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The methods of sampling, carrying and keeping, and the instruments for measuring atmospheric peroxyacetyl nitrate (PAN) and peroxypropionyl nitrate (PPN), were developed for field studies and had been used for the surveys on four remote islands and in the troposphere since 1991. PAN and PPN were detected in most of over 500 samples. Mean concentrations of PAN and PPN in the islands and in the lower troposphere(altitude; 400-4500 m) from the Yellow Sea to the Japan Sea are 0.1-0.4 ppb (10-9, v/v) and 0.01-0.03 ppb, respectively. Good correlation between PAN and PPN at each point was observed, and PPN was found to be 5-9% of PAN. In addition, PAN in the urban area had been monitored continuously at Ichihara close to metropolitan Tokyo since 1985. The yearly means of PAN there were constantly around 0.4 ppbfor ten years. The ratios of PANs to NOx* or NOx+ (which were detected by chemiluminescence type or Griess-Saltzman type of NOx analyzers) were found to be mostly, 1% in the urban air, 15-20% on the remote islands, and 15-60% in the lower troposphere (occasionally exceed 80% in the upper 2500 m altitude). PANs in the remote area were confirmed to be relatively more important, compared with in the urban area. The higher ratios in aircraft surveys were partly related to the atmospheric temperature in the sampling area. [ABSTRACT FROM AUTHOR]

Objective: Mirtazapine and SSRIs are widely prescribed as first-line agents for late-life depression. However, evidence for these drugs is mostly based on non-elderly patients. Therefore, we reanalyzed a randomized controlled trial of mirtazapine versus SSRIs for depression in a sub-population of late-life patients., Methods: A randomized controlled trial was conducted with 141 patients, of whom 41 were elderly, and 100 were non-elderly. This study compared SSRIs and mirtazapine in late-life depression, examined late-onset and early adult-onset separately and compared elderly and non-elderly patients for each drug. Treatment effects and adverse events were assessed using the Hamilton Depression Rating Scale and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale, respectively., Results: In late-life depression, mirtazapine showed faster HAM-D total score improvement (3.3 points difference, p = 0.021) and higher improvement in insomnia (1.7 points difference, p = 0.001) and appetite (1.2 points difference, p = 0.020). Similar findings were observed for late-onset depression with the HAM-D total score (4.3 points difference, p = 0.007) and appetite (0.9 points difference, p = 0.004), favoring mirtazapine. Depressive symptoms were generally less improved in late-life depression than in non-late-life depression. Regarding the effect of mirtazapine on appetite, late-life depression showed greater improvement (0.7 points difference, p = 0.008). Nausea and micturition disturbances were more common with SSRIs in late-life depression than in non-late-life depression. In contrast, somnolence was less common in late-life depression with mirtazapine., Conclusion: The potential usefulness of mirtazapine in elderly patients was demonstrated. The results also showed differences in the treatment response to SSRIs and mirtazapine between elderly and non-elderly patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The treatment course for depression is multifactorial, and the gold standard method for antidepressant selection remains unclear. Therefore, we focused on patients' personality as a possible indicator of the treatment response to mirtazapine and selective serotonin reuptake inhibitors (SSRIs) and whether it can contribute to antidepressant selection., Methods: One hundred one patients with major depressive disorder were randomized at baseline to receive either mirtazapine or SSRI treatment. Their personality was measured using the NEO Five-Factor Inventory at baseline, and depressive symptoms were evaluated using the Hamilton Rating Scale for Depression at baseline and 4 and 8 weeks. Stepwise multivariable logistic regression and receiver operating characteristic analyses were performed to determine the association of personality traits with remission and better antidepressant selection., Results: Neuroticism had the substantial influence on remission at 4 and 8 weeks among the entire sample. The cutoff T-score of neuroticism for predicting remission at 4 weeks was 62.5. The patients with moderate neuroticism (scores below the cutoff) were more likely to experience remission after 4-week mirtazapine treatment (remission rate: 73.7 %) than after SSRI treatment (40.0 %); those with high neuroticism (scores above the cutoff) were more likely to experience remission after 8-week SSRI treatment (74.1 %) than after mirtazapine treatment (35.7 %)., Limitations: The small sample size increased the confidence intervals., Conclusions: The treatment response of the patients with depression differed according to the type of antidepressants and degree of neuroticism. Measuring personality traits at treatment initiation may help in selecting better antidepressants and predicting the time to remission., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The JCOG0212 trial was a randomized controlled trial comparing mesorectal excision alone to mesorectal excision with lateral lymph node dissection for stage II/III lower rectal cancer patients without clinical lateral lymph node enlargement. This study aimed to identify clinicopathological prognostic factors for relapse-free survival and overall survival of lower rectal cancer in the trial., Methods: Prospective data were selected from 663 patients with complete data. Uni and multivariable Cox regression model was applied to evaluate the preoperative and the combined preoperative and postoperative factors, respectively. Preoperative factors included age, sex, performance status, clinical T, clinical N and operative procedures. Postoperative factors included histological grade, pathological T, number of metastatic lymph nodes and number of dissected lymph nodes. No patient received neoadjuvant treatment., Results: Regarding preoperative factors, multivariable analysis revealed that performance status 1 (vs. 0: HR 2.079, P = 0.0041) and cT4a (vs. cT2-3: HR 2.721, P = 0.0002) were independent risk factors for relapse-free survival, and those for overall survival were male (vs. female: HR 1.660, P = 0.0228) and cT4a (vs. cT2-3: HR 2.486, P = 0.0473). The only independent preoperative risk factor common for relapse-free survival and overall survival was cT4a. Taking preoperative and postoperative factors together, the number of metastatic lymph nodes was the only independent risk factor common for relapse-free survival and overall survival., Conclusions: Clinical stage II/III lower rectal cancer patients with cT4a should be a target of therapeutic development of neoadjuvant therapy. Postoperatively, intensive chemotherapy should be investigated for patients with more metastatic lymph nodes., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Clostridium perfringens type A-induced gas gangrene is characterized by severe myonecrosis, and α-toxin has been revealed to be a major virulence factor involved in the pathogenesis. However, the detailed mechanism is unclear. Here, we show that CD31 + endothelial cell counts decrease in muscles infected with C. perfringens in an α-toxin-dependent manner. In vitro experiments revealed that α-toxin preferentially and rapidly induces the death of human umbilical vein endothelial cells (HUVECs) compared with C2C12 murine muscle cells. The toxin induces apoptosis of HUVECs by increasing ceramide. Furthermore, the specificity might be dependent on differences in the sensitivity to ceramide between these cell lines. Together, our results suggest that α-toxin-induced endothelial cell death promotes severe myonecrosis and is involved in the pathogenesis of C. perfringens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A 43-year-old man underwent a low anterior resection of the rectum due to upper rectal cancer. The pathological Stage was Ⅳ with para-aortic lymph node metastasis. Postoperative chemotherapy with CapeOX was initiated, but para-aortic lymph node metastasis was discovered 4months after the surgery. Chemoradiation therapy with Cape and Bev, and 70 Gy/28 Fr led to the disappearance of the metastasized lesions. At 13months after the surgery, FDG accumulation was observed in the Virchow's lymph node, and chemotherapy with IRIS and Bev was initially administered. Subsequently, chemoradiation therapy with S-1 and Bev, and 66 Gy/33Fr was administered, followed by chemotherapy with S-1 and Bev, S-1. These therapies led to complete response(CR). However, 35 months after the surgery, the Virchow's lymph node had enlarged again, and chemoradiation therapy with S-1 and 60 Gy/30Fr was administered. Although no FDG accumulation was detected in the lymph node at 40 months after the surgery, metastasis was found in the mediastinal lymph nodes. Panitumumab therapy achieved CR, and no metastasis had been identified at 60 months after the final therapy. Chemoradiation therapy is a treatment option to improve the prognosis of patients with metastasis only in the Virchow's lymph node.

Clostridium perfringens type A causes gas gangrene characterized by myonecrosis and development of an effective therapy for treating affected patients is of clinical importance. It was recently reported that the expression of granulocyte colony-stimulating factor (G-CSF) is greatly up-regulated by C. perfringens infection. However, the role of G-CSF in C. perfringens -mediated myonecrosis is still unclear. Here, we assessed the destructive changes in C. perfringens -infected skeletal muscles and tested whether inhibition of G-CSF receptor (G-CSFR) signaling or administration of recombinant G-CSF affects the tissue injury. Severe edema, contraction of muscle fiber diameter, and increased plasma creatine kinase activity were observed in mice intramuscularly injected with C. perfringens type A, and the destructive changes were α-toxin-dependent, indicating that infection induces the destruction of skeletal muscle in an α-toxin-dependent manner. G-CSF plays important roles in the protection of tissue against damage and in the regeneration of injured tissue. However, administration of a neutralizing antibody against G-CSFR had no profound impact on the destructive changes to skeletal muscle. Moreover, administration of recombinant human G-CSF, filgrastim, imparted no inhibitory effect against the destructive changes caused by C. perfringens . Together, these results indicate that G-CSF is not beneficial for treating C. perfringens α-toxin-mediated myonecrosis, but highlight the importance of revealing the mechanism by which C. perfringens negates the protective effects of G-CSF in skeletal muscle.

Background: Mesorectal excision (ME) is the standard surgical procedure for lower rectal cancer. However, in Japan, total or tumor-specific ME with lateral pelvic lymph node dissection (LLND) is the standard surgical procedure for patients with clinical stages II or III lower rectal cancer, because lateral pelvic lymph node metastasis occasionally occurs in these patients. The aim of study was to elucidate the predictive factors of pathological lateral pelvic lymph node metastasis in patients without clinical lateral pelvic lymph node metastasis., Methods: Data form the clinical trial (JCOG0212) was analyzed. The JCOG0212 was a randomized controlled trial to confirm the non-inferiority of mesorectal excision alone to mesorectal excision with lateral lymph node dissection for clinical stage II/III patients who don't have clinical lateral pelvic lymph node metastasis in terms of relapse free survival. This study was conducted at a multitude of institution33 major hospitals in Japan. Among the 351 patients who underwent lateral lymph node dissection in the JCOG0212 study, 328 patients were included in this study. Associations between pathological lateral pelvic lymph node metastasis and preoperative and postoperative factors were investigated. The preoperative factors were age, sex, clinical stage, tumor location, distance from anal verge, tumor size, and short-axis diameter of lateral pelvic lymph node on computed tomography and the postoperative factors were pathological T, pathological N, and histological grade., Results: Among the 328 patients, 24 (7.3%) had pathological lateral pelvic lymph node metastasis. In multivariable analysis of the preoperative factors, patient age (p = 0.067), tumor location (p = 0.025), and short-axis diameter of lateral pelvic lymph node (p = 0.002) were significantly associated with pathological lateral pelvic lymph node metastasis., Conclusions: Patient age, tumor location, and short-axis diameter of lateral pelvic lymph node were predictive factors of pathological lateral pelvic lymph node metastasis., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

During bacterial infection, granulocyte colony-stimulating factor (G-CSF) is produced and accelerates neutrophil production from their progenitors. This process, termed granulopoiesis, strengthens host defense, but Clostridium perfringens α-toxin impairs granulopoiesis via an unknown mechanism. Here, we tested whether G-CSF accounts for the α-toxin-mediated impairment of granulopoiesis. We find that α-toxin dramatically accelerates G-CSF production from endothelial cells in response to Toll-like receptor 2 (TLR2) agonists through activation of the c-Jun N-terminal kinase (JNK) signaling pathway. Meanwhile, α-toxin inhibits G-CSF-mediated cell proliferation of Ly-6G + neutrophils by inducing degradation of G-CSF receptor (G-CSFR). During sepsis, administration of α-toxin promotes lethality and tissue injury accompanied by accelerated production of inflammatory cytokines in a TLR4-dependent manner. Together, our results illustrate that α-toxin disturbs G-CSF-mediated granulopoiesis by reducing the expression of G-CSFR on neutrophils while augmenting septic shock due to excess inflammatory cytokine release, which provides a new mechanism to explain how pathogenic bacteria modulate the host immune system., Competing Interests: The authors declare no competing interests.

Objective: The aim of the study was to confirm the noninferiority of mesorectal excision (ME) alone to ME with lateral lymph node dissection (LLND) in terms of efficacy., Background: Lateral pelvic lymph node metastasis is occasionally found in clinical stage II or III lower rectal cancer, and ME with LLND is the standard procedure in Japan. ME alone, however, is the international standard surgical procedure for rectal cancer., Methods: Eligibility criteria included histologically proven rectal cancer at clinical stage II/III; main lesion located in the rectum, with the lower margin below the peritoneal reflection; no lateral pelvic lymph node enlargement; Peformance Status of 0 or 1; and age 20 to 75 years. Patients were intraoperatively allocated to undergo ME with LLND or ME alone in a randomized manner. The primary endpoint was relapse-free survival, with a noninferiority margin for the hazard ratio of 1.34. Secondary endpoints included overall survival and local-recurrence-free survival. Analysis was by intention to treat., Results: In total, 701 patients were randomized to the ME with LLND (n = 351) and ME alone (n = 350) groups. The 5-year relapse-free survival in the ME with LLND and ME alone groups were 73.4% and 73.3%, respectively (hazard ratio: 1.07, 90.9% confidence interval 0.84-1.36), with a 1-sided P value for noninferiority of 0.0547. The 5-year overall survival, and 5-year local-recurrence-free survival in the ME with LLND and ME alone groups were 92.6% and 90.2%, and 87.7% and 82.4%, respectively. The numbers of patients with local recurrence were 26 (7.4%) and 44 (12.6%) in the ME with LLND and ME alone groups, respectively (P = 0.024)., Conclusions: The noninferiority of ME alone to ME with LLND was not confirmed in the intent-to-treat analysis. ME with LLND had a lower local recurrence, especially in the lateral pelvis, compared to ME alone.

We aimed to compare the efficacy and tolerability of mirtazapine versus SSRIs and to assess whether "non-response at week 4" may be a clinical indicator for combining mirtazapine and SSRIs for subsequent treatment. One-hundred fifty-four outpatients with MDD were randomized to receive mirtazapine or SSRIs in step I (4 weeks). Non-responders in step I were randomly assigned to either mirtazapine or SSRIs monotherapy or their combination in step IIa while responders in step I continued the same monotherapy in step IIb for 4 weeks. In step I, mirtazapine showed significantly faster improvement as shown by higher remission rate at week 2 with NNT = 8 compared to SSRIs. Somnolence rate was higher in mirtazapine and nausea rate was higher in SSRIs. In step IIa, combination therapy showed a more favorable time course than SSRIs monotherapy. For subjects taking SSRIs in step I, combination therapy showed significant better improvement in the Hamilton Depression Rating (HAM-D) score both at week 6 (p = 0.006) and 8 (p = 0.013) than SSRIs monotherapy. About 80% of responders at week 4 could reach remission at week 8 and 64% of non-responders could not reach remission at week 8 for patients who continued monotherapy. When mirtazapine was added on for SSRIs non-responders at week 4, the remission rate increased by 5% and HAM-D score improved by 4 points. While for mirtazapine non-responders, SSRIs add-on was not equally effective. Mirtazapine may provide a faster improvement and "non-response at week 4" may be indicator to mirtazapine add-on for patients receiving SSRIs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Major surgery in hemophilia patients has been facilitated by the development of coagulation concentrates. However, it is still difficult to manage bleeding during major surgery in patients with inhibitors to FVIII/IX. In addition, there have been few reports of major surgery in hemophilia B with high responding inhibitors. We report a 26-year-old hemophilia B patient with high responding factor IX inhibitor who demonstrated severe hemophiliac arthropathy in his left hip joint. Total hip arthroplasty was performed with a high dose of FIX followed by recombinant FVIIa. His inhibitor titer was decreased from 111 BU/ml to 1.0 BU/ml at surgery by avoiding the use of FIX concentrates. Thus, we could use high dose FIX for the management of surgical bleeding. Anamnestic response occurred on the 7th day after surgery and FIX concentrates were switched to recombinant FVIIa. The whole process was safely managed without any excess bleeding or adverse effects. The successful use of high dose FIX followed by recombinant FVIIa suggests that even major surgery could be safely performed in hemophilia B patients with a low titer of high responding inhibitors.

Background: Factors associated with liver stiffness (LS) are unknown and normal reference values for LS have not been established. Individuals at high risk for alcoholic (ALD) and non-alcoholic fatty (NAFLD) liver disease need to be non-invasively discriminated during routine health checks. Factors related to LS measured using a FibroScan and normal reference values for LS are presented in this report., Methods: We measured LS using a FibroScan in 416 consecutive individuals who presented for routine medical checks. We also investigated the relationship between LS and age, body mass index (BMI), liver function (LF), alcohol consumption, and fatty liver determined by ultrasonography. We identified individuals at high-risk for ALD and NAFLD as having a higher LS value than the normal upper limit detected in 171 healthy controls., Results: The LS value for all individuals was 4.7 +/- 1.5 kPa (mean +/- SD) and LS significantly and positively correlated with BMI and LF test results. The LS was significantly higher among individuals with, than without fatty liver. Liver stiffness in the 171 healthy controls was 4.3 +/- 0.81 kPa and the upper limit of LS in the normal controls was 5.9 kPa. We found that 60 (14.3%) of 416 study participants had abnormal LS. The proportion of individuals whose LS values exceeded the normal upper limit was over five-fold higher among those with, than without fatty liver accompanied by abnormal LF test results., Conclusions: Liver stiffness could be used to non-invasively monitor the progression of chronic liver diseases and to discriminate individuals at high risk for ALD and NAFLD during routine health assessments.

The patient was a 56-year-old female. At the age of 35 years, she had under gone left mastectomy and axillary lymph node dissection for breast cancer. After surgery, hormonal therapy was continued for 3 years. Then, no treatment was performed. In this study, single therapy with an AI agent was started to treatbilateral supraclavicular fossa/mediastinal lymphnode metastases. After 6 months, a partial response(PR)was achieved. However, progression of the disease(PD)was noted after 1 year. Thereafter,the regimen was switched to single high-dose(120mg/day)TOR therapy. CT revealed the disappearance of the bilateral supraclavicular fossa lymphnodes and a marked reduction of the other lymphnodes. Currently, the patient is being treated, with an interval of 10 months from the start of TOR therapy.

Pregnancy-associated breast carcinoma is generally defined as cancer that occurs during pregnancy or within 1 year of delivery, although treatment options are the most complicated when the disease is diagnosed during pregnancy. We report the case of a 30-year-old woman who was diagnosed with breast cancer at her 9th week of pregnancy. The patient initially had mastectomy with axillary lymph node dissection. She began adjuvant therapy with 3 courses of epirubicin/cyclophosphamide at 19 weeks of gestation. After delivery of a healthy child, she received one course of epirubicin/cyclophosphamide and 4 courses of docetaxel. Although the data are limited, pregnant patients with cancer can be treated with systemic chemotherapy with minimal risks to the fetus during the second or third trimester. Management of breast cancer during pregnancy requires an interdisciplinary care team and careful consideration of the patient's stage of disease, the gestational age of the fetus, and the preferences of the patient and her family.

A 72-year-old female was admitted to our hospital with the complaint of left neck lymph node swelling. Abdominal computed tomography (CT) revealed wall thickening of the small intestine and multiple lymph node metastases. Barium meal study of the small intestine showed circular stenosis. The patient was operated on under a diagnosis of tumor of the small intestine and left neck lymph node swelling. Needle biopsy of the left neck lymph node and partial resection of the small intestine was done without regional lymph node dissection because of Virchow lymph node metastasis. On the resected material a 5 x 4 cm type 2 tumor was identified. Pathological findings included poorly-differentiated adenocarcinoma, si (bladder), n 4, P 0, ly 3, v 3, H 0, M(-), Stage IV. The patient received the chemotherapy with TS-1. TS-1(80 mg/body/day) orally administered for 4 weeks followed by a drug-free 2-week period as one course. CT revealed that the metastatic lesion had shrunk markedly after the second course. A complete response (CR) was observed after one year. There were no drug side effects. At present, 3 years and 9 months after the operation, cervical and abdominal CT reveals no evidence of enlargement of the cervical and intraperitoneal lymph nodes.

Frequent chromosomal aberrations and/or losses of heterozygosity involving the short arm of chromosome 3 in carcinomas of the lung, kidney and other tissues imply that multiple putative tumor suppressor genes may be present on this chromosomal arm. To search for one of these genes, we determined DNA sequences in the genomic region at 3p22-21.3 where we had previously detected a homozygous deletion in a lung cancer cell line. The DNA sequence results of an about 685-kb region indicated that the size of the homozygously deleted segment was 638,489 bp, in which we identified only four genes including the integrin alpha RLC and the trans-Golgi p230 genes, both reported previously. The predicted amino acid sequences of one of the two novel genes showed high homology to villin, a human cytoskeleton protein; those of the other gene, termed HYA22, revealed significant homology to YA22, a hypothetical protein predicted from DNA sequences of Schizosaccharomyces pombe. The computer programs HEXON or GRAIL were able to predict three-fourths of the exons; the smallest exon predicted by either program was 46 base pairs. Repetitive sequences contained in the genomic region included 151 copies of the Alu sequence (1 copy/every 4.5 kb), 19 copies of the L1 sequence (1 copy/every 36 kb), and 10 copies of the THE sequence.

An advanced gastric cancer with liver metastasis was treated with the combination MMC, Etoposide and UFT. Etoposide was administered orally at 25-50 mg/day to the gastric cancer patient with liver metastasis. In operative findings, there was no liver and lymphoid node metastasis. The gastric tumor diminished in size and changed its characteristics due to the chemotherapy. In 19 months, no liver nor LN metastasis was observed by CT scan. Presently, the patient feels well and receives outpatient treatment.

A randomized comparative study of anticancer chemotherapy CE (CDDP plus etoposide) and CE-AVN (ACNU, VCR plus procarbazine) was carried out on 27 patients with small cell lung cancer (SCLC) without previous chemotherapy. In CE therapy, 12 patients received injection of CDDP (80 mg/m2 on day 1) and etoposide (75 mg/m2 on day 1-5) every 4 weeks (Protocol 1). Fifteen patients received 2 courses of CE and 1 course of AVN therapy (ACNU 100 mg/m2 on day 1, vincristine 0.7 mg/m2 once a week and procarbazine 50 mg/day, daily) for 6 to 8 weeks (Protocol 2). One patient (8%) and 2 patients (20%) achieved complete response with Protocol 1 and 2, respectively. Seven patients (58%) and 9 patients (60%) achieved partial response with Protocol 1 and 2, respectively. The median survival time (MST) was 12 and 14 months, and duration of remission was 4.5 and 7 months in patients treated with Protocol 1 and 2, respectively. No significant difference in MST and duration of remission in each group was observed. However, 2 patients (13%) treated with Protocol 2 survived more than 3 years. Both protocols were well tolerated with only moderate gastrointestinal symptoms, mild bone marrow toxicity and alopecia.