Serum NGAL can act as an early renal safety biomarker during long-term nucleos(t)ide analogue antiviral therapy in chronic hepatitis B.

Tubular renal toxicity is a side-effect of long-term therapy with nucleos(t)ide analogue(s) (NA) in chronic hepatitis B (CHB). There are no established surrogate markers in plasma of early NA-related toxicity. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein produced by tubular cells following renal damage. We aimed therefore to retrospectively compare conventional renal markers (estimated glomerular filtration rates (eGFR) and urinary protein/creatinine ratio uPCR) with a sensitive biomarker (NGAL) in CHB patients on long-term NA therapy and assess the ability of new markers to predict NA-related renal toxicity (new onset of nonalbumin proteinuria). A total of 192 naïve CHB patients (median age 41 years, 78% males, 25% HBeAg+, 35% cirrhosis) were NA treated for at least 5 years (median 8.34 years, range 5.54-11.1 years). The eGFR and uPCR were compared at baseline and last clinical visit with serum NGAL concentrations measured by ELISA at same time-points and assessed according to the presence/absence of nonalbumin proteinuria at last visit. While baseline and last visit eGFR were similar (median:78 vs 84 mL/min), serum NGAL concentrations increased during therapy (median:9.4 vs 16.4 ng/mL, P < .05). The proportion of patients with proteinuria (uPCR > 15) increased between baseline and last visit (4.6% vs 21.4%, P < .05), with 30 (16%) patients having de novo nonalbumin proteinuria at last visit. High baseline NGAL concentrations were exclusive to patients with de novo nonalbumin proteinuria (median:31.7 vs 7.8 ng/mL, P < .01) and baseline NGAL levels >25 mg/mL were predictive of nonalbumin proteinuria at last visit (AUROC = 0.813). In conclusion, serum NGAL can act as a surrogate marker of early renal injury (de novo nonalbumin proteinuria) in CHB on long-term NA therapy.

HBsAg plasma level kinetics: a new role for an old marker as a therapy response predictor in vertically infected children on combination therapy.

We aimed to investigate the ability of HBsAg plasma level kinetics to predict therapy response by studying 23 children with infancy-acquired chronic hepatitis B (CHB) during combination sequential therapy with lead-in lamivudine (LAM) and add-on interferon-α (IFN-α) [5 responders (R = anti-HBs seroconversion) and 18 nonresponders (NR)] and to assess their relationship with pretreatment intrahepatic HBV-DNA and cccDNA and HBsAg and HBcAg liver expression. Plasma HBsAg levels were measured in samples before (treatment week 0 = TW0), during (TW9, TW28, TW52) and after (follow-up week = FUW24) therapy by Abbott ARCHITECT(®) assay [log10 IU/mL]. Baseline liver HBV-DNA and cccDNA were quantified by real-time TaqMan PCR [log10 copies/ng genomic DNA]. HBsAg and HBcAg liver expression was evaluated by immunostaining of formalin-fixed, paraffin-embedded specimens [number of positive cells/1000 hepatocytes]. All results are presented as medians. Plasma: at baseline, on-treatment and during follow-up, HBsAg levels were lower in R than NR (TW0: 4.36 vs 4.75;TW28: 2.44 vs 4.35;TW52: 0 vs 4.08 and FUW24: 0.17 vs 4.35, all P < 0.05). Liver: baseline HBV-DNA (3.82 vs 4.71, P = 0.16) and cccDNA (1.98 vs 2.26, P = 0.18) tended to be lower in R than NR, HBsAg expression was lower in R than NR (0.5 vs 4.7, P = 0.03), and HBcAg expression was similar between R and NR. There were positive correlations between plasma HBsAg levels and liver HBV-DNA (r = 0.44, P = 0.04), cccDNA (r = 0.41, P = 0.04) and HBsAg liver expression (r = 0.38, P = 0.05). Lower baseline HBsAg plasma levels, lower HBsAg expression in liver and on-treatment decline of plasma HBsAg levels heralds HBsAg clearance and response to treatment in tolerant children with CHB.

Identification and complete genome analysis of a virus variant or putative new foveavirus associated with apple green crinkle disease.

A virus identified as "apple green crinkle associated virus" (AGCaV) was isolated from Aurora Golden Gala apple showing severe symptoms of green crinkle disease. Evidence was obtained of a potential causal relationship to the disease. The viral genome consists of 9266 nucleotides, excluding the poly(A) tail at the 3'-terminus. It has a genome organization similar to that of members of the species Apple stem pitting virus (ASPV), the type species of the genus Foveavirus, family Betaflexiviridae. ORF1 of AGCaV encodes a replicase-complex polyprotein with a molecular mass of 247 kDa; the proteins of ORFs 2, 3, and 4 (TGB proteins) are estimated to be 25.1 kDa, 12.8 kDa, and 7.4 kDa, respectively; and ORF5 encodes the CP, with an estimated molecular mass of 43.3 kDa. Interestingly, AGCaV utilizes different stop codons for ORF1, ORF3, and ORF5 compared to the ASPV type isolate PA66, and between the two viruses, six distinct indel events were observed within ORF5. AGCaV has four non-coding regions (NCRs), including a 5'-NCR (60 nt), a 3'-NCR (134 nt), and two intergenic (IG) NCRs: IG-NCR1 (69 nt) and IG-NCR2 (91 nt). A conserved stable hairpin structure was identified in the variable 5'-NCR of members of the genus Foveavirus. AGCaV may be a variant or strain of ASPV with unique biological properties, but there is evidence that it may be a distinct putative foveavirus.

Synthetic biology as driver for the biologization of materials sciences.

Materials in nature have fascinating properties that serve as a continuous source of inspiration for materials scientists. Accordingly, bio-mimetic and bio-inspired approaches have yielded remarkable structural and functional materials for a plethora of applications. Despite these advances, many properties of natural materials remain challenging or yet impossible to incorporate into synthetic materials. Natural materials are produced by living cells, which sense and process environmental cues and conditions by means of signaling and genetic programs, thereby controlling the biosynthesis, remodeling, functionalization, or degradation of the natural material. In this context, synthetic biology offers unique opportunities in materials sciences by providing direct access to the rational engineering of how a cell senses and processes environmental information and translates them into the properties and functions of materials. Here, we identify and review two main directions by which synthetic biology can be harnessed to provide new impulses for the biologization of the materials sciences: first, the engineering of cells to produce precursors for the subsequent synthesis of materials. This includes materials that are otherwise produced from petrochemical resources, but also materials where the bio-produced substances contribute unique properties and functions not existing in traditional materials. Second, engineered living materials that are formed or assembled by cells or in which cells contribute specific functions while remaining an integral part of the living composite material. We finally provide a perspective of future scientific directions of this promising area of research and discuss science policy that would be required to support research and development in this field.

Reactivation of latent hepatitis B virus infection with HIV-related immunosuppression.

The effect of HIV-related immunosuppression and antiretroviral therapy on the reactivation of latent hepatitis B virus (HBV) infection is unclear. We report four patients with advanced HIV-related immunosuppression and abnormal liver function tests who had evidence of HBV reactivation. Reclearance of hepatitis B occurred in two cases with HIV treatment regimens not containing lamivudine, suggesting that improved immune function may be responsible. In three cases, HBV reactivation was recognized during investigation for abnormal liver function initially attributed to drug toxicity. The possibility of HBV reactivation must be considered in the differential diagnosis of abnormal liver function in cases with advanced HIV.

Chronic ursodeoxycholic acid- and chenodeoxycholic acid-feeding-induced changes of colon mucosal cell proliferation in rats.

Hyperproliferation has been suggested to play a major role in bile acid-dependent colorectal tumor promotion. Effects of chronic feeding of chenodeoxycholic acid (CDC) and ursodeoxycholic acid (UDC) were tested on cell proliferation in the colon of male noninbred Wistar rats. By use of a dynamic method measuring actual rates of cell production, proliferation was modulated by both bile acids only in the proximal part of the colon. UDC feeding produced mild hyperproliferation of basal crypt cells (cell position 5-8: 7.6 +/- 2.0 vs. 3.5 +/- 1.3 cells/1,000 cells/hr--P less than .05; cell position 9-12: 18.1 +/- 10.7 vs. 10.3 +/- 2.9--P less than .05; cell position 13-16: 18.1 +/- 8.9 vs. 9.1 +/- 2.3--P less than .05). This finding reflected a characteristic compensatory response to superficial cell damage. However, CDC application did not effect cell regeneration in this crypt area but led to a striking drop of cell renewal in higher crypt cell positions (positions greater than or equal to 17), where no proliferation was detectable. These data suggest that CDC exerts its tumor-promoting effect by other means than hyperproliferation.

Genetic analysis of punt, a type II Dpp receptor that functions throughout the Drosophila melanogaster life cycle.

TGF-beta (transforming growth factor-beta-) mediated signal transduction affects growth and patterning in a variety of organisms. Here we report a genetic characterization of the Drosophila punt gene that encodes a type II serine/threonine kinase TGF-beta/Dpp (Decapentaplegic) receptor. Although the punt gene was originally identified based on its requirement for embryonic dorsal closure, we have documented multiple periods of punt activity throughout the Drosophila life cycle. We demonstrate that potentially related embryonic punt phenotypes, defects in dorsoventral patterning and dorsal closure, correspond to distinct maternal and zygotic requirements for punt. In addition, we document postembryonic requirements for punt activity. The tight correspondence between both embryonic and postembryonic loss-of-function punt and dpp phenotypes implicates a role for Punt in mediating virtually all Dpp signaling events in Drosophila. Finally, our comparison of punt homoallelic and heteroallelic phenotypes provides direct evidence for interallelic complementation. Taken together, these results suggest that the Punt protein functions as a dimer or higher order multimer throughout the Drosophila life cycle.

Declarative and procedural memory functioning in abstinent cocaine abusers.

BACKGROUND: We determined the nature and recovery of procedural and declarative memory functioning in a cocaine-abusing cohort in the 45-day period following use. METHODS: Thirty-seven cocaine abusers and 27 control subjects were administered the following memory and mood measures: California Verbal Learning Test, recall of the Rey-Osterrieth Complex Figure Test, Pursuit Rotor Task, and Profile of Mood States at 4 visits (within 72 hours of admission and at 10, 21, and 45 days following abstinence). RESULTS: Analysis of performance on the Rey-Osterrieth Complex Figure Test revealed that both groups improved in their recall over repeated administrations, though the control group recalled significantly more of the information than cocaine subjects during the 45-day interval. Results for the California Verbal Learning Test indicated improved learning for both subject groups over time, but no group x time interaction. On the Pursuit Rotor Task, cocaine abusers improved their performance at a faster rate than controls at visit 1. At day 45 (visit 4), cocaine abusers again showed improvement on the Pursuit Rotor Task, whereas controls demonstrated a relative plateau in rate of learning. CONCLUSIONS: This study documented a lasting detrimental effect on a sensitive nonverbal declarative memory task in cocaine-dependent subjects following abstinence of 45 days. In contrast, abstinence from cocaine during this 45-day period was associated with sustained improvement on a motor learning test in the cocaine abusers relative to controls.

Preclinical development of AMG 139, a human antibody specifically targeting IL-23.

BACKGROUND AND PURPOSE: AMG 139 is a human anti-IL-23 antibody currently in a phase II trial for treating Crohn's disease. To support its clinical development in humans, in vitro assays and in vivo studies were conducted in cynomolgus monkeys to determine the pharmacology, preclinical characteristics and safety of this monoclonal antibody. EXPERIMENTAL APPROACH: The in vitro pharmacology, pharmacokinetics (PK), pharmacodynamics and toxicology of AMG 139, after single or weekly i.v. or s.c. administration for up to 26 weeks, were evaluated in cynomolgus monkeys. KEY RESULTS: AMG 139 bound with high affinity to both human and cynomolgus monkey IL-23 and specifically neutralized the biological activity of IL-23 without binding or blocking IL-12. After a single dose, linear PK with s.c. bioavailability of 81% and mean half-life of 8.4-13 days were observed. After weekly s.c. dosing for 3 or 6 months, AMG 139 exposure increased approximately dose-proportionally from 30 to 300 mg·kg(-1) and mean accumulation between the first and last dose ranged from 2- to 3.5-fold. Peripheral blood immunophenotyping, T-cell-dependent antigen responses and bone formation markers were not different between AMG 139 and vehicle treatment. No adverse clinical signs, effects on body weight, vital signs, ophthalmic parameters, clinical pathology, ECG, organ weights or histopathology were observed in the monkeys with the highest dose of AMG 139 tested (300 mg·kg(-1) s.c. or i.v.). CONCLUSIONS AND IMPLICATIONS: The in vitro pharmacology, PK, immunogenicity and safety characteristics of AMG 139 in cynomolgus monkeys support its continued clinical development for the treatment of various inflammatory diseases.

Topographical representation of shoulder motor nuclei in the cat spinal cord as revealed by retrograde fluorochrome tracers.

The present investigation demonstrates the morphological relationships among the main shoulder motor nuclei within the spinal cord of the cat. The intraspinal position of these nuclei has been revealed by retrograde labelling of spinal motor neurones via their peripheral nerves supplying anatomically identified shoulder muscles. Multiple pressure injection of up to four fluorescent tracers (Bisbenzimide, Fast Blue, Fluoro-Gold, Rhodamine-b-isothiocyanate) in one experiment was used to show the longitudinal distribution and topographical relations of motor neurones projecting to muscles acting on the scapulo-humerus joint. Tracer-positive cells have been found from middle C5 to rostral Th2 in the cervical cord, forming coherent longitudinal cell clusters separated in medial and lateral projection fields in the ventral horn. The present data suggest that the anatomical organization of spinal shoulder motor neurones corresponds to the embryonic origin of their later target muscles. All medial motor nuclei project to muscles deriving from ventral embryonic origins, while those motor nuclei lying in lateral positions innervate muscles originating from dorsal muscle primordia. Therefore, the spinal topography of shoulder motor nuclei seems to be independent of both the position and the function of a given muscle in the adult animal.

3-Hydroxy- and 3-keto-3-phenylpropionic acids: novel metabolites of benzoic acid in horse urine.

The metabolism of benzoic acid has been examined in the horse, using 14C- and deuterium-labelled compounds. Chromatographic analysis of the urine showed the presence of hippuric acid, benzoyl glucuronide and benzoic acid and a discrete band which accounted for 2% of the dose administered. This material was isolated by solvent extraction and HPLC and, following treatment with diazomethane, examined by GC/MS. The major component of this fraction was 3-hydroxy-3-phenylpropionic acid methyl ester, which was accompanied by very much smaller amounts of cinnamic acid methyl ester and acetophenone. The two latter minor components have been shown to be artefacts produced during workup and analysis. Cinnamic acid methyl ester arises by the thermal decomposition of 3-hydroxy-3-phenylpropionic acid methyl ester on the GC column. It is proposed that acetophenone has formed, during workup, by decarboxylation of 3-keto-3-phenylpropionic acid. It is suggested that 3-hydroxy and 3-keto-3-phenylpropionic acids, which are also endogenous in horse urine, have arisen by an addition of a 2 carbon fragment to benzoyl CoA, in a sequence analogous to the reactions of fatty acid biosynthesis. Some implications of the metabolic interrelationships between xenobiotic acids and fatty acids are discussed.

Short-term triple therapy with lansoprazole 30 mg or 60 mg, amoxycillin and clarithromycin to eradicate Helicobacter pylori.

BACKGROUND: We investigated the efficacy of 30 vs. 60 mg lansoprazole daily in a 1-week triple therapy for eradication of Helicobacter pylori in a prospective randomized study. METHODS: Two hundred and fifteen consecutive out-patients with peptic ulcer disease or non-ulcer dyspepsia, in whom H. pylori infection was confirmed by histology and/or a urease biopsy test, were randomly assigned to a 1-week treatment with either 15 mg lansoprazole b.d. (LAC15 group) or 30 mg lansoprazole b.d. (LAC30 group) in combination with 1 g amoxycillin b.d. and 500 mg clarithromycin b.d. RESULTS: Eradication of H. pylori was successful in 87% (per protocol) and 82% (intention-to-treat) of the patients with LAC15 and in 94% (per protocol) and 87% (intention-to-treat) of the patients with LAC30. The difference was not significant. In both treatment groups, all peptic ulcers were healed at the check-up. Adverse effects were seen in 11 patients of the LAC15 group and 10 patients of the LAC30 group: they caused discontinuation of the therapy in four of the LAC15 group and two patients of the LAC 30 group. CONCLUSIONS: A 7-day triple therapy using lansoprazole (LAC15) is an efficient and economical regimen for the eradication of H. pylori.

Cytoarchitecture of histamine-, dopamine-, serotonin- and octopamine-containing neurons in the cricket ventral nerve cord.

The present article provides a comparative neuroanatomical description of the cellular localization of the biogenic amines histamine, dopamine, serotonin and octopamine in the ventral nerve cord of an insect, namely the cricket, Gryllus bimaculatus. Generally, different immunocytochemical staining techniques reveal a small number of segmentally distributed immunoreactive (-IR) amine-containing neurons allowing single cell reconstruction of prominent elements. Aminergic neurons share common morphological features in that they innervate large portions of neurophil and often connect different neuromeres by intersegmental 'wide-field' projections of varicose appearance. In many cases aminergic terminals are also found on the surface of peripheral nerves suggesting additional neurohemal release sites. Despite such morphological similarities histological analysis demonstrates for any given amine functionally distinct neuron types with specific innervation patterns establishing discrete pathways. Histamine-IR interneurons are characterized by both ascending and descending projections forming central and peripheral terminals. The descending branches from dopamine-IR cells mainly converge within the terminal ganglion, whereas serotonin-IR interneurons with ascending projections often terminate within the brain. Serotonin is also present in sensory and motor neurons. In contrast to other aminergic neurons, most octopamine-IR cells represent unpaired neurons projecting through motor nerves of the soma-containing neuromere. Octopamine-IR cells with intersegmental branches are only rarely found. Based on these findings, a colocalization of different amines within the same neuron seems to be unlikely to occur in the cricket ventral nerve cord. With respect to the neuroanatomical description of amine-containing neurons known physiological effects of biogenic amines and their possible neuromodulatory functions in insects are discussed.

Voltage-activated currents in identified giant interneurons isolated from adult crickets gryllus bimaculatus

The electrophysiological properties of cultured giant interneurons isolated from the terminal ganglion of adult crickets (Gryllus bimaculatus) were investigated using whole-cell patch-clamp techniques. To allow for unequivocal identification of these interneurons in cell culture, a protocol for fast and selective labeling of their cell bodies was established. Prior to cell dissociation, the giant interneurons were backfilled through their axons in situ with a fluorescent dye (dextran tetramethylrhodamine). In primary cell cultures, the cell bodies of giant interneurons were identified among a population of co-cultured neurons by their red fluorescence. Action potentials were recorded from the cell bodies of the cultured interneurons suggesting that several types of voltage-activated ion channels exist in these cells. Using voltage-clamp recording techniques, four voltage-activated currents were isolated and characterized. The giant interneurons express at least two distinct K+ currents: a transient current that is blocked by 4-aminopyridine (4x10(-3 )mol l-1) and a sustained current that is partially blocked by tetraethylammonium (3x10(-2 )mol l-1) and quinidine (2x10(-4 )mol l-1). In addition, a transient Na+ current sensitive to 10(-7 )mol l-1 tetrodotoxin and a Ca2+ current blocked by 5x10(-4 )mol l-1 CdCl2 have been characterized. This study represents the first step in an attempt to analyze the cellular and ionic mechanisms underlying plasticity in the well-characterized and behaviorally important giant interneuron pathway in insects.

Octopamine immunoreactive neurons in the fused central nervous system of spiders.

Using antisera directed against octopamine (OA), we identified and mapped octopamine-immunoreactive (OA-ir) neurons and their projections in the fused, central ganglion complex of wandering spiders, Cupiennius salei. Labeled cell bodies are concentrated in the subesophageal ganglion complex (SEG) where they are arranged serially in ventral, midline clusters. OA-ir processes from these cells project dorsally. Some neurites end close to segmental septa; others merge into longitudinal tracts connecting the neuromeres. Labeled collaterals leaving these tracts project into peripheral neuropil. In the brain, OA-ir somata were found only in the two cheliceral hemiganglia, where a cluster of 4-5 relatively large cells (soma diameter 25 microns) lies next to a group of small somata (diameter < 10 microns). Neurites originating from the large somata descend into the SEG and merge into longitudinal tracts. The central body of the brain contains profuse ascending projections. Except for fine varicosities that are confined to the roots of nerves, we found no OA-ir fibers leaving the central nervous system (CNS). Within the CNS, however, OA-ir varicosities are concentrated in neuropil and near hemolymph spaces. This distribution suggests that OA acts as a neurotransmitter and/or local neuromodulator at central synapses, while it is also released into the hemolymph and presumably acts hormonally at peripheral sites. Using high-pressure liquid chromatography measurements, the hemolymph was in fact found to contain 12-40 nM of free octopamine.

Absence of recurrent axon collaterals in motoneurones to the extrinsic digit extensor muscles of the cat forelimb.

Forelimb alpha-motoneurones were intracellularly recorded in anaesthetized cats and iontophoretically filled with horseradish peroxidase (HRP). All motoneurones to the elbow flexors, elbow extensor and to the extensor carpi radialis muscles displayed in parallel homonymous recurrent inhibitory postsynaptic potentials (RIPSPs) and axon collaterals. Homonymous RIPSPs and axon collaterals were missing in the nuclei to the long digit extensor muscles. Two populations of motoneurones, with and without recurrent axon collaterals, seem to be present in the extensor carpi ulnaris motor nucleus. These results are consistent with the hypothesis that the motoneurones to the extrinsic digit extensors lack a recurrent axonal system. This indicates that the contribution of the recurrent Renshaw systems to motor control may be more complex than hitherto assumed.

Attentional functioning in abstinent cocaine abusers.

The effect of chronic cocaine use on attention is directly relevant to the treatment of cocaine dependence, since attention underlies most other cognitive processes, and thus the ability to profit from cognitively-based interventions. This paper reviews 17 studies examining attention in patients with cocaine abuse or dependence. Findings have been inconsistent, largely due to various methodological difficulties. There has been some suggestion of reduced cognitive speed, while focused and sustained attention have generally been unimpaired. Divided attention has been largely unexplored. Thus, there is insufficient evidence either to accept or reject the hypothesis of attentional dysfunction associated with chronic cocaine use.

Transport in a grooved perfusion flat-bed bioreactor for cell therapy applications.

This study considers the transport of oxygen (a growth-associated solute) and lactate (a metabolic byproduct) in a flat-bed perfusion chamber modified to retain cells through the addition of grooves, perpendicular to the direction of flow, at the chamber bottom. The chamber has been successfully applied to hematopoietic cell culture and may be useful for other basic and applied biomedical applications. The objective of this study is to characterize the culture environment in terms of solute transport under various operational conditions. This will allow one to improve the design and operating strategy of the perfusion system for maximizing cell numbers. The system is numerically simulated using the finite element package FIDAP. The reaction kinetics describing oxygen uptake by cells are simplified to zero order to give an upper bound for the oxygen consumption. A flat-bed chamber without grooves is considered here as a benchmark. We show that the growth environment is not oxygen limited (local oxygen concentration above 10 microM) for a variety of flow rates and culture conditions (qO2 = 0.1 micromol/(10(6) cells h)). With a medium flow rate of 2.5 mL/min through the reactor, the model predicts that the 29-cm2 reactor can support at least 33.4 x 10(6) total cells when the inlet medium is in equilibrium with high (20%) oxygen concentration. The culture becomes oxygen limited however for the same flow rate for low (5%) oxygen concentration and can only support 7.2 x 10(6) total cells. Comparison of grooved vs nongrooved chambers reveals that the presence of grooves only affects solute transport on a local scale. This result is attributed to the small size (200 microgram) of the cavities relative to the chamber dimensions. The comparison also yields an empirical relation that allows for rapid estimation of oxygen and lactate concentrations in the grooves using only the numerical simulation of the simpler nongrooved chamber. Finally, our investigation shows that, while decreasing the spacing between cavities decreases the total number of cells the reactor can support, the efficiency of the reactor is increased by 25% (on an area basis) without growth restriction.

Dietary analysis with programmable calculator: a simplified method.

The use and applications of programmable calculator in dietary analysis are presented. Results which approximate those of large computers can be obtained with considerably less time, money, and data manipulation. Program flexibility allows operators to determine the number of foods and nutrients to be analyzed. Input, data checking, and results of total nutrient consumption are achieved within minutes. The dietary analysis described in this article is well suited for small hospitals and clinics, for teaching purposes and dietary surveys and for use by non-nutritionists who have a one-time or regular need to incorporate dietary information into their work.

Self-report and objective measures of cognitive deficit in patients entering substance abuse treatment.

The relationship between self-reported cognitive deficits and objectively measured cognitive performance was examined in 86 patients entering substance abuse treatment. Self-ratings of cognitive impairment were strongly correlated with indices of depression and vulnerability to stress, but not with objective cognitive performance. Confirming the lack of relationship between self-report and objective cognitive measures, cognitive performance did not differ between patients at the extremes of the cognitive-complaint distribution; and cognitively impaired patients did not differ from cognitively intact patients in their self-ratings of impairment.