A Series of Bisamide-Substituted Diacetylenes Exhibiting a Terminal Alkyl Odd/Even Parity Effect on Mechanoactivated Photopolymerization.

Diacetylene derivatives exhibit solid-state polymerization to polydiacetylene initiated by UV light or γ-ray irradiation. The activation of the photopolymerization relies on the monomer diynes arrangement. Recently, it has been demonstrated that the first mechanoresponsive bisamide substituted diacetylenes (DAs) show dramatic switching from light-inert to light-reactive states at a given pressure. The origin of this unique phenomenon was apparently related to the pressure-sensitive crystalline transition in DAs, but the molecular mechanism remains elusive. To obtain more insight, herein a series of DAs with varying terminal alkyl spacer length is presented, and their molecular structural effect on the intermolecular hydrogen bonding and steric repulsion is examined. In pristine states, even-parity DAs were inactive upon UV irradiation (λ=254 nm) unless external pressure was applied. By contrast, odd-parity DAs were easily polymerized upon UV irradiation without pressure application. However, the pressure-induced crystalline phase transition exhibiting photopolymerization was valid for all DAs regardless of their alkyl spacer length. A systematic investigation revealed that the terminal alkyl spacer length, especially its odd/even parity plays a key role in determining the intrinsic intermolecular hydrogen-bonding nature of DA crystals and the resultant molecular packing. In addition, the relevant thermochromic behavior was also observed from photopolymerized polydiacetylenes.

Synthesis and Properties of Aromatic-Terminated Diacetylene Organogelators and Their Application to Photopatterning of Polydiacetylenes.

A series of simply structured diacetylene-diamide-based gelators (DAGs) with aromatic terminals were synthesized, and their gelation and subsequent photopolymerization abilities were analyzed. DAGs with an adequate spacer length (n) and tolyl terminals (DA-Tn) interacted with aromatic solvents, such as benzene and xylenes, at elevated temperatures. During the subsequent cooling process, the DAGs interacted with each other through CH-π interactions at their terminal positions. They also formed one-dimensional hydrogen bonding arrays through secondary amides, leading to stable organogels. These gels polymerized into π-conjugated polydiacetylenes (PDAs) under ultraviolet irradiation. In the p-xylene gels of DA-Tn, the spacer length exerted characteristic odd-even effects on the photopolymerization rates over a certain range (n = 3-6), which can be explained by periodic changes in the uniformity of the molecular packing modes. When the gelling solvent was changed to cyclohexane, the gelation and photopolymerization abilities were greatly improved because the DA-Tn gel networks became highly crystallized and transparent to ultraviolet light (254 nm). The ultimate conversion to PDA from DA-T8/cyclohexane gels was 45.2 wt %. Applying photolithographic techniques to the DAG with excellent photopolymerizability in the film state, we successfully fabricated microscale photopatterns of PDA. We also established a convenient removal process (development process) of DA monomers in unexposed areas. The resulting PDA patterns were quite stable to ambient light stimuli.

[Chronic Encapsulated Intracerebral Hematoma Associated with Arteriovenous Malformation, Shrinking after Feeder Embolization with Clinical Improvement:A Case Report].

Chronic encapsulated intracerebral hematoma(CEIH)with arteriovenous malformation(AVM)is rare. We report a case of CEIH shrinking after feeder embolization for AVM. A 60-year-old man experiencing headaches for 2 weeks was admitted to our hospital due to intracerebral hematoma detected by MRI. The hematoma was shown as a low-density mass lesion on CT scans. Angiography and enhanced MRI showed an AVM in the right temporal lobe associated with the CEIH. Mild disturbance of consciousness and headaches gradually worsened, as the CEIH grew. Before AVM resection, feeder embolization was performed. On the day after the embolization, symptoms improved and the CEIH shrunk in size. A week following the embolization, the AVM including the partial hematoma capsule was resected without neurological deficit. Previous literature showed similarities between CEIH and chronic subdural hematoma(CSDH)in clinical features and pathological findings of the capsule. This case indicated that feeder embolization might be a treatment option for CEIH with AVM, such as embolization of middle meningeal artery for intractable CSDH.

The relationship between widespread changes in gravity and cerebral blood flow.

OBJECTIVES: We investigated the dose-effect relationship between wide changes in gravity from 0 to 2.0 Gz (Δ0.5 Gz) and cerebral blood flow (CBF), to test our hypothesis that CBF has a linear relationship with levels of gravity. SUBJECTS AND METHODS: Ten healthy seated men were exposed to 0, 0.5, 1.0, 1.5, and 2.0 Gz for 21 min, by using a tilt chair and a short-arm human centrifuge. Steady-state CBF velocity (CBFV) in the middle cerebral artery by transcranial Doppler ultrasonography, mean arterial pressure (MAP) at the heart level (MAPHeart), heart rate, stroke volume, cardiac output and respiratory conditions were obtained for the last 6 min at each gravity level. Then, MAP in the middle cerebral artery (MAPMCA), reflecting cerebral perfusion pressure, was estimated. RESULTS: Steady-state CBFV decreased stepwise from 0.5 to 2.0 Gz. Steady-state heart rate, stroke volume, estimated MAPMCA and end-tidal carbon dioxide pressure (ETCO2) also changed stepwise from hypogravity to hypergravity. On the other hand, steady-state MAPHeart and cardiac output did not change significantly. Steady-state CBFV positively and linearly correlated with estimated MAPMCA and ETCO2 in most subjects. CONCLUSION: The present study demonstrated stepwise gravity-induced changes in steady-state CBFV from 0.5 to 2.0 Gz despite unchanged steady-state MAPHeart. The combined effects of reduced MAPMCA and ETCO2 likely led to stepwise decreases in CBFV. We caution that a mild increase in gravity from 0 to 2.0 Gz reduces CBF, even if arterial blood pressure at the heart level is maintained.

Speed ratio but cabin temperature positively correlated with increased heart rates among professional drivers during car races.

OBJECTIVES: The present study measures heart rate (HR) on a number of professional race-car drivers during actual car races through annual seasons to test hypotheses that faster relative speed and higher cabin temperature would induce higher HR. METHODS: Heart rates in fifteen male drivers (31.2 ± 5.5 years old) were obtained by chest-strap sensors during official-professional 13 races. Average HR was calculated while the driver was racing from the start to the end of each race. RESULTS: The average HR during races was 164.5 ± 15.1 beats min-1 and the average amount of time each driver spent driving per race was 54.2 ± 13.7 min. Average HR significantly and positively correlated with mean speed ratio (P < 0.001), but not with the average cabin temperatures (P = 0.533, range 25.6-41.8 °C) by the multiple linear regression analysis. Both average HR and mean speed ratio were significantly lower under wet, than dry conditions (151.9 ± 16.5 vs. 168.3 ± 12.5 beats min-1, 86.9 ± 4.4 vs. 93.4 ± 1.5 %). CONCLUSIONS: The cardiovascular system of drivers is considerably stressed at extremely high HR. This high average HR positively correlated with mean speed ratio, suggesting that faster driving speed would induce greater cardiovascular stress to professional drivers during actual races. However, contrary to our hypothesis, cabin temperature was not significantly correlated with average HR. It is speculated that direct body cooling systems used in this professional race category work well against increases in HR by thermal stress under the temperature range found herein.

Blunted cutaneous vasoconstriction and increased frequency of presyncope during an orthostatic challenge under moderate heat stress in the morning.

PURPOSE: In normothermia, the tolerance time to presyncope during an orthostatic challenge is shortened during the early morning. Heat stress reduces tolerance to presyncope and the degree of cutaneous vasoconstriction prior to presyncope. However, whether these changes show diurnal variations remains unknown. Therefore, we examined diurnal changes in orthostatic tolerance and cutaneous vascular conductance (CVC) during an orthostatic challenge under moderate heat stress. METHODS: Each lower body negative pressure (LBNP) under normothermia and whole body heat stress was applied for 7 min or until the appearance of presyncopal symptoms in 16 males at both 08:00 (a.m.) and 17:00 hours (p.m.). Measurements included internal and skin temperatures, forearm skin blood flow, arterial pressure, and heart rate. CVC was calculated as skin blood flow/mean arterial pressure, normalized to CVC prior to LBNP and expressed as %CVC. RESULTS: The average tolerance time in eight subjects exhibiting presyncopal symptoms due to LBNP and moderate heat stress was significantly shorter in the a.m. than in the p.m. (3.7 ± 0.8 versus 6.7 ± 0.3 min, respectively; P = 0.005). Neither %CVC during LBNP in these subjects under moderate heat stress nor normothermia were significantly decreased in the a.m. (P > 0.05, respectively). CONCLUSIONS: These findings indicate an orthostatic challenge even during moderate heat stress that led to an increase in the frequency of presyncope, especially in the morning. The reduction in tolerance was accompanied by blunted cutaneous vasoconstriction prior to presyncope. Hence, diurnal changes in cutaneous vascular responses during combined orthostatic and heat stresses should contribute, at least partly, to heat-induced orthostatic intolerance in the morning.

Preliminary Experience With Novel Straight 3-Fr Guiding Sheath for Transradial Access in Endovascular Treatment: Feasibility and Safety.

BACKGROUND AND OBJECTIVES: Radial artery diameter may limit whether a guiding sheath (GS) can be used via transradial artery access (TRA). A smaller GS may reduce the risk of access site-related complications. This study investigated the feasibility and safety of endovascular treatment (EVT) using a straight-shaped 3-Fr GS (Axcelguide; Medikit). METHODS: Patients who underwent EVT with a straight-shaped 3-Fr GS at 3 institutions between April 2022 and March 2024 were retrospectively reviewed. Patient background, anatomic and procedural factors, and complications were recorded. RESULTS: Twenty-six pathologies were treated with EVT using a 3-Fr GS. Median radial artery diameter was 1.9 mm, and distal TRA (73.1%) was selected more often than TRA (26.9%) as the access site. The breakdown of target pathologies and the role of the 3-Fr GS were as follows: 12 unruptured cerebral aneurysms for intra-aneurysmal coiling, with 5 dural arteriovenous fistulas, 5 brain or head and neck tumors, 2 chronic subdural hematoma, 1 arteriovenous malformation, and 1 hereditary hemorrhagic telangiectasia for transarterial embolization. A success rate of 96.2% was achieved, with no access site- or non-access site-related complications observed within 30 days. CONCLUSION: The straight-shaped 3-Fr GS may be applicable for selected pathologies, allowing access even with RAs <2 mm in diameter and facilitating EVT without complications. Preliminary experience with the 3-Fr GS via TRA demonstrated excellent feasibility and safety.

Intermediate catheter use is associated with complete occlusion and dense packing in coil embolization of unruptured cerebral aneurysms: a propensity score matched study.

BACKGROUND: An intermediate catheter (IMC) can improve the maneuverability and stability of the microcatheter. OBJECTIVE: To investigate the efficacy and safety of using an IMC in triaxial systems for coil embolization of unruptured cerebral aneurysms (UCAs). METHODS: A total of 2430 consecutive saccular UCAs (2259 patients) that underwent initial coil embolization at three institutions between November 2003 and May 2023 were retrospectively reviewed. Patients were classified into two groups: with IMC (IMC(+)) and without IMC (IMC(-)). To investigate whether IMC use increased the rate of complete occlusion and the packing density, a propensity score-matched analysis was used to control for clinical, anatomical, and procedural features. RESULTS: Ultimately, 595 (24.5%) coil embolization used an IMC. Propensity score matching was successful for 424 paired IMC(+) and IMC(-) aneurysms. Compared with the IMC(-) group, the IMC(+) group had significantly higher rate of Raymond-Roy Occlusion Classification class 1 immediately after treatment (30.0% vs 20.8%, P=0.003) and at 6 months (28.8% vs 20.0%, P=0.004) and a higher volume embolization ratio (27.2% (SD 6.5%) vs 25.9% (SD 6.2%), P=0.003). Re-treatment rates were not significantly different between the two groups (0.7% vs 0.2%, P=0.624). No significant differences in the incidences of ischemic and hemorrhagic complications and IMC-related parent artery dissection were found between the two groups. CONCLUSION: Use of IMCs in triaxial systems can provide effective and safe support in coil embolization of UCAs because complete occlusion and dense coil packing can be achieved without increased complications.

Risk factors and management of intraprocedural rupture during coil embolization of unruptured intracranial aneurysms: role of balloon guiding catheter.

Introduction: Intraprocedural rupture (IPR) is a serious complication of endovascular coil embolization of unruptured intracranial aneurysms (UIAs). Although outcomes after IPR are poor, methods to prevent subsequent neurological deterioration have not yet been investigated. We evaluated the risk factors and management strategies for IPR, particularly the role of balloon guiding catheters (BGCs) in rapid hemostasis. Methods: We retrospectively reviewed all UIA cases treated with coil embolization at three institutions between 2003 and 2021, focusing on preoperative radiological data, operative details, and outcomes. Results: In total, 2,172 aneurysms were treated in 2026 patients. Of these, 19 aneurysms in 19 patients (0.8%) ruptured during the procedure. Multivariate analysis revealed that aneurysms with a bleb (OR: 3.03, 95% CI: 1.21 to 7.57, p = 0.017), small neck size (OR: 0.56, 95% CI: 0.37 to 0.85, p = 0.007), and aneurysms in the posterior communicating artery (PcomA) (OR: 4.92, 95% CI: 1.19 to 20.18, p = 0.027) and anterior communicating artery (AcomA) (OR: 12.08, 95% CI: 2.99 to 48.79, p < 0.001) compared with the internal carotid artery without PcomA were significantly associated with IPR. The incidence of IPR was similar between the non-BGC and BGC groups (0.9% vs. 0.8%, p = 0.822); however, leveraging BGC was significantly associated with lower morbidity and mortality rates after IPR (0% vs. 44%, p = 0.033). Discussion: The incidence of IPR was relatively low. A bleb, small aneurysm neck, and location on PcomA and AcomA are independent risk factors for IPR. The use of BGC may prevent fatal clinical deterioration and achieve better clinical outcomes in patients with IPR.

Intermediate catheter use is associated with intraprocedural rupture during coil embolization of ruptured intracranial aneurysms: a retrospective propensity score-matched study.

Introduction: An intermediate catheter (IMC) may pose a risk of intraprocedural rupture (IPR) during coil embolization of ruptured intracranial aneurysms (RIAs), because the pressure on the microcatheter and coil might be more direct. To verify this hypothesis, this study explored whether use of an IMC might correlate with an increased rate of IPR during coil embolization for RIAs. Methods: We retrospectively reviewed 195 consecutive aneurysms in 192 patients who underwent initial coil embolization for saccular RIAs at our institution between January 2007 and December 2023. Patients were divided into two groups with aneurysms treated either with an IMC (IMC group) or without an IMC (non-IMC group). To investigate whether IMC use increased the rate of IPR, a propensity score-matched analysis was employed to control for age, sex, maximal aneurysm size, neck size, bleb formation, aneurysm location, proximal vessel tortuosity, balloon-assisted coiling, type of microcatheter, and type of framing coil. Results: Ultimately, 43 (22%) coil embolization used IMC. In univariate analysis, the incidence of IPR was significantly higher in the IMC group compared with the non-IMC group (14.0 vs. 3.3%, p = 0.016). Propensity score matching was successful for pairs of 26 aneurysms in the IMC group and 52 aneurysms in the non-IMC group. The incidence of IPR was still significantly higher in the IMC group than in the non-IMC group (23.1 vs. 3.8%, p = 0.015). No significant differences in the incidences of ischemic complications and IMC-related parent artery dissection were observed between the two groups. Discussion: When using IMC for coil embolization of RIAs, the surgeons should be more careful and delicate in manipulating the microcatheter and inserting the coils to avoid IPR.

Spontaneous shrinkage of vestibular schwannoma with the recovery of impaired hearing: A case report and literature review.

Background: Sporadically occurring vestibular schwannomas (VSs) are the most frequent tumors in the cerebellopontine cistern and internal meatus and are commonly associated with hearing loss. These tumors have demonstrated spontaneous shrinkage rates of 0-22%; however, the relationship between tumor shrinkage and changes in hearing remains unclear. Case Description: We report a case of a 51-year-old woman with a diagnosis of a left-sided VS and accompanying moderate hearing loss. The patient was treated with a conservative approach for 3 years, and the tumor showed a regression along with an improvement in her hearing ability during the yearly follow-ups. Conclusion: The spontaneous shrinkage of a VS along with an associated improvement in hearing is a rare phenomenon. Our case study may support that the "wait and scan" approach is an alternative option for patients with VS and moderate hearing loss. Further investigations are needed to understand spontaneous VS regression and hearing changes.

Histological transition from minimal change disease to THSD7A-associated membranous nephropathy in a patient receiving long-term steroid treatment: A case report.

RATIONALE: A predominant Th2 immune response is suggested in the pathogenesis of both minimal change disease (MCD) and membranous nephropathy (MN); however, consecutive development of the 2 diseases in a patient is extremely rare. PATIENT CONCERN: A Japanese man, who developed nephrotic syndrome in his 50s and was diagnosed with MCD by renal biopsy, experienced a relapse of proteinuria approximately 3 years later during long-term steroid treatment. Since the proteinuria was resistant to increase in steroid dosage, repeat renal biopsy was performed, which revealed a small amount of glomerular subepithelial immune deposits containing immunoglobulin (Ig)G (dominantly IgG4). Immunostaining for thrombospondin-type-1-domain-containing-7A (THSD7A) was positive on the glomerular capillary walls, whereas that for other causative antigens of MN, such as phospholipase A2 receptor or neural epidermal growth factor-like 1 protein, was negative. Detailed examination found no associated condition, including malignancies and allergic diseases. DIAGNOSIS: The diagnosis of THSD7A-associated idiopathic MN was made. INTERVENTIONS AND OUTCOMES: He received further increased dose of steroids. Thereafter he maintained clinical improvement because his urinary protein level was decreased. LESSONS: The present case suggested that histological transition from MCD to MN is possible and repeat biopsy would be crucial for accurate diagnosis.

IMbrave150: Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Patients with Barcelona Clinic Liver Cancer Stage B Unresectable Hepatocellular Carcinoma: An Exploratory Analysis of the Phase III Study.

Introduction: The phase III IMbrave150 study established atezolizumab + bevacizumab as standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis reports efficacy and safety results in patients with baseline Barcelona Clinic Liver Cancer (BCLC) stage B disease. Methods: Patients with systemic treatment-naive unresectable HCC and Child-Pugh class A liver function were randomized 2:1 to receive 1,200 mg of atezolizumab plus 15 mg/kg of bevacizumab or 400 mg of sorafenib. Co-primary endpoints were overall survival (OS) and progression-free survival (PFS) per independent review facility (IRF)-assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in the BCLC stage B subgroup. Patients in this analysis had BCLC stage B disease at baseline per electronic case report form. Secondary efficacy endpoints included the objective response rate (ORR) and change in the sum of longest diameters (SLD) of target lesions from baseline per IRF RECIST 1.1 and modified RECIST (mRECIST) for HCC. Results: Of 501 enrolled patients, 74 (15%) had BCLC stage B disease at baseline (atezolizumab + bevacizumab, n = 49; sorafenib, n = 24). For this group, median follow-up was 19.7 months. A trend toward improved OS and PFS per IRF RECIST 1.1 was observed with atezolizumab + bevacizumab versus sorafenib (OS: hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.29, 1.34; PFS: HR: 0.64; 95% CI: 0.36, 1.12). ORRs per IRF RECIST 1.1 and HCC mRECIST were 43% and 50% with atezolizumab + bevacizumab and 26% and 30% with sorafenib, respectively. Percentage change in SLD of target lesions from baseline per IRF RECIST 1.1 and HCC mRECIST showed durable responses with atezolizumab + bevacizumab treatment. Safety data were consistent with known profiles of atezolizumab and bevacizumab, as seen in the overall study population. Discussion/Conclusion: Efficacy benefits were observed with atezolizumab + bevacizumab in patients with baseline BCLC stage B disease, consistent with the intention-to-treat population.

Subfoveal choroidal thickness and foveal retinal thickness during head-down tilt.

INTRODUCTION: To reveal subtle morphological changes in the eye during simulated microgravity for spaceflights, we measured subfoveal choroidal thickness and foveal retinal thickness during 10 degrees head-down tilt (HDT). We hypothesized that elevated ophthalmic vein pressure during simulated microgravity increases subfoveal choroidal thickness via enlargement of the choroidal vasculature and greater choroidal blood volume. METHODS: The right eyes of nine healthy subjects (seven men, two women) were examined. Subfoveal choroidal thickness and foveal retinal thickness were measured using spectral domain-optical coherence tomography in the sitting position, and after 15 and 30 min of 10 degrees HDT. Intraocular pressure was also measured. RESULTS: Mean subfoveal choroidal thickness (+/- SEM) increased from 300 +/- 31 microm in the sitting position to 315 +/- 31 microm with 15-min HDT, and 333 +/- 31 microm with 30-min HDT. However, no change in foveal retinal thickness was observed (228 +/- 9 microm in the sitting position, 228 +/- 10 microm with 15-min HDT and 228 +/- 9 microm with 30-min HDT). Intraocular pressure increased from 14 +/- 1 mmHg in the sitting position to 21 +/- 2 mmHg with 30-min HDT (54 +/- 6%, N = 5). DISCUSSION: Subfoveal choroidal thickness and intraocular pressure were increased by HDT during simulated microgravity, although no change in foveal retinal thickness was observed.

The effect of dexmedetomidine on arterial-cardiac baroreflex function assessed by spectral and transfer function analysis.

PURPOSE: The α(2)-adrenergic receptor agonist dexmedetomidine reportedly weakens heart rate (HR) responses to 'rapid' (during a few seconds) reduction in arterial pressure, but does not affect HR responses to 'gradual' (during 60 s) reduction in arterial pressure. As the speed of neurotransmission along the parasympathetic nerve is relatively rapid, alteration of parasympathetic-mediated arterial-cardiac baroreflex function plays a more important role in HR responses to 'rapid' changes in arterial pressure. We therefore hypothesized that dexmedetomidine attenuates parasympathetic-mediated arterial-cardiac baroreflex function. METHODS: Twelve healthy men received placebo, low-dose (loading, 3 µg/kg/h for 10 min; maintenance, 0.2 µg/kg/h for 60 min) (low-DEX), or moderate-dose (loading, 6 µg/kg/h for 10 min; maintenance, 0.4 µg/kg/h for 60 min) (moderate-DEX) dexmedetomidine infusions in a randomized, double-blind, crossover study. Before and after 70 min of infusion, arterial-cardiac baroreflex function was assessed by spectral and transfer function analysis between arterial pressure variability and HR variability. RESULTS: The high-frequency power of systolic arterial pressure (SAP) variability increased significantly with low-DEX and moderate-DEX infusions (significant interaction effects, P = 0.005), whereas the high-frequency power of R-wave-R-wave interval (RRI) variability (as an index of cardiac parasympathetic activity) did not change significantly at any dose infusions. Then, transfer function gain in the high-frequency range (as an index of parasympathetic arterial-cardiac baroreflex) decreased significantly with low-DEX and moderate-DEX infusions (significant interaction effects, P = 0.007). CONCLUSIONS: The present results suggest that dexmedetomidine attenuates parasympathetic-mediated arterial-cardiac baroreflex function, implying weakened HR response to 'rapid' reduction in arterial pressure.

Enhancement of antitumor immune response by radiation therapy combined with dual immune checkpoint inhibitor in a metastatic model of HER2-positive murine tumor.

PURPOSE: Treatments for metastatic human epidermal growth factor receptor 2 (HER2)-positive tumors are improving but remain inadequate. We investigated activating antitumor immune response by combining radiation therapy with immune checkpoint inhibitors using mouse tumors overexpressing HER2, a pivotal driver oncogenic antigen, to develop new immunotherapies for metastatic HER2-positive tumors. MATERIALS AND METHODS: NT2.5 cells were inoculated into the two mammary fat pads of FVB/N mice, which were divided into four groups: no treatment (Non), anti-PD-1 and anti-CTLA4 antibodies (P1C4), irradiation of the large tumor (Rad), and combination (R + P1C4) groups. Tumor growth, immunostaining of tumor-infiltrating lymphocytes, and the proportion of HER2-tumor antigen-specific CD8-positive T cells in the spleen and tumor-infiltrating lymphocytes were analyzed. RESULTS: In the Rad group, unirradiated and irradiated tumors shrank after treatment. Besides the directly irradiated tumors, the unirradiated tumors in the R + P1C4 group shrank the most. In the unirradiated tumors, CD8-positive T cells and FOXP3-positive T cells accumulated significantly more in the R + P1C4 group than in the P1C4 and the Rad groups (all p < 0.001). CD4-positive helper T cells accumulated significantly more in the R + P1C4 group than in the Rad group (p < 0.05), but this was not significantly different from the P1C4 group. HER2-specific CD8-positive T cells in the spleen and tumor-infiltrating lymphocytes were significantly increased in the R + P1C4 group compared to the P1C4 and Rad groups (all p < 0.0001). CONCLUSION: Irradiation of HER2-positive tumors induced an antitumor immune effect against the unirradiated tumor, which was enhanced by the combined use of immune checkpoint inhibitors and was mediated by enhanced recruitment of HER2-tumor antigen-specific cytotoxic T lymphocytes at the tumor site in an HER2-positive mouse tumor model. Harnessing the distant antitumor immune response induced by the combination of radiation therapy and immune checkpoint inhibitors could be a promising treatment strategy for metastatic HER2-positive tumors.

[Approach to elucidating the influences and factors affecting circulation system in humans in space environment].

Many physiological changes associated with spaceflight, including decreases in orthostatic tolerance, exercise capacity, and blood volume have been reported. Orthostatic intolerance is a problem affecting many astronauts immediately postspaceflight. In particular, the relationship between orthostatic intolerance and cerebral autoregulation has been the focus of study in our research group. Although impairment of cerebral autoregulation was speculated to be one of the factors resulting in reduced post flight orthostatic tolerance, a 2-wk spaceflight study revealed that human cerebral autoregulation is preserved or even improved during and immediately after spaceflight in nonsymptomatic astronauts. To investigate the influences of the different kinds of reduction in central blood volume, we performed two ground-based studies. It is suggested that the mild intravascular dehydration partly explains the improved dynamic cerebral autoregulation observed during and immediately after a short-term spaceflight. Moreover, we also studied the relationship between orthostatic intolerance and cerebral autoregulation under hyperthermic conditions, because hyperthermia leads to orthostatic intolerance. Furthermore, we planned to conduct a study at the International Space Station (ISS) and ground-based studies to elucidate the influences and factors affecting the circulation system in humans in a space environment.

Non-Hodgkin's lymphoma of the vaginal wall in a hemodialysis patient with hepatocellular carcinoma.

A 66 year old woman with end-stage renal disease and liver cirrhosis due to chronic hepatitis C virus infection was introduced to hemodialysis therapy in 2003. In 2007, hepatocellular carcinoma was identified and the patient underwent radio frequency ablation (RFA) and ethanol injection therapy (EIT) under laparotomy. A large vaginal tumor was incidentally found at gynecological examination. Histological diagnosis was diffuse large B-cell lymphoma (Stage IE). During the first course of chemotherapy, the vaginal tumor began to prolapse from the vaginal wall due to an excellent response to the chemotherapy and finally was resected. The patient received another course of chemotherapy followed by radiotherapy. The vaginal tumor was undetectable in the follow-up imaging studies. Although patients with end-stage renal disease are at increased risk for several cancers, the occurrence of malignant lymphoma following hepatocellular carcinoma is rare. Furthermore, lymphomas arising from the female genital tract are very uncommon.

Effective Control of Brain Metastases Irrespective of Distance from Isocenter in Single-isocenter Multitarget Stereotactic Radiosurgery.

BACKGROUND/AIM: Few previous studies have evaluated the effectiveness of single-isocenter multitarget (SIMT) stereotactic radiosurgery (SRS) in clinical practice. PATIENTS AND METHODS: Gross tumor volumes of 113 metastases in 13 patients were measured by contrast-enhanced magnetic resonance imaging. Prescribed doses were set at 20-24 Gy. Based on tumor reduction rates (TRRs) measured before and after SIMT SRS, tumor shrinkage effect was categorized into four grades; almost disappeared: TRR=1, decreased: 0.3≤TRR<1, stable: -0.2

Comparison of Clinical Outcomes After Stent-Assisted Coiling with 3 Types of Self-Expanding Laser-Cut Stents in Patients with Wide-Necked Intracranial Aneurysms.

OBJECTIVE: We report the clinical outcomes of stent-assisted coiling for wide-necked intracranial aneurysms using 3 low-profile laser-cut stents and compare the results according to stent type. METHODS: All patients treated with stent-assisted coiling for their intracranial aneurysms at our hospital between July 2010 and September 2019 were reviewed. We selected patients with Enterprise, Neuroform EZ, or Neuroform Atlas stents who underwent imaging follow-up and investigated aneurysm and stent features, stent-related complications, recanalization, and retreatment rates. We compared the retreatment risk among the patients treated with the 3 stent types using Kaplan-Meier survival analysis and Cox regression analysis. RESULTS: We evaluated 364 consecutive cases (103 Enterprise, 105 Neuroform EZ, and 156 Neuroform Atlas stents). Neuroform Atlas was more frequently used in distal vessels: 8 (7.8%) Enterprise, 2 (1.9%) Neuroform EZ, and 41 (26.3%) Neuroform Atlas cases, respectively. The median follow-up durations were 6.49, 4.91, and 1.24 years for the Enterprise, Neuroform EZ, and Neuroform Atlas cases, respectively, and retreatment was performed in 11 (10.1%), 9 (8.6%), and 6 (3.8%) cases. In the first 2 years of follow-up, the estimated retreatment risk ratios for Neuroform EZ and Neuroform Atlas with Enterprise as reference were 0.63 (95% confidence interval, 0.24-1.65; P = 0.35) and 0.54 (95% confidence interval, 0.18-1.59; P = 0.26), respectively. CONCLUSIONS: Neuroform Atlas stents were more frequently deployed in small-caliber vessels compared with the other 2 types of stents. The complication rate and retreatment risk until at least 1 year after the aneurysm treatment appeared to be similar for the 3 stent types.