Surgical repair for SUI can result in temporary AG-881 supplier VD in the minority of patients, highlighting the complex interplay that is emerging in the urethral bladder functioning complex in women. Conclusions: Women with impaired bladder emptying present with a wide range of LUTS, and PVR measurement is essential for diagnosis. OAB and VD can clearly coexist and accurate diagnosis of underlying pathophysiology is required. Recommendations for clinical practice and research are provided including: investigation of VD in women with OAB; evaluation of PVR values to determine appropriate therapy and identification of BOO. There is clearly a need for further research

into the impact of alpha-blockers in women with VD as well as an evaluation of PVR changes in women with OAB before

and after antimuscarinic therapy. Neurourol. Urodynam. CDK inhibitor 31: 422-428, 2012. (C) 2012 Wiley Periodicals, Inc.”
“Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric procedure. The objective of this study is to describe a series of patients who were subjected to LSG and then developed gastric stenosis, with an emphasis on their treatment and a discussion of the possible underlying mechanisms. From January 2006 to October 2012, 717 patients with morbid obesity underwent LSG in our institution. Out of 717 patients, 571 (79.6 %) were women. The mean age was 36.9 years with a BMI of 37.3 kg/m(2). Five patients (0.69 %) developed gastric stenosis. Treatment of this website the stenosis

was endoscopic dilatations; however, one patient required a conversion to laparoscopic Roux-en-Y gastric bypass. Stenosis after LSG is rare but requires early diagnosis and treatment.”
“Objective: To test the impact of an advance letter on response and cooperation rates in a nationwide telephone survey, given previous inconsistent results.

Study Design and Setting: Within the context of a larger telephone survey, 1,000 Australian households were randomly selected to take part in this trial. Half were randomly allocated to receive an advance letter, whereas the remainder did not receive any advance communication. Response and cooperation rates were compared between the two groups.

Results: A total of 244 interviews were completed, 134 of which were with households that had been sent an advance letter. Intention-to-treat analysis revealed no significant difference in response between those who had received a letter and those who had not (26.8% vs. 22.0%, respectively). In addition, there was no significant difference between the groups in terms of either cooperation (78.4% vs. 79.7%) or response rate (56.3% vs. 57.9%), and no clear differences emerged in terms of the demographic characteristics of the two groups.

Conclusion: An advance letter was not seen to be effective in increasing response or cooperation rates in a nationwide telephone survey.

The brain stimulation treatment protocol used is called Neuro Psycho Physical Optimization (NPPO) with a Radio Electric Asymmetric Conveyer (REAC) device.

Methods: Psychological stress and PPD were measured for a group of 888 subjects using the Psychological Stress Measure (PSM) test, a self-administered questionnaire. Data were collected immediately before and after the 4-weeks of REAC treatment cycle.

Results: This study showed a significant reduction in scores measuring subjective perceptions EPZ015666 molecular weight of stress

for subjects treated with a cycle of NPPO REAC treatment. At the end-point the number of subjects reporting symptoms of stress-related PPD on the PSM test was significantly reduced, whereas in the placebo group the difference was not

significant.

Conclusion: A cycle of NPPO treatment with REAC was shown to reduce subjective perceptions of stress measured by the PSM test and in particular on PPD.”
“Past increases in yield potential of wheat have largely resulted from improvements in harvest index rather than increased biomass. Further large increases in harvest index are unlikely, but an opportunity Selleckchem DMXAA exists for increasing productive biomass and harvestable grain. Photosynthetic capacity and efficiency are bottlenecks to raising productivity and there is strong evidence that increasing photosynthesis will increase crop yields provided that other constraints do not become limiting. Even small increases in the rate of net photosynthesis can translate into large increases in biomass and hence yield, since carbon assimilation is integrated over the entire growing season and crop canopy. This review discusses the strategies to increase photosynthesis that are being proposed by the wheat yield consortium in order to increase wheat yields. These include: selection for photosynthetic capacity and efficiency, increasing ear photosynthesis, optimizing canopy photosynthesis, introducing chloroplast CO(2) pumps, increasing RuBP regeneration, improving the thermal

stability of Rubisco activase, and replacing wheat Rubisco with that from other species with different kinetic properties.”
“A plasticizer, polyethylene MLN2238 inhibitor glycol ( PEG), was used to disperse multiwalled carbon nanotubes (MWCNTs) in biodegradable poly(L-lactide) during one-step melt mixing. Incorporation of PEG significantly promotes the formation of a percolating MWCNT network in the plasticized composites, as revealed by rheological measurements and morphological observations. It, in turn, results in the retarded glass transition and cold crystallization behaviors in these plasticized composites as a result of constrained chain relaxation. It is believed that noncovalent wrapping of MWCNTs by PEG is responsible for the improved affinity between MWCNTs and the poly(L-lactide) matrix. (C) 2011 Wiley Periodicals, Inc.

The accuracy of the saturation magnetization is further confirmed by ferromagnetic resonance experiments. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3527968]“
“2,4-Dichlorophenoxyacetic acid (2,4-D), check details a worldwide-used herbicide, has been shown to produce a wide range of adverse effects in the health-from embryotoxicity and teratogenicity to neurotoxicity-of animals and humans. In this study, neuronal morphology and biochemical events in rat cerebellar granule cell (CGC) cultures have been analyzed to define some of the possible mechanisms involved in 2,4-D-induced cell death. For that purpose,

amphetamine (AMPH) that has been shown to accelerate the recovery of several functions in animals with brain injury has been used as a pharmacologycal tool and was also investigated as a possible protecting agent. Addition of 2,4-D to CGC cultures produced a drastic decrease in cell viability, in association with an increased incidence of necrosis and apoptosis, and an increased level

of reactive oxygen species, a decrease in glutathione content, and an abnormal activity of some enzymes with respect to the control group. The adverse effects of 2,4-D were partly attenuated in presence of AMPH. Some deleterious effects on several ultrastructural features of the cells, as well as the enhanced incidence of apoptosis, SBE-β-CD solubility dmso were partially preserved in AMPH-protected cultures as compared with those which were exposed to 2,4-D alone.

The collected evidences (1) confirms the previously observed, deleterious PLX3397 effects of 2.4D on the same or a similar model; (2) suggests that the 2,4-D-induced apoptosis could have been mediated by or associated to an oxidative imbalance in the affected cells, and (3) shows some evidence of a protective effect of AMPH on 2,4-D-induced cell death, which could have been exerted through a reduction in the oxidative stress.”
“Analysis of motor performance variability in tasks with redundancy affords insight about synergies underlying central nervous system (CNS) control. Preferential distribution of variability in ways that minimally affect task performance suggests sophisticated neural control. Unfortunately, in the analysis of variability the choice of coordinates used to represent multidimensional data may profoundly affect analysis, introducing an arbitrariness which compromises its conclusions. This paper assesses the influence of coordinates. Methods based on analyzing a covariance matrix are fundamentally dependent on an investigator’s choices. Two reasons are identified: using anisotropy of a covariance matrix as evidence of preferential distribution of variability; and using orthogonality to quantify relevance of variability to task performance. Both are exquisitely sensitive to coordinates. Unless coordinates are known a priori, these methods do not support unambiguous inferences about CNS control.

The composition of copolymer was analyzed by fluoride ion selective electrode analysis, (19)F NMR, FTIR,

crosslinking degree determination, and epoxy-acetone method. The results showed that the fluorine monomer, silicon monomer and epoxy resin had copolymerized with acrylic monomers. The optimum mass ratio between the curing agent TEA and epoxy resin was 1.36 : 6. The determination results of stabilities (electrolyte stability freeze-thaw stability, high temperature stability and mechanical stability) of latices showed that the incorporation Of fluorine monomer and silicon monomer improved freeze-thaw stability and mechanical stability, whereas the epoxy resin did not have obvious effect oil the stabilities. (C) 2008 Wiley Periodicals, Inc. J Appl Polym Sci 112: 181-187, 2009″
“Background: There selleck compound are no recent reports of giant cell tumors of bone in a large series of Chinese people. The present study was designed to review the epidemiological characteristics and outcomes

of surgical management SNS-032 in vivo in a large series of Chinese patients with giant cell tumor of an extremity, treated at a single institution.

Methods: The records and images of 621 patients in whom a benign-giant cell tumor in an extremity was treated between 1989 and 2009 were reviewed retrospectively. There were 359 male and 262 female patients. The mean age at diagnosis was 31.4 years (range, eleven to seventy-one years). Sixty-six percent of the giant cell tumors were localized around the knee. Surgical treatments primarily included curettage, extensive curettage, and resection. The median duration of follow-up was forty-nine months (range, eighteen to 256 months).

Results: Giant cell tumor accounted for 13.7% of all primary bone tumors treated at our institution. Multivariate Cox regression analysis indicated that the only variable that contributed to recurrence-free survival was the type of surgical treatment. The local recurrence rate after extensive BIBF 1120 in vitro curettage was 8.6%, which was significantly lower than the 56.1% recurrence rate after curettage alone. Bone-grafting did not affect

local tumor control after extensive curettage; the local recurrence rate was 11.1% if bone graft was used. Recurrent giant cell tumor can be treated by further curettage or resection, with acceptable re-recurrence rates of 6.7% and 9.3% respectively. The Musculoskeletal Tumor Society Score for patients treated with extensive curettage was 92.6%, which was significantly higher than that for patients treated with resection. Twenty-one (3.4%) of the 621 patients developed benign pulmonary metastasis, with a favorable outcome, and three patients presented with multifocal giant cell tumors.

Conclusions: The incidence of giant cell tumor in the Chinese population may be higher than that in Western countries, and it has a male predilection.

Conclusion. C1LMS of 95.5% and C2PS of 92.8% were confirmed to be in good position. None of the screws including the malpositioned caused VA injury, clinically or radiographically. The technique for C1LMS and C2PS fixation appears to be safe and effective.”
“Animal models are being used for several decades to study fibrogenesis and to evaluate the anti-fibrotic potential of therapies and strategies. Although immensely valuable for our understanding of pathophysiological processes, they remain models and none of them reproduces a human disease. Each model (meaning stimulus, design, strain and species) displays specific characteristics

in the nature of the pathogenesis, the topography and the evolution of fibrosis. We review here the most used as well as some newly described

but potentially interesting models including models for studying biliary, immune, alcohol-induced, NASH-associated and viral fibrosis and provide insight MK-8776 nmr on underlying disease processes and practical details. We attempted to delineate the benefits, advantages, limitations and drawbacks of those models. We also report the new opportunities provided by genetically engineered mice for Captisol mw tracking and manipulating cells that participate to fibrosis. Finally, we emphasize the importance of adapting study design to the question addressed. (C) 2011 Elsevier Ltd. All rights reserved.”
“Macrophages display two activation states that are considered mutually exclusive: classical macrophage activation (CMA), inducible by IFNG, and alternative macrophage activation (AMA), inducible by IL4 and IL13. CMA is prominent in allograft rejection and AMA is associated with tissue remodeling after injury. We studied expression of AMA markers in mouse kidney allografts and in kidneys with acute tubular necrosis (ATN). In rejecting allografts, unlike interferon gamma (IFNG) effects and T-cell infiltration that

developed rapidly and plateaued by day 7, AMA transcripts (Arg1, Vadimezan manufacturer Mrc1, Mmp12 and Ear1) rose progressively as tubulitis and parenchymal deterioration developed at days 21 and 42, despite persistent IFNG effects. AMA in allografts was associated with transcripts for AMA inducers IL4, IL13 and inhibin A, but also occurred when hosts lacked IL4/IL13 receptors, suggesting a role for inhibin A. Kidneys with ATN injured by ischemia/reperfusion also had increased expression of AMA markers and inhibin A. Thus kidneys undergoing T-cell-mediated rejection progressively acquire macrophages with alternative activation phenotype despite strong local IFNG effects, independent of IL4 and IL13. Although the mechanisms and causal relationships remain to be determined, high AMA transcript levels in rejecting allografts are strongly associated with and may be a consequence of parenchymal deterioration similar to ATN.”
“Study Design. Prospective clinical series.

Objective.

(Obstet Gynecol 2011; 117: 452-5) DOI: 10.1097/AOG.0b013e3181f7381f”
“Jatropha curcas a member of the Euphorbiaceae family is a drought resistant small tree of great economic importance in developing countries because of its several industrial and medicinal values. The antioxidative properties, total phenolic content and DNA protection potential of raw and processed kernel meal extracts of Jatropha were analyzed. The samples were extracted with 70% acetone and used for the evaluation of its antioxidant potential. The total phenolic content of raw and processed Jatropha kernel buy WH-4-023 meal samples ranged between 9.06

and 22.22 mg TAN/g extract. The results of the study revealed that autoclaving and dry heat treatment causes a significant (P < 0.05) increases in the total phenolic content and antioxidant properties. Nevertheless, raw samples exhibited a high metal chelating activity (0.97 mg EDTA/g extract) compared to the processed samples. However, autoclaving with NaHCO3 and ash solution recorded the highest phenolic content (22.22 mg TAN/g extract), FRAP (2861.11 mmoL Fe(II)/g extract), phosphomolybdenum (353.61 click here mu moL ascorbic acid/g extract), DPPH (6.29g extract/g DPPH), nitric oxide (55%), superoxide (67%) and hydroxyl radical (49%) scavenging activity when compared to the raw and other processed samples. The present studies may be of importance in varietal

MI-503 nmr improvement, nutraceuticals and bio-pharmaceuticals as possible sources of cost-effective natural antioxidants. (C) 2012 Elsevier B.V. All rights reserved.”
“Mitosis is known to be regulated by protein kinases, including MPF, Plk1, Aurora kinases, and so on, which become active in M-phase and phosphorylate a wide range of substrates to control multiple aspects of mitotic entry, progression, and exit. Mechanistic investigations of these kinases not only provide key insights into cell cycle regulation, but also hold great promise for cancer therapy. Recent studies,

largely in Xenopus, characterized a new mitotic kinase named Greatwall (Gwl) that plays essential roles in both mitotic entry and maintenance. In this study, we generated a panel of mouse monoclonal antibodies (MAbs) specific for Xenopus Gwl and characterized these antibodies for their utility in immunoblotting, immunoprecipitation, and immunodepletion in Xenopus egg extracts. Importantly, we generated an MAb that is capable of neutralizing endogenous Gwl. The addition of this antibody into M-phase extracts results in loss of mitotic phosphorylation of Gwl, Plk1, and Cdk1 substrates. These results illustrate a new tool to study loss-of-function of Gwl, and support its essential role in mitosis. Finally, we demonstrated the usefulness of the MAb against human Gwl/MASTL.”
“Background and Purpose: Surgery is a high-stakes “”performance.

“
“Alopecia areata has been associated with many autoimmune diseases. There is a common belief that the prevalance of pernicious anemia is increased in GSK3326595 ic50 patients with alopecia areata. In this study, we sought to investigate vitamin B12, folate and homocysteine metabolism in alopecia areata. We measured holotranscobalamine (holoTC), vitamin B12, folate and homocysteine levels in 75 patients with

alopecia areata and 54 controls. We did not find any significant differences in these parameters between these groups. We think that alopecia areata may not be associated with vitamin B12 deficiency. The co-occurence of pernicious anemia and alopecia areata in rare autoimmune syndromes, may not justify routine measurements of these parameters in alopecia areata patients.”
“Topiramate JNJ-26481585 is an anticonvulsant drug used for the treatment of epilepsy and prophylaxis of migraine. Some authors have proposed its use as a mood stabilizer

and have reported its efficacy in reducing impulsiveness and improving mood regulation, possibly via its antagonism to glutamatergic transmission in the lateral hypothalamus, although this indication is still controversial. Weight loss is a side effect consistently reported in the medical literature in patients treated with topiramate. Given its potential role in stabilizing mood and reducing impulse control problems and weight, topiramate has been proposed as a treatment for obese patients with binge eating disorder

(BED). The aim of this paper is to review published data on the efficacy and safety of topiramate for the treatment of obese subjects with BED. Although the evidence is preliminary, topiramate appears to be a relatively safe and effective treatment for obese subjects with BED. Limitations of the studies and future directions for research are discussed.”
“Background and objective: The aim of this study was to determine whether high levels of pleural adenosine deaminase (pADA) are predictive for tuberculosis when pleural effusions do not satisfy the criteria for lymphocytic effusions or show neutrophil predominance.

Methods: This was a retrospective observational study of 147 consecutive patients with exudative pleural effusions that were diagnosed by analysis of fluid samples during a 3-year period from 1 April 2007 to 31March 2010. Multiple linear correlation tests were used to assess clinical variables MEK inhibition as possible predictors of high pADA levels.

Results: High pleural LDH (pLDH) and pleural potassium (pK) levels were associated with high pADA levels (P < 0.0001). Although there was a linear correlation between pLDH and pADA levels in patients with parapneumonic effusions (PPE) (n = 75), tubercular effusions (n = 21), malignant effusions (n = 41) and miscellaneous effusions (n = 10), a significant linear correlation between pK and pADA levels was observed only in patients with PPE (r = 0.525, P < 0.0001). When the cut-off value for pK was set at 5.

In vitro angiogenesis assays on DENV-2 exposed SK Hep1 cells in the matrigel system showed inhibition compared with the controls. Importantly, transfection and transient expression of the DENV-2 envelope glycoprotein (E) in these cells showed drastic alterations in cell shapes and the E protein could be localized by fluorescence microscopy in terminal knob-like EPZ015666 Epigenetics inhibitor structures. Therefore, SK Hep1, a human hepatic sinusoid-derived endothelial cell line, may constitute a potential model to study DENV-endothelial cell interactions in

vitro, especially towards understanding the possible virus-induced changes in hepatic endothelium and its role in disease pathogenesis.”
“Purpose: To evaluate a susceptibility-corrected multiecho magnetic resonance (MR) relaxometry technique for an accurate and robust determination of Delta R2(star) as a noninvasive surrogate parameter of the perfused tumor blood volume.

Materials and Methods: All experiments were approved by the institutional animal care committee. In a glass tube phantom with different superparamagnetic iron oxide (SPIO) particle concentrations and at tumor mice xenografts with DU-4475, HT-1080, and MDA-MB-435 tumors (n = 15 total, n = 5 per model) with different degrees of neovascularization after injection of different ultrasmall SPIO (USPIO)

doses selleck chemicals changes of the transverse relaxation rate (Delta R2(star)) were determined by using a fixed echo time (TE) of 22 msec and a susceptibility-corrected multigradient-echo technique. The mean Delta R2(star) value and the vascular volume fraction (VVF) of each tumor was determined and compared with independent in vivo fluorescent tumor perfusion measurements and histologic analysis helped determine microvessel density (MVD). Statistical differences were tested by using analysis of variance and linear correlations.

Results: For the phantom study, Delta R2(star) maps calculated with a fixed TE of 22 msec showed a higher standard deviation of MLN2238 cost the noise index compared with the susceptibility-corrected multiecho technique. For the

xenograft model, mean tumor Delta R2(star) values (+/- standard error of the mean) showed signifi cant differences between the various tumors (eg, DU-4475: 12.3 sec(-1) +/- 2.67, HT-1080: 36.47 sec(-1) +/- 5.84, and MDA-MB-435: 64.01 sec(-1) +/- 8.87 at 80 mu mol of iron per kilogram; P< .05). Delta R2(star) values increased dose dependently and in a linear fashion, resulting in reproducibly stable VVF measurements. Fluorescent tumor perfusion measurements and MVD counts corroborated the MR results.

Conclusion: Susceptibility-corrected multiecho MR relaxometry allows a highly accurate and robust determination of Delta R2(star) and VVF with an excellent dynamic range for tumor characterization at clinically relevant doses of USPIO.”
“This paper presents an analytical model for the internal capacitances of short-channel ion-implanted GaAs MESFETs under dark and illuminated conditions.

We suggest that insufficiently

bombarded films develop a Maxwell-Wagner type polarization along columnar voids. The void structure and the associated dielectric response vary with distance from the sputtering source due to variations in ion density and angle from the sputtering source. A similar dielectric response is observed in depositions on Selonsertib mouse on-axis substrates as a function of angle from the central sputter gun axis. Our results suggest that ion bombardment is necessary for good quality sputtered dielectric films but that a controlled Ar(+) flux is essentially equivalent to the uncontrolled O(2)(-)/O(2-) flux of on-axis reactive sputtering. (C) 2009 American Institute of Physics. [doi: 10.1063/1.3253719]“
“Our objective was to translate and validate a Portuguese version of the Urinary Incontinence-Specific Quality-of-Life Instrument (I-QOL), a questionnaire that is widely used in clinical trials.

Fifty patients completed the same questionnaire twice at a 2-week interval. During the first visit, we conducted a face-to-face interview and collected demographic data. The King’s Health Questionnaire was completed during the same visit for comparisons.

The results showed that the Portuguese version of the Selleck MK-8931 I-QOL has very good psychometrics

properties. Reliability was assessed by Cronbach’s alpha (0.93), reproducibility was calculated through the intraclass correlation coefficient (0.88), construct validity was determined by comparing the I-QOL scores and King’s Health scores, and discriminant validity was calculated by comparing the total I-QOL scores with measures of gravity.

We conclude that the Portuguese version of the I-QOL is a very good tool for the evaluation quality-of-life in women with urinary incontinence in Portuguese-speaking countries.”
“Background The pediatric difficult airway can be unexpected, leading to significant

morbidity and mortality. Standardized emergency airway equipment should be available on a regularly checked difficult airway trolley (DAT). We conducted a survey to investigate pediatric anesthetists’ knowledge, experience, and confidence with the DAT.

Methods Members of the Association of Paediatric Anaesthetists of Great Britain and Ireland (APAGBI), European Society for Paediatric Anaesthesiology (ESPA) and Natural Product Library their national societies, Canadian Pediatric Anesthesia Society (CPAS), and Society for Paediatric Anaesthesia in New Zealand and Australia (SPANZA) were invited to complete a survey between January and April 2011.

Results Six hundred and ninety-three anesthetists replied to the questionnaire. Six hundred and thirty-three (92%) stated they have a DAT in their theater suite, with 587 (98%) knowing its location. Three hundred and eight-seven (56%) anesthetists received formal DAT training. The lowest training levels were observed in Australia and the UK; 42% and 59%, respectively.

Wild-type (WT) and mutant channels were expressed in TSA201 cells for electrophysiological study. Green fluorescent protein (GFP)-fused WT or mutant genes were used to assess channel trafficking.

Results: A novel SCN5A mutation, P1008S, was identified in all family members displaying first-degree atrioventricular block, but not in unaffected family members nor in 430 reference alleles. Peak P1008S current was 11.77% of WT (P < 0.001). Confocal microscopy showed that WT channels tagged with GFP were localized on the cell surface, whereas GFP-tagged

www.selleckchem.com/products/c188-9.html P1008S channels remained trapped in intracellular organelles. Trafficking could be rescued by incubation at room temperature, but not by incubation with mexiletine (300 mu M) at 37 degrees C. We also identified a novel polymorphism (D601E) in CACNB2b that slowed inactivation of L-type calcium current (I(Ca,L)), significantly increased total charge. Using the Luo-Rudy action potential (AP) model, we show that the reduction in sodium current (I(Na)) can cause loss of the right ventricular epicardial AP dome in the absence but not in the presence of the slowed inactivation of I(Ca,L). Slowed conduction was present in both cases.

Conclusions: Our Autophagy inhibitor concentration results suggest genetic variations leading to a loss-of-function in I(Na) coupled with a gain of function in I(Ca,L) may underlie the development of cardiac conduction disease without BrS. (PACE 2010; 33:274-285)”
“The

changes of blood perfusion of contralateral testis after unilateral testicular torsion remain controversial. In this study, 28 New Zealand white male rabbits were randomly divided into five groups. Group A (n = 8), the control group, underwent a sham operation on the unilateral testis without inducing testicular torsion. In groups B, C, and D ( n = 5 each), unilateral testicular torsion was induced, and, after 3,

6 or 24 h, respectively, detorsion was performed. In group E (n = 5), permanent unilateral testicular torsion was applied. Contrast-enhanced ultrasound was used to observe the blood perfusion of the contralateral testis at the following stages: pre-torsion (preopration), immediately post-torsion (postopration), pre-detorsion, Captisol mouse immediately post-detorsion, and late-stage post-detorsion (6-12 h post-detorsion in groups B-D) or at a similar time point (15-21 h post-torsion in group E). Time-intensity curves were generated, and the following parameters were derived and analyzed: arrival time, time to peak intensity, peak intensity, and half-time of the descending peak intensity. The analysis revealed that blood perfusion of the contralateral testis increased immediately after testicular torsion on the opposite side (P < 0.05), which increased with prolonged testicular torsion of the other testis. This research demonstrated that contrast-enhanced ultrasound was valuable in evaluating blood perfusion of the contralateral testis after unilateral testicular torsion.