Relationship between Thermal Environmental Acceptability and Individual Characteristics in an Office

We examine the acceptability of the thermal environment to office workers using data recorded with the Ostracon voting device. Although temporal changes in the overall indoor thermal environment were seemingly small, the spatial distribution of the thermal environment changed. Unacceptable votes in the middle of the thermal environment occurred regardless of the perimeter thermal environment, suggesting that temperature was less relevant to acceptability in the middle of the thermal environment

Effect of TU-100 in NASH

Background : Non-alcoholic steatohepatitis (NASH) is associated with a higher risk of hepatocellular carcinoma (HCC), and the importance of the gut–liver axis has been recognized in NASH-associated HCC. We investigated the effect of TU-100 on the intestinal microbiome and hepatocarcinogenesis in a NASH model. Methods : Seven-week-old Tsumura Suzuki obese diabetes mice, a model that shows the spontaneous onset of NASH and HCC, were used. They were divided into a TU-100 treated group and a control group. Mice were sacrificed at 24 and 48 weeks to evaluate hepatic steatosis, fibrosis, carcinogenesis, cytokine expression, and microbiome abundance. Results : At 24 weeks, the TU-100 group showed significantly lower expression of IL6, IL1B, and ACTA2 mRNA in the liver (P < 0.05). At 48 weeks, the TU-100 group showed significantly lower levels of serum alanine aminotransferase. The TU-100 group also showed a lower rate of NASH than the control group (28% vs 72% ; P = 0.1). Tumor diameter was significantly smaller in the TU-100 group compared with that in the control group (P < 0.05). Regarding the intestinal microbiome, the genera Blautia and Ruminococcus were increased in the TU-100 group (P < 0.05), whereas Dorea and Erysipelotrichaceae were decreased in the TU-100 group (P < 0.05). Conclusions : TU-100 regulates the intestinal microbiome and may suppress subsequent hepatocarcinogenesis in the NASH model

Genotype prevalence and age distribution of human papillomavirus from infection to cervical cancer in Japanese women: A systematic review and meta-analysis

Background: National HPV vaccination coverage in Japan is less than one percent of the eligible population and cervical cancer incidence and mortality are increasing. This systematic review and meta-analysis aimed to provide a comprehensive estimate of HPV genotype prevalence for Japan. Methods: English and Japanese databases were searched to March 2021 for research reporting HPV genotypes in cytology and histology samples from Japanese women. Summary estimates were calculated by disease stage from cytology only assessment – Normal, ASCUS, LSIL, HSIL and from histological assessment – CIN1, CIN2, CIN3/AIS, ICC (ICC-SCC, and ICC-ADC), and other. A random-effects meta–analysis was used to calculate summary prevalence estimates of any-HPV, high-risk (HR) and low-risk (LR) vaccine types, and vaccine genotypes (bivalent, quadrivalent, or nonavalent). This study was registered with PROSPERO: CRD42018117596. Results: A total of 57759 women with normal cytology, 1766 ASCUS, 3764 LSIL, 2017 HSIL, 3130 CIN1, 1219 CIN2, 869 CIN3/AIS, and 4306 ICC (which included 1032 ICC-SCC, and 638 ICC-ADC) were tested for HPV. The summary estimate of any-HPV genotype in women with normal cytology was 15·6% (95% CI: 12·3–19·4) and in invasive cervical cancer (ICC) was 85·6% (80·7–89·8). The prevalence of HR-HPV was 86·0% (95% CI: 73·9–94·9) for cytological cases of HSIL, 76·9% (52·1–94·7) for histological cases of CIN3/AIS, and 75·7% (68·0–82·6) for ICC. In women with ICC, the summary prevalence of bivalent vaccine genotypes was 58·5% (95% CI: 52·1–64·9), for quadrivalent genotypes was 58·6% (52·2–64·9) and for nonavalent genotypes was 71·5% (64·9–77·6), and of ICC cases that were HPV positive over 90% of infections are nonavalent vaccine preventable. There was considerable heterogeneity in all HPV summary estimates and for ICC, this heterogeneity was not explained by variability in study design, sample type, HPV assay type, or HPV DNA detection method, although studies published in the 1990s had lower prevalence estimates of any-HPV and HR HPV genotypes. Interpretations: HPV prevalence is high among Japanese women. The nonavalent vaccine is likely to have the greatest impact on reducing cervical cancer incidence and mortality in Japan

Adhesiveness of β5 integrin variant lacking FNK767–769 is similar to that of the prototype containing FNKFNK764–769

金沢大学大学院医学系研究科保健学専攻Little is known about the functions of two different β5 integrins: repeated-FNK (FNKFNK764–769) and single-FNK (FNK764–766) amino acid sequences in the cytoplasmic domain. We examined whether they occurred as germ line mutations or somatic mutations associated with neoplastic transformation, and whether there were functional alterations. Out of six cultured cell lines, only KATO-III cells had the single-FNK β5 sequence. The single-FNK β5 was found in 9 out of 79 patients with colon carcinoma, but no somatic mutations were detected in cancerous tissues. CHO cells were transformed with expression vectors containing single-FNK or repeated-FNK β5 cDNA, which were derived from KATO-III cells. CHO cells transfected with single-FNK and repeated-FNK showed similar adhesiveness to, and proliferative activity on, vitronectin substrates

Metastatic Renal Cell Carcinoma to the Left Sphenoid Sinus: A Case Report in Light of the Literature

A 79-year-old Japanese woman presented with a rare case of metastatic renal cell carcinoma to the left sphenoid sinus with left nasal bleeding. She had previously had right radical nephrectomy for renal cell carcinoma at the age of 64 years and brain and spinal cord infarction at 74 years. Endoscopic examination revealed no mass in the nasal cavity. CT and MRI revealed a tumor in the left sphenoid sinus. The size of the tumor increased gradually from 12 to 15 years after the radical nephrectomy. Complete resection with endoscopic surgery was performed without preoperative embolization. The tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. These findings were identical to the pathological findings of the surgical specimen of the renal cell carcinoma from 15 years previous. A pathological diagnosis of metastatic renal cell carcinoma of clear cell type (grade 1) was made. PET-CT demonstrated no metastasis. The patient’s condition was successfully managed with excision of the tumor, and she remains well with no evidence of recurrence and metastasis 36 months after treatment. Metastatic renal cell carcinoma to the sphenoid sinus is rare, but it might be considered in the differential diagnosis of masses in the paranasal sinus even long after initial treatment of renal cancer

Investigation of drugs for the prevention of doxorubicin-induced cardiac events using big data analysis

Aim: Doxorubicin, an anthracycline anti-tumour agent, is an essential chemotherapeutic drug; however, the adverse events associated with doxorubicin usage, including cardiotoxicity, prevent patients from continuing treatment. Here, we used databases to explore existing approved drugs with potential preventative effects against doxorubicin-induced cardiac events and examined their efficacy and mechanisms. Methods: The Gene Expression Omnibus (GEO), Library of Integrated Network-based Cellular Signatures (LINCS), and Food and Drug Administration Adverse Events Reporting System (FAERS) databases were used to extract candidate prophylactic drugs. Mouse models of doxorubicin-induced cardiac events were generated by intraperitoneal administration of 20 mg/kg of doxorubicin on Day 1 and oral administration of prophylactic candidate drugs for 6 consecutive days beginning the day before doxorubicin administration. On Day 6, mouse hearts were extracted and examined for mRNA expression of apoptosis-related genes. Results: GEO analysis showed that doxorubicin administration upregulated 490 genes and downregulated 862 genes, and LINCS data identified sirolimus, verapamil, minoxidil, prednisolone, guanabenz, and mosapride as drugs capable of counteracting these genetic alterations. Examination of the effects of these drugs on cardiac toxicity using FAERS identified sirolimus and mosapride as new prophylactic drug candidates. In model mice, mosapride and sirolimus suppressed the Bax/Bcl-2 mRNA ratio, which is elevated in doxorubicin-induced cardiotoxicity. These drugs also suppressed the expression of inflammatory cytokines Il1b and Il6 and markers associated with myocardial fibrosis, including Lgal3 and Timp1. Conclusion: These findings suggest that doxorubicin-induced cardiac events are suppressed by the administration of mosapride and sirolimus

Efficacy of Prednisolone in Generated Myotubes Derived From Fibroblasts of Duchenne Muscular Dystrophy Patients

Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy characterized by progressive muscle degeneration. This disease is caused by the mutation or deletion of the dystrophin gene. Currently, there are no effective treatments and glucocorticoid administration is a standard care for DMD. However, the mechanism underlying prednisolone effects, which leads to increased walking, as well as decreased muscle wastage, is poorly understood. Our purpose in this study is to investigate the mechanisms of the efficacy of prednisolone for this disease. We converted fibroblasts of normal human cell line and a DMD patient sample to myotubes by MyoD transduction using a retroviral vector. In myotubes from the MyoD-transduced fibroblasts of the DMD patient, the myotube area was decreased and its apoptosis was increased. Furthermore, we confirmed that prednisolone could rescue these pathologies. Prednisolone increased the expression of not utrophin but laminin by down-regulation of MMP-2 mRNA. These results suggest that the up-regulation of laminin may be one of the mechanisms of the efficacy of prednisolone for DMD

Glutamatergic neurometabolite levels in the caudate are associated with the ability of rhythm production

IntroductionGlutamatergic neurometabolites play important roles in the basal ganglia, a hub of the brain networks involved in musical rhythm processing. We aimed to investigate the relationship between rhythm processing abilities and glutamatergic neurometabolites in the caudate.MethodsWe aquired Glutamatergic function in healthy individuals employing proton magnetic resonance spectroscopy. We targeted the right caudate and the dorsal anterior cingulate cortex (dACC) as a control region. Rhythm processing ability was assessed by the Harvard Beat Assessment Test (H-BAT).ResultsWe found negative correlations between the production part of the Beat Saliency Test in the H-BAT and glutamate and glutamine levels in the caudate (r = −0.693, p = 0.002) whereas there was no such association in the dACC.ConclusionThese results suggest that higher glutamatergic neurometabolite levels in the caudate may contribute to rhythm processing, especially the ability to produce meter in music precisely

ベバシズマブ併用化学療法中に消化管穿孔をきたした再発乳癌の１例

　ベバシズマブはパクリタキセルとの併用でHER2陰性の進行・再発乳癌に対する有効性が示されており，無増悪生存期間を有意に延長させる．しかし，ベバシズマブ特有の有害事象も報告されており，投与の際には注意を要する．今回，再発乳癌に対しベバシズマブを使用し，腸管穿孔を起こした１例を経験した．症例は72歳女性．右乳癌術後５年目に多発リンパ節，肺転移を認め，化学療法で治療中に８次治療としてベバシズマブとパクリタキセル（BP）療法を開始した．１年ほど奏効したが，突然，腹痛を訴え受診した．CT で腹腔内にfree air を認めたため緊急開腹術を施行した．小腸に１か所の穿孔部位を認めた．病理組織検査では，穿孔部に乳癌の転移巣が認められた．乳癌に対するベバシズマブ併用化学療法中の消化管穿孔は報告が少ない．腹膜播種を認める症例やベバシズマブ投与期間の長い患者では，腹部膨満感や腹痛を訴えた際は消化管穿孔を念頭におく必要がある．　Combination therapy with bevacizumab and paclitaxel (BP therapy) has been reported to be effective for the treatment of HER2-negative metastatic breast cancer and to significantly prolong progression-free survival. However, there are specific adverse effects induced by bevacizumab that physicians should pay attention to. We report a recent case of metastatic breast cancer with gastrointestinal perforation during bevacizumab therapy. A 72-year-old female patient had metastases into multiple lymph nodes and lungs five years after surgery for primary breast cancer, and was treated with several chemotherapies. The patient received BP therapy as the eighth treatment regimen. Although the therapy led to stable disease for approximately one year, the patient suddenly developed abdominal pain. Emergency laparotomy was performed because computed tomography revealed free air in the peritoneal cavity. A perforated lesion was found in her small intestine. On pathological examination, breast cancer metastasis was noted around the perforated site. There are few reports of gastrointestinal perforation during bevacizumab therapy for patients with metastatic breast cancer. When a patient has peritoneal dissemination, long-term BP therapy and abdominal pain, physicians should keep in mind the possibility of gastrointestinal perforation during BP therapy. (187 words