Feasibility and Efficacy of Definitive Radiotherapy with 66 Gy and Concurrent Carboplatin-Paclitaxel Chemotherapy for Stage III Non-Small Cell Lung Cancer.

Purpose/Objectives : This study was conducted to assess the feasibility and efficacy of definitive radiotherapy (RT) with a total dose of 66 Gy and concurrent carboplatin-paclitaxel chemotherapy for patients (pts) with stage Ⅲ non-small celllung cancer. Materials/Methods : Between April 2007 and December 2013，99 pts with non-small cell lung cancer were treated using RT with concurrent carboplatin-paclitaxel chemotherapy in our hospital. Sixty-eight of them received RT with a total dose of 66 Gy. We analyzed 46 Stage Ⅲ pts who had been treated with RT using three-dimensional radiotherapy treatment planning. The prophylactic mediastinal lymph nodes were included in the clinical target volume for RT. The survival rate after the start of RT was estimated using the Kaplan-Meier method. We estimated the cumulative local failure and distant metastasis rates with the Fine-Gray method. Adverse events were evaluated according to the CTCAE (v.4.0). Results : The median age of the pts was 70.9 (52.8-78.7) years old (y.o.). The performance status (PS) of each pt was fairly good (ECOG PS 0: 25, PS 1: 20, PS 3:1), and their clinical stages (UICC 7th) were twenty-nine Ⅲ A and seventeen Ⅲ B. Diagnoses were pathologically confirmed in 32 pts. The median follow-up period was 35.7 (2.0-82.2) months among all pts, and 55.9 (40.1-82.2) months among survivors. The 3- and 5-year Kaplan-Meier overall survival rates were 52.2 and 34.0%，respectively, and the median survival time was 36.6 months. The 3- and 5-year Kaplan-Meier progression-free survival rates were 29.1 and 21.9%，respectively, and the median progression-free survival time was 9.9 months. The 5-year local failure rate was 37.6%, and the 5-year distant metastasis rate was 49.7%. Sixteen (34.8%) pts required steroid administration because of radiation pneumonitis (CTCAE Grade 2 or higher) and two of them died (Grade 5). No other severe non-hematologic toxicity (Grade 3 or higher) was observed. Conclusion : These results suggest that definitive RT with a total dose of 66 Gy and concurrent carboplatin-paclitaxel chemotherapy is feasible and may be promising for pts with Stage Ⅲ non-small cell lung cancer

Rotigotine suppresses sleep-related muscle activity augmented by injection of dialysis patients’ sera in a mouse model of restless legs syndrome

Idiopathic restless legs syndrome (RLS) has a genetic basis wherein BTBD9 is associated with a higher risk of RLS. Hemodialysis patients also exhibit higher rates of RLS compared with the healthy population. However, little is known about the relationship of BTBD9 and end-stage renal disease to RLS pathophysiology. Here we evaluated sleep and leg muscle activity of Btbd9 mutant (MT) mice after administration of serum from patients with either idiopathic or RLS due to end-stage renal disease (renal RLS) and investigated the efficacy of treatment with the dopamine agonist rotigotine. At baseline, the amount of rapid eye movement (REM) sleep was decreased and leg muscle activity during non-REM (NREM) sleep was increased in MT mice compared to wild-type (WT) mice. Wake-promoting effects of rotigotine were attenuated by injection of serum from RLS patients in both WT and MT mice. Leg muscle activity during NREM sleep was increased only in MT mice injected with serum from RLS patients of ideiopatic and renal RLS. Subsequent treatment with rotigotine ameliorated this altered leg muscle activity. Together these results support previous reports showing a relationship between the Btbd9/dopamine system and RLS, and elucidate in part the pathophysiology of RLS

Direct quark transition potential for ΛN→NN\Lambda N \to NN decay

The weak $\Lambda N\to NN$ transition is studied in the valence quark model approach. The quark component of the two baryon system is described in the quark cluster model and the weak transition potential is calculated by evaluating the matrix elements of the $\Delta S=1$ effective weak Hamiltonian. The transition potential is applied to the decay of hypernuclei and the results are compared with available experimental data. The results indicate that direct quark process is significant and qualitatively different when compared with those in conventional meson-exchange calculations. The direct quark mechanism predicts the violation of the $\Delta I = 1/2$ rule for this transition.Comment: 36 pages, LaTeX, 2 figures (uuencoded Postscript) included using epsf.te

Carboplatin-Paclitaxel Chemoradiotherapy With 66 Gy For Elderly Patients With Locally Advanced Non-Small-Cell Lung Cancer.

Background/ Aim: The common radiation dose administered with chemoradiotherapy for stage III non-small-cell lung cancer (NSCLC) is 60 Gy. We aimed to examine the feasibility and effectiveness of carboplatin-paclitaxel chemoradiotherapy with 66 Gy for elderly NSCLC patients. Patients and Methods: Forty-five patients with stage III NSCLC were enrolled from 2011 to 2014 at our hospital. They were divided into three groups according to their status and underwent different treatments. Overall survival (OS), progression-free survival (PFS), and local control (LC) were determined. Toxicity was evaluated with NCI-CTCAE ver. 4.0; intergroup differences were analysed statistically. Results: The group receiving carboplatin-paclitaxel chemotherapy with 66 Gy showed the longest median OS (40.4 months), PFS (17.9 months), and LC (44.3 months). Toxicity was acceptable in all groups. Conclusion: For elderly patients with stage III NSCLC, carboplatin-paclitaxel chemoradiotherapy with 66 Gy is suggested to be feasible and effective

Phenotyping of P105-Negative B Cell Subsets in Patients with Systemic Lupus Erythematosus

This study aimed to investigate phenotype of RP105(−) B cell subsets in patients with systemic lupus erythematosus (SLE). Flow cytometry was used for phenotyping RP105-negaive B cell subsets. Based on CD19, RP105, and CD138 expression, RP105(−) B cells consist of at least 5 subsets of late B cells, including CD19(+)RP105(int), CD19(+) RP105(−), CD19(low) RP105(−) CD138(−), CD19(low) RP105(−)CD138(int), and CD19(low) RP105(−) CD138(++) B cells. Especially, CD19(+)RP105(int) and CD19(low) RP105(−)CD138(int) B cells are significantly larger than other RP105(−) B cell subsets in SLE. By comparison of RP105(−) B cell subsets between patients with SLE and normal subjects, these subsets were detectable even in normal subjects, but the percentages of RP105(−) B cell subsets were significantly larger in SLE. The phenotypic analysis of RP105(−) B cell subsets suggests dysregulation of later B cell subsets in SLE and may provide new insights into understanding regulation of B cells in human SLE

Long-term exposure to methylmercury and psychiatric symptoms in residents of Minamata, Japan

Introduction: It is well-known that prenatal or postnatal exposure to methylmercury can produce neurological signs in adults and children, exemplified by a case of large-scale poisoning in Minamata, Japan, in the 1950s. However, evidence regarding whether pre- or postnatal exposure to methylmercury causes psychiatric symptoms (e.g., impairment of intelligence and mood and behavioral dysfunction) is still limited-excluding cases of fetal Minamata disease patients. Methods: We evaluated the effects of pre- or postnatal exposure to methylmercury on psychiatric symptoms using data derived from a 1971 population-based survey in Minamata and neighboring communities. We adopted residential areas as an exposure indicator and psychiatric symptoms as the outcome. Then, we estimated the adjusted prevalence odds ratio (POR) and confidence interval (Cl) of psychiatric symptoms in relation to residential area. Results: There were 904 participants in Minamata (high exposure area), 1700 in Goshonoura (middle exposure area), and 913 in Ariake (low exposure area). Compared to the Ariake area, participants in the Minamata area manifested psychiatric symptoms more frequently: PORs for impairment of intelligence and mood and behavioral dysfunction were 5.2 (95% Cl: 3.7-7.3) and 4.4 (95% Cl: 2.9-6.7), respectively. Furthermore, participants with psychiatric symptoms in the Minamata area more frequently had neurological signs. Peaks in prevalence of psychiatric symptoms occurred around age 20 and in older age adults in the area. These findings did not change when we excluded those who had been officially certified as Minamata disease patients by that time. Conclusions: The present study suggests a relationship between pre- or postnatal exposure to methylmercury and psychiatric symptoms among the general population in Minamata even after excluding officially certified patients

Involvement of endothelins in neuroprotection of valosin-containing protein modulators against retinal ganglion cell damage

We have previously shown that Kyoto University Substances (KUSs), valosin-containing protein (VCP) modulators, suppress cell death in retinal ganglion cells of glaucoma mouse models through alterations of various genes expressions. In this study, among the genes whose expression in retinal ganglion cells was altered by KUS treatment in the N-methyl-D-aspartic acid (NMDA) injury model, we focused on two genes, endothelin-1 (Edn1) and endothelin receptor type B (Ednrb), whose expression was up-regulated by NMDA and down-regulated by KUS treatment. First, we confirmed that the expression of Edn1 and Ednrb was upregulated by NMDA and suppressed by KUS administration in mice retinae. Next, to clarify the influence of KUSs on cell viability in relation to the endothelin signaling, cell viability was examined with or without antagonists or agonists of endothelin and with or without KUS in 661W retinal cells under stress conditions. KUS showed a significant protective effect under glucose-free conditions and tunicamycin-induced stress. This protective effect was partially attenuated in the presence of an endothelin antagonist or agonist under glucose-free conditions. These results suggest that KUSs protect cells partially by suppressing the upregulated endothelin signaling under stress conditions

Trends of preterm birth and low birth weight in Japan: a one hospital-based study

Background: The proportions of preterm birth (PTB, ie., delivered before 37 gestational weeks) and low birth weight (LBW, ie., birth weight less than 2500 g at delivery) have been rising in developed countries. We sought to examine the factors contributing to the rise in Japan, with particular focus on the effects of obstetric interventions. Methods: We used a database maintained by one large regional hospital in Shizuoka, Japan. We restricted the analysis to mothers who delivered live singleton births from 1997 to 2010 (n = 19,221). We assessed the temporal trends in PTB and LBW, then divided the study period into four intervals and compared the proportions of PTB and LBW. We also compared the newborns’ outcomes between the intervals. Results: PTB, in particular medically indicated PTB, increased considerably. The increase was largely explained by changes in caesarean sections. The neonatal outcomes did not worsen, and instead the Apgar scores and proportions requiring neonatal intensive care unit (NICU) admission improved. In particular, the risks of NICU admission in the interval from 2007 to 2010 were decreased among all births [odds ratio (OR): 0.84; 95% confidence interval (CI): 0.75, 0.95] and medically indicated births (OR: 0.44; 95% CI: 0.29, 0.68) compared with the interval from 1997 to 2000. Conclusions: Despite the increases in PTB as well as LBW, the present study suggests benefits of obstetric interventions. Rather than simple categorization of PTB or LBW, indicators such as perinatal mortality or other outcomes may be more appropriate for evaluation of perinatal health in developed countries