Oxidative stress in the cochlea: an update Poirrier, A L; Pincemail, J; Van Den Ackerveken, P ...
Current medicinal chemistry,
2010, Letnik:
17, Številka:
30
Journal Article
Recenzirano
This paper will focus on understanding the role and action of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the molecular and biochemical pathways responsible for the ...regulation of the survival of hair cells and spiral ganglion neurons in the auditory portion of the inner ear. The pivotal role of ROS/RNS in ototoxicity makes them potentially valuable candidates for effective otoprotective strategies. In this review, we describe the major characteristics of ROS/RNS and the different oxidative processes observed during ototoxic cascades. At each step, we discuss their potential as therapeutic targets because an increasing number of compounds that modulate ROS/RNS processing or targets are being identified.
The radiative effects from increased concentrations of well‐mixed greenhouse gases (WMGHGs) represent the most significant and best understood anthropogenic forcing of the climate system. The most ...comprehensive tools for simulating past and future climates influenced by WMGHGs are fully coupled atmosphere‐ocean general circulation models (AOGCMs). Because of the importance of WMGHGs as forcing agents it is essential that AOGCMs compute the radiative forcing by these gases as accurately as possible. We present the results of a radiative transfer model intercomparison between the forcings computed by the radiative parameterizations of AOGCMs and by benchmark line‐by‐line (LBL) codes. The comparison is focused on forcing by CO2, CH4, N2O, CFC‐11, CFC‐12, and the increased H2O expected in warmer climates. The models included in the intercomparison include several LBL codes and most of the global models submitted to the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4). In general, the LBL models are in excellent agreement with each other. However, in many cases, there are substantial discrepancies among the AOGCMs and between the AOGCMs and LBL codes. In some cases this is because the AOGCMs neglect particular absorbers, in particular the near‐infrared effects of CH4 and N2O, while in others it is due to the methods for modeling the radiative processes. The biases in the AOGCM forcings are generally largest at the surface level. We quantify these differences and discuss the implications for interpreting variations in forcing and response across the multimodel ensemble of AOGCM simulations assembled for the IPCC AR4.
Porous metals and metallic foams are presently the focus of very active research and development activities. There are currently around 150 institutions working on metallic foams worldwide, most of ...them focussing on their manufacture and characterisation. Various companies are developing and producing these materials which are now being used in numerous industrial applications such as lightweight structures, biomedical implants, filters, electrodes, catalysts, and heat exchangers. This review summarizes recent developments on these materials, with particular emphasis on research presented at the latest International Conference on Porous Metals and Metallic Foams (MetFoam 2007).
Porous metals and metallic foams are presently the focus of very active research and development activities. There are currently around 150 institutions working on metallic foams worldwide, most of them focussing on their manufacture and characterisation. Various companies are developing and producing these materials which are now being used in numerous industrial applications such as lightweight structures, biomedical implants, filters, electrodes, catalysts, and heat exchangers. This review summarizes recent developments on these materials, with particular emphasis on research presented at the latest International Conference on Porous Metals and Metallic Foams (MetFoam 2007).
Purpose
GANEA2 study was designed to assess accuracy and safety of sentinel lymph node (SLN) after neo-adjuvant chemotherapy (NAC) in breast cancer patients.
Methods
Early breast cancer patients ...treated with NAC were included. Before NAC, patients with cytologically proven node involvement were allocated into the pN1 group, other patient were allocated into the cN0 group. After NAC, pN1 group patients underwent SLN and axillary lymph node dissection (ALND); cN0 group patients underwent SLN and ALND only in case of mapping failure or SLN involvement. The main endpoint was SLN false negative rate (FNR). Secondary endpoints were predictive factors for remaining positive ALND and survival of patients treated with SLN alone.
Results
From 2010 to 2014, 957 patients were included. Among the 419 patients from the cN0 group treated with SLN alone, one axillary relapse occurred during the follow-up. Among pN1 group patients, with successful mapping, 103 had a negative SLN. The FNR was 11.9% (95% CI 7.3–17.9%). Multivariate analysis showed that residual breast tumor size after NAC ≥ 5 mm and lympho-vascular invasion remained independent predictors for involved ALND. For patients with initially involved node, with negative SLN after NAC, no lympho-vascular invasion and a remaining breast tumor size 5 mm, the risk of a positive ALND is 3.7% regardless the number of SLN removed.
Conclusion
In patients with no initial node involvement, negative SLN after NAC allows to safely avoid an ALND. Residual breast tumor and lympho-vascular invasion after NAC allow identifying patients with initially involved node with a low risk of ALND involvement.
Long-term experiments have been carried out to investigate the impact of Nickel (Ni) coarsening on the performance of Solid Oxide Cell. Durability tests have been performed with H2 electrode ...supported cells at 850 °C and 750 °C in fuel cell and electrolysis modes. Microstructural changes in the composite electrode of Nickel and Yttria Stabilized Zirconia (YSZ) have been characterized by synchrotron X-ray nanotomography. Analysis of the reconstructions have revealed that Ni coarsening induces a significant decrease of both the density of Triple Phase Boundary lengths (TPBls) and the Ni/gas specific surface area. However, the contact surface between Ni and YSZ is not changed upon operation, meaning the Ni sintering is inhibited by the YSZ backbone. Moreover, the Ni coarsening rate is independent of the electrode polarization. The evolution of TPBls in operation has been fitted by a phenomenological law implemented in an electrochemical model. Simulations have shown that microstructural changes in the H2 electrode explain ∼30% of the total degradation in fuel cell mode and ∼25% in electrolysis mode at 850 °C after 1000–2000 h. Moreover, it has been highlighted that the temperature at which the degradation is estimated after the durability experiment plays a major role on the result.
•Typical SOCs operated under fuel cell and electrolysis currents at 750 °C and 850 °C.•Ni-YSZ cermets reconstructed by synchrotron X-ray holotomography.•The inhibiting role of the YSZ backbone on Ni coarsening experimentally highlighted.•Local Ni particle growth independent on polarization in SOFC or SOEC modes.•Impact of Ni coarsening on cell performances computed for SOFC and SOEC modes.
To determine the causes and predictors of mortality in systemic sclerosis (SSc).
Patients with SSc (n=5860) fulfilling the American College of Rheumatology criteria and prospectively followed in the ...EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. EUSTAR centres completed a structured questionnaire on cause of death and comorbidities. Kaplan-Meier and Cox proportional hazards models were used to analyse survival in SSc subgroups and to identify predictors of mortality.
Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths, 35% were attributed to pulmonary fibrosis, 26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the non-SSc-related causes, infections (33%) and malignancies (31%) were followed by cardiovascular causes (29%). Of the non-SSc-related fatalities, 25% died of causes in which SSc-related complications may have participated (pneumonia, sepsis and gastrointestinal haemorrhage). Independent risk factors for mortality and their HR were: proteinuria (HR 3.34), the presence of PAH based on echocardiography (HR 2.02), pulmonary restriction (forced vital capacity below 80% of normal, HR 1.64), dyspnoea above New York Heart Association class II (HR 1.61), diffusing capacity of the lung (HR 1.20 per 10% decrease), patient age at onset of Raynaud's phenomenon (HR 1.30 per 10 years) and the modified Rodnan skin score (HR 1.20 per 10 score points).
Disease-related causes, in particular pulmonary fibrosis, PAH and cardiac causes, accounted for the majority of deaths in SSc.
Plasmas are an attractive medium for the next generation of particle accelerators because they can support electric fields greater than several hundred gigavolts per meter. These accelerating fields ...are generated by relativistic plasma waves-space-charge oscillations-that can be excited when a high-intensity laser propagates through a plasma. Large currents of background electrons can then be trapped and subsequently accelerated by these relativistic waves. In the forced laser wake field regime, where the laser pulse length is of the order of the plasma wavelength, we show that a gain in maximum electron energy of up to 200 megaelectronvolts can be achieved, along with an improvement in the quality of the ultrashort electron beam.
Body condition score (BCS) offers a good estimate of the amount of stored fat on the body, and its variations can be used as a proxy for energy balance. Many countries have implemented a genomic ...evaluation of BCS, including France, where estimated breeding values are based on an individual BCS determination during the first lactation. In this article, we investigate the degree to which this genomic estimated breeding value based on a single phenotype record per cow might reflect different profiles of body reserves throughout lactation and be used to predict, and perhaps limit, their mobilization during early lactation. We also investigate whether selection on BCS affects other traits. A data set including 686 lactations of 435 Holstein cows from 3 experimental farms not used in the reference population for genomic evaluation was used to estimate the effects of the BCS direct genomic value (iBCS) on BCS, body weight, feed intake, milk production, and fat and protein contents throughout the lactation period. For each trait, the model included different iBCS regressions and an effect of the direct genomic value of the trait itself when available. It thus appeared that cows with a positive iBCS always had a higher BCS than negative iBCS cows, whatever the lactation stage, and that this difference increased during the first 6 mo to reach a difference of 0.8 point. A similar effect was seen regarding body weight, but it was the opposite for milk production, with negative iBCS cows producing slightly more milk (difference of about 3% over lactation). Feed intake increased slightly faster at the beginning of lactation for cows with positive iBCS. Therefore, iBCS is a promising tool that could help to limit intense mobilization during early lactation. Should feed efficiency be included in the breeding goal, greater attention should be paid to BCS to avoid further body mobilization in early lactation.
Abstract
STUDY QUESTION
How efficacious is transplantation of ovarian cortex previously exposed to chemotherapy?
SUMMARY ANSWER
Prior exposure to chemotherapy did not disrupt the function of ...cryopreserved ovarian tissue after transplantation.
WHAT IS KNOWN ALREADY
Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) is an efficacious technique for restoration of female fertility. At least 130 children have been born following this procedure. To date, little is known about the efficacy of OTT in patients exposed to cancer chemotherapy prior to OTC.
STUDY DESIGN, SIZE, DURATION
This study evaluates the recovery of ovarian function and fertility in 31 consecutive patients who had received OTT, between 2005 and 2015.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Thirty one patients, wanting children, were transplanted with autologous ovarian cortex, among which 22 patients (71%) had been exposed to chemotherapy before OTC. Recovery of ovarian function was considered total once menstruation occurred. Ovarian function recovery (OFR), ovarian graft survival, and incidence of pregnancy were related to previous chemotherapy exposure, type of chemotherapy and graft characteristics (number of grafted fragments and follicular density).
MAIN RESULTS AND ROLE OF CHANCE
The amount of ovarian tissue collected was the only parameter to show any significant change between patients with versus without previous chemotherapy. At 1 year after OTT, the cumulative incidence of OFR was 83% (93% in patients exposed to chemotherapy and 67% in others (P = 0.14)). A low follicular density (<0.3 foll/mm2) in the transplant and a low number of grafted fragments (<16) were significantly associated with a delayed OFR. Graft survival at 2 years after OTT was 77%. It was significantly lower in patients exposed to bifunctional alkylating agents before ovarian cryopreservation and in patients with a low follicular density. The proportion of women who succeeded in having at least one live birth was 23% in the total population, 0% (0/9) in the group ‘no previous chemotherapy’, and 32% (7/22) in the group ‘previous chemotherapy’. The cumulative incidence of pregnancy (Kaplan–Meier) at 3 years after OTT was 36% overall and 49% in case of previous chemotherapy, with no difference related to previous chemotherapy exposure. In total there were 13 pregnancies and 8 births in 7 patients.
LIMITATIONS, REASONS FOR CAUTION
The pathology in the two groups of patients was not comparable. In the group of patients who had chemotherapy before OTC, there were 95% of hematological malignancies. In the group of patients who did not have chemotherapy before OTC only 1 out of 9 patients had a malignant hematological disease while 44% had some pathology affecting the ovaries. Few women are available for study and only large changes are likely to have statistical significance.
WIDER IMPLICATIONS OF THE FINDINGS
These results suggest that prior cancer chemotherapy should no longer be considered a limitation to cryopreservation of ovarian tissue and current recommendations in this regard should be revised.
STUDY FUNDING/COMPETING INTEREST(S)
This study was supported by the Agence de la Biomédecine (France’s biomedical office). There are no competing interests to report.
TRIAL REGISTRATION NUMBER
NCT02184806.
A coastwide bloom of the toxigenic diatom Pseudo‐nitzschia in spring 2015 resulted in the largest recorded outbreak of the neurotoxin, domoic acid, along the North American west coast. Elevated ...toxins were measured in numerous stranded marine mammals and resulted in geographically extensive and prolonged closures of razor clam, rock crab, and Dungeness crab fisheries. We demonstrate that this outbreak was initiated by anomalously warm ocean conditions. Pseudo‐nitzschia australis thrived north of its typical range in the warm, nutrient‐poor water that spanned the northeast Pacific in early 2015. The seasonal transition to upwelling provided the nutrients necessary for a large‐scale bloom; a series of spring storms delivered the bloom to the coast. Laboratory and field experiments confirming maximum growth rates with elevated temperatures and enhanced toxin production with nutrient enrichment, together with a retrospective analysis of toxic events, demonstrate the potential for similarly devastating ecological and economic disruptions in the future.
Key Points
The 2015 U.S. West Coast wide toxic Pseudo‐nitzschia australis bloom was facilitated by anomalous ocean conditions
The seasonal transition to upwelling provided nutrients for the bloom, and spring storms delivered toxic cells to the nearshore environment
West Coast toxic Pseudo‐nitzschia events are triggered by warm anomalies associated with El Niño and the Pacific Decadal Oscillation
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