Climate change and the urgency of decarbonizing the built environment are driving technological innovation in the way we deliver thermal comfort to occupants. These changes, in turn, seem to be ...setting the directions for contemporary thermal comfort research. This article presents a literature review of major changes, developments, and trends in the field of thermal comfort research over the last 20 years. One of the main paradigm shift was the fundamental conceptual reorientation that has taken place in thermal comfort thinking over the last 20 years; a shift away from the physically based determinism of Fanger's comfort model toward the mainstream and acceptance of the adaptive comfort model. Another noticeable shift has been from the undesirable toward the desirable qualities of air movement. Additionally, sophisticated models covering the physics and physiology of the human body were developed, driven by the continuous challenge to model thermal comfort at the same anatomical resolution and to combine these localized signals into a coherent, global thermal perception. Finally, the demand for ever increasing building energy efficiency is pushing technological innovation in the way we deliver comfortable indoor environments. These trends, in turn, continue setting the directions for contemporary thermal comfort research for the next decades.
We assessed the non-inferiority of accelerated fractionation (AF) (2.4Gy/fraction) compared with standard fractionation (SF) (2Gy/fraction) regarding progression-free survival (PFS) in patients with ...T1-2N0M0 glottic cancer (GC).
In this multi-institutional, randomized, phase III trial, patients were enrolled from 32 Japanese institutions. Key inclusion criteria were GC T1-2N0M0, age 20–80, Eastern Cooperative Oncology Group performance status of 0–1, and adequate organ function. Patients were randomly assigned to receive either SF of 66–70Gy (33–35 fractions), or AF of 60–64.8Gy (25–27 fractions). The primary end point was the proportion of 3-year PFS. The planned sample size was 360 with a non-inferiority margin of 5%.
Between 2007 and 2013, 370 patients were randomized (184/186 to SF/AF). Three-year PFS was 79.9%(95% confidence interval CI 73.4–85.4) for SF and 81.7% (95% CI 75.4–87.0) for AF (difference 1.8%, 91% CI−5.1% to 8.8%; one-sided P=0.047>0.045). The cumulative incidences of local failure at 3years for SF/AF were 15.9%/10.3%. No significant difference was observed in 3-year overall survival (OS) between SF and AF. Grade 3 or 4 acute and late toxicities developed in 22 (12.4%)/21 (11.5%) and 2 (1.1%)/1 (0.5%) in the SF/AF arms.
Although the non-inferiority of AF was not confirmed statistically, the similar efficacy and toxicity of AF compared with SF, as well as the practical convenience of its fewer treatment sessions, suggest the potential of AF as a treatment option for early GC.
UMIN Clinical Trial Registry, number UMIN000000819.
Metal artifacts reduce the quality of CT images and increase the difficulty of interpretation. This study compared the ability of model-based iterative reconstruction and hybrid iterative ...reconstruction to improve CT image quality in patients with metallic dental artifacts when both techniques were combined with a metal artifact reduction algorithm.
This retrospective clinical study included 40 patients (men, 31; women, 9; mean age, 62.9 ± 12.3 years) with oral and oropharyngeal cancer who had metallic dental fillings or implants and underwent contrast-enhanced ultra-high-resolution CT of the neck. Axial CT images were reconstructed using hybrid iterative reconstruction and model-based iterative reconstruction, and the metal artifact reduction algorithm was applied to all images. Finally, hybrid iterative reconstruction + metal artifact reduction algorithms and model-based iterative reconstruction + metal artifact reduction algorithm data were obtained. In the quantitative analysis, SDs were measured in ROIs over the apex of the tongue (metal artifacts) and nuchal muscle (no metal artifacts) and were used to calculate the metal artifact indexes. In a qualitative analysis, 3 radiologists blinded to the patients' conditions assessed the image-quality scores of metal artifact reduction and structural depictions.
Hybrid iterative reconstruction + metal artifact reduction algorithms and model-based iterative reconstruction + metal artifact reduction algorithms yielded significantly different metal artifact indexes of 82.2 and 73.6, respectively (95% CI, 2.6-14.7;
< .01). The latter algorithms resulted in significant reduction in metal artifacts and significantly improved structural depictions(
< .01).
Model-based iterative reconstruction + metal artifact reduction algorithms significantly reduced the artifacts and improved the image quality of structural depictions on neck CT images.
•We recorded ATP-induced movement of individual myosin heads electron microscopically.•In the absence of actin filament, myosin head performs recovery stroke.•In the presence of actin filament, ...myosin head performs power stroke.•Myosin head shows two modes of power stroke depending on experimental conditions.•Myosin heads decide direction of stroke by sensing presence of actin filament.
Although more than 50 years have passed since the monumental discovery of Huxley and Hanson that muscle contraction results from relative sliding between actin and myosin filaments, coupled with ATP hydrolysis, the mechanism underlying the filament sliding still remains to be a mystery. It is generally believed that the myofilament sliding is caused by cyclic attachment-detachment between myosin heads in myosin filaments and myosin-binding sites in actin filaments. Attempts to prove the myosin head movement using techniques of X-ray diffraction and chemical probes attached to myosin heads have failed to obtain clear results because of the asynchronous nature of myosin head movement. Using the gas environmental chamber (EC) attached to an electron microscope, we succeeded in recording myosin head movement in hydrated myosin filaments, coupled with ATP hydrolysis with the following results: (1)In the absence of actin filaments, myosin heads fluctuate around a definite neutral position, so that their time-averaged position remains unchanged; (2) On ATP application, myosin heads bind with ATP to be in the charged-up state, M-ADP-Pi, and perform a recovery stroke in the direction away from the myosin filament central bare zone and stay in the post-recovery stroke position; (3) In the actin-myosin filament mixture, myosin heads form rigor linkages with actin, and bind with applied ATP to be in the charged-up state, M-ADP-Pi, and perform a power stroke in the direction towards the myosin filament bare zone, while releasing ADP and Pi to stay in the post-power stroke position; (4) In both recovery and power strokes, myosin heads in the non charged-up state return to the neutral position. These results indicate that the charged-up myosin heads decide their direction of movement without being guided by actin filaments.
Vascular smooth muscle cell (VSMC) proliferation is a key event in the progression of arteriosclerosis. Clinical studies show that uremic toxins deteriorate the arteriosclerosis in renal failure ...patients. Indoxyl sulfate (IS) is a strong protein-bound uremic toxin, but the effect of IS on VSMC proliferation has not been studied. We examined the effect of IS on rat VSMC proliferation, assessed by a cell counting kit (4-3-4-lodophenyl-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate assay) and by 3Hthymidine incorporation in vitro. We further evaluated a contribution of mitogen-activated protein kinase (MAPK; p44/42 MAPK) to VSMC proliferation by IS. Immunohistochemical staining was performed for VSMCs using antirat organic anion transporter (OAT)3 antibody. The mRNA expressions of platelet-derived growth factor (PDGF)-A and -C chains, and PDGF-β receptor were evaluated by real-time PCR. IS stimulated the proliferation of VSMCs in a concentration-dependent manner and activated p44/42 MAPK. Concentration of IS needed to stimulate the proliferation of rat VSMC was about 250 μM, which is compatible with that in the serum of end-stage renal failure patients. PD98059 (10 μM), a selective inhibitor of MAPK/extracellular signal-regulated kinase, inhibited the IS-induced (250 μM) VSMC proliferation and phosphorylation of MAPK. Probenecid (0.5 mM), an inhibitor and substrate of OAT, inhibited the IS-induced (250 μM) VSMC proliferation. Rat OAT3 was detected in VSMCs. The mRNA expressions of PDGF-C chain and PDGF-β receptor were significantly increased by IS. We conclude that IS directly stimulates rat VSMC proliferation and activates MAPK in vitro. This might be one of the mechanisms underlying the progression of atherosclerotic lesions in end-stage renal disease patients.
Abstract Background Klotho, a single-pass transmembrane protein primarily expressed in the kidneys, parathyroid glands, and choroid plexus of the brain, has a short cytoplasmic tail and a long ...extracellular domain, which can be cleaved and released as a soluble form. However, information regarding the origins and kinetics of soluble serum Klotho remains poorly understood. We evaluated serial changes in serum Klotho levels among living donors before and after retroperitoneoscopic nephrectomy as well as in their renal transplant recipients. Methods The levels of soluble Klotho in serum obtained from 10 living donors and their renal transplant recipients were determined using a sandwich enzyme-linked immunosorbent assay system. Results Serum soluble Klotho was detectable in all subjects. The baseline serum Klotho concentrations in the living donors ranged from 726.4 to 1417.1 pg/mL (median, 909.8 pg/mL; interquartile ranges IR, 754.8–1132.4), whereas that in the concomitant renal transplant recipients ranged from 397.5 to 1047.2 pg/mL (median, 613.0 pg/mL; IR, 445.9–750.8; P = .003). The levels of soluble serum Klotho measured 5 days after retroperitoneoscopic nephrectomy (median, 619.0 pg/mL; IR, 544.6–688.5; P = .001) were significantly lower than the baseline values. Among the renal transplant recipients, no significant changes in serum Klotho levels were observed during the observation period. Conclusion Our data regarding soluble serum Klotho levels obtained from living donors support the idea that the kidneys are a major source of soluble serum Klotho in human subjects without a deterioration of renal function. In recipients, concomitant acute kidney injuries and immunosuppressive protocols might modulate the release of soluble Klotho from the grafts into the circulation.
Abstract Background In transplant patients with localized prostate cancer, irradiation is not proposed as often as it is in healthy adults because of the post-radiation risks, such as ureteral ...stenosis and gastrointestinal toxicity as the result of fragile tissue. The objective of the study was to analyze the efficacy and feasibility of intensity-modulated radiation therapy (IMRT) for prostate cancer in renal transplant recipients (RTRs). Methods Between May 2005 and December 2014, all patients who had undergone IMRT for clinically localized prostate cancer at our institution were retrospectively identified (n = 365). Of these patients, 2 had a history of renal transplantation. We reviewed all available clinical data. One patient had a functioning graft and the other had restarted hemodialysis 7 years after the transplantation. Results The mean time from renal transplantation to prostate cancer diagnosis was 11 years. The mean follow-up after irradiation was 43 months. The 2 patients remain free of prostate-specific antigen progression. There was no severe acute and chronic genitourinary and gastrointestinal toxicity. Renal function of the patient with a functioning graft as measured by serum creatinine was stable during and after the irradiation. Conclusions IMRT is feasible and acceptable as a minimally invasive treatment in the carefully selected RTRs with localized prostate cancer. This treatment should be considered a good option for RTRs with localized prostate cancer.
Abstract Background In young patients with localized prostate cancer, radical prostatectomy is the treatment of choice in the general population. Radiotherapy, such as low-dose rate (LDR) ...brachytherapy or intensity-modulated radiotherapy, is a viable alternative as well. However, in transplant patients, irradiation is not proposed as often as it is in healthy adults because of the risk of post-radiation ureteral stenosis and gastrointestinal toxicity as the result of fragile tissue. The objective of the study was to assess the efficacy and feasibility of LDR brachytherapy for prostate cancer in renal transplant recipients (RTRs). Methods Between May 2007 and December 2014, all patients who had undergone LDR brachytherapy for clinically localized prostate cancer at our institution were retrospectively identified (n = 203). Of these patients, 2 had a history of renal transplantation. We reviewed all available clinical data retrospectively. One patient had a functioning graft and the other had re-started hemodialysis 7 years after the transplantation. Results The mean time from renal transplantation to prostate cancer diagnosis was 16 years. The mean follow-up after seed implantation was 45 months. There were no peri-operative complications after seed implantation. The 2 patients remained free of prostate-specific antigen progression during the follow-up period. The renal function of the patient with a functioning graft, as measured by serum creatinine, was stable during and after the operation. Conclusions LDR brachytherapy is technically feasible and acceptable as a minimally invasive treatment in carefully selected RTRs with localized prostate cancer. This treatment should be considered a suitable option for RTRs with localized prostate cancer.
Recent studies have demonstrated that some microRNAs (miRNAs) inhibit bone formation by inhibiting the translation of specific genes. Several in vitro studies have suggested that miR-23a inhibits ...osteogenic differentiation by suppressing the translation of Runx2, a transcription factor essential for osteoblastogenesis, and of Satb2, a member of the special AT-rich binding protein family. In the present study, we used a gain-of-function approach to determine the roles of miR-23a in bone formation and homeostasis in vivo. The miR-23a transgenic (Tg) mice grew normally and their body size and weight were similar to those of wild-type (WT) littermates. Bone structure and morphology were similar in Tg and WT mice. Furthermore, the numbers of osteoblasts and osteoclasts, as well as their activities in bone were similar between Tg and WT mice. Our results indicate that miR-23 has limited roles in bone formation and maintenance in vivo in mice.
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