313 research outputs found

    Evaluation of heterogeneity dose distributions for Stereotactic Radiotherapy (SRT): comparison of commercially available Monte Carlo dose calculation with other algorithms

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    <p>Abstract</p> <p>Background</p> <p>The purpose of this study was to compare dose distributions from three different algorithms with the x-ray Voxel Monte Carlo (XVMC) calculations, in actual computed tomography (CT) scans for use in stereotactic radiotherapy (SRT) of small lung cancers.</p> <p>Methods</p> <p>Slow CT scan of 20 patients was performed and the internal target volume (ITV) was delineated on Pinnacle<sup>3</sup>. All plans were first calculated with a scatter homogeneous mode (SHM) which is compatible with Clarkson algorithm using Pinnacle<sup>3 </sup>treatment planning system (TPS). The planned dose was 48 Gy in 4 fractions. In a second step, the CT images, structures and beam data were exported to other treatment planning systems (TPSs). Collapsed cone convolution (CCC) from Pinnacle<sup>3</sup>, superposition (SP) from XiO, and XVMC from Monaco were used for recalculating. The dose distributions and the Dose Volume Histograms (DVHs) were compared with each other.</p> <p>Results</p> <p>The phantom test revealed that all algorithms could reproduce the measured data within 1% except for the SHM with inhomogeneous phantom. For the patient study, the SHM greatly overestimated the isocenter (IC) doses and the minimal dose received by 95% of the PTV (PTV95) compared to XVMC. The differences in mean doses were 2.96 Gy (6.17%) for IC and 5.02 Gy (11.18%) for PTV95. The DVH's and dose distributions with CCC and SP were in agreement with those obtained by XVMC. The average differences in IC doses between CCC and XVMC, and SP and XVMC were -1.14% (p = 0.17), and -2.67% (p = 0.0036), respectively.</p> <p>Conclusions</p> <p>Our work clearly confirms that the actual practice of relying solely on a Clarkson algorithm may be inappropriate for SRT planning. Meanwhile, CCC and SP were close to XVMC simulations and actual dose distributions obtained in lung SRT.</p

    A case of reversible cerebral vasoconstriction syndrome associated with anti-phospholipid antibody syndrome and systemic lupus erythematosus

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    The pathomechanisms and treatment strategy for rare presentations of reversible cerebral vasoconstriction syndrome (RCVS) with anti-phospholipid syndrome (APS) remain to be determined. We report a 67-year-old woman with APS who presented with ischemic stroke due to RCVS. She was treated with low-dose cilostazol and lomerizine hydrochloride, which resulted in functional improvement and recovery of vasoconstriction within 12 weeks. Her plasma endothelin-1 level was decreased after relief of vasoconstriction, compared with the pre-treatment condition. Increased plasma endothelin-1 may be related to the underlying pathomechanism of RCVS with APS, against which cilostazol and lomerizine hydrochloride could be effective

    Growth ability in simian cells of monkey cell-tropic HIV-1 is greatly affected by downstream region of the vif gene

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    To obtain monkey-tropic (mt) HIV-1 derivatives with distinct biological characteristics and to improve the viral growth property, we have generated several variants from a prototype mt HIV-1 designated NL-DT5R (X4-tropic). The prototype HIV-1 contains a portion of gag and entire vif genes from SIVmac in its genome. The two derivatives carrying 3’ half-genomic region of the SF162 (R5-tropic) or 89.6 (dual-tropic) isolate displayed very retarded or no viral growth, respectively, in a simian cell line HSC-F. In contrast, the three clones containing a part of env gene (encoding the V1-V4 region) from SF162, YU-2 (R5-tropic) or 89.6 showed different growth kinetics in HSC-F cells, although they grew somewhat more poorly than the NL-DT5R. Comparison of various viral proteins potentially involved in the different biological properties has revealed that, while amino acid sequences of Tat, Rev, Vpr, Vpu and Nef are quite conserved among the clones, those in the surface (SU) region of Env are relatively heterologous. Our data described here have shown that the 3’ half of viral genome other than gag and vif genes greatly affects the growth property of mt HIV-1 in simian cells

    CRMP5 (Collapsin Response Mediator Protein 5) Regulates Dendritic Development and Synaptic Plasticity in the Cerebellar Purkinje Cells

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    Collapsin response mediator protein 5 (CRMP5) is one of the CRMP members that expresses abundantly in the developing brain. To examine the in vivo function of CRMP5, we generated crmp5-deficient (crmp5(-/-)) mice. Anti-calbindin immunofluorescence studies of crmp5(-/-) mice revealed aberrant dendrite morphology; specifically, a decrease in the size of soma and diameter of primary dendrite of the cerebellar Purkinje cells at postnatal day 21 (P21) and P28, but not at P14. Coincidentally, CRMP5 is detected in Purkinje cells at P21 and P28 from crmp5(+/-) mice. In cerebellar slices of crmp5(-/-) mice, the induction of long-term depression of excitatory synaptic transmission between parallel fibers and Purkinje cells was deficient. Given that brain-derived neurotrophic factor (BDNF) plays major roles in dendritic development, we tried to elucidate the possible roles of CRMP5 in BDNF signaling. The effect of BDNF to induce dendritic branching was markedly attenuated in cultured crmp5(-/-) neurons. Furthermore, CRMP5 was tyrosine phosphorylated when coexpressed with neurotrophic tyrosine kinase receptor type 2 (TrkB), a receptor for BDNF, in HEK293T cells. These findings suggest that CRMP5 is involved in the development, maintenance and synaptic plasticity of Purkinje cells

    Analysis of hydroxy sphingomyelin

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    Sphingomyelin (SM) with N-α-hydroxy fatty acyl residues (hSM) has been shown to occur in mammalian skin and digestive epithelia. However, the metabolism and physiological relevance of this characteristic SM species have not been fully elucidated yet. Here, we show methods for mass spectrometric characterization and quantification of hSM. The hSM in mouse skin was isolated by TLC. The hydroxy hexadecanoyl residue was confirmed by electron impact ionization-induced fragmentation in gas chromatography-mass spectrometry. Mass shift analysis of acetylated hSM by time of flight mass spectrometry revealed the number of hydroxyl groups in the molecule. After correcting the difference in detection efficacy, hSM in mouse skin and intestinal mucosa were quantified by liquid chromatography-tandem mass spectrometry, and found to be 16.5 ± 2.0 and 0.8 ± 0.4 nmol/μmol phospholipid, respectively. The methods described here are applicable to biological experiments on hSM in epithelia of the body surface and digestive tract

    Smoking and adipose tissue inflammation suppress leptin expression in Japanese obese males: potential mechanism of resistance to weight loss among Japanese obese smokers

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    <p>Abstract</p> <p>Background</p> <p>The effect of smoking on leptin regulation is controversial. Smoking may induce low-grade inflammation. Recent series of studies indicated the critical role of macrophage migration in the establishment of adipose tissue inflammation. In this study, we aimed to see the effects of smoking and inflammation on leptin regulation both at cellular and epidemiological levels.</p> <p>Methods</p> <p>We compared the concentration of inflammatory markers and serum leptin levels among Japanese male subjects. Additionally, leptin and intercellular adhesion molecule (ICAM) -1 gene expression was assessed in adipocytes co-cultured with or without macrophages in the presence or absence of nicotine and/or lipopolysaccharide (LPS).</p> <p>Results</p> <p>In subjects with BMI below 25 kg/m<sup>2</sup>, both WBC counts and soluble-ICAM-1 levels are significantly higher in smokers than in non-smokers. However, leptin concentration did not differ according to smoking status. However, in subjects with BMI over 25 kg/m<sup>2</sup>, smokers exhibited significantly lower serum leptin level as well as higher WBC counts and s-ICAM-1 concentration as compared with non-smokers. Leptin gene expression was markedly suppressed in adipocytes co-cultured with macrophages than in adipocyte culture alone. Furthermore, nicotine further suppressed leptin gene expression. ICAM-1 gene expression was markedly up-regulated in adipocytes co-cultured with macrophages when stimulated with LPS.</p> <p>Conclusions</p> <p>Adipose tissue inflammation appears to down-regulate leptin expression in adipose tissues. Nicotine further suppresses leptin expression. Thus, both smoking and inflammation may diminish leptin effect in obese subjects. Therefore, obese, but not normal weight, smokers might be more resistant to weight loss than non-smokers.</p

    Time definition of reintubation most relevant to patient outcomes in critically ill patients: a multicenter cohort study

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    Background: Reintubation is a common complication in critically ill patients requiring mechanical ventilation. Although reintubation has been demonstrated to be associated with patient outcomes, its time definition varies widely among guidelines and in the literature. This study aimed to determine the association between reintubation and patient outcomes as well as the consequences of the time elapsed between extubation and reintubation on patient outcomes. Methods: This was a multicenter retrospective cohort study of critically ill patients conducted between April 2015 and March 2021. Adult patients who underwent mechanical ventilation and extubation in intensive care units (ICUs) were investigated utilizing the Japanese Intensive Care PAtient Database. The primary and secondary outcomes were in-hospital and ICU mortality. The association between reintubation and clinical outcomes was studied using Cox proportional hazards analysis. Among the patients who underwent reintubation, a Cox proportional hazard analysis was conducted to evaluate patient outcomes according to the number of days from extubation to reintubation. Results: Overall, 184,705 patients in 75 ICUs were screened, and 1849 patients underwent reintubation among 48,082 extubated patients. After adjustment for potential confounders, multivariable analysis revealed a significant association between reintubation and increased in-hospital and ICU mortality (adjusted hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.359–1.700, and adjusted HR 1.325, 95% CI 1.076–1.633, respectively). Among the reintubated patients, 1037 (56.1%) were reintubated within 24 h after extubation, 418 (22.6%) at 24–48 h, 198 (10.7%) at 48–72 h, 111 (6.0%) at 72–96 h, and 85 (4.6%) at 96–120 h. Multivariable Cox proportional hazard analysis showed that in-hospital and ICU mortality was highest in patients reintubated at 72–96 h (adjusted HR 1.528, 95% CI 1.062–2.197, and adjusted HR 1.334, 95% CI 0.756–2.352, respectively; referenced to reintubation within 24 h). Conclusions: Reintubation was associated with a significant increase in in-hospital and ICU mortality. The highest mortality rates were observed in patients who were reintubated between 72 and 96 h after extubation. Further studies are warranted for the optimal observation of extubated patients in clinical practice and to strengthen the evidence for mechanical ventilation.Tanaka A., Shimomura Y., Uchiyama A., et al. Time definition of reintubation most relevant to patient outcomes in critically ill patients: a multicenter cohort study. Critical Care 27, 378 (2023); https://doi.org/10.1186/s13054-023-04668-3
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