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Novel prognostic value and potential utility of opioid receptor gene methylation in liquid biopsy for oral cavity cancer
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）Opioids are a class of recreational drugs and prescription medications that bind to a group of G-protein-coupled receptors known as opioid receptors (ORs). ORs are involved in the development of many types of cancer; however, their role in head and neck squamous cell carcinoma (HNSCC) is complex and poorly understood. Here, we analyzed the methylation status of five OR genes in verification (301 HNSCC primary samples) and validation (five circulating tumor DNA [ctDNA] samples) studies using quantitative methylation-specific PCR (Q-MSP). OPRL1 and OPRM1 methylation levels were significantly higher in HNSCC tissues than in corresponding normal tissues from the same individuals (P=0.001 and P<0.001, respectively). In Kaplan-Meier estimate and multivariate Cox proportional hazard analyses, two genes (OPRL1 and OPRM1) were significantly associated with increased recurrence in the methylation group with oral cavity cancer. Furthermore, a validation study of ctDNA demonstrated that OPRL1 genes exhibited predictive performance as emerging biomarkers and were each capable of discriminating the plasma from tumor-free individuals. We characterized the relationship between OR gene methylation status and outcomes in oral cavity cancer. Our results highlight the potential utility of ctDNA methylation-based detection in the clinical management of oral cavity cancer
The parental involvement process regarding childhood cancer survivors becoming independent: Focus on balancing health management and social lives from adolescence to adulthood
Get PDFAim: This study aimed to elucidate the parental involvement process regarding childhood cancer survivors’ (CCSs’) independence while balancing their health management and social lives from adolescence to adulthood to obtain suggestions for long-term support for CCSs and their parents.
Methods: Semi-structured interviews were conducted with 19 parents of Japanese CCSs aged 16–25 years. The data were then qualitatively analyzed using the modified grounded theory approach.
Results: Three “categories” and 20 ‘concepts’ were generated. The connections among these categories and concepts revealed the parental involvement process regarding CCSs’ independence while balancing their health management and social lives. The first phase in this process is to “support careful behaviors,” mainly during CCSs’ treatment in the outpatient clinic or shortly after discharge. As CCSs recover after cancer treatment, parents “watch over, but feel conflicted,” with ‘conflicts between protecting their sons/daughters and giving them independence.’ Then, parents reach a phase in which they “acknowledge and entrust,” which includes ‘acknowledgment development and efforts’ of their sons/daughters, and develop an ‘attitude to entrust medical checkups to their sons/daughters, along with their preparation.’ The influencing factors of the three phases include ‘ongoing anxieties about the late effects of therapy and recurrence’ and an ‘expectation for their sons/daughters to acquire abilities for living independently.’
Conclusions: These findings suggest that nurses need to accept parents’ feelings and thoughts regarding conflicts with CCSs, recognition of CCSs’ development, and values. These processes may help nurses and health-care professionals support parents from a comprehensive perspective
Long-term effects of diffuse idiopathic skeletal hyperostosis on physical function: A longitudinal analysis
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
A convenient online desalination tube coupled with mass spectrometry for the direct detection of iodinated contrast media in untreated human spent hemodialysates.
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Taurine depletion during fetal and postnatal development blunts firing responses of neocortical layer II/III pyramidal neurons
Get PDF浜松医科大学博士（医学）doctoral医学系研究科Fetal and infant brains are rich in maternally derived taurine. We previously demonstrated that taurine action regulates the cation-chloride cotransporter activity and the differentiation and radial migration of pyramidal neuron progenitors in the developing neocortex of rodent fetuses. Here we examined the effects of fetal and infantile taurine depletion caused by knockout of the taurine transporter Slc6a6 on firing properties of layer II/III pyramidal neurons in the mouse somatosensory cortex at 3 weeks of postnatal age, using the whole-cell patch-clamp technique. The membrane excitability under resting conditions was similar between the neurons in knockout mice and those in wildtype littermates. However, the frequency of repetitive spike firing during moderate current injection was significantly lower, along with lower membrane voltage levels during interspike intervals in knockout neurons. When strong currents were injected, by which repetitive firing was rapidly abolished due to inactivation of voltage-gated Na+ channels in wildtype neurons, the firing in knockout neurons lasted for a much longer period than in wildtype neurons. This was due to much lower membrane voltage levels during interspike intervals in knockout neurons, promoting greater recovery of voltage-gated Na+ channels from inactivation. Thus, taurine depletion in pyramidal neurons blunted neuronal responses to external stimuli through increasing the stability of repetitive firing, presumably mediated by larger increases in membrane K+ conductance during interspike intervals.doctoral thesi
Palliative care for interstitial lung disease: Nationwide survey of pulmonary specialists
Get PDF雑誌掲載タイトル：Palliative care for interstitial lung disease: A nationwide survey of pulmonary specialistsBackground and objective:
Interstitial lung disease (ILD) is progressive with high symptom burdens and poor prognosis. Patients with ILD need optimal palliative care to maintain their quality of life, however, few nationwide surveys have addressed palliative care for ILD.
Methods:
A nationwide, cross-sectional survey was conducted. Questionnaires were sent by mail to pulmonary specialists certified by the Japanese Respiratory Society (n=3,423). The current practices of PC for ILD, end-of-life communication, referral to a PC team, barriers to PC for ILD, and comparison of PC between ILD and lung cancer (LC).
Results:
1,332 (38.9%) participants completed the questionnaire, and the data of 1,023 participants who had cared for ILD patients in the last year were analyzed. Most participants reported that ILD patients often or always complained of dyspnea and cough, but only 25% had referred them to a PC team. The timing of end-of-life communication tended to be later than physician-perceived ideal timing. The participants experienced significantly greater difficulty in symptomatic relief and decision-making in PC for ILD compared to LC. Prescription of opioids for dyspnea was less frequent for ILD than for LC. ILDspecific barriers in PC included an ‘inability to predict prognosis’, ‘lack of established treatments for dyspnea’, ‘shortage of psychological and social support’, and ‘difficulty for patients/families to accept the disease’s poor prognosis’.
Conclusion:
Pulmonary specialists experienced more difficulty in providing PC for ILD compared to LC and reported considerable ILD-specific barriers in PC. Multifaceted clinical studies are needed to develop optimal PC for ILD.journal articl
Association between plasma xanthine oxidoreductase activity and in-hospital outcomes in patients with stable coronary artery disease after percutaneous coronary intervention
Get PDF浜松医科大学博士（医学）doctoral医学系研究科Objectives
Reactive oxygen species generated by xanthine oxidoreductase (XOR) are associated with the progression of atherosclerosis. However, changes in plasma XOR (pXOR) activity after percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) remains unknown.
Methods
Herein, we compared the change in the pXOR activity in patients undergoing PCI with that in patients undergoing coronary angiography (CAG) and further evaluated the relation between changes in pXOR activity and in-hospital and long-term outcomes of patients undergoing PCI. The pXOR activity of 80 consecutive patients who underwent PCI and 25 patients who underwent CAG during the hospitalization was analyzed daily. The percentage changes from baseline regulated time interval was evaluated.
Results
We found that although pXOR activity decreased after PCI, and remained low until discharge, no significant changes were observed in patients undergoing CAG. Furthermore, among the patients undergoing PCI, those who experienced in-hospital adverse events, had a higher percentage of pXOR reduction 3 days after PCI. There was no association between these changes and long-term events.
Conclusions
A significant change in pXOR activity was observed in patients undergoing PCI than in patients undergoing CAG, and there seems to be a correlation between the in-hospital outcomes and the percentage reduction from baseline in pXOR activity.doctoral thesi
Assessments of therapeutic effects according to timings for combined therapy with axitinib and immune check point inhibitor in a mouse renal cell carcinoma model
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科Recently, several types of systemic therapy using tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) have been performed for advanced renal cell carcinoma (aRCC) patients; however, the optimal strategy of sequential treatment with these agents has not been well established. The objective of this study was to determine the differences of therapeutic effects according to timing for the introduction of TKI and ICI using a mouse RCC, RenCa model. The effects of combined treatment of TKI and/or ICI with axitinib, anti-mouse programmed death (PD)-1, or PD-ligand 1 (PD-L1) antibody on tumor growth and survival after subcutaneous and intravenous injection of RenCa cells, respectively, were compared according to three different treatment schedules: simultaneous administration, initial axitinib administration, and initial ICI administration. Infiltrating patterns of lymphocytes into tumors after combined treatments were evaluated by immunohistochemical staining. In mice treated with anti-PD-1 and anti-PD-L1 antibodies, significantly marked inhibitory effects on subcutaneous growth of tumors were observed in the simultaneous and initial ICI treatment groups, but not the group with the initial axitinib administration, compared to controls without treatment. Survival intervals of mice after intravenous injection of RenCa cells were significantly longer in the simultaneous and initial ICI administration, but not the initial axitinib administration, compared to the control. Furthermore, both CD8+ to CD3+ and CD8+ to CD11b+ T-lymphocyte ratios in subcutaneous RenCa tumors were significantly higher in the simultaneous and initial ICI administration, but not the initial axitinib administration, compared to the control. Favorable control against aRCC progression may be achieved by administering TKI and ICI simultaneously or ICI followed by TKI.doctoral thesi
Analysis of questionnaires regarding short and mid-term side effects following mass vaccination against COVID-19 for junior high school students in Fujinomiya City
Get PDF小児に対する新型コロナワクチン接種の中期的な影響に関する検討は限られている．我々は，ワクチンによる短・中期的な副反応を知るために，富士宮市の集団接種に参加した2107人の中学生を対象に任意のアンケートを4回行い，30～60%から回答を得た．
38℃以上の発熱は，1回目接種後に3%，2回目接種後は36%にみられた．頭痛，疲労倦怠感，食欲低下，腹痛，胸痛，めまいなどの訴えは接種を重ねるごとに増加した．中期的な症状では睡眠障害や倦怠感があった．初回接種から3か月後には，98.2％の児が打ってよかったと回答したが，事前の説明が不十分，家族と相談しなかった，家族と意見が一致しなかったと回答した児で，打たない方がよかったと回答した割合が有意に高かった．最も信頼している情報源として，テレビを挙げたものが56%と多かった．
ワクチンは大多数に受け入れられたが，年齢にあった正しい情報の伝え方や，少数の有害事象への対応について検討が必要である．journal articl
