Case report: Stereotactic body radiation therapy with 12 Gy for silencing refractory ventricular tachycardia.

Background: Encouraging results have been reported for the treatment of ventricular tachycardia (VT) with stereotactic body radiation therapy (SBRT) with 25 Gy. SBRT with 12 Gy for refractory VT was designed to reduce long-term cardiac toxicity. Methods: Stereotactic body radiation therapy-VT simulation, planning, and treatment were performed using standard techniques. A patient was treated with a marginal dose of 12 Gy in a single fraction to the planning target volume (PTV). The goal was for at least ≥ 95% of the PTV to be covered by at least 95% of 12 Gy radiation. Results: From April 2021 through June 2022, a patient with refractory VT underwent treatment. The volume for PTV was 65.8 cm3. The mean radiation dose administered to the heart (the heart volume excluding the PTV) was 2.2 Gy. No acute or late toxicity was observed after SBRT. Six months after SBRT, the patient experienced new monomorphic right ventricular outflow tract (RVOT) VT. Interestingly, the substrate of the left ventricular basal to middle posteroseptal wall before SBRT was turned into scar zones with a local voltage < 0.5 mV. Catheter ablation to treat RVOT VT was performed, and the situation remains stable to date. Conclusion: This study reports the first patient with refractory VT successfully treated with 12.0 Gy SBRT, suggesting that 12 Gy is a potential dose to treat refractory VT. Further investigations and enrollment of more patients are warranted to assess the long-term efficacy and side effects of this treatment.

Nonlinear climatic sensitivity to greenhouse gases over past 4 glacial/interglacial cycles.

The paleoclimatic sensitivity to atmospheric greenhouse gases (GHGs) has recently been suggested to be nonlinear, however a GHG threshold value associated with deglaciation remains uncertain. Here, we combine a new sea surface temperature record spanning the last 360,000 years from the southern Western Pacific Warm Pool with records from five previous studies in the equatorial Pacific to document the nonlinear relationship between climatic sensitivity and GHG levels over the past four glacial/interglacial cycles. The sensitivity of the responses to GHG concentrations rises dramatically by a factor of 2-4 at atmospheric CO2 levels of >220 ppm. Our results suggest that the equatorial Pacific acts as a nonlinear amplifier that allows global climate to transition from deglacial to full interglacial conditions once atmospheric CO2 levels reach threshold levels.

Identification of heat-shock protein 90 beta in Japanese encephalitis virus-induced secretion proteins.

Five host cellular proteins were identified in the secretion medium from Japanese encephalitis virus (JEV)-infected baby hamster kidney-21 (BHK-21) cells, including three molecular chaperones: Hsp70, GRP78 and Hsp90. Hsp90 isoforms were characterized further. Hsp90α was observed to be retained inside the nuclei, whereas Hsp90ß associated with virus particles during assembly and was released into the secretion medium upon JEV infection. The association of Hsp90ß and viral E protein was demonstrated by using sucrose-density fractionation and Western blot analysis. Moreover, JEV viral RNA replication was not affected by treatment with geldanamycin, an Hsp90 inhibitor, but impaired virus infectivity that was determined by a plaque-forming assay. Our results show that Hsp90ß, not Hsp90α, is present in the JEV-induced secretion medium and is required for JEV infectivity in BHK-21 cells.

Japanese encephalitis virus co-opts the ER-stress response protein GRP78 for viral infectivity.

The serum-free medium from Japanese encephalitis virus (JEV) infected Baby Hamster Kidney-21 (BHK-21) cell cultures was analyzed by liquid chromatography tandem mass spectrometry (LC-MS) to identify host proteins that were secreted upon viral infection. Five proteins were identified, including the molecular chaperones Hsp90, GRP78, and Hsp70. The functional role of GRP78 in the JEV life cycle was then investigated. Co-migration of GRP78 with JEV particles in sucrose density gradients was observed and co-localization of viral E protein with GRP78 was detected by immunofluorescence analysis in vivo. Knockdown of GRP78 expression by siRNA did not effect viral RNA replication, but did impair mature viral production. Mature viruses that do not co-fractionate with GPR78 displayed a significant decrease in viral infectivity. Our results support the hypothesis that JEV co-opts host cell GPR78 for use in viral maturation and in subsequent cellular infections.

A novel system for continuous peripheral arterial pressure-volume loop measurement.

This study develops a system to obtain continuous blood pressure signal and impedance plethysmography (IPG) signal, simultaneously. Based on the principle of impedance measurement, the peripheral vessel volume change can be computed from the IPG signal. Equipped with simultaneous information of pressure and volume, a pressure-volume (PV) loop can be constructed. It is well known that the left ventricular pressure-volume loop contains a number of feature points indicating the performance of cardiac function. Therefore, in this study, the same principle is used to try to discuss the peripheral vessel pressure-volume loop. Ten volunteers were recruited for this study. Subjects went through the cold pressor test by immersing their left foot into ice water. Blood pressure signal and impedance changed were recorded using a custom-made system. The results illustrated that the pressure-volume loop, as it was expected, demonstrated a contraction phenomenon after stimulation in five out of ten subjects. The areas of those pressure-volume loops reduced as much as 70% in some subject. However, loop responses to stressors varied from subject to subject and the slope of the loop did not alter significantly. In conclusion, the proposed system is a potential way to measure and to investigate the compliance and characteristic of peripheral blood vessel.