These continuing

disparities suggest possible perception

These continuing

disparities suggest possible perception bias. More research is needed to confirm this disparity and explore the underpinnings.”
“BACKGROUND: Unplanned extubation represents a threat to patient safety, and risk factors and prevention strategies for unplanned extubation have not been fully explored. OBJECTIVES: To define high-risk patients for unplanned extubation and determine clinicians’ beliefs on perceived risks for unplanned extubation METHODS: With a Web-based survey instrument we surveyed critical care clinician members of the American Association for Respiratory Care, the American Association of Critical GSK690693 mouse Care Nurses, and the Society of Critical Care Medicine. RESULTS: Surveys were completed by 1,976 clinicians, including 419 respiratory therapists, 870 critical care nurses,

and 605 critical care physicians. The majority of respondents considered an outward migration of the endotracheal tube (by 3 cm, 2 cm if an air leak is present) to represent a risk for unplanned extubation. Respondents considered the 3 following as high risk for unplanned extubation: absence of physical restraints (72% of respondents), a nurse/patient ratio of 1/3 (60%), trips out of the intensive care unit (59%), light sedation (43%), and bedside portable radiograph (29%). In addition, most respondents considered accidental removal of the nasogastric tube (71%) or tugging AZD8055 inhibitor on the endotracheal tube (87%) by the patient to be risk factors for unplanned extubation. The GDC-0994 research buy rank order of the perceived risks was related to the respondents’ primary discipline. CONCLUSIONS: We identified perceived risk factors and defined “near misses” for unplanned extubation. Our findings should inform strategies for prevention of unplanned extubation.”

new mesoporous silicotitaniumphosphate material has been synthesized by using a non-conventional phosphorous source trimethyl phosphite with the aid of Pluronic F127 as structure directing agent (SDA). The mesopores are generated due to the slow hydrolysis of the reactant materials in the presence of supramolecular-assembly of non-ionic surfactant under the evaporation induced self-assembly (EISA) process. The material has been characterized by powder XRD, N-2 sorption, TEM, SEM-EDS, TG-DTA, FT-IR, XPS, Si-29, P-31 MAS NMR and UV-vis spectroscopic techniques. This new mesoporous material has considerably high BET surface area (379 m(2) g(-1)) and narrow pore size distribution with a peak pore width of 5.4 nm. The material showed good catalytic activity in the liquid phase Friedel-Crafts benzylation reaction suggesting strong acidity on its surface. It can also be used as good adsorbent for the removal of toxic metal ions As(III/V), Cd(II) and Hg(II) from the contaminated water. (C) 2010 Elsevier B.V. All rights reserved.

Conclusion-Activation of the EP3 receptor raises baseline blo

\n\nConclusion-Activation of the EP3 receptor raises baseline blood pressure and contributes to Ang II dependent hypertension a least partially via enhancing Ca2+ sensitivity and intracellular calcium concentration in vascular smooth muscle cells. Selective targeting of the EP3 receptor may represent a potential therapeutic target for the treatment of hypertension. (Arterioscler Thromb Vasc Biol. 2012;32:3024-3032.)”
“SPIN90 is a key regulator of actin cytoskeletal organization. Using the BioGRID(beta) database (General Repository for Interaction Datasets), we identified IRSp53 as a binding partner of SPIN90, and confirmed the in vivo formation of a SPIN90-IRSp53 complex

mediated through direct association of the proline-rich domain (PRD) of

SPIN90 with the SH3 domain of IRSp53. SPIN90 and IRSp53 positively cooperated to mediate Rac Smoothened Agonist mouse activation, TPX-0005 Protein Tyrosine Kinase inhibitor and co-expression of SPIN90 and IRSp53 in COS-7 cells led to the complex formation of SPIN90-IRSp53 in the leading edge of cells. PDGF treatment induced strong colocalization of SPIN90 and IRSp53 at membrane protrusions. Within such PDGF-induced protrusions, knockdown of SPIN90 protein using siRNA significantly reduced lamellipodia-like protrusions as well as localization of IRSp53 at those sites. Finally, competitive inhibition of SPIN90-IRSp53 binding by SPIN90 PRD dramatically reduced ruffle formation, further suggesting that SPIN90 plays a key role in the formation of the membrane protrusions associated with cell motility. (C) 2009 Elsevier Inc. All rights reserved.”
“Most centres in 432 Europe have not introduced

a rapid response team (RRT), partly because of concerns that data from other health-care systems may not be relevant. We tested whether patient characteristics and outcomes for deteriorating patients differ between two health-care systems separated by distance and culture.\n\nWe obtained data from 3,063 RRT calls: 815 calls at Karolinska University Hospital (Sweden) and FRAX597 2,248 calls at Austin Hospital (Australia) and compared demographic and clinical data, as well as outcomes for patients reviewed by a RRT.\n\nAt Karolinska, 46.9% of patients were female compared with 45.1% at Austin. Mean age was 66.5 years versus 69.4 years. The unit of admission was surgical/medical in 49.1%/50.9% versus 48.8%/51.1% of patients, respectively. Overall, 56.7% versus 55.8% of the calls were out-of-hours (1700-0800 hours). There was a predominance of respiratory triggers at both centres and the “worried” criterion was frequently used in both hospitals (17.2% versus 14.4%) as a trigger for RRT activation. Overall, 30-day mortality was 27.7% versus 29.4% and allocation of Limitations of Medical Treatment (LOMT) orders was 34.2% versus 30.8%. The allocation of LOMT orders was influenced by the RRT in 14.4% versus 12.6% of cases.

Additionally, ex vivo studies of human brain slices from an indep

Additionally, ex vivo studies of human brain slices from an independent sample of patients who had AD were performed.\n\nSetting: Three university medical centers.\n\nPatients: Patients with mild-to-moderate AD.\n\nIntervention: Two consecutive cohorts of patients received 2 to 7 infusions of intravenous gantenerumab (60 or 200 mg) or placebo every 4 weeks. Brain slices from patients who had AD were coincubated with gantenerumab at increasing concentrations and with human microglial cells.\n\nMain Outcome Measures: Percent change in the ratio of regional carbon 11-labeled Pittsburgh Compound B retention in vivo and semiquantitative assessment of gantenerumab-induced

phagocytosis ex vivo.\n\nResults: Sixteen patients with end-of-treatment positron emission tomographic scans were included in the analysis. PD173074 clinical trial The mean (95% CI) percent change from baseline difference relative to placebo (n=4) in cortical brain amyloid level was -15.6% (95% CI, -42.7 to 11.6) for the 60-mg group (n=6) and -35.7% (95% CI, -63.5 to -7.9) for the 200-mg group (n=6). Two patients in the 200-mg group showed transient and focal areas of inflammation or vasogenic edema on 123 magnetic resonance imaging scans at sites with the highest level of amyloid reduction. Gantenerumab induced phagocytosis of human amyloid in a dose-dependent manner ex vivo.\n\nConclusion: Gantenerumab treatment resulted in a dose-dependent reduction in brain

amyloid level, possibly through an effector cell-mediated mechanism of action.”
“Many patients have been characterized harboring a mutation in thyroid hormone receptor (TR) beta. Surprisingly BI6727 none has yet been identified carrying a mutation in TR alpha 1. To facilitate the identification of such patients,

several animal models with a mutant TR alpha 1 have been generated. While some phenotypic characteristics, such as an adult euthyroidism, are similar in the mutant mice, other aspects such as metabolism are quite variable. This review summarizes the most important consequences of a mutation in TR alpha 1 in mice focusing on the TR alpha 1-R384C mutation, and projects the Selleck CDK inhibitor insights from the animal models to a putative phenotype of patients with a mutated TR alpha 1.”
“Background: We performed a meta-analysis to evaluate the value of (18)FDG PET-CT for the detection of gastric cancer recurrence after surgical resection.\n\nMethods: A systematic literature search was performed in the MEDLINE and EMBASE databases. We calculated the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for (18)FDG PET-CT. We also constructed summary receiver operating characteristic curves for (18)FDG PET-CT.\n\nResults: Eight studies (500 patients) were included. The sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of (18)FDG PET-CT were 0.86 (95% confidence interval [CI] = 0.71-0.94), 0.88 (95% CI = 0.75-0.94), 17.0 (95% CI = 3.5-14.0), and 0.16 (95% CI = 0.07-0.34), respectively.

All rights reserved “
“Objectives: To investigate auditory d

All rights reserved.”
“Objectives: To investigate auditory 3 dysfunction in patients with tinnitus and normal hearing thresholds using two sensitive audiological measures. Design: The study was designed to investigate the characteristics of Audioscan and DPOAE tests in tinnitus patients with normal hearing thresholds. Audioscan and DPOAE notches were analysed and compared. All tests were performed in a sound-treated chamber or in a sound-treated

room. Study sample: Forty-five tinnitus patients with normal hearing thresholds were examined following a written clinical protocol. Results: The averaged hearing levels obtained from tinnitus participants were significantly worse at high frequencies than those derived from Selleck Cl-amidine the normative data. There was a significantly higher prevalence of Audioscan and DPOAE

notches, whose central frequencies matched tinnitus frequencies in the mid-frequency regions, but not in the low-and high-frequency regions. A significant correlation was found between the centre frequencies of the Audioscan notches and the DPOAE notches from 500 to 4000 Hz. Conclusion: Tinnitus in different frequency regions may be associated with different underlying mechanisms of tinnitus generation. Some negative results on the Audioscan and DPOAE notches matching tinnitus pitches may be due to a limited set of discrete frequencies used for the tinnitus pitch matching test.”
“Structural, spectroscopic and optical properties of lead tellurite glass ceramics doped with variable amounts of erbium ions and codoped with fixed amounts of silver (Ag2O or Ag metallic nanoparticles, AgNPs) have been studied. The investigation of the samples was performed by X-ray diffraction (XRD), Fourier transform infrared (FTIR), diffuse reflectance ultraviolet visible (DR-UV-vis) and photoluminescence (PL) spectroscopies. The average unit-cell parameter, crystallite size and the quantitative ratio of the crystallographic phases in the Selleckchem PD173074 samples were evaluated from the XRD data. FTIR spectroscopy data show that

the glass ceramics network mainly consists of TeO3 and TeO4 structural units. The increase of the Er2O3 content determines a TeO3 – bigger than TeO4 conversion but the process is also influenced by the nature of the codopant (Ag2O or AgNPs) present in the samples. The optical band gap (E-g(opt)) values, determined from the DR-UV vis spectra, decrease with increasing the erbium content of the samples. Photoluminescence spectroscopy measurements evidenced the important peaks located at around 430 nm and 708 nm due to the Pb2+ ions and at 525 and 547 nm due to the Er3+ ions present in the studied samples. The Er3+ :Ag codoping was found to produce antagonistic effects (quenching/enhancement) of the luminescence emission of Er3+ ions in the studied samples. (C) 2014 Elsevier Ltd and Techna Group S.r.l. All rights reserved.

Median ratings and 432 interquartile ra

Median ratings and interquartile ranges were calculated.

Rates >7 and interquartile ranges <3 depicted important and expert-agreed parameters.\n\nResults: Thirty-nine experts compiled a list of 254 items. Twenty-eight experts reached a consensus on 49 important items associated with poor prognosis. They primarily agreed on clinical manifestations of complex regional pain syndrome I. Psychosocial factors were considered less important.\n\nConclusion: The findings of this study indicate that poor prognosis for complex regional pain syndrome 1 is primarily dependent on clinical manifestations. While evidence suggests that psychosocial factors may play a role in the development of the condition, their

Nutlin-3 concentration role in poor prognosis appears to be less important.”
“The reasons for hormone 432 therapy use have changed dramatically over time from being very popular for the purpose of preserving youth in women to menopause-related symptom management, disease prevention, and now EX 527 back to menopause-related symptom management. Over time, several important risks associated with the use of hormone therapy have become evident, causing dramatic reductions in the use of hormone therapy for periods of time following identification of these risks. Most recently, randomized controlled prevention trials that evaluated hormone therapy for the purpose of reducing or preventing coronary heart disease among women have found that hormone therapy is associated with increased rather selleck chemicals than decreased risks for coronary heart disease. The most recent of these trials again identified increased risks for breast cancer associated with estrogen plus progestogen therapy. The evolving evidence base from these randomized controlled prevention trials is complicated and in some cases contradictory. Specifically, the data suggest that the timing of when hormone therapy is initiated once a woman is postmenopausal may influence her risk

for developing heart disease and breast cancer. In this article, contradictory evidence is carefully sifted so risks and benefits can be weighed by clinicians when partnering with women to individualize decisions about using hormone therapy.”
“Women of child bearing age are at a high risk for depression. Despite the high incidence of depression during pregnancy and the postpartum period, guidelines for treating this depression are lacking It is a challenge to treat the illness effectively and also to minimize risk to the fetus or the neonate. The safety of antidepressants during pregnancy is an unresolved issue and has made it difficult to choose the appropriate antidepressant to be used during pregnancy In this review we have suggested some strategies that may be useful to the physicians.

One month and three months after implantation, samples were harve

One month and three months after implantation, samples were harvested for biological and histological analysis. New bone tissues were observed in 10/10 samples in group 1,3/10 samples in group 2, and 9/10 samples in group 3 at 3rd month in mice, but not in rabbits. In vitro, human

mesenchymal stem cells (hMSCs) were cultured with trace CaP and BCP powder, and osteogenic differentiation was observed at day 7. Our results suggested that chemical composition is the prerequisite in osteoinduction, and pore structure would contribute to more bone formation. (C) 2012 3 Elsevier B.V. All rights reserved.”
“Data from neuropsychology and neuroimaging studies indicate hemispheric asymmetries in processing object’s global form versus local parts. However the attentional mechanisms subtending visual selection of different levels of information are poorly understood. The classical left hemisphere/local-right

hemisphere/global dichotomy has been Stem Cell Compound Library mw recently challenged by studies linking the asymmetry of activation in the posterior parietal cortex (PPC) with the relative salience of the stimulus rather than with the local/global level. The present SC79 research buy study aimed to assess hemispheric asymmetry in local global and salience-based selection in hierarchical stimuli by using transcranial direct current stimulation (tDCS). To this end, tDCS has been applied to the PPC of both the hemispheres. Our data revealed that tDCS did affect the selection of the target on the basis of its relative salience in a manner that depended on the tDCS polarity applied to the two hemispheres. This result is in line with previous findings that the left PPC is critically involved in attention for low-salience stimuli in the presence of high-salience distractor information, while right PPC is involved in attending to more salient stimuli. Hemispheric asymmetries were also found in local/global selection. Overall the results suggest that neural activation

in the PPC selleck screening library is related to both the salience and the level of stimulus representations mediating responses to hierarchical stimuli. The comparison of the results from Experiments 1 and 2 in local/global-based selection suggests that the effect of stimulation could be completely opposite depending on subtle differences in demands of attentional control (sustained attention vs task switching). (C) 2012 Elsevier Ltd. All rights reserved.”
“The myxozoan Kudoa inornata is a common parasite of the skeletal muscles of spotted seatrout, Cynoscion nebulosus. This study was conducted to determine the distribution of plasmodia of K. inornata within individual C. nebulosus in order to identify muscle areas of least variation where future sampling would result in easily obtainable, repeatable, and dependable measurement of infection status. Fish were captured in the wild during June 2011. Muscle samples from 9 body areas were collected, in replicate, from each of 15 specimens of C.

In this study we addressed this gap by systematically manipulatin

In this study we addressed this gap by systematically manipulating cognition-emotion interaction in a social DM context, when the participants played a card game with a hypothetical opponent in a behavioral study (n=73) and a functional magnetic-resonance-imaging study (n = 16). We observed that payoff-based behavioral choices were influenced by emotional values carried by face pictures and identified neurocircuits involved in cognitive valuation, emotional

valuation, and concurrent cognition-emotion value integration. Specifically, while the vmPFC, amygdala, and ventral striatum were all involved in both cognitive and emotional domains of valuation, BTSA1 nmr these regions played dissociable roles in social DM. The payoff-dependent responses in vmPFC and amygdala, but not ventral striatum, were moderated

by the social context. Furthermore, the vmPFC, but not amygdala, not only encoded the opponent’s gains as if self’s losses, but also represented a “final common Fer-1 currency” during valuation-based decisions. The extent to which emotional input influenced choices was associated with the functional connectivity between the value-signaling amygdala and value integrating vmPFC, and also with the functional connectivity between the context-setting hippocampus and value-signaling amygdala and ventral striatum. These results identify brain pathways through which emotion shapes subjective values in a social DM context. (C) 2012 Elsevier Inc. All rights reserved.”
“The quaternary isoquinoline alkaloid, sanguinarine (SG) plays an important role in both traditional and modern medicine, exhibiting a wide range of biological activities. Under physiological conditions, there is an equilibrium between the Pevonedistat quaternary cation (SG(+)) and a pseudobase (SGOH) forms of SG. In the gastrointestinal tract, SG is converted to dihydrosanguinarine (DHSG). All forms exhibit bright fluorescence. However, their spectra overlap, which limited the use of powerful techniques based on fluorescence spectroscopy/microscopy. Our experiments using a combination of steady-state and time-resolved

techniques enabled the separation of individual components. The results revealed that (a) the equilibrium constant between SG(+) and SGOH is pK (a) = 8.06, while fluorescence of DHSG exhibited no changes in the pH range 5-12, (b) the SGOH has excitation/emission spectra with maxima at 327/418 nm and excited-state lifetime 3.2 ns, the spectra of the SG(+) have maxima at 475/590 nm and excited-state lifetime 2.4 ns. The DHSG spectra have maxima at 327/446 nm and 2-exponential decay with components 4.2 and 2.0 ns, (c) NADH is able to convert SG to DHSG, while there is no apparent interaction between NADH and DHSG. These techniques are applicable for monitoring the SG to DHSG conversion in hepatocytes.

Eleven (29%) of them had an incomplete form of the disease Coron

Eleven (29%) of them had an incomplete form of the disease. Coronary artery abnormalities were found in 10 (26%) children, insignificantly more often among those with incomplete KD. Each day of treatment delay increased the complication rate by almost 1.5 (OR 1.45, p = 0.009). Treatment initiated 10 days after the onset of the disease increased

this risk almost nine times (OR 8.99, p = 0.007). No significant differences in respect to age (p = 0.431), gender (p = 0.744) and laboratory test results were found between the groups with and 432 without coronary complications. A complete regression of coronary artery involvement was seen in 7 children, and partial regression was seen in one child. One child died and another needed coronary artery bypass grafting. Conclusions: Coronary artery aneurysms developed at a similar rate in both complete and incomplete forms of KD and the only significant risk factor Protein Tyrosine Kinase inhibitor Silmitasertib Metabolism inhibitor was the timing of treatment initiation. In young children with

fever of unknown cause lasting longer than 5 days, echocardiography is warranted. Despite a tendency for coronary artery aneurysms to regress, late complications may occur and all children require long-term follow up in a cardiology clinic.”
“Aims: This meta-analysis aims to evaluate the effects of common polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene on the toxicity and clinical responses of irinotecan-based Natural Product Library supplier chemotherapy in patients with colorectal cancer (CRC). Methods: The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched from their inception through November 1st, 2013 without language

restrictions. Meta-analysis was conducted with the use of the STATA 12.0 software. Crude odds ratios (ORs) and their 95% confidence intervals (95% CIs) were calculated. Seven clinical cohort studies with a total of 815 CRC patients met the inclusion criteria. Two common polymorphisms (677 C bigger than T and 1298A bigger than C) in the MTHFR gene were assessed. Results: The results from our meta-analysis suggested that MTHFR genetic polymorphisms might significantly decrease the rate of grade 3/4 toxicity of irinotecan-based chemotherapy in CRC patients (OR=0.53, 95% CI: 0.32-0.89, p=0.015). Furthermore, we also demonstrated that MTHFR genetic polymorphisms strongly correlated with good clinical responses (complete response+partial response) to irinotecan-based chemotherapy in CRC patients (OR=1.47, 95% CI: 1.05-2.04, p=0.024). Conclusions: Our findings provide empirical evidence that MTHFR genetic polymorphisms may decrease the toxicity of irinotecan-based chemotherapy and increase the clinical benefits for CRC patients. Thus, MTHFR genetic polymorphisms may be screened to predict the clinical responses to irinotecan-based chemotherapy in CRC patients.

The measured parameters were as follows: (1) the s d of 12 LV-se

The measured parameters were as follows: (1) the s.d. of 12 LV-segment time-to-peak systolic velocities (Ts-SD12), and (2) the maximal difference between peak systolic velocities of any 2 of the 12 segments (Ts-Max). Patients with Ts-SD12 >= 33 ms or Ts-Max >= 100 ms were regarded as having LV systolic dyssynchrony. Patients with systolic dyssynchrony (group 1, n=29) and without systolic dyssynchrony (group 2, n=31) were compared. Among the patients in group 1, antihypertensive treatment significantly

improved LV systolic dyssynchrony (Delta Ts-SD12, -13.1 ms; P<0.001 and Delta Ts-Max, -34.0 ms; P=0.003), whereas it did not demonstrate additional benefit among group 2 patients. The change in LV systolic dyssynchrony was significantly associated with changes in the mean annulus E’ velocity, MEK inhibitor Autophagy screening mean annulus S’ velocity and mean annulus E’/A’ ratio,

but not with changes in blood pressure and LV mass index. It is likely that chronic antihypertensive treatment could reverse the LV systolic dyssynchrony and simultaneously improve subclinical systolic and diastolic function in patients with hypertension and LV systolic dyssynchrony. Hypertension Research (2012) 35, 661-666; doi:10.1038/hr.2012.28; published online 15 March 2012″
“A new exhaust emission inventory of ocean-going vessels (OGVs) was compiled for Hong Kong by using Automatic Identification System (AIS) data for the first time to determine typical main engine load factors, through vessel speed and operation mode characterization. It was found that in 2007, container vessel

was the top emitting vessel type, contributing 9,886, 11,480, 1,173, 521 and 1166 123 tonnes of SO2, NOx, PM10, VOC and CO, respectively, or about 80%-82% of the emissions. The top five, which also included ocean cruise, oil tanker, conventional cargo vessel and dry bulk carrier, accounted for about 98% of emissions. Emission Volasertib molecular weight maps, which add a new spatial dimension to the inventory, show the key emission hot spots in Hong Kong and suggest that a significant portion of emissions were emitted at berth. Scientific evidence about the scale and distribution of ship emissions has contributed in raising public awareness and facilitating stakeholder engagement about the issue. Fair Winds Charter, the world’s first industry-led voluntary emissions reduction initiative, is a perfect example of how careful scientific research can be used in public engagement and policy deliberation to help drive voluntary industry actions and then government proposals to control and regulate marine emissions in Hong Kong and the Pearl River Delta region. (C) 2012 Elsevier Ltd. All rights reserved.”
“Worldwide, paracetamol is administered as a remedy for complaints that occur after vaccination. Recently published results indicate that paracetamol inhibits the vaccination response in infants when given prior to vaccination.

“A 63-year-old man presented with an asymptomatic papillar

“A 63-year-old man presented with an asymptomatic papillary, sessile lesion of the juxtalimbal bulbar conjunctiva that was surgically BV-6 manufacturer excised with cryotherapy. Histopathologically, the lesion created some diagnostic confusion as it displayed an endophytic, or inverted, growth pattern-with 123 squamous cells pushing into the substantia propria around fibrovascular cores, but without significant cytologic atypia, consistent with a conjunctival inverted papilloma (IP). Unlike previously reported cases of conjunctival IP, there were no goblet cells or cysts within the tumor. Immunostaining was diffusely positive for cytokeratin (CK) 7, and CK14 stained the basilar and

suprabasilar cells, as in normal conjunctiva. CK17 weakly and non-uniformly stained the tumor, ruling out a dysplasia, which is usually strongly

positive. The lesion’s cytokeratin profile therefore paralleled that of normal conjunctiva. The proliferation index with Ki67 nuclear staining was extremely low ( smaller than 1%), as was p53 nuclear staining (10-20%), both in contrast to squamous cell dysplasias or carcinomas that have a much higher percentage of positive cells. The lesion was negative for human papillomavirus subtypes associated with squamous neoplasias including carcinomas. We review the’previous literature devoted to this comparatively rare condition and contrast its benign clinical course with that of inverted papillomas of the sinonasal, lacrimal drainage, and genitourinary systems and provide a set of criteria for establishing the diagnosis. (C) 2015 Elsevier Inc. All rights reserved.”
“Inflammatory kidney disease is a major clinical problem that can result in end-stage renal failure. In this article, we show that Ab-mediated inflammatory kidney injury and renal disease in a mouse nephrotoxic serum nephritis model was inhibited by amino acid metabolism and a protective autophagic response.

The metabolic signal was driven by IFN-gamma-mediated induction of indoleamine 2,3-dioxygenase 1 (IDO1) enzyme activity with subsequent activation of a stress response dependent on the eIF2 alpha kinase SN-38 concentration general control nonderepressible 2 (GCN2). Activation of GCN2 suppressed proinflammatory cytokine production in glomeruli and reduced macrophage recruitment to the kidney during the incipient stage of Ab-induced glomerular inflammation. Further, inhibition of autophagy or genetic ablation of Ido1 or Gcn2 converted Ab-induced, self-limiting nephritis to fatal end-stage renal disease. Conversely, increasing kidney IDO1 activity or treating mice with a GCN2 agonist induced autophagy and protected mice from nephritic kidney damage. Finally, kidney tissue from patients with Ab-driven nephropathy showed increased IDO1 abundance and stress gene expression.