Revisiting the Mechanism of Electric Field Sensing in Graphene Devices.

Electric field sensing has various real-life applications, such as early prediction of lightning. In this study, we effectively used graphene as an electric field sensor that can detect both positive and negative electric fields. The response of the sensor is recorded as the change in drain current under the application of an electric field. In addition, by systematic analysis, we established the mechanism of the graphene electric field sensor, and it is found to be different from the previously proposed one. The mechanism relies on the transfer of electrons between graphene and the traps at the SiO2/graphene interface. While the direction of charge transfer depends on the polarity of the applied electric field, the amount of charge transferred depends on the magnitude of the electric field. Such a charge transfer changes the carrier concentration in the graphene channel, which is reflected as the change in drain current.

Cancer-associated fibroblasts promote an immunosuppressive microenvironment through the induction and accumulation of protumoral macrophages.

Stromal cells in the tumor microenvironment (TME) closely interact with tumor cells and affect tumor cell behavior in diverse manners. We herein investigated the mechanisms by which cancer-associated fibroblasts (CAFs) affect the functional polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC) in vitro and in human cancer samples. The expression of CD68, CD14, CD163, CD200R, CD206, HLA-G, CD80, and CD86 was higher in CD14-positive cells co-cultured with the culture supernatants of CAFs established from OSCC specimens (CAF-educated cells) than in control cells. The gene expression level of ARG1, IL10, and TGFB1 was increased in CAF-educated cells. CAF-educated cells suppressed T cell proliferation more strongly than control cells, and the neutralization of TGF-ß IL-10, or arginase I significantly restored T cell proliferation. We then investigated the relationship between the infiltration of CAFs and TAMs using tissue samples obtained from patients with OSCC. The infiltration of CAFs was associated with the numbers of CD68-positive and CD163-positive macrophages. It also correlated with lymphatic invasion, vascular invasion, lymph node involvement, and the TNM stage. The infiltration of CAFs was identified as an independent prognostic factor in OSCC. Our results indicate that CAFs play important roles in shaping the tumor immunosuppressive microenvironment in OSCC by inducing the protumoral phenotype of TAMs. Therapeutic strategies to reverse CAF-mediated immunosuppression need to be considered.

[A Case Report of Acute Angioedema that Showed Dramatic Response to Administration of a C1-inactivator].

Angioedema is characterized by rapid and severe swelling of the subcutaneous and submucosal tissues. Angioedema involving the upper airway can lead to life-threatening airway obstruction, and needs prompt diagnosis and treatment. Herein, we report a case of acute angioedema which was suspected as having been caused by estrogen imbalance. A 32-year-old woman who was taking a fertility drug for infertility treatment, presented with sudden swelling of the face and neck region and breathing difficulty. Her symptoms continued to progress despite antibiotic and corticosteroid administration. We suspected hereditary angioedema (HAE), and administered a C1-inactivator, which led to immediate and dramatic resolution of the symptoms. Since the C4 and C1-inhibitor levels were normal, the possibility of HAE type III was considered. However, another possibility was that her complicated hormonal condition, including oral intake of a fertility drug, menstruation, and mental stress may have led to estrogen imbalance causing angioedema. Currently, a variety of hormone therapies is widely used ; therefore, caution is needed against the development of estrogen-dependent angioedema.

A Case of Maxillary Arteriovenous Fistula Rupture Treated by Vascular Interventional Radiology.

A 64-year-old woman with neurofibromatosis type 1 was admitted because of a sudden hematoma in her right neck and throat. To prevent an airway obstruction, tracheostomy was performed, but bleeding into the trachea persisted and was difficult to stop. Bleeding arose from a vessel lesion in the right parapharyngeal space, passed through the paratracheal space, and finally reached the tracheostomy wound. An arteriovenous fistula (AVF) in the maxillary artery was revealed by angiography. We diagnosed rupture of the varix resulting from venous high pressure caused by the AVF. The patient was treated by vascular interventional radiology (IVR). A large number of platinum coils were inserted and N-butyl-2-cyanoacrylate (NBCA) was embolized in the AVF and varix. Although innovative vascular IVR was better than surgery to treat AVF of the head and neck lesion, some problems were encountered. The cost for the provided medical services was high, and NBCA was not approved by the pharmaceutical affairs law in Japan.

Imidapril and enalapril similarly inhibit plasma matrix metalloproteinase activities and attenuate left ventricular remodeling in patients with acute myocardial infarction.

Matrix metalloproteinase (MMP) plays a critical role in the development of ventricular remodeling after acute myocardial infarction (AMI). Imidapril, an angiotensin-converting enzyme inhibitor, has been shown to inhibit MMP activity. We investigated whether imidapril inhibits plasma MMP activities and attenuates ventricular remodeling in patients with AMI in comparison with enalapril. We enrolled 70 patients with AMI. All patients underwent primary percutaneous coronary intervention and were randomly assigned either to imidapril (n = 35) or to enalapril (n = 35) treatment. Left ventriculography was performed in acute (day 14) and chronic (6 months) phases, and plasma MMP-2 and MMP-9 activities were measured by zymography. Any changes in left ventricular end-diastolic volume index and ejection fraction from acute to chronic phases did not differ between the 2 groups. The plasma MMP-2 and MMP-9 activities at day 14 were both significantly decreased compared with those at day 1 in both groups (all P < 0.05). At 6 months, MMP-9 activity still remained decreased in both groups (P < 0.05 vs. day 1). Overall, there were no differences between the 2 groups both in plasma MMP-2 and MMP-9 activities. These results demonstrate that imidapril exerts inhibitory effects on plasma MMP activities and attenuates left ventricular remodeling in patients with AMI similar to enalapril.

Successful management of hypoparathyroidism following total thyroidectomy with vitamin D(3) alone.

OBJECTIVE: To assess the efficacy and safety of a single administration of vitamin D3 for postoperative hypoparathyroidism. PATIENTS AND METHODS: Twelve patients with postoperative hypoparathyroidism were enrolled for this study. They had taken calcium and vitamin D3 orally after the surgery and had shown no symptoms of hypoparathyroidism. Then, all patients had changed their regimen to a single administration of vitamin D3 (1α(OH)D3) with monitoring of serum calcium, urine calcium (u-Ca) and creatinine (u-Cre). The dose of vitamin D3 was started at 2.0µg/day and appropriately adjusted to maintain the ratio of u-Ca and u-Cre (u-Ca/u-Cre) at less than 0.3. The physical findings were carefully checked and the serum intact-parathyroid was also estimated. Those data and physical findings were monitored for at least two years. RESULT: The maintenance dose of vitamin D3 varied from 0.5 to 3.5µg/day, and the mean dose was 2.04µg/day. All patients tolerated changes of regimen without any symptoms of hyper-/hypocalcemia. CONCLUSION: A single administration of vitamin D3 is not only safe but also an easy and cost-effective regimen. This also makes drug control easy and worthwhile both for patients and clinicians. LEVEL OF EVIDENCE: 2c.

Comparison of the effects of long-acting nifedipine CR and diltiazem R in patients with vasospastic angina: Aomori coronary spastic angina study.

OBJECTIVES: We compared the efficacy of once-daily administration of nifedipine CR 40 mg (N) with that of twice-daily diltiazem R 100mg (D) in patients with vasospastic angina (VSA) registered in 8 cardiovascular institutes in Aomori Prefecture. METHODS AND RESULTS: VSA was diagnosed by the ischemic ST segment changes during chest pain attacks at rest and/or acetylcholine induction test done during coronary angiography. Thirty-seven patients were randomly allocated to either the N (n=20) or D group (n=17). The number of symptomatic attacks and amount of short-acting nitrate use were examined based on data in diaries written by the patients. There were no significant differences in the baseline characteristics between the two groups. The mean number (median number) of attacks per week was significantly decreased in the N group from 2.56 (2.0) at baseline to 0.41 (0.0) after 4 weeks of treatment, to 0.24 (0.0) after 8 weeks, and to 0.36 (0.0) after 12 weeks (all p<0.05 vs. baseline). It was also decreased in D group from 2.71 (2.0) at baseline to 0.55 (0.0) after 4 weeks, to 0.32 (0.0) after 8 weeks, and to 0.27 (0.0) after 12 weeks (all p<0.05 vs. baseline). The numbers of attacks before and after treatment were comparable between N and D groups. In one patient in each of the N and D groups, the allocated drug was crossed over to the other due to recurrence of the attacks. One patient in each group experienced adverse effects and the drug was changed to the other. CONCLUSION: Once-daily administration of nifedipine CR was as effective as twice-daily diltiazem R in the prevention of VSA attacks.