Development of an experimental platform for the investigation of laser-plasma interaction in conditions relevant to shock ignition regime.

The shock ignition (SI) approach to inertial confinement fusion is a promising scheme for achieving energy production by nuclear fusion. SI relies on using a high intensity laser pulse (≈1016 W/cm2, with a duration of several hundred ps) at the end of the fuel compression stage. However, during laser-plasma interaction (LPI), several parametric instabilities, such as stimulated Raman scattering and two plasmon decay, nonlinearly generate hot electrons (HEs). The whole behavior of HE under SI conditions, including their generation, transport, and final absorption, is still unclear and needs further experimental investigation. This paper focuses on the development of an experimental platform for SI-related experiments, which simultaneously makes use of multiple diagnostics to characterize LPI and HE generation, transport, and energy deposition. Such diagnostics include optical spectrometers, streaked optical shadowgraph, an x-ray pinhole camera, a two-dimensional x-ray imager, a Cu Kα line spectrometer, two hot-electron spectrometers, a hard x-ray (bremsstrahlung) detector, and a streaked optical pyrometer. Diagnostics successfully operated simultaneously in single-shot mode, revealing the features of HEs under SI-relevant conditions.

Buffering effects of safe, supportive, and nurturing relationships among women with childhood histories of maltreatment.

BACKGROUND: Adults who were victims of childhood maltreatment tend to have poorer health compared with adults who did not experience abuse. However, many are in good health. We tested whether safe, supportive, and nurturing relationships buffer women with a history of childhood maltreatment from poor health outcomes in later life. METHODS: Participants included women from the Environmental Risk (E-Risk) Longitudinal Twin Study who were involved in an intimate relationship at some point by the time their twin children were 10 years old. Women were initially interviewed in 1999-2000 (mean age = 33 years) and 2, 5, and 7 years later. They reported on their physical and mental health, and their health-risk behaviours. RESULTS: Compared with women who did not experience abuse in childhood, women with histories of maltreatment were at elevated risk for mental, physical, and health-risk behaviours, including major depressive disorder, sleep, and substance use problems. Cumulatively, safe, supportive, and nurturing relationships characterized by a lack of violence, emotional intimacy, and social support buffered women with a history of maltreatment from poor health outcomes. CONCLUSIONS: Our findings emphasize that negative social determinants of health - such as a childhood history of maltreatment - confer risk for psychopathology and other physical health problems. If, however, a woman's current social circumstances are sufficiently positive, they can promote good health, particularly in the face of past adversity.

Childhood bullying victimization is associated with use of mental health services over five decades: a longitudinal nationally representative cohort study.

BACKGROUND: Research supports robust associations between childhood bullying victimization and mental health problems in childhood/adolescence and emerging evidence shows that the impact can persist into adulthood. We examined the impact of bullying victimization on mental health service use from childhood to midlife. METHOD: We performed secondary analysis using the National Child Development Study, the 1958 British Birth Cohort Study. We conducted analyses on 9242 participants with complete data on childhood bullying victimization and service use at midlife. We used multivariable logistic regression models to examine associations between childhood bullying victimization and mental health service use at the ages of 16, 23, 33, 42 and 50 years. We estimated incidence and persistence of mental health service use over time to the age of 50 years. RESULTS: Compared with participants who were not bullied in childhood, those who were frequently bullied were more likely to use mental health services in childhood and adolescence [odds ratio (OR) 2.53, 95% confidence interval (CI) 1.88-3.40] and also in midlife (OR 1.30, 95% CI 1.10-1.55). Disparity in service use associated with childhood bullying victimization was accounted for by both incident service use through to age 33 years by a subgroup of participants, and by persistent use up to midlife. CONCLUSIONS: Childhood bullying victimization adds to the pressure on an already stretched health care system. Policy and practice efforts providing support for victims of bullying could help contain public sector costs. Given constrained budgets and the long-term mental health impact on victims of bullying, early prevention strategies could be effective at limiting both individual distress and later costs.

Editor's Choice - Subsequent Results for Arch Aneurysm Repair with Inner Branched Endografts.

OBJECTIVES: The aim was to evaluate the current results of aortic arch aneurysm repair using inner branched endografts performed in three high volume aortic endovascular centers and to compare them to the pioneering global experience with this technology. METHODS: Included patients underwent repair of aortic arch aneurysms >55 mm in diameter using inner branched endograft technology between April 2013 and November 2014. All patients were deemed unfit for open surgery. Inner branches were designed to perfuse the brachiocephalic trunk and the left common carotid artery in all cases. A left subclavian artery (LSA) revascularization was performed prior to the arch endovascular repair. Data were collected retrospectively in an electronic database. Parameters included length of procedure, fluoroscopy time, contrast volume, technical success, presence of endoleaks, early and late complications, and mortality. RESULTS: Twenty-seven patients were included in the study. Technical success was achieved in all cases. No patients died during the 30 day post-operative period. Early neurologic events included two major strokes (7.4%) and one minor stroke (3.7%). Transient spinal cord ischemia with full recovery was observed in two patients (7.4%). Four patients (14.8%) underwent early (<30 day) re-interventions; these were for an access complication, an ischemic limb and exploration of the left ventricle through a sternotomy in two patients. During follow up (median 12 months), one patient (3.7%) died from a remote thoraco-abdominal aneurysm rupture. There were three Type 2 endoleaks (11.1%). Two re-interventions (7.4%) were performed, one to treat a Type 2 endoleak and one to treat a septic false aneurysm. A significant decrease in overall mortality was observed when comparing patients from the early experience with patients from the current report. CONCLUSIONS: The early outcomes associated with this technology are favorable. Branched endografting of aortic arch aneurysms should be considered in patients unfit for open surgery.

Bullying victimization in childhood predicts inflammation and obesity at mid-life: a five-decade birth cohort study.

BACKGROUND: We aimed to test whether childhood bullying victimization increases risk for age-related disease at mid-life using biological markers including inflammation and adiposity, independent of other childhood risk factors and key adult variables. METHOD: The present study was a 50-year prospective longitudinal birth cohort study of all births in Britain in 1 week in 1958. Exposure to bullying was assessed prospectively when participants were aged 7 and 11 years (27.7% occasionally bullied; 14.6% frequently bullied). Blood inflammation biomarkers [C-reactive protein (CRP) and fibrinogen] and adiposity [body mass index (BMI) and waist:hip ratio] were measured at age 45 years. RESULTS: Participants who had been frequently bullied in childhood showed increased levels of CRP at mid-life [ß = 0.07, 95% confidence interval (CI) 0.04-0.10] and higher risk for clinically relevant inflammation cut-off [CRP > 3 mg/l: 20.4% v. 15.9%, odds ratio (OR) = 1.35, 95% CI 1.12-1.64]. Women who were bullied in childhood had higher BMI than non-bullied participants and were at increased risk of being obese (BMI ≥ 30 kg/m2: occasionally bullied: 26.0% v. 19.4%, OR = 1.45, 95% CI 1.18-1.77; frequently bullied: 26.2% v. 19.4%, OR = 1.41, 95% CI 1.09-1.83). Findings remained significant when controlling for childhood risk factors (e.g. parental social class; participants' BMI and psychopathology in childhood) and key adult variables (e.g. adult social class, smoking, diet and exercise). CONCLUSIONS: Bullied children show increases in risk factors for age-related disease in middle adulthood, independent of co-occurring childhood and adult risks. Given the high prevalence of bullying victimization in childhood, tackling this form of psychosocial stress early in life has the potential of reducing risk for age-related disease and its associated burden.

Increased expression of HLA-DR and CD86 in nasal epithelial cells in allergic rhinitics: antigen presentation to T cells and up-regulation by diesel exhaust particles.

BACKGROUND: A proportion of nasal epithelial cells (NEC) in patients with allergic rhinitis (AR) are known to express the major histocompatibility complex Class II molecule (HLA-DR). OBJECTIVE: We hypothesized that NEC may play a role in antigen presentation to T cells. To elucidate the possible role of NEC in antigen presentation, we examined the expression of HLA-DR, CD80 and CD86 in NEC, their regulation by cytokines and the capacity of NEC to induce antigen-specific proliferation of T cells. METHODS: We examined the expression of HLA-DR, CD80 and CD86 in nasal epithelial scrapings of patients with seasonal allergic rhinitis (SAR) to Japanese cedar pollen pre-season and in-season, by immunohistochemistry. Next, we examined the effect of IL-1beta, TNF-alpha, (IFN-gamma), IL-4 alpha, IL-13 and diesel exhaust particles (DEP) on the HLA-DR, CD80 and CD86 expression in cultured nasal epithelial cells (CNEC), by flow cytometry. Further, we analysed the capacity of mite antigen (Der f II)-pulsed mitomycin-C-treated CNEC to induce proliferation of autologous T cells from patients with perennial allergic rhinitis. RESULTS: NEC constitutively expressed HLA-DR and CD86, but not CD80. The expression of HLA-DR and CD86 in NEC was significantly increased in-season, in patients with SAR as compared with that of pre-season. While IFN-gamma up-regulated the expression of HLA-DR, IL-1beta and TNF-alpha up-regulated the expression of CD86 in CNEC. Furthermore, in the presence of mite antigen, CNEC induced the proliferation of autologous peripheral blood T lymphocytes. Anti-CD86 and anti-HLA-DR monoclonal antibody but not anti-CD80 inhibited the epithelial cell-induced T cell proliferation. Stimulation with a combination of DEP and mite antigen significantly up-regulated HLA-DR and CD86 expression in CNEC. CONCLUSIONS: These studies suggest that NEC in patients with AR may play a role in antigen presentation through the enhanced expression of HLA-DR and CD86. Furthermore, these results suggest the possibility that DEP may enhance the antigen-presenting function of CNEC.

[Experience of specific immunotherapy with standardized Japanese cedar pollen extract].

A study was conducted in 165 subjects with Japanese cedar pollinosis (JC) to evaluate the switching to the new standardized extract (SE) for patients who are going on specific immunotherapy (SP-IT) with conventional non-standardized extracts, products of Trii Co. or Hollister-Stier Co. Eight of 137 subjects exhibited adverse systemic reactions such as general skin eruption and despnea when JC allergen extract of Hollister-Stier Co. was switched to JC-SE. There were 6 cases where concentration of the extract had to be decreased due to extraordinary late reactions, while none of 28 subjects exhibited adverse side effect, when conventional allergen extract by Torii Pharmaceutical Co. was switched to JC-SE. Careful switching to high concentration of SE is required, because eight cases with adverse side effect were shown in switching to 200 JAU/ml and 2000 JAU/ml. 20 subjects started with SP-IT by JC-SE after spread of JC in the year of 2000 exhibited no adverse side effects in our protocol.

Stem cell factor mRNA expression and production in human nasal epithelial cells: contribution to the accumulation of mast cells in the nasal epithelium of allergy.

BACKGROUND: In allergic rhinitis, mast cells are increased in number in the epithelium of the nasal mucosa and play an important role in the immediate response. However, the mechanism of the accumulation is not known. OBJECTIVE: The purpose of this study was to determine whether the nasal epithelial cells produce stem cell factor (SCF), the mast cell growth and chemoattractant factor, and contribute mast cell hyperplasia in the epithelium of allergic rhinitis. METHODS: We have characterized the cellular localization of SCF using immunohistochemistry, reverse transcribed-PCR, and ELISA; compared SCF production of cultured epithelial cells between patients with allergic rhinitis and nonallergic subjects; and compared the SCF production with the number of mast cells and the histamine content in the nasal epithelial scrapings. RESULTS: Immunohistochemically, SCF was identified in the nasal epithelium of the biopsy specimens and in cultured nasal epithelial cells. SCF mRNA was expressed by cultured nasal epithelial cells not only in patients with allergy but also in subjects with no allergy. However, the SCF/beta-actin mRNA ratio and SCF production in day 7 cultured epithelial cells was significantly higher in allergic than in nonallergic subjects (P =. 0424, P =.0085, respectively). SCF production from nasal scrapings in culture was strongly correlated with the number of mast cells (r = 0.506, P =.0023) and the histamine content (r = 0.480, P =.0040). CONCLUSIONS: These findings demonstrate that nasal epithelial cells produce SCF and may be important in the attraction, proliferation, and activation of mast cells in allergic inflammation in the nose.

[Study of the favorable culture condition to produce granulocyte. Macrophage colony stimulating factor and interleukin-6 by human nasal epithelial cells].

Allergic rhinitis and nasal polyposis are upper airway inflammatory conditions characterized by increased numbers of eosinophils and metachromatic cells in the epithelial layer of the nasal mucosa. However, the mechanism by which these cells accumulate still remains obscure in many respects. It is suggested that the granulocyte-macrophage colony stimulating factor (GM-CSF) plays an important role in the nasal mucosa, since the supernatant of cultured epithelial cells induce differentiation of peripheral mononuclear cells into metachromatic cells and eosinophils, and this activity was inhibited by the anti-GM-CSF antibody. In addition, the presence of several cytokines in the supernatant of nasal epithelial cell cultures has been reported. These observations suggest the possibility that GM-CSF and cytokines play an important role in the allergic and inflammatory reactions of the nasal mucosa. In the present study epithelial cells of nasal mucosa were cultured under different conditions to find out the optimal conditions of production for GM-CSF and interleukin-6 (IL-6). When the concentration of fetal calf serum (FCS) in the culture medium was varied, the number of cultured epithelial cells and the concentration of GM-CSF and IL-6 in the supernatant showed an FCS concentration-dependent increase. When nasal mucosal epithelial cells were cultured in 15% FCS, production of both GM-CSF and IL-6 was increased with increasing duration of incubation. There was no significant difference in production of GM-CSF or IL-6 between the patients with allergic rhinitis and those with nasal polyps. These results suggest that neither allergic rhinitis and nor nasal polyposis are associated with the ability of epithelial cells to produce cytokines, but the interplay of various factors in the epithelial layer, as well as of diseases, affects their ability to produce cytokines. When the condition of epithelial cell propagation was rendered favorable or unfavorable by varying the concentration of FCS in the culture medium, using the same culture system, production of GM-CSF and IL-6 was increased in a dose-dependent manner (%) favoring epithelial cell growth. These observations indicate that epithelial cells produce GM-CSF and IL-6 only when conditions are favorable for their proliferation is required.

[Generation of tumor necrosis factor alpha by human nasal epithelial cells and inhibition by fluticasone propionate].

Accumulation of mast cells and eosinophils in the nasal epithelial layer occurs in nasal allergic reaction, However, the mechanism of accumulation of these cells has not yet been well clarified. We hypothesized that cytokines generated from the nasal epithelial cells contributed to the accumulation of these cells in the nasal epithelial layer. Recently tumor necrosis factor (TNF) was shown to promote polymorphonuclear neutrophils and eosinophils migration. And also TNF increased eosinophil binding to vascular endothelial cells. In this in vitro study we examined whether or not nasal epithelial cells can produce TNF-alpha and also whether or not glucocorticosteroid fluticasone propionate (FP) can modulate TNF-alpha production from nasal epithelial cells. Nasal epithelial cells constitutively produce TNF-alpha in accordance with the nasal epithelial cells' number and this was substantially increased in the state of nasal epithelial cell's proliferating. FP significantly reduced the level of TNF-alpha in the supernatant of cultured nasal epithelial cells for a period of 6 days. In addition, preincubation of nasal epithelial cells with FP for 6 days caused significant reduction of TNF-alpha level in the supernatant of cultured nasal epithelial cells during a further period of 6 days without FP. These data support the concept that structural cells play an active role in the control of allergic and related inflammatory processes.

[Cytokines of nasal inverted papilloma: quantification and distribution].

We previously found that an increased number of mucosal mast cells accumulated in the tumor site of nasal inverted papilloma as well as in the epithelial layer of the allergic nasal mucosa. However, the mechanism of accumulation of mucosal mast cells has not yet been clarified. The purpose of this study was to evaluate the cytokines produced by inverted papilloma cells, which would be important for the accumulation of mucosal mast cells. We found that the supernatant of the monolayer of cultured inverted papilloma cells contained GM-CSF, IL-6 and IL-8. IL-2, IL-3, IL-4 and IL-5 were not detected. Contrary to the quantities of cytokines detected in the supernatant of cultured allergic nasal epithelial cells, the quantities of IL-6 and IL-8 were greater in the supernatant of cultured inverted papilloma, whereas that of GM-CSF was less. Immunohistochemical study revealed the distribution of cytokines: GM-CSF was detected near the basement membrane of the tumor site, while IL-6 and IL-8 were detected in the superficial layer of nasal inverted papilloma. Interestingly, the tumor site near the basement membrane is also the site of accumulation of mucosal mast cells, suggesting that GM-CSF produced by nasal inverted papilloma cells may be one of the most important factors in the accumulation of mucosal mast cells.

Role of Lys108 in the enzymatic activity of RNase Rh from Rhizopus niveus.

In order to elucidate on the mechanism of action of RNase Rh from Rhizopus niveus, we investigated the role of Lys108, which is conserved among the RNase T2 family RNases except for two cases. The RNase activities of Lys108 mutant RNases, RNase RNAP K108R and K108L, are about 33.5 and 3.1% of that of the wild type enzyme, respectively. The relative rates of cleavage of dinucleoside phosphates by these two mutant enzymes were comparable to those with RNA as a substrate. The kinetic parameters of RNases RNAP K108R and K108L towards XpGs (where X is one of A, G, U, and C) were measured. The data indicated that the Km values of the two mutant enzymes are similar to those of the wild-type enzyme. The rates of release of the four nucleotides from RNA by digestion with the mutant enzymes were in the order A > G > U > C, which is qualitatively the same as that of the wild-type enzyme. From these data, we concluded that the Lys108 residue participates in the catalytic process, but not in the binding, and the positive charge of Lys108 is indispensable for the catalytic process, that is, the positive charge of Lys108 may stabilize the pentacoordinated intermediate in the transition state as proposed in the case of Lys41 in RNase A, or may polarize the phosphate moiety of the substrate.

[Fluticasone propionate reduced the production of GM-CSF, IL-6 and IL-8 generated from cultured nasal epithelial cells].

Accumulation of mast cells and eosinophils in the nasal epithelial layer occurs in nasal allergic reactions and nasal polyps. We have already demonstrated that fluticasone propionate (FP) inhibits the accumulation of mast cells and eosinophils locally, and also improves the nasal symptoms of patients with allergic rhinitis. We hypothesized that cytokines generated from nasal epithelial cells possibly contribute to the accumulation of cells and eosinophils in the nasal epithelial layer. In this experiment we examined the inhibitory effect of FP on the production of GM-CSF, IL-6 and IL-8 by culturing of nasal epithelial cells in vitro. Our results show that FP significantly reduces the level of GM-CSF, IL-6 and IL-8 in the supernatant of culture media of nasal epithelial cells for a period of 6 days. In addition, preincubation of nasal epithelial cells with FP for 6 days causes a significant reduction of GM-CSF levels in the supernatant of culture-media of cultured nasal epithelial cells during the subsequent period of 6 days without FP. These results provide evidence that FP inhibits the accumulation of mast cells and eosinophils in the mucoepithelial layer of the nasal membrane.

[Study of endothelin: distribution in the airway and release from nasal epithelial cells].

In order to clarify the existence and the role of endothelin in the respiratory tract, we investigated the distribution of endothelin in the respiratory mucosa by immunohistochemistry. The endothelin release from cultured nasal epithelial cells of allergic mucosa and polyp mucosa was also studied by RIA. Endothelin was distributed in the epithelium, endothelium of vessels, and submucosal glands in both nasal and bronchial mucosa. Moreover, in bronchial mucosa smooth muscles of bronchus had also positive staining of endothelin. On the other hand, 1.8 x 10(-11) pg of endothelin was released to culture medium from single cultured epithelial cell of allergic nasal mucosa, and 2.8 x 10(-11) pg of endothelin was released to culture medium from that of nasal polyp. These increase of endothelin was correlated with an increase of cultured epithelial cells from both nasal allergy mucosa and nasal polyp, of which the cell number was increased depend on the concentration of FCS. These results indicate that endothelin in the respiratory mucosa acts on not only control of blood flow and air flow, but also has some reaction which was related on the mucosal epithelium such as epithelial cilially movement. Endothelin has some role in inflammation because endothelin was increased more in nasal polyp culture medium than in allergic mucosa culture medium.