa, and that they are closely associated with the development of oral leukoplakia. It is postulated that the microorganisms in the epithelial cells could be bacteria, particularly mycoplasmas.

An extremely rare case of a congenital fistula with an island of vermilion-epithelium in the paramidline of the upper lip in a 17-year-old male is presented. The fistula was located in the paramidline of the philtrum dimple, and mucoid secretion from the fistula was noted. The fistula's orifice opened in the center of a well-defined, slightly dimpled, round, vermilion-like epithelium just above the vermilion border. The fistulous tract terminated in a cul-de-sac and its end was located near the alveolar process. Fistulectomy was carried out via an extra-oral approach and the epithelial defect was closed using a rotation flap. Histological examination revealed that the fistula was lined by squamous epithelium with sebaceous and mucous glands, and vermilion-like area island consisted of thin keratinized stratified squamous epithelium without skin appendages, the same as the epithelium of the lip vermilion.

The study reviews oronasal fistulae occurring after palatoplasty. Subjects were fifty-two patients who had received palatoplasty in our clinic from 1981 to 1987. In twenty-one cases (40%) oronasal fistulae persisted. Two-thirds of these fistulae were slits or pinholes. The ratio of fistula occurrence was relatively high compared to other reports. Most of them were observed at the junction of the premaxilla and maxilla. There was no significant difference between fistula formation and the distance of the push back, and also there was no correlation with the width of the cleft.