c-rel(-/-) mice displayed significant deficits in freezing behavi

c-rel(-/-) mice displayed significant deficits in freezing behavior 24 h after

training for contextual fear conditioning but showed normal freezing behavior in cued fear conditioning and in short-term contextual fear conditioning. In a novel object recognition test, wild-type littermate mice exhibited a significant preference for a novel object, but c-rel(-/-) mice did not. These results indicate that c-rel(-/-) RepSox in vitro mice have impaired hippocampus-dependent memory formation. To investigate the role of c-Rel in long-term synaptic plasticity, baseline synaptic transmission and long-term potentiation (LTP) at Schaffer collateral synapses in c-rel(-/-) mice was assessed. c-rel(-/-) slices had normal baseline synaptic transmission but exhibited significantly less LTP than did wild-type littermate slices. Together, our results demonstrate that c-Rel is necessary for long-term synaptic potentiation in vitro and hippocampus-dependent memory formation in vivo.”

To evaluate the effect of the extrusion-cooking process with the addition of different acids concentration on the stability of B-aflatoxins in sorghum.

Methods and Results: Experimental units (EU) of sorghum flour contaminated with B-aflatoxins (140 ppb) were extrusion cooked with aqueous lactic or citric acid at six different concentrations. The effects of the two extrusion variables (moisture content and acid concentration) were analysed as a completely randomized factorial selleck chemicals llc ADAM7 3 x 6 design. Under some conditions, the aflatoxin reduction is more effective when using aqueous citric acid (up to 92%), than when using aqueous lactic acid (up to 67%).

Conclusions: With citric acid, some extrusion treatments produced higher aflatoxin degradation

rates, than those produced with lactic acid.

Significance and Impact of the Study: Aflatoxin contamination is a great risk both for human as well as for animal health in underdeveloped countries; consequently, practical and economical detoxification procedures are needed that eliminate or at least minimize the aflatoxin risk, through lowering aflatoxin concentrations in grains. Under these considerations, extrusion process can be used for reduction in the aflatoxin content in contaminated grains.”
“Aims To compare three methods for DNA extraction from Mycobacterium bovis, Mycobacterium tuberculosis and Mycobacterium avium subsp. avium.

Methods and Results: The DNA was extracted from mycobacterial cultures using enzymatic extraction, combined bead beating and enzymatic extraction and cetyltrimethylammonium bromide (CTAB) extraction. The yield and quality of DNA were compared by spectrophotometry, agarose gel electrophoresis, restriction endonuclease analysis and PCR. The combined bead beating and enzymatic extraction method yielded more DNA. However, that method produced some sheared DNA, visible either by agarose gel electrophoresis or by restriction endonuclease analysis.

The relative bladder cancer risk was adjusted for age and smoking

The relative bladder cancer risk was adjusted for age and smoking. The adjusted odds ratio ( OR) for bladder cancer was elevated in 7 painters ( OR 1.98, 95% CI 0.64-6.11), 4 hairdressers ( OR 4.9, 95% CI 0.85-28.39), and 16 cases who reported a wood processing occupation ( OR 1.19, 95% CI 0.58-2.41). Ten of these 16 cases reported chronic exposure to colorants ( OR 1.84, 95% CI 0.68-4.95). The results of this epidemiological study confirm Verteporfin cell line the hypothesis that individuals exposed to colorants show an elevated bladder cancer risk.”
“The relationship between exposure to carcinogenic substances and development

of bladder cancer was assessed from a case-control study conducted in North Rhine-Westphalia, Germany. The study consisted of 156 cases with bladder cancer and 336 controls with prostate cancer. The primary focus was the role of polycyclic aromatic hydrocarbons ( PAHs), since most individuals were considered exposed mainly to substances in this group. Data were collected from

male patients who had applied for cancer rehabilitation treatment. Nominally significant smoking-adjusted odds ratio ( OR) estimates were obtained for frequent exposures to bitumen ( OR = 2.92, 95% CI 1.32-6.48) and tar ( OR = 2.09, 95% CI 1.04-4.21) and an ever exposure to paints ( OR = 1.69, 95% CI 1.10-2.61). A frequent exposure to pitch showed a non-significant elevated risk ( OR = 3.06, 95% CI 0.77-12.10).”
“Between 1946 and 1990 uranium mining was undertaken on a large scale in East Germany. This study evaluates www.selleckchem.com/products/BIBF1120.html the proportional lung cancer risk of German uranium miners from radon, quartz, and arsenic exposure during mining operations at

the WISMUT Corporation. The database of the WISMUT tissue repository and a comprehensive job-exposure matrix were used to compare exposure levels of lung cancer cases with deaths from diseases of the circulatory system for risk analysis. In addition, the ratio of lung cancer cases was compared to cases from diseases C-X-C chemokine receptor type 7 (CXCR-7) of the circulatory system to the corresponding ratio in the general population. The proportional lung cancer mortality of German uranium miners was 2.9-fold higher than in the general population of East Germany. Cumulative radon, quartz, and arsenic exposure were determined as risk factors for lung cancer among German uranium miners, where silicosis modified the risk of cumulative radon and quartz exposure. Silicotics were exposed to higher levels of quartz, radon, and arsenic than nonsilicotics. Because selection of the study population was based on a tissue repository, the results need to be interpreted with caution.”
“Single-nucleotide polymorphisms ( SNP) in genes of styrene-metabolizing enzymes could modulate biomarker concentrations in blood or urine after exposure to styrene.

The latter possibility could modify the current theoretical under

The latter possibility could modify the current theoretical understanding of cardiac conduction, help explain paradoxical experimental findings, and open up entirely new avenues for

antiarrhythmic therapy. We review recent structural insights into the perinexus and its potential novel functional role in cardiac-excitation spread, highlighting presently unanswered questions, the evidence for ephaptic conduction in the heart and how structural insights may help complete this picture. (c) 2013 Elsevier Inc. All rights reserved.”
“Background/Aims: Hyperuricemia is associated with obesity and the metabolic syndrome. URAT1 is a urate transporter, and we tested the association of URAT1 transporter gene (SLC22A12) polymorphisms with obesity and the metabolic syndrome in hypertensive subjects. Methods: Patients with essential PI3K inhibitor hypertension (n = 414) from a randomized controlled study were genotyped for SLC22A12 SNPs rs11602903, rs505802 and rs11231825. Results: In Caucasians, SLC22A12 SNPs were associated with the body mass index (BMI).

rs11602903 was associated with BMI (p < 0.0001), waist circumference (p = 0.003), HDL cholesterol (p = 0.018) and the metabolic syndrome (p = 0.033), and accounted for 7% of the variation of BMI in Caucasians. In African Americans, SLC22A12 SNP rs11602903 Selleck Tipifarnib was not associated with BMI, waist circumference, Ponatinib mw HDL cholesterol or triglycerides. Conclusion: The URAT1 gene SLC22A12 polymorphism may play a role in obesity and the metabolic syndrome in Caucasian hypertensive subjects. Copyright (C) 2012 S. Karger AG, Basel”
“The effects of sigma receptor antagonists on methamphetamine (METH)-induced stereotypy have not been examined. We examined the effects of sigma antagonists on METH-induced stereotypy in mice.

The administration of METH (10 mg/kg) to male ddY mice induced stereotyped behavior consisting of biting (90.1%), sniffing (4.2%), head bobbing (4.1%), and circling

(1.7%) during an observation period of 1 h. Pretreatment of the mice with BMY 14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol; 1, 5, and 10 mg/kg), a non-specific sigma receptor antagonist, significantly increased METH-induced sniffing (19.2%, 30.5%, and 43.8% of total stereotypical behavior) but decreased biting (76.6%, 66.9%, and 49.3% of total stereotypical behavior) in a dose-dependent manner. This response was completely abolished by (+)-SKF 10,047 ([2S-(2 alpha,6 alpha,11R)]-1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(2-propenyl)-2,6-methano-3-benzazocin-8-ol; 4 and 10 mg/kg), a putative sigma(1) receptor agonist, and partially by PB 28 (1-cyclohexyl-4-[3-(1,2,3,4-tetrahydro-5-methoxy-1-naphthalen-1-yl)-n-propyl]piperazine; 1 and 10 mg/kg), a putative sigma(2) receptor agonist.

Historically, studies of the auditory system have lagged behind o

Historically, studies of the auditory system have lagged behind other sensory systems due to the small size and inaccessibility of the inner ear. With the advent of new molecular genetic tools, this gap is narrowing. Here, we summarize recent insights into the cellular and molecular cues that guide the development

of spiral ganglion neurons, from their origin in the proneurosensory domain of the otic vesicle to the formation of specialized selleck chemicals synapses that ensure rapid and reliable transmission of sound information from the ear to the brain. (C) 2011 Elsevier Ltd. All rights reserved.”
“Activating mutations in the NOTCH1 pathway are frequent in pediatric T-cell acute lymphoblastic leukemia (T-ALL) but their role in refining risk stratification is unclear. We screened 162 pediatric T-ALL patients treated on the MRC UKALL2003 trial for NOTCH1/FBXW7 gene mutations and related genotype to response to therapy and long-term outcome. Overall, 35% were wild-type (WT) for both genes (NOTCH1(WT)FBXW7(WT)), 38% single NOTCH1 mutant (NOTCH1(Single)FBXW7(WT)), 3% just FBXW7 mutant (NOTCH1(WT)FBXW7(MUT)) and 24% either double NOTCH1 mutant (NOTCH1(Double)FBXW7(WT)) or mutant in both genes (NOTCH1(MUT)FBXW7(MUT)), hereafter called as NOTCH1 +/- FBXW7(Double). https://www.selleckchem.com/products/KU-55933.html There was no difference between groups in early response to therapy, but NOTCH1 +/- FBXW7(Double) patients were more likely to be associated with negative minimal residual

disease (MRD) post-induction than NOTCH1(WT)FBXW7(WT) patients (71% versus 40%, P=0.004). Outcome improved according to the number of mutations, overall survival at 5 years 82%, 88% and 100% for NOTCH1(WT)FBXW7(WT), NOTCH1(Single)FBXW7(WT) and NOTCH1 +/- FBXW7(Double) patients, Racecadotril respectively (log-rank P for trend = 0.005). Although 14 NOTCH1 +/- FBXW7(Double) patients were classified as high risk (slow response and/or MRD positive), only

two had disease progression and all remain alive. Patients with double NOTCH1 and/or FBXW7 mutations have a very good outcome and should not be considered for more intensive therapy in first remission, even if slow early responders or MRD positive after induction therapy. Leukemia (2013) 27, 41-47; doi:10.1038/leu.2012.176″
“To the Editor: In their Perspective article, Betses and Brennan (Sept. 12 issue)(1) state that overdose of a controlled substance has become the second-leading cause of accidental death in the United States. They go on to discuss the ethical duty of pharmacists to combat this growing public health problem. To this end, they report on the effort undertaken by their employer, CVS Caremark, to curtail the inappropriate prescribing of narcotics. However, the senior vice president and chief medical officer of CVS Caremark neglect to mention that in April 2013, their company paid $11 million in fines to settle charges brought …”
“Alzheimer’s disease (AD) is characterized clinically by an insidious decline in cognition.

Coinfections expand the range of susceptible hosts, and coinfecte

Coinfections expand the range of susceptible hosts, and coinfected plants remain symptomless several weeks after infection, so a potentially important problem for disease prevention and management. These results provide an explanation of the observed epidemiological pattern in terms of genetic and ecological interactions among the different viral strains. Thus, mixed infections appear to be contributing to shaping the genetic structure and dynamics of PepMV populations.”
“Hypoxic preconditioning (HP) selleck chemicals is a novel strategy to make stem cells resistant to the ischemic environment they

encounter after transplantation into injured tissue; this strategy improves survival of both the transplanted cells and the host cells at the injury site. Using both in vitro and in vivo injury models, we confirmed that HP-treated adipose tissue-derived mesenchymal stem cells (HP-AT-MSCs) increased cell survival and enhanced the expression of marker genes in DsRed-engineered neural stem cells (NSCs-DsRed). Similar to untreated AT-MSCs, HP-AT-MSCs

had normal morphology and were positive for the cell surface markers CD90, CD105, and CD29, but not CD31. In three in vitro ischemic-mimicking injury models, HP-AT-MSCs Selleckchem EPZ5676 significantly increased both the viability of NSCs-DsRed and the expression of DsRed and clearly reduced the number of annexin-V-positive apoptotic NSCs-DsRed and the expression of the apoptotic factor Box. Consistent with the in vitro assay, co-transplantation of NSCs-DsRed with HP-AT-MSCs significantly improved the survival of the NSCs-DsRed, resulting in an increased expression of the DsRed reporter

gene at the transplantation site in a rat spinal cord injury (SCI) model. These findings suggest that the co-transplantation of HP-AT-MSCs with engineered NSCs can improve both the cell survival and the gene expression of the engineered NSCs, indicating that this novel strategy can be used to augment the therapeutic efficacy of combined stem cell and gene therapies for SCI. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Infection of host cells with human cytomegalovirus (HCMV) induces cell cycle dysregulation. Two HCMV immediate-early (IE) proteins, IE1-72 and IE2-86, are promiscuous transactivators that have been implicated Chorioepithelioma in the dysregulatory events. Cellular p53 protein is accumulated to high levels in HCMV-infected cells, but the indicative marker of p53 transcriptional activity, p21, is markedly decreased. Both IE1-72 and IE2-86 were able to transactivate the p53 promoter and interact with p53 protein in DNA-transfected or HCMV-infected cells. HCMV UL84, a multiregulatory protein expressed in early periods of HCMV infection, also interacted with p53. HCMV IE1-72 prevented or disrupted p53 binding to p53-specific DNA sequences, while IE2-86 and/or UL84 enhanced p53 binding and induced supershift of this DNA-protein complex.

PGs have been implicated in bone resorption associated with infla

PGs have been implicated in bone resorption associated with inflammation and metastatic bone disease, and also in bone formation associated with fracture healing and heterotopic ossification. Recent studies have identified roles for inducible cyclooxygenase (COX)-2 and PGE2 receptors in these processes. Although the effects of PGs have been most often associated with cAMP production and protein kinase A activation, PGs can engage an extensive G-protein signaling network. Further analysis of COX-2 and PG receptors and their downstream G-protein signaling in bone could provide important clues

to BIBW2992 the regulation of skeletal cell growth in both health and disease.”
“The New York City terrorist attacks on Sept 11, 2001 (9/11), killed nearly 2800 people and thousands more had subsequent health problems. In this Review

of health effects in the short and medium terms, strong evidence is provided for associations between experiencing or witnessing events related to 9/11 and post-traumatic stress disorder and respiratory illness, with a correlation between prolonged, intense exposure and increased overall illness and disability. Rescue and recovery workers, especially those who arrived early at the World Trade Center site or worked for longer periods, were more likely to develop respiratory illness than were other BMS202 exposed groups. Risk factors for post-traumatic stress disorder included proximity to the site on 9/11,

living or working in lower Manhattan, rescue or recovery work Resminostat at the World Trade Center site, event-related loss of spouse, and low social support. Investigators note associations between 9/11 exposures and additional disorders, such as depression and substance use; however, for some health problems association with exposures related to 9/11 is unclear.”
“This is the case report of RB, a 68-year-old retired woman who, following an extensive right sided ischaemic stroke, showed hemiplegia, anosognosia and allochiria, but no somato-sensory deficits and no visuospatial neglect. A high resolution 3D MRI structural scan of her brain was acquired to define the structural damage in detail. Morphometric analyses of grey and white matter data revealed a large lesion which involved most of her right parietal, temporal, and mesial frontal cortex, with partial sparing of the right dorsolateral prefrontal cortex and part of the posterior corpus callosum. Detailed examination showed that RB attributed sensory stimuli, both on the left and on the right, to the opposite side of her body. This mirror reversed representation of her body caused misattribution of items even in the absence of stimulation, as for instance when the patient spontaneously reported pain in her right knee while pointing to her left knee. RB’s neuropsychological profile showed normal or borderline performance on most cognitive tasks.

Consistent with the previous findings in healthy participants, th

Consistent with the previous findings in healthy participants, these findings suggest that the broad cortical network, including the prefrontal, premotor, supplementary motor, and parietal cortical areas in both hemispheres, was essential for balance control even in poststroke patients. NeuroReport 23:314-319 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“A one-step real-time RT-PCR assay using a minor

groove binding probe was developed for the specific detection of Chinese wild-type classical swine fever virus (CSFV). The assay detected wild-type I-BET-762 molecular weight CSFV strains representing different genotypes, but did not amplify viral RNA from the Hog Cholera Lipinized Virus (HCLV) vaccine-strain and other porcine viruses. The assay had a detection limit of 10 copies/reaction or 3.0 median tissue culture infective dose/reaction. OSI-027 purchase In comparison to the sequencing

nested RT-PCR assay, the sensitivity and specificity of the assay were 98.3% and 94.3%. respectively, when testing 515 veterinary samples. Wild-type CSFV RNA was detected in nasal swabs 2-4 days before detection in serum samples from pigs exposed to infection by contact. and 2-4 days prior to the onset of clinical disease. HCLV RNA remained undetectable in nasal swabs and serum samples from vaccinated pigs. In conclusion, the novel assay described in this study provides a rapid and sensitive method for differentiating between wild-type and the HCLV-strain of CSFV. It could be used for monitoring in CSF outbreak

areas or as a screening method for CSFV eradication strategies. (C) 2011 Elsevier B.V. Wilson disease protein All rights reserved.”
“Rationale Many antipsychotics cause orthostatic hypotension possibly due to antagonist action on resistance vessel alpha(1A)-adrenoceptors (alpha(1A)-AR).

Objective We have tested this possibility by determining in Wistar rats how the orthostatic hypotensive effect of several antipsychotic drugs compares with their affinity for adrenoceptors in mesenteric small arteries (MSA with mainly alpha(1A)-AR) and aorta ( mainly alpha(1D)-AR).

Materials and methods Using a tilt setup, orthostatic hypotension was measured in anaesthetized rats for prazosin and the antipsychotics haloperidol, sertindole, risperidone, clozapine, ziprasidone, domperidone, olanzapine, and aripiprazole. For in vitro studies, segments of MSA and aorta were mounted on a wire myograph for isometric tension recording. Cumulative concentration-response curves were constructed to phenylephrine ( PE) in the absence and presence of the drugs. Apparent affinity (pA(2)) was calculated by Schild analysis.

Results Prazosin antagonized tilt-induced and PE responses in both studies ( threshold 4 ng/ml, pA(2) 9.52 MSA, 10.1 aorta).

The index of effectiveness of thermoregulation (a numerical ratin

The index of effectiveness of thermoregulation (a numerical rating of thermoregulatory activity) was not different among Sirolimus size groups of dragons. However, the index of closeness of thermoregulation, which rates the variability of body temperature, suggests a greater precision for regulating a preferred body temperature for medium compared to small and large dragons. Reference copper cylinders simulating small, medium and large Komodo dragons heated and cooled at the same rate, whereas actual dragons of all size groups heated faster than they cooled. Larger dragons heated and cooled more slowly than smaller ones. The mean operative environmental temperatures of copper cylinders representing medium sized

dragons were 42.5, 32.0 and 29.4 degrees C for savannah, forest and mangrove habitats, respectively. The index for average thermal quality of a habitat as measured by FK506 concentration the absolute difference between operative

environmental temperature and the dragon’s thermal range suggests the forest habitat offers the highest thermal quality to dragons and the savannah the lowest. The percent of total daytime that the operative environmental temperature was within the central 50% of the body temperatures selected by dragons in a thermal gradient (Phillips, 1984) was 45%, 15%, and 9% for forest, mangrove and savannah, respectively. Forest habitat offers the most suitable thermal environment and provides the greatest number of hours with conditions falling within the dragon’s thermal

activity zone. (C) 2010 Elsevier Ltd. All rights reserved.”
“The molecular mechanisms underlying MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced dopaminergic (DAergic) neuronal death in vivo are still not fully understood. To investigate Clomifene the selective DAergic neurotoxicity, we have developed an immunological technique to isolate DAergic synaptosomes from mouse striatal tissues using an antibody against 20 amino acid residues in the extracellular second loop of dopamine transporter (DAT). The DAT protein level in the isolated DAergic synaptosomes was markedly decreased at 16 h after a single injection of 30 mg/kg MPTP, but not in striatal homogenate and crude synaptosomes fraction. GBR-12909, a dopamine uptake inhibitor, completely reversed the MPTP-induced decrease of DAT protein in the DAergic synaptosomes. These results suggest that the isolated DAergic synaptosomes can be useful to identify mechanisms of loss of the nerve terminals. (c) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“The combined thermal load created by exercise and a hot environment is associated with an exaggerated core temperature response. The elevated core temperature is believed to increase the total stress of the exercise. Increased stress during exercise has been associated with increased levels of cortisol. The association of cortisol with increased inflammatory responses following exercise in the heat is equivocal.

Experimental data suggest that fibrates have anti-inflammatory pr

Experimental data suggest that fibrates have anti-inflammatory properties, and PPAR alpha is essential for the differentiation of endothelial progenitor cells (EPC) which diminished pool in rheumatoid arthritis (RA) contributes to accelerated atherosclerosis. The data on fibrates’ effects in patients with RA are limited. The aim of this study was to investigate changes

in disease activity, inflammatory markers, lipid VS-4718 in vitro profile, and circulating EPC in active RA patients treated with fenofibrate. Twenty-seven patients with active RA taking traditional disease-modifying antirheumatic drugs (DMARDs) were prescribed fenofibrate (145 mg/day) for 3 months. All patients received background traditional DMARDs in stable doses. The outcomes measured were clinical disease activity variables, circulating cytokines, adipokines, lipids, and EPC. Twenty-five patients completed the Selleck CP673451 study. At the end of treatment, there was a significant reduction in DAS28, all individual DAS28 components except tender joint count, the duration of morning stiffness, and in the patient’s assessment of disease activity. Fifteen (60 %) patients achieved good/moderate EULAR response, while 10 (40 %) patients satisfied ACR20 response criteria. Treatment with fenofibrate resulted in significant decrease in CRP and IL-6 concentrations and improvement in lipid profile. There was no change in

the concentrations of circulating EPC. In conclusion, fenofibrate treatment is associated with reduced inflammation and improved lipid profile in RA patients. Large randomized controlled studies are needed to confirm these results and to define the role of fibrates in the treatment for RA.”
“The aim of this study was to investigate the percentage

of regulatory T cells and the correlation Loperamide with clinical activity in Beh double dagger et’s disease. Forty Beh double dagger et’s disease (BD) patients, 18 males and 22 females, were included in the study. The patients were diagnosed according to the published BD criteria. Twenty age- and sex-matched volunteer healthy donors were also included. At the time of sampling, clinical activity was assessed for activity signs and symptoms according to the BD Current Activity Form. We considered active those patients with a clinical activity index equal to and/or above 2. Eleven patients had active disease and the remaining were considered as clinically inactive. We have studied the percentages of CD4+CD25+FOXP3+, CD4+CD25+ and CD4+FOXP3+regulatory T cells by flow cytometry and investigated the correlation with disease activity. Percentage of CD4+CD25+FOXP3+Treg in active patients was lower than clinically inactive patients and healthy controls. Percentage of CD4+CD25+Treg was not different between active and inactive patients and healthy controls.

12 (95% confidence interval [CI], 0 87 to 1 44) for a BMI of 25 0

12 (95% confidence interval [CI], 0.87 to 1.44) for a BMI of 25.0 to 27.4, 1.31 (95% CI, 1.01 to 1.72) for a BMI of 27.5 to 29.9, 1.27 (95% CI, 0.99 to 1.64) for a BMI of 30.0 to 34.9, 1.51 (95% CI, 1.13 to 2.02) for a BMI of 35.0 to 39.9, and 2.19 SHP099 (95% CI, 1.62 to 2.95) for a BMI of 40.0 to 49.9 (P < 0.001 for trend). A large waist circumference was associated with an increased risk of death from any cause among women with a BMI of less than 30.0.


The risk of death from

any cause among black women increased with an increasing BMI of 25.0 or higher, which is similar to the pattern observed among whites. Waist circumference appeared to be associated with an increased risk of death only among nonobese women. (Funded by

the National Cancer Institute.)”

In 2009, Blue Cross Blue Shield of Massachusetts (BCBS) implemented a global payment system called the Alternative Quality Contract (AQC). Provider groups in the AQC system assume accountability for spending, similar to accountable care organizations that bear financial risk. Moreover, groups are eligible to receive bonuses for quality.


Seven provider organizations began 5-year contracts as part of the AQC system in 2009. We analyzed 2006-2009 claims for 380,142 enrollees whose primary care physicians (PCPs) were in the AQC system (intervention group) and for 1,351,446 enrollees whose PCPs were not EPZ5676 concentration in the system (control group). We used a propensity-weighted difference-in-differences approach, adjusting for age, sex, health status,

and secular trends to isolate the treatment effect of the AQC in comparisons of spending and quality between the intervention group and the control group.


Average spending increased for enrollees in both the intervention and control groups in 2009, but the increase was smaller for enrollees in the intervention group $15.51 (1.9%) less per quarter (P = 0.007). Savings derived largely from shifts in outpatient care toward facilities enough with lower fees; from lower expenditures for procedures, imaging, and testing; and from a reduction in spending for enrollees with the highest expected spending. The AQC system was associated with an improvement in performance on measures of the quality of the management of chronic conditions in adults (P < 0.001) and of pediatric care (P = 0.001), but not of adult preventive care. All AQC groups met 2009 budget targets and earned surpluses. Total BCBS payments to AQC groups, including bonuses for quality, are likely to have exceeded the estimated savings in year 1.


The AQC system was associated with a modest slowing of spending growth and improved quality of care in 2009. Savings were achieved through changes in referral patterns rather than through changes in utilization. The long-term effect of the AQC system on spending growth depends on future budget targets and providers’ ability to further improve efficiencies in practice.