Retrotransposon silencing by DNA methylation can drive mammalian genomic imprinting

Among mammals, only eutherians and marsupials are viviparous and have genomic imprinting that leads to parent-of-origin-specific differential gene expression. We used comparative analysis to investigate the origin of genomic imprinting in mammals. PEG10 (paternally expressed 10) is a retrotransposon-derived imprinted gene that has an essential role for the formation of the placenta of the mouse. Here, we show that an orthologue of PEG10 exists in another therian mammal, the marsupial tammar wallaby (Macropus eugenii), but not in a prototherian mammal, the egg-laying platypus (Ornithorhynchus anatinus), suggesting its close relationship to the origin of placentation in therian mammals. We have discovered a hitherto missing link of the imprinting mechanism between eutherians and marsupials because tammar PEG10 is the first example of a differentially methylated region (DMR) associated with genomic imprinting in marsupials. Surprisingly, the marsupial DMR was strictly limited to the 5′ region of PEG10, unlike the eutherian DMR, which covers the promoter regions of both PEG10 and the adjacent imprinted gene SGCE. These results not only demonstrate a common origin of the DMR-associated imprinting mechanism in therian mammals but provide the first demonstration that DMR-associated genomic imprinting in eutherians can originate from the repression of exogenous DNA sequences and/or retrotransposons by DNA methylation

Baseline Neutrophil-to-Lymphocyte Ratio and Glasgow Prognostic Score are Associated with Clinical Outcome in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Treated with Nivolumab

Recurrent or metastatic head and neck squamous cell carcinoma (R/MHNSCC) has a poor prognosis. Although nivolumab is approved in Japan for treating R/MHNSCC, the response rate is low. Therefore, identifying pretreatment prognostic factors is necessary. This study assessed the utility of the neutrophil-to-lymphocyte ratio (NLR) and Glasgow Prognostic Score (GPS) as biomarkers of response to nivolumab. We retrospectively collected the data of 56 R/MHNSCC patients treated with nivolumab between May 2017 and December 2019. The Kaplan–Meier method and log-rank test were used to estimate overall survival (OS) and progression-free survival (PFS), and multivariate Cox hazard regression analysis was used to identify independent predictors of survival. Patients with a low pretreatment NLR had prolonged OS, and patients with a low pretreatment GPS had increased OS and PFS. A performance score (PS) of 0-1, development of immune-related adverse events, and GPS of 0-1 were significantly associated with OS in multivariate analysis. In summary, baseline pretreatment NLR and GPS are independently associated with OS in R/MHNSCC patients treated with nivolumab. Administration of nivolumab while maintaining the PS reflects a immune status of the host and leads to a good OS

A Case of Primary Osteosarcoma of the Mandible That Responded to Preoperative Chemotherapy: p16 as a Potential Prognostic Factor

We report a case of mandibular osteosarcoma in a Japanese woman in her 70s who was p16-positive. Despite the rapid growth of the tumor, the patient responded well to chemotherapy and was then able to undergo surgery. Head and neck osteosarcoma (HNOS) is a very rare cancer, and although the importance of surgery has been pointed out, the effectiveness of chemotherapy is unclear. Resection margin negativity and response to chemotherapy have been reported as prognostic factors; another report assessed the effectiveness of the immunohistochemical expression of p16 protein as a predictor of response to chemotherapy

Comparison of Nasal Nitric Oxide Levels between the Inferior Turbinate Surface the Middle Meatus in Patients with Symptomatic Allergic Rhinitis

ABSTRACTBackground: Because of the anatomical complexity and the high output of the human nose, it has been unclear whether nasal nitric oxide (NO) serves as a reliable marker of allergic rhinitis (AR). We examined whether nasal NO levels in the inferior turbinate (IT) surface and the middle meatus (MM) differ in symptomatic AR patients.Methods: We measured fractional exhaled NO (FeNO) and nasal NO in normal subjects (n = 50) and AR patients with mild symptoms (n = 16) or moderate or severe symptoms (n = 27). Nasal NO measurements were obtained using an electrochemical analyzer connected to a catheter and an air-suction pump (flow rate 50 mL/ sec).Results: Compared to the normal subjects, the AR patients showed significantly higher nasal FeNO and nasal NO levels in the IT area. No significant difference in the MM area was observed among the three groups. The MM area showed higher NO levels than the IT area in all three groups. The ratio of nasal NO levels of the MM area to the IT area (MM/IT ratio) was significantly lower in the AR groups. The moderate/severe AR patients showed significantly higher nasal NO in the IT area (104.4 vs. 66.2 ppb) and lower MM/IT ratios than those in the mild AR patients. The analysis of nasal brushing cells revealed significantly higher eosinophil cationic protein and nitrotyrosine levels in the AR groups.Conclusions: Nasal NO assessment in the IT area directly reflects persistent eosinophilic inflammation and may be a valid marker to estimate the severity of AR

Management of Intractable Nasal Hyperreactivity by Selective Resection of Posterior Nasal Nerve Branches

The posterior nasal nerves emerge from the sphenopalatine foramen and contain sensory and autonomic nerve components. Posterior nasal neurectomy is an effective method to remove pathological neural networks surrounding the inferior turbinate that cause unregulated nasal hypersensitivity with excess secretion in patients with severe allergic rhinitis (AR). We describe the sophisticated endoscopic surgical procedure that allows feasible access to the confined area and selective resection of the nerve branches with the preservation of the sphenopalatine artery (SPA). We retrospectively analyzed the cases of 23 symptomatic severe AR patients who failed to respond to standard medical treatment and underwent surgery. There have been no major complications after surgery including nasal bleeding or transient numbness of the upper teeth. The mean total nasal symptom scores (TNSS) were decreased by 70.2% at 12 months after the procedure. Our comparison of the clinical effectiveness based on the number of severed nerve branches revealed that the improvement of the TNSS was significantly higher in patients with >2 branches. We conclude that this minimally invasive technique that preserves the SPA is clinically useful and decreases the rate of postoperative complications. This trial is registered with UMIN000029025

Survival of Bacteria at a Subfreezing Temperature (－1°C)

Preservation of foodstuffs at temperatures around ?1°C has attracted special interest recently. We investigated whether bacteria contaminating foodstuffs, especially contaminating fish, were killed or survived at ?1°C compared with 37°C. Survival rates of Escherichia coli K12 and Staphylococcus aureus IFO12732 in nutrient broth at ?1°C for 7 days were 52% and 31%, respectively. However, the survival rate of Vibrio parahaemolyticus in nutrient broth containing 3% NaCl at ?1°C for 7days was only 0.03%. When the bacteria were kept in a soy sauce solution containing alcohol and some seasonings (the soy sauce solution) at ?1°C, survival rates of E. coli K12 and S. aureus IFO12732 after 2 days were 56% and 54%, respectively, but V. parahaemolyticus was completely killed after 24 h at ?1°C in the soy sauce solution. When E. coli K12 and O157 and V. parahaemolyticus were incubated at ?1°C in the soy sauce solution containing some pieces of raw fish (the improved soy sauce solution), 3 strains of the bacteria were not killed. These results indicate that bacteria contaminating fish are not killed at ?1°C and that storage of fish at ?1°C is not always effective in diminishing food poisoning

Evaluation of Role of Prophylactic Swallowing Rehabilitation in Chemoradiotherapy for Advanced Head and Neck Cancer Using Novel Software Analysis of Videofluorography Images

Concurrent chemoradiotherapy (CRT) for head and neck cancer (HNC) is associated with substantial side effects, most notably those related to swallowing function. Recently, early implementation of protective exercises has been recommended as an important intervention in patients treated with chemoradiotherapy. Several studies, including randomized controlled trials, have evaluated prophylactic swallowing exercises and swallowing outcomes. Although several clinical outcome measures to assess the severity of swallowing dysfunction are available, they are indirect measures. Videofluorography is the most popular and efficient examination that visually demonstrates the dynamic state of swallowing. This study aimed to determine whether prophylactic swallowing rehabilitation provided to HNC patients receiving CRT would result in better swallowing outcomes. Thirty patients were enrolled in this study. Fifteen patients (the control group) received swallowing rehabilitation after CRT on demand, and the other 15 (the rehabilitation group) received prophylactic swallowing rehabilitation from the beginning. Swallowing motion was evaluated with motion analysis software. There were statistically significant differences in hyoid bone displacement, duration of swallowing onset, larynx elevation time, and total swallowing time between the control and rehabilitation groups. Based on the results of this study, prophylactic swallowing rehabilitation seems to reduce the extent and severity of the functional problems that occur after CRT.This study was supported in part by Tsuchiya Medical Foundation Grant (no. 3010281)

Retrotransposon Silencing by DNA Methylation Can Drive Mammalian Genomic Imprinting

Among mammals, only eutherians and marsupials are viviparous and have genomic imprinting that leads to parent-of-origin-specific differential gene expression. We used comparative analysis to investigate the origin of genomic imprinting in mammals. PEG10 (paternally expressed 10) is a retrotransposon-derived imprinted gene that has an essential role for the formation of the placenta of the mouse. Here, we show that an orthologue of PEG10 exists in another therian mammal, the marsupial tammar wallaby (Macropus eugenii), but not in a prototherian mammal, the egg-laying platypus (Ornithorhynchus anatinus), suggesting its close relationship to the origin of placentation in therian mammals. We have discovered a hitherto missing link of the imprinting mechanism between eutherians and marsupials because tammar PEG10 is the first example of a differentially methylated region (DMR) associated with genomic imprinting in marsupials. Surprisingly, the marsupial DMR was strictly limited to the 5′ region of PEG10, unlike the eutherian DMR, which covers the promoter regions of both PEG10 and the adjacent imprinted gene SGCE. These results not only demonstrate a common origin of the DMR-associated imprinting mechanism in therian mammals but provide the first demonstration that DMR-associated genomic imprinting in eutherians can originate from the repression of exogenous DNA sequences and/or retrotransposons by DNA methylation

Fabrication of a ring groove on tube-inner surface by ironing from outer surface using displacement control of tube bottom end

This paper presents a improving method in a press forming for transferring convex shapes of an inner plug projection onto the tube-inner surface by applying outer-die ironing from the tube-outer surface. The previous study found that the concave shape was not perfectly formed and some “Non-filled-area” appeared around the upper and lower parts of the plug projection. This study tried to verify the effect of applying the reaction force on the tube-end surface by the finite element analysis (FEA) and experiment. The FEA showed the suitable amount of the reaction force and the optimum timing for reducing the force. The analytical results were verified by the experiment and the “Non-filled-area” was successfully reduced by the proposed method

Ganglioneuroma in The Neck Region: A Case Report

Ganglioneuroma, which rarely occurs in the neck region, is a well-differentiated benign tumor of the sympathetic nervous system. A 39-year-old man presented with neck swelling for a year. A giant tumor was located on the left side of the neck. Schwannoma was suspected on preoperative cytology and core needle biopsy, and the postoperative diagnosis on pathological examination was ganglioneuroma. The origin of the tumor was considered to be the sympathetic nervous system based on the postoperative appearance of Horner’s syndrome. The treatment choice for ganglioneuromas is complete surgical resection, contrary to the nerve-sparing resection of schwannomas. Therefore, making the definitive diagnosis before surgical resection could be important. In this report, we focus on the differential diagnosis obtained with radiological findings and the treatment strategy for the tumor with a literature review