Life satisfaction of multicultural married couples: Actor-Partner Interdependence Model analysis.

We aimed to identify the actor and partner effects of health status, relationship satisfaction, and depression on the life satisfaction of married immigrant women and their husbands in South Korea. We used a cross-sectional design that included 2865 multicultural married couples with data from the 2015 national survey of multicultural families in Korea. We analyzed the data using path analyses within the Actor-Partner Interdependence Model (APIM) framework. Health status, depression, and relationship satisfaction had actor effects in both wives and husbands, while depression had no partner effects on either. Health status had partner effects only for wives, and relationship satisfaction had partner effects for both husbands and wives. Given that factors influencing life satisfaction differed in couples and since those with depression and poor health were more susceptible to lower life satisfaction, it is essential to introduce efforts to prevent depression and improve relationships considering differences of partner effects.

Experts' perspectives on the role of medical marijuana in oncology: A semistructured interview study.

BACKGROUND: Expansion of medical marijuana (MM) laws in the United States may offer oncology new therapeutic options. However, the scientific evidence for MM remains in infancy. This study qualitatively explored professional opinion around the role of MM in cancer care. METHODS: Semistructured interviews were administered to a sample of individuals with expertise at the interface of MM and oncology nationally. Key informant criteria included an oncologic clinical or research background and any of the following: publications, research, or lectures on cannabinoids or cancer symptoms; involvement in the development of MM dispensaries or legislation; and early adoption of state MM certification procedures. A gold standard, grounded, inductive approach was used to identify underlying themes. RESULTS: Participants (N = 15) were predominantly male, in their sixth decade, working in academic settings. Themes ranged from strong beliefs in marijuana's medical utility to reservations about this notion, with calls for expansion of the scientific evidence base and more stringent MM production standards. All participants cited nausea as an appropriate indication, and 13 of 15 pain. Over one-third believed MM to have a more attractive risk profile than opioids and benzodiazepines. CONCLUSIONS: Expert opinion was divided between convictions in marijuana's medicinal potential and guardedness in this assertion, with no participant refuting MM's utility outright. Emergent themes included that MM ameliorates cancer-related pain and nausea and is safer than certain conventional medications. Participants called for enhanced purity and production standards, and further research on MM's utility.

Impact of hospitalization on medication adherence estimation in claims data.

WHAT IS KNOWN AND OBJECTIVE: Pharmacy claims are commonly used to assess medication adherence. It is unclear how different approaches to handling hospitalizations compare to the gold standard of using outpatient and inpatient drug data. This study aimed to compare the impact of different approaches to handling hospitalizations on medication adherence estimation in administrative claims data. METHODS: We identified ß-blocker initiators after myocardial infarction (MI) and statin initiators regardless of hospitalization histories in the population-based, Taiwan database, which includes outpatient and inpatient drug claims data. Adherence to ß-blockers or to statins during a 365-day follow-up period was estimated in outpatient pharmacy claims using the proportion of days covered (PDC) in three ways: ignoring hospitalizations (PDC1); subtracting hospitalized days from the denominator (PDC2); and assuming drug use on all hospitalized days (PDC3). We compared these to an approach that incorporated inpatient drug use (PDC4). We also used a hypothetical example to examine variations across approaches in several scenarios, such as increasing hospitalized days. RESULTS AND DISCUSSION: Mean 365-day PDC was 74% among 1729 post-MI ß-blocker initiators (range: 73.1%-74.9%) and 44% among 69 435 statins initiators (range: 43.5%-44.0%), which varied little across approaches. Differences across approaches increased with increasing number of hospitalized days. For patients hospitalized for >28 days, mean difference across approaches was >15%. PDC3 consistently yielded the highest value and PDC1 the lowest. WHAT IS NEW AND CONCLUSIONS: On average, different approaches to handling hospitalizations lead to similar adherence estimates to the gold standard of incorporating inpatient drug use. When patients have many hospitalization days during follow-up, the choice of approach should be tailored to the specific setting.

The von Hippel-Lindau tumour suppressor gene: uncovering the expression of the pVHL172 isoform.

BACKGROUND: The von Hippel-Lindau (VHL) gene encodes two mRNA variants. Variant 1 encodes two protein isoforms, pVHL213 and pVHL160, that have been extensively documented in the literature. Variant 2 is produced by alternative splicing of exon 2 and encodes a pVHL isoform of 172 amino acids with a theoretical molecular weight of 19 kDa (pVHL172), the expression of which has never been demonstrated so far due to the absence of suitable antibodies. METHODS: We have generated an anti-pVHL monoclonal antibody (JD-1956) using pVHL172 recombinant protein. We tested the antibody against exogenous or endogenous expressed proteins in different cell lines. We identified the pVHL172 using a silencing RNA strategy. The epitope of the antibody was mapped using a peptide array. RESULTS: We efficiently detected the three different isoforms of pVHL in cell lines and tumorigenic tissues by western blotting and immunohistochemistry and confirmed for the first time the endogenous expression of pVHL172. CONCLUSIONS: The endogenous expression of the three isoforms and particularly the pVHL172 has never been shown before due to a lack of a highly specific antibody since none of the available commercial antibodies distinguish the three isoforms of pVHL in cells or in both normal and cancerous human tissues. Evidence of pVHL172 expression emphasises the need to further study its implication in renal tumorigenesis and VHL disease.

Risk of death associated with the use of conventional vs. atypical antipsychotic medications: evaluating the use of the Emilia-Romagna Region database for pharmacoepidemiological studies.

WHAT IS KNOWN AND OBJECTIVE: Since 2005, a mounting base of evidence has identified that conventional antipsychotic medications are associated with an increased risk of mortality among elderly patients when compared to atypical antipsychotics. This study sought to explore the feasibility of using the Emilia-Romagna Region (RER) database for comparative safety analyses by replicating and refining risk estimates of this well-known drug safety example through meta-analysis. METHODS: We identified a cohort of 23 681 Italian RER patients (aged ≥65) who initiated treatment with a conventional or atypical antipsychotic between 1 July 2009 and 30 June 2011. We compared 180-day mortality using Cox proportional hazards models adjusted for risk factors for death, use of other medications and measures of health services utilization intensity, all measured before antipsychotic initiation. We conducted a meta-analysis of studies with similar methods against which to compare our results. RESULTS: Among 14 462 and 9219 patients prescribed conventional and atypical antipsychotics, respectively, we observed 2402 (16·6%) and 821 (8·9%) deaths during follow-up. Conventional antipsychotic initiators were older and generally had higher prevalence of outcome risk factors and higher baseline health service use intensity. The crude hazard ratio (HR) was 1·95 [95% confidence interval (CI), 1·80-2·11], which decreased to 1·47 (95% CI, 1·35-1·60) after full adjustment. We identified seven published studies that examined this association using similar methods. The pooled HR from these studies was 1·34 (95% CI, 1·28-1·39). Including our study, the meta-analysis yielded a summary estimate of 1·35 (95% CI, 1·31-1·40) and did not introduce any heterogeneity (I(2)  = 0%; P = 0·455). WHAT IS NEW AND CONCLUSIONS: Our results support the use of the RER database for pharmacoepidemiological studies and provide an up-to-date and pooled estimate of the magnitude of the association between mortality and conventional vs. atypical antipsychotics.

Impact of ALLHAT publication on antihypertensive prescribing patterns in Regione Emilia-Romagna, Italy.

BACKGROUND AND OBJECTIVE: Studies from the US and Canada observed changes in antihypertensive prescribing patterns in accordance with Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study findings immediately after the study's publication, but little is known about the impact of ALLHAT in Italy. The objective of this study was to examine antihypertensive prescribing patterns in Regione Emilia-Romagna (RER), Italy, following the publication of the ALLHAT main results. METHODS: We conducted a time series analysis using automated pharmacy data of approximately 4 million RER residents between 1 January 2000 and 31 December 2003. We computed monthly relative percentages of prescriptions for all antihypertensive medications and separately for all new antihypertensives defined as no recorded antihypertensive use in the previous year. A stepwise auto-regressive forecasting model based on data prior to the ALLHAT publication was used to estimate predicted relative percentages for the 12 months following the ALLHAT publication. Observed and predicted values were compared. RESULTS AND DISCUSSION: Use of thiazide-type diuretics showed a general increasing trend over the study period, but the difference between the observed and predicted values reached statistical significance only for new prescriptions in October 2003 (3.71% vs. 2.32%; P = 0.0170). The relative percentage of new angiotensin-converting enzyme inhibitor and angiotensin receptor blocker (ACE/ARB) prescriptions was higher than predicted for the months May to August 2003 (P < 0.05), but no significant differences were observed for total ACE/ARB prescriptions. Modest changes in patterns of prescribing of calcium channel blockers and alpha-blockers were observed. CONCLUSION: We found little evidence that the ALLHAT study had an impact on antihypertensive prescribing patterns in RER in the year following their publication.

Functional reorganization of the human auditory pathways following hemispherectomy: an fMRI demonstration.

The present study investigated the functional reorganization of ipsilateral and contralateral auditory pathways in hemispherectomized subjects. Functional reorganization was assessed using functional Magnetic Resonance Imaging (fMRI) and stimulation with complex sounds presented binaurally and monaurally. For neurologically intact control subjects, results showed that binaural stimulations evoked balanced activity in both hemispheres while monaural stimulations induced strong contralateral activity and weak ipsilateral activity. The results obtained from hemispherectomized subjects were substantially different from those obtained from control subjects. Specifically, activity in the intact hemisphere showed a significant decrease in response to contralateral stimulation but, concomitantly, an increase in response to ipsilateral stimulation. The present findings suggest that a substantial functional reorganization takes place in the auditory pathways following an early hemispherectomy. The exact nature of this functional reorganization remains to be specified.

Prevalence and predictors of potential drug-drug interactions in Regione Emilia-Romagna, Italy.

BACKGROUND AND OBJECTIVE: Drug-drug interactions (DDIs) are preventable medication errors associated with potentially serious adverse events and death. Several studies have examined the prevalence of potential DDIs among ambulatory patients in various countries. Limited recent data on the prevalence of potential DDIs in Italy are available in the medical literature. The objective of this study was to estimate the prevalence of clinically important potential DDIs among the approximately 4 million residents of Regione Emilia-Romagna (RER), Italy, and to examine possible predictors of potential DDI exposure. METHODS: A retrospective follow-up study of 2004 outpatient prescription data from RER was conducted. A previously published list of clinically important potential DDIs was refined to include only pairs of drugs in which both drugs were reimbursed by the 2004 Italian National Formulary. A potential DDI was defined as the presence of a minimum 5-day overlap in days supply for drugs in an interacting pair. The 1-year period prevalence of each potential DDI was quantified. A logistic regression analysis was conducted to examine patient characteristics as predictors of potential DDIs. RESULTS AND DISCUSSION: The list of clinically important potential DDIs included 12 drug pairs that could be captured using the RER database. These 12 potential DDIs occurred 8894 times in the RER population in 2004. The most commonly identified potentially interacting medication pairs were warfarin and non-steroidal anti-inflammatory drugs (6824 cases), theophylline/aminophylline and ciprofloxacin/fluvoxamine (930), and warfarin and barbiturates (567). Odds of exposure were highest among those aged 65 years or older, males, and those with more chronic conditions. Odds of exposure increased 1.39 times with each addition of a prescription medication. CONCLUSION: A substantial number of clinically important potential DDIs were identified, particularly among warfarin users. Awareness of the most prevalent potential DDIs can help practitioners prevent concomitant use of these dangerous medication combinations.

Time-resolved laser fluorescence spectroscopy of organic ligands by europium: Fluorescence quenching and lifetime properties.

Time-resolved Laser Fluorescence Spectroscopy (TRLFS) has proved its usefulness in the fields of biophysics, life science and geochemistry to characterize the fluorescence probe molecule with its chemical environment. The purpose of this study is to demonstrate the applicability of this powerful technique combined with Steady-State (S-S) measurements. A multi-mode factor analysis, in particular CP/PARAFAC, was used to analyze the interaction between Europium (Eu) and Humic substances (HSs) extracted from Saint Lawrence Estuary in Canada. The Saint Lawrence system is a semi-enclosed water stream with connections to the Atlantic Ocean and is an excellent natural laboratory. CP/PARAFAC applied to fluorescence S-S data allows introspecting ligands-metal interactions and the one-site 1:1 modeling gives information about the stability constants. From the spectral signatures and decay lifetimes data given by TRLFS, one can deduce the fluorescence quenching which modifies the fluorescence and discuss its mechanisms. Results indicated a relatively strong binding ability between europium and humic substances samples (LogK value varies from 3.38 to 5.08 at pH 7.00). Using the Stern-Volmer plot, it has been concluded that static and dynamic quenching takes places in the case of salicylic acid and europium interaction while for HSs interaction only a static quenching is observed.

Use of olmesartan and enteropathy outcomes: a multi-database study.

BACKGROUND: Multiple case reports suggest that olmesartan may be linked to sprue-like enteropathy; however, few epidemiological studies have examined this association and results have been mixed. AIM: To assess whether olmesartan is associated with a higher rate of enteropathy vs other angiotensin II receptor blockers (ARBs). METHODS: We conducted a cohort study among ARB initiators in 5 US claims databases representing different health insurance programmes. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for enteropathy-related outcomes, including coeliac disease, malabsorption, concomitant diagnoses of diarrhoea and weight loss, and non-infectious enteropathy, comparing olmesartan initiators to initiators of other ARBs after propensity score (PS) matching. RESULTS: We identified 1 928 469 eligible patients. The unadjusted incidence rates were 0.82, 1.41, 1.66 and 29.20 per 1000 person-years for coeliac disease, malabsorption, concomitant diagnoses of diarrhoea and weight loss, and non-infectious enteropathy respectively. HRs after PS matching comparing olmesartan to other ARBs were 1.21 (95% CI, 1.05-1.40), 1.00 (95% CI, 0.88-1.13), 1.22 (95% CI, 1.10-1.36) and 1.04 (95% CI, 1.01-1.07) for each outcome. HRs were larger for patients aged 65 years and older (eg for coeliac disease, 1.57 [95% CI, 1.20-2.05]), for patients receiving treatment for more than 1 year (1.62 [95% CI, 1.24-2.12]), and for patients receiving higher cumulative olmesartan doses (1.78 [95% CI, 1.33-2.37]). CONCLUSIONS: This large-scale, multi-database study found a higher rate of enteropathy in olmesartan initiators as compared to initiators of other ARBs, although the absolute incidence rate was low in both groups.

Province-wide population survey of acute appendicitis in Canada. New twists to an old disease.

BACKGROUND: This study, sponsored and conducted by Le Collège des Médecins du Québec, audited the management of acute appendicitis in the Province of Québec (Population 7.6 million), Canada, over a period of 1 year (April 2002-March 2003). METHODS: A questionnaire was sent to the Health Records Department of all hospitals surgically treating appendicitis in the province. Data from 85 (100%) hospitals were received and reviewed. RESULTS: During the study period, 7,599 appendectomies were performed, and 5,707 (75%) were selected for study (55% men). The rate of normal and perforated appendix was 5.4% and 15.9% respectively. Median hospital stay for simple and perforated appendicitis was 2.6 and 5.8 days, respectively. At least one imaging procedure was done in 86% of cases (23% computed tomography [CT], 55% ultrasound). Antibiotics were not given in 7% of cases and in 8% of patients with a perforation. Seventeen percent of patients did not receive preoperative or intraoperative doses, and postoperatively, 69% of patients received unnecessary doses. Laparoscopy was used in 35% of cases and was associated with a reduction in postoperative stay for simple (2.6 versus 2.9 days, p < 0.001) and perforated appendicitis (4.6 versus 5.9 days, p = 0.004). A low rate of laparoscopy (<25%) was found in 53% of teaching (University and Affiliated) and 45% of nonteaching institutions. Conversion to open surgery was necessary in 9.7% of simple appendicitis and 29.3% of perforated ones (p < 0.001). CONCLUSIONS: Although results of this survey are comparable to those of similar published series, a few concerns emerge. Many have to do with patient noncompliance with recommended antibiotic usage for acute appendicitis. Further, although laparoscopy seems to be slowly making its way into the surgical armamentarium, the low rate of laparoscopic appendectomies in teaching hospitals raises the issue of appropriate resident training.

Pharmacoepidemiologic Methods for Studying the Health Effects of Drug-Drug Interactions.

A drug-drug interaction (DDI) occurs when one or more drugs affect the pharmacokinetics (the body's effect on the drug) and/or pharmacodynamics (the drug's effect on the body) of one or more other drugs. Pharmacoepidemiologic studies are the principal way of studying the health effects of potential DDIs. This article discusses aspects of pharmacoepidemiologic research designs that are particularly salient to the design and interpretation of pharmacoepidemiologic studies of DDIs.

Severe hypoglycemia in users of sulfonylurea antidiabetic agents and antihyperlipidemics.

Drug-drug interactions causing severe hypoglycemia due to antidiabetic drugs is a major clinical and public health problem. We assessed whether sulfonylurea use with a statin or fibrate was associated with severe hypoglycemia. We conducted cohort studies of users of glyburide, glipizide, and glimepiride plus a statin or fibrate within a Medicaid population. The outcome was a validated, diagnosis-based algorithm for severe hypoglycemia. Among 592,872 persons newly exposed to a sulfonylurea+antihyperlipidemic, the incidence of severe hypoglycemia was 5.8/100 person-years. Adjusted hazard ratios (HRs) for sulfonylurea+statins were consistent with no association. Most overall HRs for sulfonylurea+fibrate were elevated, with sulfonylurea-specific adjusted HRs as large as 1.50 (95% confidence interval (CI): 1.24-1.81) for glyburide+gemfibrozil, 1.37 (95% CI: 1.11-1.69) for glipizide+gemfibrozil, and 1.63 (95% CI: 1.29-2.06) for glimepiride+fenofibrate. Concomitant therapy with a sulfonylurea and fibrate is associated with an often delayed increased rate of severe hypoglycemia.

Successful Comparison of US Food and Drug Administration Sentinel Analysis Tools to Traditional Approaches in Quantifying a Known Drug-Adverse Event Association.

The US Food and Drug Administration's Sentinel system has developed the capability to conduct active safety surveillance of marketed medical products in a large network of electronic healthcare databases. We assessed the extent to which the newly developed, semiautomated Sentinel Propensity Score Matching (PSM) tool could produce the same results as a customized protocol-driven assessment, which found an adjusted hazard ratio (HR) of 3.04 (95% confidence interval [CI], 2.81-3.27) comparing angioedema in patients initiating angiotensin-converting enzyme (ACE) inhibitors vs. beta-blockers. Using data from 13 Data Partners between 1 January 2008, and 30 September 2013, the PSM tool identified 2,211,215 eligible ACE inhibitor and 1,673,682 eligible beta-blocker initiators. The tool produced an HR of 3.14 (95% CI, 2.86-3.44). This comparison provides initial evidence that Sentinel analytic tools can produce findings similar to those produced by a highly customized protocol-driven assessment.

Demonstration of a near-IR line-referenced electro-optical laser frequency comb for precision radial velocity measurements in astronomy.

An important technique for discovering and characterizing planets beyond our solar system relies upon measurement of weak Doppler shifts in the spectra of host stars induced by the influence of orbiting planets. A recent advance has been the introduction of optical frequency combs as frequency references. Frequency combs produce a series of equally spaced reference frequencies and they offer extreme accuracy and spectral grasp that can potentially revolutionize exoplanet detection. Here we demonstrate a laser frequency comb using an alternate comb generation method based on electro-optical modulation, with the comb centre wavelength stabilized to a molecular or atomic reference. In contrast to mode-locked combs, the line spacing is readily resolvable using typical astronomical grating spectrographs. Built using commercial off-the-shelf components, the instrument is relatively simple and reliable. Proof of concept experiments operated at near-infrared wavelengths were carried out at the NASA Infrared Telescope Facility and the Keck-II telescope.

Binding properties of glutamate receptors in streptozotocin-induced diabetes in rats.

The biochemical mechanisms by which diabetes modulates cognitive function are not well established. Here, we determined the effects of streptozotocin (STZ) administration on the binding properties of alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) subtypes of glutamate receptors in rats, using quantitative autoradiographic analysis of (3)H-AMPA and [(3)H]glutamate binding on brain tissue sections. The STZ injection (70 mg/kg intraperitoneally) produced a reduction of (3)H-AMPA binding in various brain regions, an effect that is due to a decrease in receptor affinity. The STZ-induced reduction of (3)H-AMPA binding varied in different brain structures, being more pronounced in the striatum, cerebral cortex, and hippocampus and almost absent in the cerebellum. Western blots performed on hippocampal membranes revealed that the decrease in (3)H-AMPA binding is possibly associated with changes in immunologic properties for one glutamate receptor subunit (GluR1). Finally, the effect of STZ-induced diabetes appeared to be specific to the AMPA subtype of glutamate receptors, as the same treatment did not modify [(3)H]glutamate binding to NMDA receptors. These changes in AMPA receptor properties may have important implications for understanding the biochemical mechanisms underlying cognitive impairment in diabetes.

Laparoscopic colon surgery performed safely by general surgeons in a community hospital: a review of 154 consecutive cases.

BACKGROUND: The primary end point of this study was documentation of the feasibility, safety, and benefits of laparoscopic colon resection (LCR) performed by general surgeons in a community hospital. METHODS: The charts of 154 patients who underwent LCR between March 1998 and August 2003 by a group of three surgeons working in a community hospital were reviewed. Data extracted from the charts included patients' demographics, surgical indications and procedures, conversion rate, history, operative time, postoperative recovery time, and complication rates. RESULTS: Of the 154 patients, 70 were men. The mean age of the patients was 60 years. Overall, 62% of the patients had a history of prior abdominal surgery. In the majority of cases (77%), LCR was performed for benign disease. Segmental resection involving the left colon was performed for 122 patients, and right hemicolectomy was performed for 32 patients. The rates of conversion were 9.6% for open surgery and 12% for diverticulitis (n = 83). For LCR, the median operative time was 120 min, and the median hospital stay was 5 days. The complication rate was 21.6% for LCR, and the mortality rate was 2.1%. CONCLUSION: The outcomes for LCR performed by a team of general surgeons working together in a community hospital are similar to the historical results from academic health science centers.

Presensitization and the renal allograft recipient.

We examined data from the New England Organ Bank to characterize the influence of patient sensitization on allograft survival, and our current crossmatching strategy. To evaluate our recipient eligibility criteria, we compared computer-predicted crossmatch results to 3622 actual crossmatches. A computer-predicted positive crossmatch was highly predictive of an actual positive crossmatch, for patients with a percentage reactive antibody of 40% of more (positive predictive value 91-99%), thus obviating the need to perform the actual crossmatch. Given the high prevalence of sensitized patients on our waiting list, very few individuals are inappropriately excluded from consideration for an available organ. In contrast, a negative computer prediction was never sufficiently predictive of a negative crossmatch to dispense with the actual crossmatching procedure. We also compared graft survival in patients with positive antidonor crossmatches using historical (greater than 6 months old) sera with those with negative historical crossmatches (or with no history of humoral sensitization). One-year actuarial graft survival in the first group was 61.0 +/- 6.0%, compared with 85.2 +/- 1.4% in those without positive historical crossmatches (P less than 0.001). This adverse effect of a positive historical crossmatch was true in both first transplants (n = 41, 1-year graft survival 67.9 +/- 7.4% vs. 86.2 +/- 1.6%, P less than 0.05) and in regrafted individuals (n = 29, 1-year graft survival 50.7 +/- 9.8% vs. 78.9 +/- 3.7%, P less than 0.01). The inability to accurately predict negative crossmatches, and the possible adverse effect of positive historical crossmatches on graft survival, represent potential obstacles to a goal of national organ sharing.

Cholinergic systems and long-term potentiation in memory-impaired apolipoprotein E-deficient mice.

Impairments in cholinergic neurotransmitter systems of the basal forebrain are a hallmark of Alzheimer's disease pathophysiology. The presence of the epsilon4 allele of apolipoprotein E was recently implicated as a major risk factor in both familial and sporadic Alzheimer's disease. The present study examined the integrity of cholinergic and non-cholinergic systems in apolipoprotein E-deficient, memory-impaired mice. Choline acetyltransferase activity, hippocampal acetylcholine release, nicotinic and muscarinic (M1 and M2) receptor binding sites and acetylcholinesterase cell or terminal density showed no signs of alteration in either three-month or 9.5-month-old apolipoprotein E-deficient mice compared to controls. In contrast, long-term potentiation was found to be markedly reduced in these mice, but increases in the strength of stimulation induced the same level of long-term potentiation as that observed in controls. These alterations did not appear to be the consequence of modifications in the binding properties of glutamatergic receptors (N-methyl-D-aspartate and [RS]-alpha-amino-3-hydroxy-5-methylisoxazole propionic acid) but from defective regulation of the (RS)-alpha-amino-3-hydroxy-5-methylisoxazole propionic acid receptor by phospholipase A2 activity. These results support the notion that apolipoprotein E plays a fundamental role in neuronal plasticity, which could in turn affect cognitive performance through imbalances in extra- and intracellular lipid homeostasis.