High Efficacy of Preoperative Low-Dose Radiotherapy with Sanazole (AK-2123) for Extraskeletal Ewing's Sarcoma: A Case Report

Extraskeletal Ewing's sarcoma is a rare soft tissue tumor that is morphologically indistinguishable from Ewing's sarcoma of bone. We report a case of extraskeletal Ewing's sarcoma with several systemic problems. A 69-year-old man presented with a 5-month history of a rapidly enlarging mass in the right thigh. Because preoperative radiotherapy with sanazole (AK-2123) contributed the tumor mass reduction down to 40% in size, the tumor was successfully resected with clear surgical margins and repaired with a musculocutaneous flap. The high efficacy of pre-operative low-dose radiotherapy with sanazole was histologically confirmed that the resected tumor specimen involved no viable tumor cells and showed 100% necrosis. Based on clinical outcomes in this case, the combined modality of pre-operative low-dose radiotherapy with hypoxic cell radiosensitizer and adequate surgical resection might provide for the useful clinical application of extraskeletal Ewing's sarcoma treatment

Electrical Storm in Idiopathic Ventricular Fibrillation Is Associated With Early Repolarization

ObjectivesThis study sought to characterize patients with idiopathic ventricular fibrillation (IVF) who develop electrical storms.BackgroundSome IVF patients develop ventricular fibrillation (VF) storms, but the characteristics of these patients are poorly known.MethodsNinety-one IVF patients (86% male) were selected after the exclusion of structural heart diseases, primary electrical diseases, and coronary spasm. Electrocardiogram features were compared between the patients with and without electrical storms. A VF storm was defined as VF occurring ≥3 times in 24 h and J waves >0.1 mV above the isoelectric line in contiguous leads.ResultsFourteen (15.4%) patients had VF storms occurring out-of-hospital at night or in the early morning. J waves were more closely associated with VF storms compared to patients without VF storms: 92.9% versus 36.4% (p < 0.0001). VF storms were controlled by intravenous isoproterenol, which attenuated the J-wave amplitude. After the subsidence of VF storms, the J waves decreased to the nondiagnostic level during the entire follow-up period. Implantable cardioverter-defibrillator therapy was administered to all patients during follow-up. Quinidine therapy was limited, but the patients on disopyramide (n = 3), bepridil (n = 1), or isoprenaline (n = 1) were free from VF recurrence, while VF recurred in 5 of the 9 patients who were not given antiarrhythmic drugs.ConclusionsThe VF storms in the IVF patients were highly associated with J waves that showed augmentation prior to the VF onset. Isoproterenol was effective in controlling VF and attenuated the J waves, which diminished to below the diagnostic level during follow-up. VF recurred in patients followed up without antiarrhythmic agents

microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity

褐色脂肪細胞の燃焼を促す新たなメカニズムを解明 --体の熱産生にマイクロRNA-33が関与--. 京都大学プレスリリース. 2021-02-17.Adaptive thermogenesis is essential for survival, and therefore is tightly regulated by a central neural circuit. Here, we show that microRNA (miR)-33 in the brain is indispensable for adaptive thermogenesis. Cold stress increases miR-33 levels in the hypothalamus and miR-33−/− mice are unable to maintain body temperature in cold environments due to reduced sympathetic nerve activity and impaired brown adipose tissue (BAT) thermogenesis. Analysis of miR-33f/f dopamine-β-hydroxylase (DBH)-Cre mice indicates the importance of miR-33 in Dbh-positive cells. Mechanistically, miR-33 deficiency upregulates gamma-aminobutyric acid (GABA)A receptor subunit genes such as Gabrb2 and Gabra4. Knock-down of these genes in Dbh-positive neurons rescues the impaired cold-induced thermogenesis in miR-33f/f DBH-Cre mice. Conversely, increased gene dosage of miR-33 in mice enhances thermogenesis. Thus, miR-33 in the brain contributes to maintenance of BAT thermogenesis and whole-body metabolism via enhanced sympathetic nerve tone through suppressing GABAergic inhibitory neurotransmission. This miR-33-mediated neural mechanism may serve as a physiological adaptive defense mechanism for several stresses including cold stress

The Difference in Sterility due to High Temperatures during the Flowering Period among Japonica-Rice Varieties

The objectives of this study are to compare the floret sterility induced by a high temperature given in the daytime during the flowering period among nine japonica rice varieties, and to clarify the mechanism of the high-temperature-induced sterility. Nine japonica rice varieties were subjected to 35.0, 37.5 or 40.0°C day- temperature conditions (1000-1600) for six consecutive days using sun-lit phytotrons, and the percentage of fertility, pollination and germinated pollen grains on the stigmas were examined. The temperature that caused 50% sterility varied with the variety, and a difference of approximately 3.0°C was observed between the most tolerant and susceptible varieties. Under the 37.5°C day-temperature condition, the percentage of florets with 10 or more germinated pollen grains was roughly coincident with the percent fertility, but under the 40° C day-temperature condition, it was higher than the percent fertility. Many of the florets with less than 10 germinated pollen grains had less than 20 total pollen grains on their stigmas under both temperature conditions. From these results, we concluded that sure pollination under high-temperature conditions is an important factor and that the high-temperature tolerance of the processes following pollen germination is also required for fertility under excessively high temperature conditions

High Temperature at Flowering Inhibits Swelling of Pollen Grains, a Driving Force for Thecae Dehiscence in Rice (Oryza sativa L.)

To clarify the mechanism of high temperature-induced floret sterility in rice (Oryza sativa L.), we studied the effects of high temperature at flowering on the ability of thecae to dehisce and on pollen-grain swelling which causes thecae dehiscence. Two japonica rice cultivars, grown in four L pots under submerged soil conditions were subjected to high (39°C) and moderate (34°C) temperatures from 10 : 00 to 16 : 00 for three consecutive days at the flowering stage. The percentage of the thecae dehisced in response to artificial opening of the florets by removing lemma and the mean diameter of the pollen grains measured during four minutes after the artificial opening were examined to determine the ability of the thecae to dehisce and that of the pollen grains to swell, respectively. The high temperature given on the day of flowering decreased both the percentage of the dehisced thecae and the diameter of the pollen grains but did not affect the relationship between them. The thecae of the plants which had been subjected to the high temperature for one or two days before flowering, however, showed a lower dehiscence percentage than those of the plant treated on the day of flowering against the same pollen-grain diameter. We concluded that high temperature given on the day of flowering decreased the ability of the pollen grains to swell resulting in poor thecae dehiscence, and that, besides this decrease, high temperature given just before the days of flowering lowered the function of thecae themselves to dehisce, causing poorer thecae dehiscence

Comparison between Anthers of two Rice (Oryza saliva L.) Cultivars with Tolerance to High Temperatures at Flowering or Susceptibility

Anthers of rice cultivar, cv. Nipponbare, which showed floret fertility even when the temperature at flowering was high(tolerant) and cv. Hinohikari, which showed floret sterility at high temperatures (susceptible) were compared. The anther of Nipponbare had better developed cavities for dehiscence and thicker locule walls than Hinohikari. The well-developed cavities enable easy rupture of the septa in response to swelling of the pollen grains. The thick locule walls promote the swelling of pollen grains by retaining water in the locules. Since the swelling of pollen grains is the driving force to open the theca and the septum rupture is an indispensable process for the theca dehiscence, the well-developed cavities and the thick locule walls may be responsible for the tolerance to high temperatures in Nipponbare

Rapid Swelling of Pollen Grains in Response to Floret Opening Unfolds Anther Locules in Rice (Oryza sativa L.)

The changes in pollen grain diameter were examined in relation to the floret opening and anther dehiscence in rice (Oryza sativa L.). In the first experiment, the florets were artificially opened by excising the top of the glumes at various times before the expected natural flowering time. Pollen diameter increased rapidly in the artificially opened florets, but slowly in the controls in which the glumes were left intact. The time of anther dehiscence coincided well with the time when pollen grains reached their maximum diameter. In addition, the pollen grain diameter was significantly correlated with the percentage of dehisced anthers in the florets artificially opened at various times. These results indicate that floret opening induces the swelling of pollen grains and that the swelling is an important event for anther dehiscence. In the second experiment, anther segments with pollen left remaining intact and those with pollen removed were immersed in water. The septa in the anther segments without pollen failed to rupture in water, whereas 70% of the septa in the anther segments with pollen left remaining ruptured, indicating that the septa can be ruptured by the swelling pressure of pollen grains resulting in unfolding of anther locules. From these findings, we infer that the rapid swelling of pollen grains in response to floret opening is a driving force to rupture the septum and unfold the locules

Stealth-nanoparticle strategy for enhancing the efficacy of steroids in mice with noise-induced hearing loss.

This study aimed to investigate the efficacy of encapsulating steroids, which is a primary choice for the treatment of sensorineural hearing loss, in polyethylene glycol-coated polylactic acid nanoparticles for drug delivery to the cochlea