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This article presents information on serum IgE concentrations estimated in thirty-nine patients with Down Syndrome. Patients aged between six and twenty-three years, of which six were over fifteen years of age. The control group consisted of the following two categories mental retardation controls, consisting of forty miscellaneous, non-D.S. mental retardation patients admitted to the two institutions, and non-mental retardation controls, consisting of thirty patients who visited Sapporo Nishi National Hospital, having no history of allergic diseases. The age range of the latter two groups was between six and fifteen years. Serum IgE levels were determined by radioimmune assay. Serum samples were separated within three hours after blood withdrawals and were stored at 20°G until tested.

The dermatoglyphs of 13 Japanese (eight males and five females) with duplication of the thumb were studied. The dermal patterns on the thumb were compared with those on the extra digit. A whorl on the thumb was associated with a whorl on the extra digit in two cases, a radial loop in four cases, and an arch in two cases. Where the thumb pattern was a loop the pattern on the extra digit was a loop in all three cases. Where the thumb and extra digit are both well developed the pattern tends to be the same on both digits. When the extra digit is poorly developed it tends to have a different pattern from the thumb. [ABSTRACT FROM PUBLISHER]

The dermatoglyphs of 28 Japanese with Klinefelter's syndrome [24 XXY; 2 XXYY; 1 XXXY; 1 XXXXY] were compared with 544 male and 129 female controls. These patients showed high frequencies of fingertip arches pattern, right third interdigital loops, right hypothenar patterns (Lr) and line C terminating 0 in the right hand. The mean summed a-b ridge count of Klinefelter's syndrome patients was significantly lower than that of the male controls. We suggest that an increase in the number of X or Y chromosomes decreased the a-b ridge count in a similar way to the decrease in total finger ridge count. [ABSTRACT FROM PUBLISHER]

In thoracoscopic surgery for mediastinal or chest wall lesions the suitable position of ports( trocars) are required depending on the position of a target lesion in a particular patient. We have therefore developed a virtual reality (VR) simulation system using the specific data of each individual patient. The model data generation system, PASS-GEN, is customized for thoracic surgery. The chest wall and organs around the tumor are extracted from DICOM image data of computed tomography (CT) scan, and three-dimensional (3D) virtual images are constructed. Rehearsal of ports insertion is carried out by locating the scope and the forceps anywhere on the chest wall on PC monitor. The constructed VR images clearly show three dimensional relationships between the target and surrounding structures. This system also simulates circumstances where on the chest wall a thoracoscope and tools should be inserted for the better view and more comfortable manipulation. Particularly in mediastinal or chest wall surgery VR simulation is more practical because those structures would be less transformed during operation.

Strategies for gene and nucleic acid delivery to skeletal muscles have been extensively explored to treat Duchenne muscular dystrophy (DMD) and other neuromuscular diseases. Of these, effective intravascular delivery of naked plasmid DNA (pDNA) and nucleic acids into muscles is an attractive approach, given the high capillary density in close contact with myofibers. We developed lipid-based nanobubbles (NBs) using polyethylene-glycol-modified liposomes and an echo-contrast gas and found that these NBs could improve tissue permeability by ultrasound (US)-induced cavitation. Herein, we delivered naked pDNA or antisense phosphorodiamidate morpholino oligomers (PMOs) into the regional hindlimb muscle via limb perfusion using NBs and US exposure. pDNA encoding the luciferase gene was injected with NBs via limb perfusion into normal mice with application of US. High luciferase activity was achieved in a wide area of the limb muscle. DMD model mice were administered PMOs, designed to skip the mutated exon 23 of the dystrophin gene, with NBs via intravenous limb perfusion, followed by US exposure. The number of dystrophin-positive fibers increased in the muscles of mdx mice. Combining NBs and US exposure, which can be widely delivered to the hind limb muscles via the limb vein, could be an effective therapeutic approach for DMD and other neuromuscular disorders.

Background and Objective: For the purpose of facilitating a wide view and working space during surgery such as a thymectomy procedure, as well as that for treatment of anterior mediastinal lesions, anterior chest wall lifting began to be employed. In this article, previous reports of various kinds of chest wall lifting methods are reviewed., Methods: The present study focused on procedures used for anterior chest wall lifting in a review of related studies primarily available in English. A search of the PubMed database was conducted in 1st March 2016. The first description about lifting method was reported in 1988., Key Comments and Findings: Although objective evaluation regarding the effectiveness of lifting is difficult, in view of a balance among safety, reliability, and minimal invasiveness, surgeons may consider chest wall lifting as an optional method., Conclusions: Anterior chest wall lifting began to be employed for enlarging the working space long before the advent of endoscopic surgery. Some originally developed retractors were used in transcervical thymectomy procedures. After general acceptance of transsternal extended thymectomy for myasthenia gravis, these transcervical approaches remained an important option along with anterior chest wall lifting. Thoracoscopic surgery for the treatment of anterior mediastinal lesions was introduced in the 1990s. Particularly in cases of surgery in the supine position, various creative methods and devices of lifting the sternum body, the anterior part of the rib, or the xiphoid process were reported., Competing Interests: Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-21-43/coif). Hiroyuki Shiono serves as an unpaid editorial board member of Mediastinum., (2022 Mediastinum. All rights reserved.)

The appearance of Meadow saffron (Colchicum autumnale), which contains colchicine, closely resembles Alpine leek (Allium victorialis), a popular edible wild vegetable in Northern Japan. This often results in the accidental ingestion of Meadow saffron and acute colchicine poisoning deaths. Here, we report on a case of acute colchicine poisoning death caused by the accidental ingestion of Meadow saffron. A man in his 70 s had been given wild vegetables from his neighborhood, which were then cooked and eaten by himself and his wife. Several hours later, they suffered from abdominal pain, vomiting, and diarrhea. They immediately went to the hospital and received routine treatment. While his wife made a full recovery, he died at home two days after consumption of the vegetables. A forensic autopsy was conducted five days after ingestion of the Meadow saffron and a lethal concentration (21.5 ng/mL) of colchicine in the peripheral blood sample was detected by liquid chromatography-tandem mass spectrometry. Distribution of colchicine in body fluids, tissues and gastrointestinal contents was also investigated. Some of the plants he had eaten were identified as Alpine leek or Meadow saffron by genetic analysis of his stomach contents. Histopathological examination showed apoptotic cells and cell cycle arrest at the metaphase in the intestinal crypts and testis. In addition, we detected high concentrations of endotoxins and tumor necrosis factor-α in his blood, indicating that intestinal mucosal injury induced by colchicine poisoning had allowed endotoxins to invade the body, causing death by endotoxin shock., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Various surgical procedures have been performed to decrease the recurrence of primary spontaneous pneumothorax after video-assisted thoracic surgery. This study aimed to examine the efficiency of pleural coverage for the prevention of postoperative recurrence in relatively young patients., Methods: Between January 2008 and December 2012, a total of 357 cases of 345 patients (age 15-29 years) with primary spontaneous pneumothorax who underwent bullectomy at 13 institutions were enrolled in this multi-institutional retrospective cohort study. A concurrent bilateral operation was counted as two cases. Polyglycolic acid sheets were used in 238 cases, and oxidized regenerated cellulose sheets were used in 37 cases to cover the visceral pleura, with no pleural coverage in 82 cases. The average observation period was 4.2 ± 2.0 years., Results: Postoperative recurrence was observed in 50 cases (14.0%) after video-assisted thoracic surgery. Twenty-six cases (10.9%) in the polyglycolic acid group, eight (21.6%) in the oxidized regenerated cellulose group, and sixteen (19.5%) in the non-coverage group experienced postoperative recurrence. Kaplan-Meier analysis revealed that the rate of freedom from postoperative recurrence in the polyglycolic acid group was significantly higher than that in the non-coverage group. Multivariate analysis showed that age ≥ 20 years and coverage with polyglycolic acid sheets were associated with reduced risk factors for postoperative recurrence., Conclusion: Pleural coverage with a polyglycolic acid sheet is suggested to be effective in preventing postoperative recurrence of pneumothorax compared with non-coverage in relatively young patients., (© 2021. The Japanese Association for Thoracic Surgery.)

Rationale: The relationship between thymic tumors and Sjögren syndrome (SjS) is unknown, and surgical resection has not been optimized. Especially, thymic carcinoma with autoimmune disease is rare. Analysis of SS-A52, germinal centers, plasma cells, and Foxp3+ Treg in thymic carcinoma has never been reported, and their pathological roles in causing SjS have not been studied., Patient Concerns: A 78-year-old man presented with sputum production and xerostomia while asleep. Chest computed tomography showed a homogeneous and hypodense mass in the anterosuperior mediastinum. Serum levels of the antinuclear antibody, antibody to SS-A, and antibody to SS-B were positive., Diagnoses: Thymic carcinoma (squamous cell carcinoma) and SjS., Interventions: Video-assisted thoracoscopic resection of the mediastinal tumor and postoperative radiation therapy was performed., Outcomes: The histological diagnosis was thymic squamous cell carcinoma. Histologically, the squamous carcinomatous cells were arranged in nests and cords in the fibrohyaline stroma with capsular invasion. In the stroma, dense lymphoid tissues containing large reactive germinal centers and many plasma cells were also noted. In the involuted thymus, CD20-positive mature lymphocytes infiltrated, and germinal centers were noted. Double immunohistochemical staining revealed that SS-A52 antigen was positive in both the carcinoma component and CD20-positive mature B cells. Postoperatively, the xerostomia persisted, and serum SS-A and SS-B remained positive. No evidence of carcinoma recurrence with chest computed tomography scan was observed at 18-months follow-up., Lessons: In the surgical treatment of thymic tumors with SjS, extended thymectomy might be worth considering to stop the progressive destruction of the targets of SjS-specific autoantibodies. However, the postoperative symptoms may not dramatically improve because the target organs might have changed irreversibly, and memory B cells might persist. This is the first report that demonstrated the SS-A52 antigen presentation in a thymic tumor to the best of our knowledge., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Solitary pulmonary nodules caused by nontuberculous mycobacteriosis are included as a category of pulmonary nontuberculous mycobacterium disease. Clinical characteristics, treatments and prognosis are not fully known because there are a few related reports., Methods: This was a multi-center retrospective study of 101 cases diagnosed as solitary nodular type of nontuberculous mycobacteriosis from January 2000 to March 2017 that underwent resection at 9 related facilities belonging to the Thoracic Surgery Study Group of Osaka., Results: The most common pathogen was Mycobacterium avium complex (n=77, 87.5%), followed by Mycobacterium kansasii (n=8, 9.1%). Chest computed tomography results showed subpleural locations that were difficult to distinguish from lung cancer. Fluorodeoxyglucose positron emission tomography/computed tomography was performed in 58 cases and positive results were obtained in 35 (60.3%), with an average maximum standardized uptake value of 3.87. The purpose of resection in most cases was for diagnosis. The surgical procedure was wedge resection in 87, segmentectomy in 3, and lobectomy in 11, while 77 underwent thoracoscopic surgery. Postoperative complications occurred in 7 cases, though no infections caused by nontuberculous mycobacteriosis were noted. The median observation period was 27 months. A worsened condition occurred in 10 (9.9%) with Mycobacterium avium complex , though none had local recurrence., Conclusions: Solitary pulmonary nodules due to nontuberculous mycobacteriosis is difficult to diagnose based on preoperative examination results or distinguish from lung cancer. Among the present cases, none had local complications or recurrence, even in those that underwent a wedge resection, thus postoperative chemotherapy was not considered necessary if a complete resection was performed. On the other hand, some cases showed reinfection after a long period following resection, thus patients should be informed of that future possibility., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-3108). The authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Background: The clinical outcome of patients undergoing hemodialysis (HD) has not yet been clarified in lung cancer surgery. The aims of this study were to assess the clinical features, outcomes, and main cause of death after lung cancer surgery in patients undergoing HD and to evaluate the risk factors for postoperative complications., Methods: The study identified 39 patients undergoing HD who had lung cancer surgery in 9 institutions under the Thoracic Surgery Study Group of Osaka University in Japan between 2007 and 2016. Study investigators retrospectively analyzed the surgical outcomes of these patients., Results: Most patients were male and were smokers. Diabetes mellitus was the most common cause of primary renal disease. Lobectomy with systemic lymph node dissection was performed in 16 patients, and an extended operation was performed in 6 patients. Most patients had a diagnosis of pathologic stage IA (69.2%) lung cancer. The overall complication and mortality rates were 30.8% and 7.7%, respectively. Pneumonia was the most frequently observed complication. Extended operation was significantly associated with complications (P = .04). The 5-year overall survival rate was 57.9%, and the most common cause of death was not primary lung cancer but was a disease related to HD., Conclusions: Lung cancer surgery for patients undergoing HD provides favorable long-term outcomes despite higher postoperative mortality and morbidity rates. Because an extended operation is significantly associated with postoperative complications, thoracic surgeons should carefully select the type of resection on the basis of a balance between therapeutic benefit and invasiveness in these patients., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Winged scapula is a rare condition caused by injuries to the long thoracic nerve (LTN) and accessory nerves. A 69-year-old man underwent surgery for right lung cancer. Video-assisted thoracic surgery was converted to axillary thoracotomy at the fourth intercostal space. The latissimus dorsi was protected, and the serratus anterior was divided on the side anterior to the LTN. Two months after discharge, he presented with difficulty in elevating his right arm and protrusion of the scapula from his back. Active forward flexion of the right shoulder was limited to 110° and abduction to 130°. He was diagnosed with winged scapula. After 6 months of occupational therapy, the symptoms improved. The LTN may have been overstretched or damaged by the electric scalpel. We recommend an increased awareness of the LTN, and to divide the serratus anterior at a site as far as possible from the LTN to avoid postoperative winged scapula., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Colchicine binds to intracellular tubulin and prevents mitosis. Colchicine is also used as an anti-inflammatory drug. Meanwhile, excess administration of medication or accidental ingestion of colchicine-containing plants can cause acute colchicine poisoning, which initially results in gastrointestinal effects that may be followed by multiorgan dysfunction. However, the mechanism of colchicine poisoning remains unclear, and there are no standard therapeutic strategies., Aims: We focused on intestinal barrier function and attempted to reveal the underlying mechanism of colchicine poisoning using an animal model., Methods: Colchicine was orally administered to C57Bl/6 mice. Then, we performed histopathological analysis, serum endotoxin assays, and intestinal permeability testing. Additionally, the LPS-TLR4 signaling inhibitor TAK-242 was intraperitoneally injected after colchicine administration to analyze the therapeutic effect., Results: We observed villus height reduction and increased numbers of apoptotic cells in the gastrointestinal epithelium of colchicine-treated mice. Both intestinal permeability and serum endotoxin levels were higher in colchicine-treated mice than in control mice. Although colchicine-poisoned mice died within 25 h, those that also received TAK-242 treatment survived for more than 48 h., Conclusion: Colchicine disrupted intestinal barrier function and caused endotoxin shock. Therapeutic inhibition of LPS-TLR4 signaling might be beneficial for treating acute colchicine poisoning.

Feasibility is one of the major concerns during adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. A phase II clinical trial of adjuvant chemotherapy with four courses of carboplatin (AUC 5 at day 1) and S-1 (80 mg/m 2 /day for 2 weeks followed by a 2-week rest) was performed to evaluate the feasibility (UMIN 9101). The primary endpoint was the completion rate and the secondary endpoints were adverse events, 2-year overall survival and disease-free rates. Thirty-five non-small cell lung cancer patients were enrolled. The adjuvant chemotherapy completion rate was 85.3% (29/34); 17/34 (50%) patients completed 4 courses without dose reduction. There were no treatment-related deaths, and Grade 3/4 adverse events included neutropenia (38.2%), leukocytopenia (14.7%), anemia (20.6%), thrombocytopenia (20.6%), anorexia (5.9%), fatigue (5.9%), and oral mucositis (2.9%). Two-year overall and disease-free survival rates were 96.3% and 53.3%, respectively. Adjuvant chemotherapy with carboplatin plus S-1 is safe and feasible.

Background: Hypothermia, either therapeutically induced or accidental (ie, an involuntary decrease in core body temperature to <35°C), results in hemostatic disorders. However, it remains unclear whether hypothermia enhances or inhibits coagulation, especially in severe hypothermia. The present study evaluated the thrombocytic and hemostatic changes in hypothermic mice., Methods: C57Bl/6 mice were placed at an ambient temperature of -20°C under general anesthesia. When the rectal temperature decreased to 15°C, 10 mice were immediately euthanized, while another 10 mice were rewarmed, kept in normal conditions for 24 hours, and then euthanized. These treatments were also performed in 20 splenectomized mice., Results: The hypothermic mice had adhesion of CD62P-positive platelets with high expression of von Willebrand factor (vWF) in their spleens, while the status of the peripheral platelets was unchanged. Furthermore, the plasma levels of platelet factor 4 (PF4) and pro-platelet basic protein (PPBP), which are biomarkers for platelet degranulation, were significantly higher in hypothermic mice than in control mice, indicating that hypothermia activated the platelets in the splenic pool. Thus, we analyzed these biomarkers in asplenic mice. There was no increase in either PF4 or PPBP in splenectomized hypothermic mice. Additionally, the plasma D-dimer elevation and microthrombosis were caused in rewarmed mice, but not in asplenic rewarmed mice., Conclusions: Our results indicate that hypothermia leads to platelet activation in the spleen via the upregulation of vWF, and this activation causes hypercoagulability after rewarming., (© 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.)

BACKGROUND Herein, we describe a case of eosinophilic pneumonia that was likely to have been induced by vancomycin. CASE REPORT A 65-year-old man on maintenance hemodialysis presented with chest pain and dyspnea. He subsequently developed methicillin-resistant Staphylococcus aureus-positive acute pleural empyema in an evacuated right-sided pneumothorax. Surgical thoracoscopic curettage was ultimately performed, but dyspnea recurred postoperatively. Computed tomography depicted widespread reticular shadowing of the left lung, and peripheral eosinophilia was detected. The proportion of eosinophils found in bronchoalveolar lavage fluid was also remarkable (43%). All symptoms and the results of laboratory tests immediately improved after the discontinuation of vancomycin and initiation of prednisolone therapy. CONCLUSIONS We attribute this case of eosinophilic pneumonia to vancomycin, because all other candidate causes were ruled out, and only vancomycin fulfilled the criteria of both drug-induced eosinophilic pneumonia and drug-induced lung injury. If confirmed, this constitutes the first reported case of vancomycin-induced eosinophilic pneumonia.

We retrospectively analyzed adverse effects(AEs), overall survival(OS), and progression-free survival(PFS)in 15 consecutive patients treated with FOLFIRINOX as the first-line treatment for recurrent or unresectable pancreatic ductal adenocarcinoma( PDAC)between February 2014 and December 2017 in our hospital. Eleven patients were treated for unresectable PDAC with distant metastases(UR-M), and 4 were treated for locally advanced unresectable PDAC(UR-LA). The median age was 56(range: 40-75)years. Nine patients were male, and 6 were female. The performance status was 0 or 1 in all patients. Tumors were located in the pancreas head in 8 cases and in the body-tail in 7 cases. Grade 5 AEs were observed in 1 case in which liver abscess causing sepsis resulted in mortality. The response rate was 20.0%, and the disease control rate was 66.7%. Two patients underwent conversion surgery after FOLFIRINOX treatment. Seven patients received a nab-paclitaxel plus gemcitabine regimen as second-line treatment. The median OS and PFS were 17.0 and 8.4 months, respectively, and the 1-year survival rate was 66.7%. FOLFIRINOX for recurrent and unresectable PDAC showed relatively good tumor control. However, strict attention is required for severe AEs. Conversion surgery might be effective in patients who are good responders even if they have metastatic disease.

Locked nucleic acid (LNA) has been widely used for various genetic analyses, and has many benefits, in terms of the specificity or sensitivity of amplification, because LNA-containing primers/probes form more stable duplexes with template DNA than probes lacking LNA. Here, we developed a new method for discriminating HV1 haplotypes from mitochondrial DNA (mtDNA) mixtures by applying PCR clamping using LNA. PCR clamping is based on the selective inhibition of amplification using LNA-containing probes, which can discriminate single-nucleotide differences. Before designing probes, we selected 171 sequences with single-nucleotide variations from the HV1 region, and evaluated the specificity of LNA-containing probes for them by predicting Tm values. The differences of Tm between mismatched and exactly matched probe-template duplexes depended markedly on the type of LNA nucleotides for discriminating single-nucleotide differences, and the cytosine LNA nucleotide at the site of variations in the probes was most effective to discriminate these differences. For mixture analysis, each probe targeted one or two variations (16209C, 16217C, 16257A/16261T, 16297C/16298C, 16304C, 16362C, or 16362T) that are particularly common in the Japanese population, and seven designed probes completely inhibited the amplification of exactly matched templates. We prepared mixed samples by mixing DNA from two individuals at a ratio of 1:9, 1:4, 1:1, 4:1, or 9:1, and then performed Sanger sequencing analysis after PCR clamping with each probe. Our method distinguished each haplotype at lower ratios from two-person mixtures, and enabled sensitive detection at 12 pg of total DNA including 600 copies of mtDNA. Moreover, we analyzed three-person mixtures with representative sequences, and detected the minor haplotype of one individual present at a rate of 10% by adding two selected probes. The ability to discriminate haplotypes in mixed samples by using LNA-mediated PCR clamping indicates the potential value of mtDNA analysis in criminal investigations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Patients with adenocarcinoma of the lung are routinely screened for anaplastic lymphoma kinase (ALK) rearrangement because they can be treated by ALK-specific targeted therapy. The clinical and molecular characteristics of large-cell neuroendocrine carcinoma (LCNEC) associated with ALK rearrangement are still unclear. Herein, we assessed the ALK status in a series of patients with LCNEC by testing methods commonly used for adenocarcinoma., Materials and Methods: ALK expression was first examined by immunohistochemistry. For a positively stained tumor, molecular analyses were then conducted. The ALK fusion partner found in a patient with ALK rearrangement was further identified by direct DNA sequencing. Patient clinicopathological features were also analyzed, focusing on the ALK rearrangement-positive case., Results: Immunohistochemistry of seven patients identified strong ALK expression in one case of stage IV LCNEC. Molecular analysis identified a novel rearranged gene resulting from the fusion of kinesin family member 5B (KIF5B) exon 17 to ALK exon 20. The patient was treated with ALK-specific inhibitors, crizotinib and later, alectinib, and has remained alive for more than 24 months without disease progression. Three of the remaining six patients without ALK rearrangement had stage IV cancer and received cytotoxic chemotherapies. Their average overall survival was 5.4 months., Conclusion: To our knowledge, this is the first report of a KIF5B-ALK fusion gene in LCNEC. The patient was successfully treated with ALK inhibitors, suggesting that sensitivity to ALK inhibitor may define a specific LCNEC subtype. We propose that screening for ALK rearrangement in patients with LCNEC may assist in selecting potential candidates for targeted therapy., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Direct lymphatic drainage from a primary tumor to the right paratracheal or aortic window lymph nodes is often noted in pN2 disease. This multi-institutional retrospective study investigated the outcomes of upfront surgery in patients with clinical skip N2 disease (N2 disease without N1 disease) and a tumor in the right upper lobe or left upper segment based on results of modern radiological examinations, including positron emission tomography (PET)., Methods: We identified 143 patients with cN2 disease who underwent upfront surgery in 12 institutions under the Thoracic Surgery Study Group of Osaka University between January 2006 and December 2013. Among 143 patients, 94 who underwent PET were analyzed. We classified these patients into Group A (n=39; clinical skip N2 disease and a tumor in the right upper lobe or left upper segment) and Group B (n=55; other)., Results: The median follow-up was 56.5 months. Among the 94 patients, 50 (53.2%) had skip N2 disease and 65 (69.1%) had a tumor in the right upper lobe or left upper segment. The 5-year overall survival (OS) rates of the 94 patients with cN2 disease was 47.9%. The 5-year OS rates for the cN2pN0/1 (n=22) and cN2pN2 (n=70) groups were 74.9% and 41.2%, respectively (P=0.034). The univariate analysis of OS revealed no significant differences in age, sex, histology, carcinoembryonic antigen (CEA) level, tumor size, PET findings, and number of metastatic lymph nodes when these parameters were dichotomized. A significantly better 5-year OS rate was observed in Group A than in Group B (64.0% vs. 37.0%; P=0.039). The multivariate analysis of OS revealed that Group A was a significantly prognostic factor (P=0.030)., Conclusions: Patients with cN2 disease in Group A had a more favorable prognosis. Upfront surgery may be a treatment option for such selected patients with non-small lung cancer in the specific group., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

We analyzed the degradation level of DNA from buccal cells under humid conditions using quantitative PCR analysis. Gauze samples with buccal cells were incubated for up to 12 months under three different conditions (25 °C/dry, 25 °C/humid, or 40 °C/humid). The degradation was evaluated based on two degradation ratios (129:41 and 305:41 bp). DNA degraded slowly under the 25 °C/humid condition, and significant differences in the two degradation ratios were detected between 25 °C/dry and 25 °C/humid conditions after 12 months. Moreover, the degradation rapidly progressed under the 40 °C/humid condition, and the two degradation ratios in this condition were much lower than those from 25 °C/dry and 25 °C/humid conditions after a short incubation period (3 months). To evaluate the effect of DNA repair on low-copy degraded DNA, degenerate oligonucleotide-primed PCR (DOP-PCR) was performed before short tandem repeats (STR) genotyping. As a standard DOP-PCR, we used a 22-base primer with 10 degenerate sequences (5'-CTCGAGNNNNNNNNNNATGTGG-3'), and additionally designed DOP-PCR primers with 2, 4, 6, or 8 locked nucleic acids (LNAs). When slightly degraded DNA (305:41-bp ratio = 0.60) was used, DOP-PCR significantly increased the fluorescent intensity and success rate of genotyping using Identifiler and Globalfiler kits. In particular, the reaction with four LNAs produced the highest value. However, such benefits were not observed in the analysis of moderately degraded DNA (305:41-bp ratio = 0.13). Although the recovery rates of STR profiles by DOP-PCR were dependent on the degradation level of low-copy DNA, the effectiveness of DOP-PCR highlights the potential of LNA for degenerate sequences., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Paraquat (PQ) is a widely used herbicide in the world despite being highly toxic to humans. PQ causes fatal damage to multiple organs, especially the lungs. While oxidative stress is the main toxic mechanism of PQ, there is no established standard therapy for PQ poisoning. In this study, we investigated the cytoprotective effect of 4-phenylbutyrate (4PBA) on PQ toxicity in human lung adenocarcinoma A549 cells. Phosphorylation levels of major survival signaling kinases Akt and ERK, as well as expression levels of antioxidant enzymes catalase and superoxide dismutase 2 (SOD2) were examined. The cytoprotective mechanism of 4PBA against PQ was compared with the antioxidant reagent trolox. We demonstrated that both 4PBA and trolox attenuated PQ toxicity, but their mechanisms were different. 4PBA increased ERK2 phosphorylation levels, which could be inhibited by the PI3K inhibitor LY294002. The cytoprotective effect of 4PBA was also inhibited by LY294002. Catalase expression levels were increased by 4PBA, although this increase was not inhibited by LY294002. 4PBA did not increase SOD2 expression. Trolox did not affect phosphorylation of Akt or ERK, or the expression of antioxidant enzymes. These results suggest that 4PBA attenuated PQ cytotoxicity by ERK2 activation via PI3K. Our study may provide new findings for understanding the molecular mechanism underlying cytoprotection by 4PBA, as well as new therapeutic targets for PQ poisoning., (Copyright © 2018 Elsevier Inc. All rights reserved.)