(C) 2007 Elsevier Ltd. All rights reserved.”
“Methyldopa is used for treatment of hypertension in pregnancy. Side effects of methyldopa include AG-014699 mouse anemia, which could result from decreased formation or accelerated death of circulating erythrocytes. Several drugs cause anemia by triggering of suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling, the latter leading to phosphatidylserine exposure at the erythrocyte surface. Stimulators of erythrocyte membrane scrambling include increased cytosolic Ca(2+) concentration

([Ca(2+)](i)) and ceramide. Phosphatidylserine-exposing cells are rapidly cleared from circulating blood. The present study explored whether eryptosis could be triggered by methyldopa. Erythrocytes from healthy volunteers were exposed to methyldopa, and phosphatidylserine exposure (annexin A5 binding), cell volume (forward scatter), [Ca(2+)](i) (Fluo3-dependent fluorescence), and ceramide formation (anti-ceramide-fluorescein isothiocyanate antibody) were determined by flow cytometry. Methyldopa (6 mu g/ml) did not increase [Ca(2+)](i) but led to stimulation of ceramide formation resulting in significant phosphatidylserine exposure and, at higher concentrations, to cell shrinkage. Methyldopa further decreased

the GSH/GSSG ratio, pointing to oxidative stress. The scavenger N-acetyl-L-cysteine significantly blunted methyldopa-induced eryptosis. Clearance of erythrocytes Fedratinib in vivo from circulating blood was significantly accelerated by treatment with methyldopa. The present observations disclose a novel action of methyldopa, which may well contribute to drug-induced anemia. Copyright (C) 2008 S. Karger AG, Basel”
“The primate cortex represents and produces events in a distributed way, which calls for a mechanism that integrates their features into coherent structures. Visuomotor integration seems to be driven by dopaminergic (DA) pathways but which subsystems are involved is currently unknown. The present study compared the impact of the recreational use of two drugs on visuomotor integration: cannabis, which primarily

targets dopaminergic D1 receptors, and cocaine, which mainly targets D2 receptors. Our findings show that C1GALT1 cannabis but not cocaine use affects the strength of the binding between task-relevant stimulus features and the accompanying response. In contrast, cocaine but not cannabis use eliminates the inhibition of return. The observed pattern suggests that visuomotor integration is driven by DA/D1, but not DA/D2 receptor systems. (C) 2008 Elsevier Ltd. All rights reserved.”
“Background: The aim of this study was to assess the relationship between kidney dimensions and creatinine clearance (Ccr) in patients with Balkan endemic nephropathy (BEN), nephrosclerosis (NSc), glomerulonephritis (GN), diabetic nephropathy (DN) and in healthy persons.

S-nitrosoglutathione (GSNO), a potent NO donor formed by the interaction of NO with intracellular glutathione (GSH), is a major factor in this pathway and is considered one of the strongest naturally occurring nitrosating agent. We previously

described the broad-spectrum antimicrobial activity of a nanoparticulate platform capable of controlled and sustained release of NO (NO-np). Interestingly, in vivo efficacy of the NO-np surpassed in vitro data generated. We hypothesized that the enhanced activity was in part achieved via the interaction between the generated NO and available GSH, forming GSNO. In the current study, we investigated the efficiency of NO-np to form GSNO in the presence of GSH was evaluated, and selleck chemical assessed the antimicrobial activity of the formed GSNO against methicillin resistant Staphylococcus aureus (MRSA). Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. When GSH was combined with NO-np, GSNO was rapidly produced and significant concentrations of GSNO were maintained for >24 h. The GSNO generated was more effective compared to NO-np alone against all bacterial strains examined, with P. aeruginosa being the most sensitive and K. pneumoniae the most LY294002 ic50 resistant. We conclude that the combination of NO-np with GSH is an effective

means of generating GSNO, and presents a novel approach to potent antimicrobial therapy. (C) 2011 Elsevier Inc. All rights reserved.”
“Hyperphosphatemia is the major risk factor associated with vascular calcification (VC) in end-stage renal disease. As oxidative stress is increased in Magnesium chelatase uremia, we studied the role of mitochondrial reactive

oxygen species (ROS) and nuclear factor-kappa B signaling in phosphate-induced VC. In an in vitro calcification model (beta-glycerophosphate (BGP) induction) using bovine aortic smooth muscle cells, the production of intracellular and mitochondrial ROS, or superoxide anion, was stimulated by increased mitochondrial membrane potential. This effect was blocked by the superoxide dismutase (SOD) mimic MnTMPyP, a respiratory chain inhibitor rotenone, or a protonophore. Calcium deposition and the switch of smooth muscle cells from a contractile to an osteogenic phenotype were decreased when mitochondrial ROS generation was inhibited by the respiratory chain inhibitor, MnTMPyP, or the overexpression of SOD1 and SOD2 and uncoupling protein 2. The phosphorylation of IkK beta, I kappa B alpha degradation, and p65 nuclear translocation were increased by BGP but reversed when mitochondrial ROS production was blocked by protonophore or MnTMPyP. Knockdown of endogenous p65 or overexpression of I kappa B alpha reduced calcium deposition in the cultured cells. Furthermore, in a rat model of dietary adenine-induced chronic renal failure, MnTMPyP reduced aortic ROS levels, p65 activation, and calcium deposition.

“
“By 2012 the pharmaceutical industry has generally recognized MX69 datasheet the value proposition offered through ‘personalized medicine’: shorter regulatory reviews and higher prices as a tradeoff for a more specific patient market. Examples of companion diagnostics (Cdx) exist not only in oncology, but across therapeutic areas that allow us to define treatment benefit and identify the ‘best patients’ for a given treatment approach or combination thereof. In the 13 years since the co-approval of trastuzumab (Herceptin (R)) from Genentech

and the HercepTest (R) from Dako, the regulatory and commercial environments have yet to adopt a standard methodology for co-development and co-approval. Furthermore, a one-size-fits-all approach is unlikely to emerge despite attempts by various stakeholders to create an environment of conformity for approval and reimbursement issues.

Captisol What has emerged, however, is the experience of clinical developers and commercial teams in bringing these products to market. In this article, we focus on the many factors that should be considered to successfully develop and market a companion diagnostic, based on lessons learned from recent case studies. A proposed framework of questions to be addressed at the various stages of developing highly effective companion diagnostic products is also presented.”
“RNF2, a member of polycomb group (PcG) proteins, is involved in chromatin remodeling. However, mechanisms that regulate RNF2 function are unknown. To identify such mechanisms, RNF2 was expressed in HEK-293 cells and analyzed by 2-D electrophoresis. RNF2 was resolved into at least seven protein spots, migrating toward the lower pI from its expected pI of 6.38, suggesting

that RNF2 undergoes post-translational modifications. Western blotting indicated that majority of these RNF2 spots contained phosphoserine(s), which PIK-5 were completely dephosphorylated upon treatment with a phosphatase. SB203580, a specific inhibitor of p38 MAPK, inhibited RNF2 phosphorylation at one site. on the other hand, PD98059, an inhibitor of MEK1/2, inhibited majority of the phosphorylation events in RNF2. Mass spectrometry analysis identified that RNF2 expressed in Sf9 insect cells undergoes co-translational excision of (1)Met coupled to N-acetylation of (2)Ser, and phosphorylation of (41)Ser. Interestingly, (41)Ser is a predicted p38/MAPK phosphorylation site, consistent with the loss of phosphorylation induced by SB203580. Further analysis indicated that RNF2 phosphorylation differentially modulates the expression of transcription factors and histone 2B acetylation. These results provide first evidence for phosphorylation of RNF2, and suggest that the mitogen activated protein kinases including p38 MAPK and ERK1/2 regulate growth, stress response, differentiation and other cellular processes, through phosphorylation of RNF2.

A total of 28 patients with peripheral arterial BD were identified. There were 24 males (85.7 %), with mean age of 40.0 +/- A 9.0 years (range 21-59). Arterial involvements were confirmed with computed tomography Z IETD FMK angiography, magnetic resonance image angiography, or ultrasound. Immunosuppressive agents were administrated to all patients. Indications of intervention were acute symptoms due to arterial occlusion and aneurysmal changes with or without rupture. Among 28 patients with peripheral arterial

BD, 10 endovascular and 24 surgical interventions were performed in 21 patients. All 21 patients who underwent endovascular and surgical intervention were followed up for a mean duration of 78.7 +/- A 52.5 months (range 0-182 months). There was one mortality due to the rupture of pseudoaneurysm in patient who underwent stent-graft insertion for abdominal aortic aneurysm. New arterial involvements of BD occurred in 10 patients. All patients were male, and median age was 33.5 years (range 29-59 years). Mean time of onset of the new arterial lesion was 32.7 +/- A 32.1 months. Pitavastatin In conclusion, the result of endovascular and surgical interventions is satisfactory in patients with acute peripheral arterial BD. Accurate diagnosis with immunosuppressive

therapy is mandatory to prevent recurrence and activation of peripheral arterial BD.”
“Interleukin-15 (IL-15) is a pleotrophic cytokine that is involved in the pathogenesis of diverse inflammatory

rheumatic diseases. The aims of this study were to compare serum IL-15 levels and expression of its receptor (IL-15R alpha) in Beh double dagger et’s disease (BD) with those in other rheumatic diseases and to identify the relationship between serum IL-15 levels and various clinical parameters in BD. One hundred fifty-eight subjects consisting of 40 BD, 38 systemic lupus erythematosus (SLE), 40 rheumatoid arthritis (RA), and 40 healthy controls were enrolled. Serum IL-15 levels were measured using an enzyme-linked immunosorbent assay. The proportion of IL-15R alpha expression on each leukocyte subset was measured by flow cytometry. Erythrocyte sediment rate (ESR) and C-reactive protein (CRP) were measured for each enrolled subject. The clinical activity index of BD was Celastrol assessed for BD patients. Serum IL-15 levels in BD patients are significantly higher than those of healthy controls, SLE, and RA patients (p < 0.001, p < 0.001, and p < 0.001, respectively). Serum IL-15 levels in BD were closely related to ESR (r = 0.405, p = 0.027), but not to CRP or the clinical activity index of BD (p > 0.05 for both). Additionally, there was no difference in serum IL-15 levels between active and inactive disease states in BD (p > 0.05). The proportion of IL-15R alpha expression on total leukocytes was much lower for all rheumatic diseases, including BD, than in healthy controls (p < 0.01 for SLE, p < 0.01 for RA, and p < 0.05 for BD).

By numerical

simulations, it is found that the model also exhibits some other complicated dynamical behaviors. A subcritical Hopf bifurcation, a fold bifurcation of equilibria and a limit point bifurcation of limit cycles are detected, which induce five typical patterns of dynamical behaviors including the bistable phenomenon. (C) 2012 Elsevier Ltd. All rights reserved.”
“We introduce a game theory model of individual decisions to cooperate by contributing personal resources to group decisions versus by free riding on the contributions of other members. In contrast to most public-goods games that assume group returns are linear in individual contributions, the present model assumes decreasing marginal group production as a function of aggregate individual contributions. www.selleckchem.com/products/lonafarnib-sch66336.html This diminishing marginal returns assumption is more realistic and generates starkly different

predictions compared to the linear model. One important implication MLN0128 price is that, under most conditions, there exist equilibria where some, but not all, members of a group contribute, even with completely self-interested motives. An agent-based simulation confirmed the individual and group advantages of the equilibria in which behavioral asymmetry emerges from a game structure that is a priori perfectly symmetric for all agents (all agents have the same payoff function Cell Cycle inhibitor and action space but take different actions in equilibria). A behavioral experiment demonstrated that cooperators and free riders coexist in a stable

manner in groups performing with the nonlinear production function. A collateral result demonstrated that, compared to a dictatorial decision scheme guided by the best member in a group, the majority/plurality decision rules can pool information effectively and produce greater individual net welfare at equilibrium, even if free riding is not sanctioned. This is an original proof that cooperation in ad hoc decision-making groups can be understood in terms of self-interested motivations and that, despite the free-rider problem, majority/plurality decision rules can function robustly as simple, efficient social decision heuristics.”
“To the Editor: The important findings of Awad et al. (June 20 issue)(1) regarding the G2032R mutation as a cause of crizotinib resistance in lung cancer suggest an intriguing hypothesis. Despite good tumor-cell content, the allele frequencies of the mutation were very low in some tumor regions and metastases (see Fig. S2 in the Supplementary Appendix, available with the full text of the article at NEJM.org), strongly suggesting that the mutation was subclonal. This finding challenges the prevailing concept that metastases are descendants of a single founder cell. A tenable alternative is that the subclone harboring the G2032R mutation may …

Two expired immediately after diagnosis, and the other two could have potentially been treated with improvements in transfer and diagnosis times. Age, individual injuries, Silmitasertib datasheet and measures of injury severity were similar between patients undergoing open surgical or endovascular repair. Patients who underwent endovascular repair experienced a significantly lower intraoperative (0% vs 18%; P < .05) and overall hospital mortality (12% vs 37%; P < .05). Additionally, endovascular repair was associated with reductions in operative time, estimated blood loss, and intraoperative blood transfusions. Five endovascular patients required secondary interventions to treat endograft-related complications,

including malapposition to the aortic arch (n = 3), midendograft stenosis (n = 1), and left upper extremity ischemia (n = 1).

Conclusions: Blunt thoracic aortic injury to the descending thoracic aorta is associated with a high overall hospital mortality. Thoracic

endovascular aortic repair is associated with significantly lower operative times, procedural blood loss, intraoperative find more blood transfusion, as well as intraoperative and overall hospital mortality compared with conventional open surgical repair. Consideration of this form of therapy as the initial form of treatment is warranted in anatomically acceptable candidates. (J Vasc Surg 2012;56:1274-80.)”
“Postoperative cognitive dysfunction (POCD) is characterized by the progressive deterioration of intellectual/cognitive function following surgery. It has been suggested that the senile brain, which characteristically expresses higher levels of central proinflammatory

cytokines, interleukin (IL)-6, IL-1 beta, and tumor necrosis factor (TNF)-alpha, is more susceptible to additional insult following surgery. The authors of this study investigated the expression of central cytokines IL-6 and TNF-alpha. and hippocampal glial cell activation selleck products in aged and adult rats following partial hepatectomy.

Cognitive function was assessed in a reversal-learning version of the Morris water maze (MWM) before and after surgery. Hippocampal pro-inflammatory cytokines IL-6 and TNF-alpha and glial cell activation markers glial fibrillary acidic protein (GFAP) and SWOP were measured at each time point; CD200 and CD200R were also measured to explore potential mechanisms of glial cell activation.

Surgical trauma resulted in impairments in distance and latency only on postoperative day 1 (p<0.001, respectively) in adult rats. Aged rats exhibited impairments on day 1 (p<0.001) that persisted until postoperative day 3 (p = 0.002 and p = 0.001, respectively). All significant impairments paralleled upregulated cytokine IL-1 beta, and IL-6 expression. Immunohistochemistry assay further showed more hippocampal glial cell activation in aged rats compared to that in adults.

Overall, these findings suggest that surgical trauma, rather than anesthesia, resulted in cognitive function impairment potentiated by aging.

The present results improve our understanding of the early components of the TMS-evoked EEG signal, which reflect cortical excitability, and may thus have widespread use in clinical and scientific studies. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Superinfection exclusion or homologous interference, a phenomenon in which a primary Roscovitine mw viral infection prevents a secondary infection with the same or closely related virus, has been observed commonly for viruses in various systems, including viruses of bacteria, plants, and animals. With plant viruses, homologous interference initially was used as a test of virus relatedness to define whether two virus isolates were “”strains”" of the

same virus or represented different viruses, and subsequently purposeful infection with a mild isolate was implemented as a protective measure against isolates of the virus causing severe disease. In this

study we examined superinfection exclusion of Citrus tristeza virus (CTV), a positive-sense RNA closterovirus. Thirteen naturally occurring isolates of CTV representing five different virus strains and a set of isolates originated from virus constructs engineered based on an infectious cDNA clone of T36 isolate of CTV, including hybrids containing sequences from different isolates, were examined for their ability to prevent superinfection by another isolate of the virus. We show that superinfection exclusion occurred only Fedratinib between isolates of the same strain and not between isolates of different strains. When isolates of the same strain were used for sequential plant inoculation, the primary infection provided complete exclusion of the challenge isolate, whereas isolates from heterologous strains appeared to have no effect on replication, movement or systemic infection by the challenge virus. Surprisingly, substitution of extended cognate sequences from isolates of the T68 or T30 strains into T36 did not confer the ability of resulting hybrid viruses to exclude superinfection by those donor strains. Overall, these results do not appear to be explained by mechanisms proposed

previously for other viruses. Moreover, these observations bring an understanding of some previously unexplained fundamental features ID-8 of CTV biology and, most importantly, build a foundation for the strategy of selecting mild isolates that would efficiently exclude severe virus isolates as a practical means to control CTV diseases.”
“Persistent infection of domestic cats with feline coronaviruses (FCoVs) can lead to a highly lethal, immunopathological disease termed feline infectious peritonitis (FIP). Interestingly, there are two serotypes, type I and type II FCoVs, that can cause both persistent infection and FIP, even though their main determinant of host cell tropism, the spike (S) protein, is of different phylogeny and displays limited sequence identity. In cell culture, however, there are apparent differences.

Angiographic vasospasm was assessed by the use of catheter angiography 7 to 11 days after SAH, and delayed ischemic neurological deficit (DIND) was determined clinically. Extended Glasgow Outcome Score (GOSE) was assessed 3 months after SAH, and poor outcome was defined as death, vegetative state, or severe disability. Multivariable ordinal and binary logistic regression QNZ molecular weight were used.

RESULTS: There was no significant difference in the rate of clot clearance between patients undergoing clipping

or coiling (P = .56). Coiling was independently associated with decreased severity of angiographic vasospasm (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.33-0.86), but not with DIND or GOSE. Greater clot clearance decreased the risk of severe angiographic vasospasm (OR 0.86, 95% CI 0.81-0.91), whereas higher baseline Hijdra score

predicted increased angiographic vasospasm (OR 1.17, 95% CI 1.11-1.23) and poor GOSE (OR 1.09, 95% CI 1.04-1.14).

CONCLUSION: Aneurysm coiling and increased clot clearance were independently associated with decreased severity of angiographic vasospasm in multivariate analysis, although no differences in clot clearance were seen between coiled and clipped patients.”
“This Buparlisib in vivo paper reviews Bacillus genes encoding monooxygenase enzymes producing unique fatty acid metabolites. Specifically, it examines standard monooxygenase electron transfer schemes and

related domain structures of these fused domain enzymes on route to understanding the observed oxygenase activities. A few crystallographic analyses of the standard bearer enzyme P450(BM-3) are discussed to try to rationalize the common chemistries of this important enzyme family. Detailed P450(BM-3) enzyme activities toward different substrates and the unique substrate-specific primary oxidation products are examined. A few orthologs to the many recurring P450(BM-3) enzyme as well as related small single-to-triple nucleotides changed mutants are also discussed. Finally, preliminary data characterizing unique in vivo-based primary and secondary products of a novel ortholog, the ALA2 strain, are presented. This later strain synthesizes several unique multi-oxidized reaction products that require additional study to further understand. It is hoped that a better understanding of these oxygenase reactions, particularly the ALA2 strain, will allow for realistically priced production of target multiple-oxygenated compounds with potential uses as specialty chemicals or as therapeutic agents. (c) 2007 Elsevier Ltd. All rights reserved.”
“The P-II signal transduction proteins have key functions in coordinating the regulation of central metabolic processes. Signals from the carbon, nitrogen and energy status of the cells are converted into different conformational (and modification) states of the P-II proteins.

These data indicate that stimulation of GABA receptors in ventral pallidum produces behavioral effects similar to those produced by accumbens dopamine depletions. Ventral pallidum appears to

be a component of the brain circuitry regulating response allocation and effort-related choice behavior, and may act to convey information from nucleus accumbens to Dinaciclib cell line other parts of this circuitry. This research may have implications for understanding the brain mechanisms involved in energy-related psychiatric dysfunctions such as psychomotor retardation in depression, anergia, and apathy. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Permanent bilateral lesions of the medial preoptic area anterior hypothalamus (MPOA/AH) produce a drastic inhibition of male

sexual behavior in all species studied to date. The present experiment was designed to evaluate if temporal inactivation of the MPOA/AH by infusions of lidocaine also inhibits sexual behavior in male rats. This would allow us to rule out the possibility that the behavioral effects observed after damage of the MPOA/AH could be associated with plastic changes induced by the lesion in other brain regions. We also evaluated sexual incentive motivation in males after the infusion of lidocaine in a test in which copulation is not possible but where males maintain approach behavior to the estrous females despite repeated testing. The percentage of animals displaying mounts, intromissions and ejaculation

was significantly reduced while mount and intromission latency were prolonged after infusion of lidocaine. No changes were observed in sexual behavior after infusion of lidocaine Staurosporine research buy in animals with cannulae outside the MPOA/AH suggesting that the inhibitory effects are specific to this brain region. Sexual incentive motivation was also affected by administration of lidocaine. Males consistently showed a clear preference for the sexually receptive female except when infused with lidocaine. After the infusion of the compound a significant reduction in the time spent in the incentive zone of the stimulus female was observed. These results support the hypothesis that neurons of the MPOA/AH are involved in the control of male sexual motivation. (C) 2008 IBRO. Published by 3-mercaptopyruvate sulfurtransferase Elsevier Ltd. All rights reserved.”
“Background In old age, reduction in physical function leads to loss of independence, the need for hospital and long-term nursing-home care, and premature death. We did a systematic review to assess the effectiveness of community-based complex interventions in preservation of physical function and independence in elderly people.

Methods We searched systematically for randomised controlled trials assessing community-based multifactorial interventions in elderly people (mean age at least 65 years) living at home with at least 6 months of follow-up. Outcomes studied were living at home, death, nursing-home and hospital admissions, falls, and physical function.

The first primary outcome occurred in 68% of the

Selleck DihydrotestosteroneDHT infants in the prenatal-surgery group and in 98% of those in the postnatal-surgery group (relative risk, 0.70; 97.7% confidence interval [CI], 0.58 to 0.84; P<0.001). Actual rates of shunt placement were 40% in the prenatal-surgery group and 82% in the postnatal-surgery group (relative risk, 0.48; 97.7% CI, 0.36 to 0.64; P<0.001). Prenatal surgery also resulted in improvement in the composite score for mental development and motor function at 30 months (P = 0.007) and in improvement in several secondary outcomes, including hindbrain herniation by 12 months and ambulation by 30 months. However, prenatal surgery was associated with an increased risk of preterm delivery and uterine dehiscence at delivery.

CONCLUSIONS

Prenatal surgery for myelomeningocele reduced the need for shunting and improved motor outcomes at 30 months but was associated with maternal and fetal risks.”
“The VP1-encoding gene of the duck hepatitis type 1 virus (DHV-1) HP-1 strain was cloned and expressed in Escherichia coil. The open reading frame (ORF) of VP1 comprised

714 bp and encoded 238 amino acids, with a predicated molecular mass of 26.5 kDa. The expressed VP1 fusion protein in E. coli was detected by Western blotting with duck anti-DHV-1 polyclonal serum. A VP1-ELISA using the expressed VP1 protein as a coating antigen for the detection of antibodies to DHV-1 in ducks was developed. In comparison with the virus neutralization test, the specificity and sensitivity of the VP1-ELISA was 92.5% and 96.7%. Comparative E7080 analysis between Western blots and the VP1-ELISA showed that the concordance between the two methods was 86%. The VP1-ELISA did not react with the anti-sera to other duck viral pathogens, implying that this protein is specific for the recognition of duck anti-DHV-1 antibodies. Taken together, the VP1-ELISA is a highly sensitive and specific test that could be used for screening for DHV-1 infection and monitoring antibody titres against DHV-1. (c) 2010 Elsevier B.V. All rights

reserved.”
“BACKGROUND

Research has underscored the effects of exposure and sensitization to allergens on the severity of asthma in inner-city children. It has also revealed the limitations of environmental remediation and guidelines-based ROS1 therapy in achieving greater disease control.

METHODS

We enrolled inner-city children, adolescents, and young adults with persistent asthma in a randomized, double-blind, placebo-controlled, parallel-group trial at multiple centers to assess the effectiveness of omalizumab, as compared with placebo, when added to guidelines-based therapy. The trial was conducted for 60 weeks, and the primary outcome was symptoms of asthma.

RESULTS

Among 419 participants who underwent randomization (at which point 73% had moderate or severe disease), omalizumab as compared with placebo significantly reduced the number of days with asthma symptoms, from 1.96 to 1.