Kidney International (2010) 77, 662-668; doi:10.1038/ki. 2009.559; published online 3 February 2010″
“BACKGROUND: Hyperhidrosis (HH) profoundly affects

a patient’s well-being.

OBJECTIVE: We report indications and outcomes of 322 patients treated for HH via thoracoscopic sympathectomy or sympathotomy at the Barrow Neurological Institute.

METHODS: A prospectively maintained database of all patients who underwent sympathectomy or sympathotomy between 1996 and 2008 was examined. Additional follow-up was obtained in clinic, by phone, or by written questionnaire.

RESULTS: A total of 322 patients (218 female patients) had thoracoscopic treatment (mean age 27.6 years; range, 10-60 years). Mean follow-up was 8 months. Presentations included HH of Depsipeptide the palms (43 patients, 13.4%), axillae (13 patients, 4.0%), craniofacial region (4 patients,

1.2%), or some combination (262 patients, 81.4%). Sympathectomy and find more sympathotomy were equally effective in relieving HH. Palmar HH resolved in 99.7% of patients. Axillary or craniofacial HH resolved or improved in 89.1% and 100% of cases, respectively. Hospital stay averaged 0.5 days. Ablating the sympathetic chain at T5 increased the incidence of severe compensatory sweating (P = .0078). Sympathectomy was associated with a significantly higher incidence of Horner’s syndrome compared with sympathotomy (5% vs 0.9%, P = .0319). Patients reported Oxalosuccinic acid satisfaction and willingness to undergo the procedure again in 98.1% of cases.

CONCLUSION: Thoracoscopic sympathectomy is effective and safe treatment for severe palmar, axillary, and craniofacial HH. Ablating the T5 ganglion tends to increase the severity of compensatory sweating. Sympathectomy led to a higher incidence of ipsilateral Horner’s syndrome compared with sympathotomy.”
“Cirrhosis induces extra-cellular fluid volume expansion, which when the disease is advanced can be severe and poorly responsive to therapy. Prevention and/or effective therapy for cirrhotic edema requires understanding the stimulus that initiates and maintains sodium

retention. Despite much study, this stimulus remains unknown. Work over the last several years has shown that signals originating in the liver can influence a variety of systemic functions, including extracellular fluid volume control. We review work on the afferent mechanisms triggering sodium retention in cirrhosis and suggest that the data are most consistent with the existence of a sensor in the hepatic circulation that contributes to normal extra-cellular fluid volume control (that is, a ‘volume’ sensor) and that in cirrhosis, the sensor is pathologically activated by the hepatic circulatory abnormalities caused by the disease. Detailed analysis of the hepatic circulation in normal conditions and cirrhosis is needed. Kidney International (2010) 77, 669-680; doi:10.1038/ki.2010.

This ratio and homovanillic acid/DA-ratio were declined in Snca(tm(A30P))

mice. Our results demonstrate that the two differently constructed A30P-aSyn mouse strains have distinct behavioral and biochemical characteristics, some of which are opposite. Since the two lines with the same background were not identically produced, the deviations found may be partially caused by factors other than aSyn-related genetic differences. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The growing interest in the application of proteomic technologies to solve toxicology issues and its relevance in ecotoxicology research has resulted www.selleckchem.com/products/pf-04929113.html in the emergence of “”ecotox-icoproteomics”". There is a general consensus that

ecotoxicoproteomics is a powerful tool to spot early molecular events involved in toxicant responses, which are responsible for the adverse effects observed at higher levels of biological organization, thus contributing to elucidate the mode of action of stressors and to identify specific biomarkers. Ultimately, early-warning indicators can then be developed and deployed in “”in situ”" bioassays and in environmental risk assessment. The number of field experiments or laboratory trials using ecologically relevant test-species and involving proteomics has been, until recently, selleck kinase inhibitor insufficient to allow a critical analysis of the real benefits of the application of this approach to ecotoxicology. This article intends to present an overview on the applications of proteomics in the context of ecotoxicology, focusing mainly on the prospective research to be done in invertebrates. Although these represent around 95% of all animal species and in spite of the key structural and functional roles they play in ecosystems, proteomic research in invertebrates is still in an incipient stage. We will review applications of ecotoxicoproteomics by evaluating the technical methods employed, the organisms and the contexts studied, the advances achieved until now and lastly the limitations yet to overcome will be discussed.”
“Objective: The

Japan Cardiovascular Surgery Database (JCVSD) was established in 2000 and initiated a benchmarking project to improve the quality of cardiovascular surgery. Although the importance of quality improvement initiatives has been emphasized, few studies have reported the effects selleck on outcomes.

Methods: To examine the time-trend effects in initial JCVSD participants (n = 44), we identified 8224 isolated coronary artery bypass graft (CABG) procedures performed between 2004 and 2007. The impact of surgery year was examined using a multiple logistic regression model that set previously identified clinical risk factors and surgery year as fixed effects. To examine the difference in outcomes between initial participants (n = 44) and halfway participants (n = 55), we identified 3882 isolated CABG procedures performed in 2007.

A significant relationship was found between true and calculated volume (mean difference -3 ml, mean absolute difference 23, r(2) = 0.97, p < 0.01). The Bland-Altman 95% limits of agreement were -57 to 51 ml.

Conclusions: The proposed method performs well to estimate female bladder volume greater than 100 ml.”
“Recently, nitric oxide has been investigated as a potential anti-cancer therapy because of its cytotoxic activity. Previously, we found that S-nitrosylated human

serum albumin (SNO-HSA) induced apoptosis in C26 cells, demonstrating for the first time that SNO-HSA has potential as an anti-cancer drug. In the present study, the anti-tumor activity of SNO-HSA in another tumor type of cancer cell was investigated SB431542 cost using murine tumor LY-80 cells. Mitochondrial depolarization, activation of caspase-3 and GSK2126458 DNA fragmentation were induced in LY-80 cells by SNO-HSA treatment in a dose-dependent manner. Inhibition of caspase activity resulted in complete inhibition of DNA fragmentation induced by SNO-HSA. The cytotoxic effects of SNO-HSA on LY-80 were concentration-dependent. Tumor growth in LY-80-tumor-bearing rats was significantly inhibited by administration of SNO-HSA compared with saline- and HSA-treatment. These results suggest that SNO-HSA has potential as a chemopreventive and/or chemotherapeutic agent because it induces apoptosis in tumor

cells. (C) 2009 Elsevier Inc. All rights reserved.”
“Purpose: We investigated the relationship between experimental neuromiaging and self-reported urinary incontinence measures.

Materials

and Methods: We evaluated 14 functionally independent, community dwelling women older than 60 years with moderate to severe urgency urinary Florfenicol incontinence. All underwent detailed clinical assessment (3-day bladder diary, 24-hour pad test and quality of life assessment), urodynamic testing and functional brain scanning. Brain activity during reported urgency was assessed using a method that combines functional magnetic resonance imaging with simultaneous urodynamic monitoring during repeat bladder filling/emptying cycles. We used the statistical parametric mapping program SPM2 (http://www.fil.ion.ucl.ac.uk/spm/spm2.html) to correlate brain activity with relevant clinical covariates, including the number of urgency incontinent episodes, amount of urine leakage and psychological burden as assessed by the Urge Impact Scale questionnaire.

Results: Activity in rostral and subgenual anterior cingulate gyrus, insula, inferior frontal gyrus, orbitofrontal. cortex, dorsal and posterior cingulate gyrus, parahippocampus, cuneus and parts of parietotemporal lobe correlated positively with daytime incontinence frequency and urine loss. Different brain regions correlated with the psychological burden and the associations were inverse, that is precuneus/cuneus and posterior cingulate gyrus, and superior temporal,. supramarginal and transverse gyrus.

We analyzed the cancer detection rate of real-time elastography and systematic biopsy.

Results: Cancer was found in 27 of 94 patients (28.7%). Real-time elastography detected cancer in 20 patients (21.3%) and systematic

biopsy detected it in 18 (19.1%). Positive cancer cores were found in real-time elastography targeted cores in 38 of 158 cases (24%) and in systematic cores in 38 of 752 (5.1%) (chi-square test p <0.0001). The cancer detection rate per core was 4.7-fold greater for targeted than for systematic biopsy.

Conclusions: Real-time elastography targeted biopsy allows prostate KU-60019 cancer detection in men with prostate specific antigen 1.25 ng/ml or greater and 4 ng/ml or less with a decreased H 89 number of cores compared with that of systematic biopsy.”
“Adult mammalian brains are capable of some structural plasticity. Although the basic cellular mechanisms underlying learning and memory are being revealed, extrinsic factors contributing to this plasticity remain unspecified. White-footed mice (Peromyscus leucopus) are particularly well suited to investigate brain plasticity because they show marked seasonal changes in structure and function

of the hippocampus induced by a distinct environmental signal, viz., photoperiod (i.e. the number of hours of light/day). Compared to animals maintained in 16 h of light/day, exposure to 8 h of light/day for 10 weeks induces several phenotypic changes in P. leucopus, including reduction in brain mass and hippocampal volume. To investigate the functional consequences of reduced hippocampal size, we examined the effects of photoperiod on spatial learning and memory in the Barnes maze, and on long-term potentiation (LTP)

in the hippocampus, a leading candidate for a synaptic mechanism underlying spatial learning and memory in rodents. Exposure to short days for 10 weeks decreased LIP in the Schaffer collateral-CA1 pathway of the hippocampus and impaired spatial learning and memory ability in the Barnes maze. Taken together, these results demonstrate Ergoloid a functional change in the hippocampus in male white-footed mice induced by day length. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Purpose: Accumulating evidence shows that androgen deprivation therapy is associated with osteoporosis and fragility fractures of the spine, hip and wrist. One study suggested that androgen deprivation therapy may also be associated with nonfragility fractures in older men. Whether other clinical risk factors independently increase the risk of fractures is not certain.

Materials and Methods: Using linked administrative databases in Ontario, Canada, we matched 19,079 men 66 years old or older with prostate cancer with at least 6 months of continuous androgen deprivation therapy or bilateral orchiectomy with men with prostate cancer who had never received androgen deprivation.

Neuronal damages were observed in all the brain regions. Exogenous melatonin supplementation retrieved all the parameters. These results suggest that melatonin protects PCB-induced oxidative stress and prevents neuronal damage in brain regions. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Purpose: The majority of patients presenting with frank hematuria have no diagnosis. There is a paucity of literature on the recurrence of frank hematuria and the incidence of urological cancers in these patients, and this study addresses both issues.

Materials and Methods: We performed Cisplatin a prospective cohort study

of 578 consecutive patients referred with frank hematuria between 1999 and 2001 who underwent full investigations with a mean followup of 6.9 years. The primary outcome measure was the probability of frank hematuria recurrence after the initial negative investigations and the incidence of urological cancers in these patients.

Results: Diagnosis was made in 206 (35.6%) patients at initial presentation. Diagnosis was not made at initial presentation in the remaining 372 (64.4%) patients, of whom 81 died without a diagnosis during followup (32 within 2 years of presentation). A total of 81 patients (21.8%) with no

learn more diagnosis died during the followup period (32 within 2 years of the investigations). A questionnaire was mailed to the remaining 291 patients and 202 (69.4%) responded. Of the responders 41 (20.3%) reported frank hematuria recurrence (single Baricitinib episode in 10 and multiple episodes in 31). A significant urological diagnosis was made upon repeat evaluation in 21 (10.4%) patients which included urological malignancy in 4 (2%).

Conclusions: Approximately 80% of cases cleared by initial investigation remained clear and 9.8% with frank hematuria recurrence were diagnosed with a urological malignancy. Frank hematuria recurrence requires vigilance and repeat investigations as appropriate.”
“We investigated the chicken auditory system to understand how an interaural level difference (ILD) is processed. Sound intensity is extracted in the nucleus

angularis (NA) and an ILD is processed in the dorsal lateral lemniscal nucleus (LLD). We found that the neural activity in these nuclei is affected by the interaural phase difference (IPD). Activity in the NA was suppressed by strong contralateral sound when binaural stimuli were presented in-phase, but the activity was enhanced by out-of-phase stimuli. These IPD dependent suppression or enhancement probably occurs through acoustic interference across the interaural canal connecting the middle ears of the two sides. The LLD neurons were excited by contralateral sound and inhibited by ipsilateral sound, reflecting excitation by the contralateral NA and inhibition from the ipsilateral NA, probably through the contralateral LLD as in the barn owl.

However, these primer removals, mediated by the RNase H activity of Tf1 RT, are quite inefficient. Interestingly, the integrase

of Tf1 stimulated the specific Tf1 RT-directed cleavage of both the self-primer and PPT, although there was no general enhancement of the RT’s RNase H activity AICAR in vivo (and the integrase by itself is devoid of any primer cleavage). The RTs of two prototype retroviruses, murine leukemia virus and human immunodeficiency virus, showed only a partial and nonspecific cleavage of both Tf1-associated primers with no stimulation by Tf1 integrase. Mutagenesis of Tf1 integrase revealed that the complete Tf1 integrase protein (excluding its chromodomain) is required for stimulating the Tf1 RT primer removal activity. Nonetheless, a double mutant integrase that has lost its integration functions can

still stimulate the RT’s activity, though heat-inactivated integrase cannot enhance primer removals. These findings PD-1/PD-L1 Inhibitor 3 suggest that the enzymatic activity of Tf1 integrase is not essential for stimulating the RI-mediated primer removal, while the proper folding of this protein is obligatory for this function. These results highlight possible new functions of Tf1 integrase in the retrotransposon’s reverse transcription process.”
“Objective: To explore the prevalence of Type D personality-the combination of negative affectivity and social inhibition-in the general population and its relationship to other cardiovascular risk factors, including psychopathological symptoms. Type D personality has been identified as a prognostic risk factor for various cardiovascular disease conditions. Methods: In a representative sample of 2698

individuals ( aged 35-74 years), psychological, lifestyle, and somatic risk factors were investigated with laboratory testing, self-report measures, and a clinical interview. Type D was assessed with the German Type D Scale-14. Results: The prevalence of Type D was 23.4% (95% confidence interval [CI], 21.2-25.6) in men and 26.9% ( 95% CI, 23.7-30.1) in women and, thus, in the range of classical risk factors ( e. g., hypercholesterolemia). In age-adjusted GPX6 analysis, Type D was associated with psychopathological symptoms, including depression and somatic symptom burden. With the exception of physical inactivity in both sexes, hypertension in women and hypercholesterolemia in men, Type D was not associated with classical cardiovascular risk factors. Multivariate analysis revealed depression, exhaustion, anxiety, and low self-rated health as associated with Type D in both sexes ( odds ratios, 1.97-3.21 in men, 1.52-2.44 in women). Conclusions: A Type D personality disposition can be found in about a quarter of the general population, which is comparable to the prevalence of classical cardiovascular risk factors. In both sexes, an independent association to Type D appeared mainly in psychopathological symptoms.

It is recognised that miRNAs play essential roles in the immune system and for correct function in the brain. Moreover, it is now clear that abnormal miRNA expression P505-15 mw is a common feature of several diseases involving the immune system including multiple sclerosis (MS). Expression analysis for miR-21, miR-146a and -b, miR-150, miR-155 was carried out in peripheral mononuclear cells (PBMC) from a cohort of 29 MS patients and 19 controls. Subsequently, a case control study for miR-146 rs2910164 variant was performed

in an overall population of 346 MS cases and 339 controls. A statistically significant increased expression of miR-21, miR-146a and -b was observed in relapsing remitting (RR)MS patients as compared with controls (1.44 +/- 0.13 vs 0.79 +/- 0.06, P=0.036; 1.50 +/- 0.12 vs 0.84 +/- 0.08, P=0.039: 1.54 +/- 0.15 vs 0.72 +/- 0.08. P=0.001 respectively). On the contrary, no differences were found in the expression levels of both miR-150 and miR-155 in patients as compared with controls (P>0.05). The genetic association study failed to find any differences in the frequencies of rs2910164 between patients and controls. miRNA dysregulation may contribute to the pathogenesis of MS and highlights the MG-132 order possibility to define different disease

entities with specific miRNAs profile. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“In addition to blocking dopamine (DA) uptake, cocaine also causes an unconditioned increase in DA release. In drug naive rats, this effect is most robust within the nucleus accumbens (NAc) shell. Recent studies have shown that, in rats trained to self-administer cocaine, cocaine may act in the periphery to enhance mesolimbic DA release. Further, these studies have suggested that

peripheral cocaine action may also enhance unconditioned DA release. Here, we test if it is necessary for cocaine to enter the brain to evoke unconditioned increases in DA release within the NAc shell. Administration of a cocaine analogue that crosses the blood brain barrier (cocaine HCI) enhances electrically evoked DA release and the number of O-methylated flavonoid cocaine-evoked phasic DA release events (i.e., DA transients) within the NAc shell. However, administration of a cocaine analogue that does not cross the blood brain barrier (cocaine MI) does not alter either measure. We therefore conclude that cocaine must act within the central nervous system to evoke unconditioned DA release within the NAc shell. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Reduced olfactory bulb (OB) volume and olfactory sensitivity have been observed in depressed patients, the exact mechanisms underlying, however, are still unknown. Our previous study found that decreased neurogenesis and pre-synaptic dysfunction in the OB of a rat model of depression may be responsible for the phenomena. Nevertheless, whether the apoptosis would also play a certain role in this process is not clear.

“
“Bacterial infection has become a focus of attention in the pathogenesis of primary biliary cirrhosis (PBC). We earlier reported that the bacterial lipoteichoic acid was detected at the sites of inflammation around damaged bile ducts in the livers of PBC, and PBC patients’ sera showed high titers against streptococcal histone-like protein. Here, we investigated whether chronic bacterial exposure could trigger PBC-like epithelial cell damage in normal mouse. BALB/c mice were

repeatedly inoculated with various bacteria for 8 weeks. At 1 week (Group 1) and 3, 4, or 20 months (long term; Group 2) after the final inoculation, mice were killed to obtain samples. In the livers of the Streptococcus intermedius (S.i.)-inoculated

mice in Group 1, cellular infiltration was predominantly observed around the bile ducts over the hepatic parenchyma. check details In the S.i.-inoculated mice in Group 2, portal but not parenchymal inflammation was observed in the livers, and periductal cellular infiltrates were detected in the salivary glands. Both S. i.-inoculated Groups 1 and 2 BALB/c mice sera PX-478 mw had antibodies against HuCCT1 biliary epithelial cells, anti-nuclear antibodies, and anti-gp210 antibodies, but not anti-mitochondrial antibodies. Immunoreactivity to histone-like DNA-binding protein of S.i. (S.i.-HLP) was detectable around the sites of chronic nonsuppurative destructive cholangitis in the portal area in the livers of both S. i.-inoculated Groups 1 and 2 BALB/c mice. Furthermore, anti-S.i.-HLP antibody bound to synthetic gp210 peptide, as well. Bacteria triggered PBC-like cholangitis, multifocal

epithelial inflammation, and autoantibody production. Bacteria are likely involved in the pathogenesis of PBC and of associated multifocal epithelial inflammation. Laboratory Investigation (2010) 90, 577-588; doi: 10.1038/labinvest.2010.40; published online 8 February 2010″
“BACKGROUND: Surgical treatment of arachnoid cysts remains Megestrol Acetate under debate. Although many authors favor endoscopic techniques, others attribute a higher recurrence rate to the endoscope.

OBJECTIVE: The authors report their experience with endoscopic procedures for arachnoid cyst.

METHODS: All pure endoscopic procedures for arachnoid cysts performed by the authors were analyzed. Particular reference was given to surgical complications and patient outcome in relation to cyst location and endoscopic technique.

RESULTS: Sixty-six endoscopic procedures were performed in 61 patients (mean age, 28 years; range, 23 days to 74 years; 35 males, 26 females). The main presenting symptoms were cephalgia (61%), hemisymptoms (18%), and macrocephalus (18%).

We also found that activity in the Zygomaticus Major, the facial muscle responsible for smiling, was greater for reflection patterns. However, we were able to reverse this effect by changing the task so that participants had to treat random patterns as the target stimuli. We conclude that participants spontaneously select reflectional symmetry as the target, and positive affective responses automatically follow from successful target detection. This work provides a new account of the neural mechanisms involved in visual symmetry perception. (C) 2012 Elsevier Ltd. All rights reserved.”
“Objective: To examine the early

results of the David V valve-sparing aortic root replacement procedure in expanded, higher risk clinical scenarios with appropriately selleck inhibitor selected patients.

Methods: From 2005 to 2011, 150 David V valve-sparing aortic root replacements were performed within Emory Healthcare. A total of 78 patients (expanded group) had undergone the David V in expanded, difficult clinical settings such as emergent type A dissection (n = 29), grade 3+ or greater aortic insufficiency (AI) (n = 53), or reoperative cardiac surgery (n = 14). These patients were evaluated and compared with selleckchem a group of 72 patients (traditional group) with less than grade 3+AI who underwent

a David V in a traditional, elective setting. The mean follow-up was 19 months (range, 1-72), and the follow-up Amoxicillin data were 88% complete.

Results: There were 3 operative deaths (2.2%), all occurring in the expanded group. The overall patient survival at 6 years was 95%. Three patients required aortic valve replacement: two for severe AI and one for fungal endocarditis. Both groups had concomitant cusp repairs performed in conjunction with the David V (traditional, n = 10; and expanded, n = 16; P = .27). At follow-up, freedom from moderate AI was 93%, and the freedom from aortic valve replacement was 98%. No significant difference was observed in the freedom from moderate AI between the expanded and traditional groups (91% vs 95%, respectively; P = .16).

Conclusions: In selected patients

possessing appropriate aortic cusp anatomy, the David V can be safely and effectively performed for the expanded indications of aortic dissection, severe AI, and reoperative cardiac surgery with low operative risk. Valve function has remained excellent in the short term, providing evidence of durability and a low rate of valve-related complications. (J Thorac Cardiovasc Surg 2012;143:879-84)”
“Gating of sensory responses is impaired in schizophrenic patients and animal models of schizophrenia. Ketamine, an N-methyl-d-aspartate receptor antagonist, is known to induce schizophrenic-like symptoms including sensory gating deficits in humans.

This study aims to investigate the mechanisms underlying ketamine’s effect on gating of auditory evoked potentials in the hippocampus of freely moving rats.

We used Signed Differential Mapping (SDM), a novel neuroimaging meta-analytical method, to assess global and regional GM volume differences in MS. Meta-regression methods were used to explore potential effects of disease duration and degree of functional disability. We found a highly localized pattern of regional GM volume

loss in Relapsing Remitting MS involving bilateral thalamus, basal ganglia structures, pre/postcentral regions and cingulate gyrus. These results remained largely unchanged after subgroup and sensitivity analyses. Furthermore, GM volume loss in left pre/postcentral regions correlated with increasing functional disability in MS. These results demonstrate that GM atrophy occurs as

a regional selleck chemicals rather than global process in MS, and that functional disability learn more is specifically associated with atrophy of the left pre/post central gyrus. Further investigation is needed to determine whether these structures are targeted by neurodegenerative processes and to establish their clinical and neurocognitive correlates. (C) 2013 Elsevier Ltd. All rights reserved.”
“In this study, the effects of capsaicin on expression of skeletal muscle proteins in Sprague Dawley rats fed with a high-fat diet (HFD) were investigated. Rats were fed a HFD with or without capsaicin treatment for 8 wk. After HFD

feeding, capsaicin-treated rats weighed an average of Phosphoglycerate kinase 8% less than those of the HFD control group. Gastrocnemius muscle tissue from lean and obese rats with or without capsaicin treatment was arrayed using 2-DE for detection of HFD-associated markers. Proteomic analysis using 2-DE demonstrated that 36 spots from a total of approximately 600 matched spots showed significantly different expression; 27 spots were identified as gastrocnemius muscle proteins that had been altered in response to capsaicin feeding, and 6 spots could not be identified by mass fingerprinting. Expression of various muscle proteins was determined by immunoblot analysis for the determination of molecular mechanisms, whereby capsaicin caused inhibition of adipogenesis. Immunoblot analysis revealed increased uncoupling protein 3 (UCP3) protein expression in HFD-fed rats, whereas contents were reduced with capsaicin treatment. Compared with the HFD control group, capsaicin treatment increased phosphorylation of AMP-activated protein kinase (AMPIC) CP3 and acetyl-CoA carboxylase (ACC). To support this result, we also analyzed in vitro differential protein expression in L6 skeletal muscle cells. These data suggest that the AMPK-ACC-malonyl-CoA metabolic signaling pathway is one of the targets of capsaicin action.