Charted-particle therapy (CPT) benefits cancer patients by localizing doses in the tumor volume while minimizing the doses delivered to normal tissue through its unique physical and biological characteristics. The world’s first CPT applied on humans was proton beam therapy (PBT), which was performed in the mid-1950s. Among heavy ions, carbon ions showed the most favorable biological characteristics for the treatment of cancer patients. Carbon ions show coincidence between the Bragg peak and maximum value of relative biological effectiveness. In addition, they show low oxygen enhancement ratios. Therefore, carbon-ion radiotherapy (CIRT) has become mainstream in the treatment of cancer patients using heavy ions. CIRT was first performed in 1977 at the Lawrence Berkeley Laboratory. The CPT technology has advanced in the intervening decades, enabling the use of rotating gantry, beam delivery with fast pencil-beam scanning, image-guided particle therapy, and intensity-modulated particle therapy. As a result, as of 2019, a total of 222,425 and 34,138 patients with cancer had been treated globally with PBT and CIRT, respectively. For more effective and efficient CPT, many groups are currently conducting further studies worldwide. This review summarizes recent technological advances that facilitate clinical use of CPT.

Charted-particle therapy (CPT) benefits cancer patients by localizing doses in the tumor volume while minimizing the doses delivered to normal tissue through its unique physical and biological characteristics. The world’s first CPT applied on humans was proton beam therapy (PBT), which was performed in the mid-1950s. Among heavy ions, carbon ions showed the most favorable biological characteristics for the treatment of cancer patients. Carbon ions show coincidence between the Bragg peak and maximum value of relative biological effectiveness. In addition, they show low oxygen enhancement ratios. Therefore, carbon-ion radiotherapy (CIRT) has become mainstream in the treatment of cancer patients using heavy ions. CIRT was first performed in 1977 at the Lawrence Berkeley Laboratory. The CPT technology has advanced in the intervening decades, enabling the use of rotating gantry, beam delivery with fast pencil-beam scanning, image-guided particle therapy, and intensity-modulated particle therapy. As a result, as of 2019, a total of 222,425 and 34,138 patients with cancer had been treated globally with PBT and CIRT, respectively. For more effective and efficient CPT, many groups are currently conducting further studies worldwide. This review summarizes recent technological advances that facilitate clinical use of CPT.

Background: Aerobic exercise training and drug therapy are well-established interventions for the prevention and treatment of hypertension and dyslipidemia. We investigated the synergistic effects of aerobic exercise and olmesartan/rosuvastatin on epicardial fat thickness (EFT) and endothelial function in patients with hypertension and dyslipidemia. Methods: A sample of 75 participants with hypertension and dyslipidemia was evaluated for multifactorial cardiovascular risk at baseline and at 6 months of intervention according to anthropometric and hemodynamic components, lipid profile, glycemia, brachial artery flow-mediated dilation (FMD), and EFT. After 3 months of drug therapy only, participants were allocated to one of three conditions: treadmill (n=22), exergame (n=29), or control (n=24). Results: After 12 weeks of drug therapy only, systolic and diastolic blood pressure (3% and 2%, both p<0.05), total cholesterol (6.3%, p<0.01), low-density lipoprotein cholesterol (4.9%, p<0.05), triglycerides (11.1%, p<0.05), fasting blood glucose (10.2%, p<0.01), and glycosylated hemoglobin (3%, p<0.01) were significantly reduced. After 12 weeks of combined aerobic exercise and drug therapy, both the treadmill and exergame groups showed a significant improvement in FMD (both p<0.001) and reduction in EFT (both p<0.001). Systolic and diastolic blood pressures decreased in the treadmill group only (1.9% and 2.7%, respectively, p<0.05). Conclusions Incorporating aerobic exercise into drug therapy regimens can yield synergistic effects, particularly in improving endothelial function and reducing EFT, providing a comprehensive approach to managing cardiovascular risk in patients with hypertension and dyslipidemia.

Background: Aerobic exercise training and drug therapy are well-established interventions for the prevention and treatment of hypertension and dyslipidemia. We investigated the synergistic effects of aerobic exercise and olmesartan/rosuvastatin on epicardial fat thickness (EFT) and endothelial function in patients with hypertension and dyslipidemia. Methods: A sample of 75 participants with hypertension and dyslipidemia was evaluated for multifactorial cardiovascular risk at baseline and at 6 months of intervention according to anthropometric and hemodynamic components, lipid profile, glycemia, brachial artery flow-mediated dilation (FMD), and EFT. After 3 months of drug therapy only, participants were allocated to one of three conditions: treadmill (n=22), exergame (n=29), or control (n=24). Results: After 12 weeks of drug therapy only, systolic and diastolic blood pressure (3% and 2%, both p<0.05), total cholesterol (6.3%, p<0.01), low-density lipoprotein cholesterol (4.9%, p<0.05), triglycerides (11.1%, p<0.05), fasting blood glucose (10.2%, p<0.01), and glycosylated hemoglobin (3%, p<0.01) were significantly reduced. After 12 weeks of combined aerobic exercise and drug therapy, both the treadmill and exergame groups showed a significant improvement in FMD (both p<0.001) and reduction in EFT (both p<0.001). Systolic and diastolic blood pressures decreased in the treadmill group only (1.9% and 2.7%, respectively, p<0.05). Conclusions Incorporating aerobic exercise into drug therapy regimens can yield synergistic effects, particularly in improving endothelial function and reducing EFT, providing a comprehensive approach to managing cardiovascular risk in patients with hypertension and dyslipidemia.

Background: Aerobic exercise training and drug therapy are well-established interventions for the prevention and treatment of hypertension and dyslipidemia. We investigated the synergistic effects of aerobic exercise and olmesartan/rosuvastatin on epicardial fat thickness (EFT) and endothelial function in patients with hypertension and dyslipidemia. Methods: A sample of 75 participants with hypertension and dyslipidemia was evaluated for multifactorial cardiovascular risk at baseline and at 6 months of intervention according to anthropometric and hemodynamic components, lipid profile, glycemia, brachial artery flow-mediated dilation (FMD), and EFT. After 3 months of drug therapy only, participants were allocated to one of three conditions: treadmill (n=22), exergame (n=29), or control (n=24). Results: After 12 weeks of drug therapy only, systolic and diastolic blood pressure (3% and 2%, both p<0.05), total cholesterol (6.3%, p<0.01), low-density lipoprotein cholesterol (4.9%, p<0.05), triglycerides (11.1%, p<0.05), fasting blood glucose (10.2%, p<0.01), and glycosylated hemoglobin (3%, p<0.01) were significantly reduced. After 12 weeks of combined aerobic exercise and drug therapy, both the treadmill and exergame groups showed a significant improvement in FMD (both p<0.001) and reduction in EFT (both p<0.001). Systolic and diastolic blood pressures decreased in the treadmill group only (1.9% and 2.7%, respectively, p<0.05). Conclusions Incorporating aerobic exercise into drug therapy regimens can yield synergistic effects, particularly in improving endothelial function and reducing EFT, providing a comprehensive approach to managing cardiovascular risk in patients with hypertension and dyslipidemia.

Background: Aerobic exercise training and drug therapy are well-established interventions for the prevention and treatment of hypertension and dyslipidemia. We investigated the synergistic effects of aerobic exercise and olmesartan/rosuvastatin on epicardial fat thickness (EFT) and endothelial function in patients with hypertension and dyslipidemia. Methods: A sample of 75 participants with hypertension and dyslipidemia was evaluated for multifactorial cardiovascular risk at baseline and at 6 months of intervention according to anthropometric and hemodynamic components, lipid profile, glycemia, brachial artery flow-mediated dilation (FMD), and EFT. After 3 months of drug therapy only, participants were allocated to one of three conditions: treadmill (n=22), exergame (n=29), or control (n=24). Results: After 12 weeks of drug therapy only, systolic and diastolic blood pressure (3% and 2%, both p<0.05), total cholesterol (6.3%, p<0.01), low-density lipoprotein cholesterol (4.9%, p<0.05), triglycerides (11.1%, p<0.05), fasting blood glucose (10.2%, p<0.01), and glycosylated hemoglobin (3%, p<0.01) were significantly reduced. After 12 weeks of combined aerobic exercise and drug therapy, both the treadmill and exergame groups showed a significant improvement in FMD (both p<0.001) and reduction in EFT (both p<0.001). Systolic and diastolic blood pressures decreased in the treadmill group only (1.9% and 2.7%, respectively, p<0.05). Conclusions Incorporating aerobic exercise into drug therapy regimens can yield synergistic effects, particularly in improving endothelial function and reducing EFT, providing a comprehensive approach to managing cardiovascular risk in patients with hypertension and dyslipidemia.

Background: Aerobic exercise training and drug therapy are well-established interventions for the prevention and treatment of hypertension and dyslipidemia. We investigated the synergistic effects of aerobic exercise and olmesartan/rosuvastatin on epicardial fat thickness (EFT) and endothelial function in patients with hypertension and dyslipidemia. Methods: A sample of 75 participants with hypertension and dyslipidemia was evaluated for multifactorial cardiovascular risk at baseline and at 6 months of intervention according to anthropometric and hemodynamic components, lipid profile, glycemia, brachial artery flow-mediated dilation (FMD), and EFT. After 3 months of drug therapy only, participants were allocated to one of three conditions: treadmill (n=22), exergame (n=29), or control (n=24). Results: After 12 weeks of drug therapy only, systolic and diastolic blood pressure (3% and 2%, both p<0.05), total cholesterol (6.3%, p<0.01), low-density lipoprotein cholesterol (4.9%, p<0.05), triglycerides (11.1%, p<0.05), fasting blood glucose (10.2%, p<0.01), and glycosylated hemoglobin (3%, p<0.01) were significantly reduced. After 12 weeks of combined aerobic exercise and drug therapy, both the treadmill and exergame groups showed a significant improvement in FMD (both p<0.001) and reduction in EFT (both p<0.001). Systolic and diastolic blood pressures decreased in the treadmill group only (1.9% and 2.7%, respectively, p<0.05). Conclusions Incorporating aerobic exercise into drug therapy regimens can yield synergistic effects, particularly in improving endothelial function and reducing EFT, providing a comprehensive approach to managing cardiovascular risk in patients with hypertension and dyslipidemia.

We investigated the use of Polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) composites with applied mechanical stimulation as scaffold for bone tissue engineering. PCL-based three-dimensional (3D) structures were fabricated in a solvent-free process using a 3D-printing technique. The mass fraction of β-TCP was varied in the range 0–30%, and the structure and compressive modulus of the specimens was characterized. The shape and interconnectivity of the pores was found to be satisfactory, and the compressive modulus of the specimens was comparable with that of human trabecular bone. Human mesenchymal stem cells were seeded on the composites, and various biological evaluations were performed over 9 days. With a mass fraction of β-TCP of 30%, differentiation began earlier; however, the cell proliferation rate was lower. Through the use of mechanical stimulation, however, the proliferation rate recovered, and was comparable with that of the other groups. This stimulation effect was also observed in ECM generation and other biological assays. With mechanical stimulation, expression of osteogenic markers was lower on samples with a β-TCP content of 10 wt% than without β-TCP; however, with mechanical stimulation, the sample with a β-TCP content of 30 wt% exhibited significantly greater expression of those markers than the other samples. We found that mechanical stimulation and the addition of β-TCP interacted closely, and that a mass fraction of β-TCP of 30% was particularly useful as a bone tissue scaffold when accompanied by mechanical stimulation.
Biological Assay ; Bone and Bones ; Cell Proliferation ; Humans ; Mesenchymal Stromal Cells

In this study, we examined the morphine-induced modulation of the nociceptive spinal dorsal horn neuronal activities before and after formalin-induced inflammatory pain. Intradermal injection of formalin induced time-dependent changes in the spontaneous activity of nociceptive dorsal horn neurons. In naive cats before the injection of formalin, iontophoretically applied morphine attenuated the naturally and electrically evoked neuronal responses of dorsal horn neurons. However, neuronal responses after the formalin-induced inflammation were significantly increased by morphine. Bicuculline, GABAA antagonist, increased the naturally and electrically evoked neuronal responses of dorsal horn neurons. This increase in neuronal responses due to bicuculline after the formalin-induced inflammation was larger than that in the naive state, suggesting that basal GABAA tone increased after the formalin injection. Muscimol, GABAA agonist, reduced the neuronal responses before the treatment with formalin, but not after formalin treatment, again indicating an increase in the GABAergic basal tone after the formalin injection which saturated the neuronal responses to GABA agonist. Morphine-induced increase in the spinal nociceptive responses after formalin treatment was inhibited by co-application of muscimol. These data suggest that formalin-induced inflammation increases GABAA basal tone and the inhibition of this augmented GABAA basal tone by morphine results in a paradoxical morphine- induced increase in the spinal nociceptive neuronal responses after the formalin-induced inflammation.
Animals ; Bicuculline ; Cats ; Formaldehyde ; GABA Agonists ; Inflammation ; Injections, Intradermal ; Morphine ; Muscimol ; Neurons ; Nociceptors ; Posterior Horn Cells* ; Spinal Cord

PURPOSE: This study aimed to investigate the incidence and risk factors of early postoperative small bowel obstruction (EPSBO) after laparotomy for trauma patients. METHODS: From 2009 to 2016, consecutive patients who had undergone laparotomy for trauma were retrospectively evaluated. EPSBO was defined as the presence of signs and symptoms of obstruction between postoperative days 7 and 30, or obstruction occurring anytime within 30 days and lasting more 7 days. RESULTS: Among 297 patients who met the inclusion criteria, 72 (24.2%) developed EPSBO. The length of hospital stay was significantly longer in patients with EPSBO than in those without EPSBO (median [interquartile range], 34 [21–48] days 24 [14–38] days, P < 0.001). Multivariate logistic analysis identified male sex (adjusted odds ratio [AOR], 3.026; P = 0.008), intraoperative crystalloid (AOR, 1.130; P = 0.031), and Abbreviated Injury Scale (AIS) score for mesenteric injury (AOR, 1.397; P < 0.001) as independent risk factors for EPSBO. The incidence of adhesive small bowel adhesion after 30 days postoperatively did not significantly differ between the 2 groups (with EPSBO, 5.6% without EPSBO, 5.3%; P = 0.571). Most of the patients with EPSBO were recovered by conservative treatment (95.8%). CONCLUSION: After laparotomy for trauma patients, the incidence of EPSBO was 24.2% in our study. EPSBO was associated with a longer hospital stay. Male sex, use of intraoperative crystalloid, and AIS score for mesenteric injury were significant independent risk factors for EPSBO. Patients with these risk factors should be followed-up more carefully.
Abbreviated Injury Scale ; Abdominal Injuries ; Adhesives ; Humans ; Ileus ; Incidence ; Laparotomy ; Length of Stay ; Male ; Odds Ratio ; Retrospective Studies ; Risk Factors