Anterior cingulate cortex γ-aminobutyric acid deficits in youth with depression.

Abnormally low γ-aminobutyric acid (GABA) levels have been consistently reported in adults with major depressive disorder (MDD). Our group extended this finding to adolescents, and documented that GABA deficits were associated with anhedonia. Here we aimed to confirm our prior finding of decreased brain GABA in youth with depression and explore its associations with clinical variables. Forty-four psychotropic medication-free youth with MDD and 36 healthy control (HC) participants (12-21 years) were studied. Participants represent a combined sample of 39 newly recruited youth (MDD=24) and 41 youth from our previously reported study (MDD=20). GABA levels and the combined resonances of glutamate and glutamine (Glx) were measured in vivo in the anterior cingulate cortex using proton magnetic resonance spectroscopy. Youth with depression exhibited significantly lower GABA levels than HC in both the newly reported (P=0.003) and the combined (P=0.003) samples. When depressed participants were classified based on the presence of anhedonia, only the anhedonic MDD subgroup showed reduced GABA levels compared to HC (P=0.002). While there were no associations between any clinical measures and GABA or Glx levels in the new sample, GABA was negatively correlated with only anhedonia severity in the combined MDD group. Furthermore, in the combined sample, hierarchical regression models showed that anhedonia, but not depression severity, anxiety or suicidality, contributed significant variance in GABA levels. This report solidifies the evidence for a GABA deficit early in the course of MDD, which correlates specifically with anhedonia in the disorder.

Over 75% incident-photon-to-current efficiency without solid electrodes.

The efficiency of photoelectrochemical reactions is conventionally defined in terms of the ratio between the current responses arising from the collection of carriers at electrical contacts and the incident photon flux at a given wavelength, i.e. the incident-photon-to-current-efficiency (IPCE). IPCE values are determined by a variety of factors such as the absorption constant of the active layer, bulk and surface recombination of photogenerated carriers, as well as their characteristic diffusion length. These parameters are particularly crucial in nanostructured photoelectrodes, which commonly display low carrier mobility. In this article, we examine the photoelectrochemical responses of a mesoporous TiO2 film in which the IPCE is enhanced by fast extraction of carriers via chemical reactions. TiO2 films are spontaneously formed by destabilisation of colloidal particles at the polarisable interface between two immiscible electrolyte solutions. The photocurrent arises from hole-transfer to redox species confined to the organic electrolyte, which is coupled to the transfer of electrons to oxygen in the aqueous electrolyte. The dynamic photocurrent responses demonstrate that no coupled ion transfer is involved in the process. The interplay of different interfacial length scales, molecularly sharp liquid/liquid boundary and mesoporous TiO2 film, promotes efficiencies above 75% (without correction for reflection losses). This is a significant step change in values reported for these interfaces (below 1%), which are usually limited to sub-monolayer coverage of photoactive molecular or nanoscopic materials.

Increased ventricular cerebrospinal fluid lactate in depressed adolescents.

BACKGROUND: Mitochondrial dysfunction has been increasingly examined as a potential pathogenic event in psychiatric disorders, although its role early in the course of major depressive disorder (MDD) is unclear. Therefore, the purpose of this study was to investigate mitochondrial dysfunction in medication-free adolescents with MDD through in vivo measurements of neurometabolites using high-spatial resolution multislice/multivoxel proton magnetic resonance spectroscopy. METHODS: Twenty-three adolescents with MDD and 29 healthy controls, ages 12-20, were scanned at 3T and concentrations of ventricular cerebrospinal fluid lactate, as well as N-acetyl-aspartate (NAA), total creatine (tCr), and total choline (tCho) in the bilateral caudate, putamen, and thalamus were reported. RESULTS: Adolescents with MDD exhibited increased ventricular lactate compared to healthy controls [F(1,41)=6.98, P=0.01]. However, there were no group differences in the other neurometabolites. Dimensional analyses in the depressed group showed no relation between any of the neurometabolites and symptomatology, including anhedonia and fatigue. CONCLUSIONS: Increased ventricular lactate in depressed adolescents suggests mitochondrial dysfunction may be present early in the course of MDD; however it is still not known whether the presence of mitochondrial dysfunction is a trait vulnerability of individuals predisposed to psychopathology or a state feature of the disorder. Therefore, there is a need for larger multimodal studies to clarify these chemical findings in the context of network function.

Charge transport across high surface area metal/diamond nanostructured composites.

High surface area composites featuring metal nanostructures and diamond particles have generated a lot of interest in the fields of heterogeneous catalysis, electrocatalysis, and sensors. Diamond surfaces provide a chemically robust framework for active nanostructures in comparison with sp(2) carbon supports. The present paper investigates the charge transport properties of high surface area films of high-pressure, high-temperature diamond particles in the presence and absence of metal nanostructures, employing electrochemical field-effect transistors. Oxygen- and hydrogen-terminated surfaces were generated on 500 nm diamond powders. Homogeneously distributed metal nanostructures, with metal volume fractions between ca. 5 and 20%, were either nucleated at the diamond particles by impregnation or incorporated from colloidal solution. Electrochemical field-effect transistor measurements, employing interdigitated electrodes, allowed the determination of composite conductivity as a function of electrode potential, as well as in air. In the absence of metal nanostructures, the lateral conductivity of the diamond assemblies in air is increased by over one order of magnitude upon hydrogenation of the particle surface. This observation is consistent with studies at diamond single crystals, although the somewhat modest change in conductivity suggests that charge transport is not only determined by the intrinsic surface conductivity of individual diamond particles but also by particle-to-particle charge transfer. Interestingly, the latter contribution effectively controls the assembly conductivity in the presence of an electrolyte solution as the difference between hydrogenated and oxygenated particles vanishes. The conductivity in the presence of metal nanoparticles is mainly determined by the metal volume fraction, while diamond surface termination and the presence of electrolyte solutions exert only minor effects. The experimental trends are discussed in terms of the electrochemical formation of charge carriers in the diamond particles, percolation theory, and charge screening at the double layer.

A dosimetric analysis of tomotherapy based intensity modulated radiation therapy with and without bone marrow sparing in gynecologic malignancies.

Whole pelvic radiotherapy with concurrent chemotherapy is the standard of care for locally advanced cervical carcinoma. Published literature reports that the pelvic bone marrow (BM) dosimetric parameters of V10 > 90% and V20 > 80% are associated with higher rates of hematologic toxicities using this approach. Here, we investigate the ability of Tomotherapy based intensity modulated radiation therapy (IMRT) to reduce dose to pelvic BM while evaluating dose distribution to critical structures and planning target volume (PTV) coverage. Ten patients were selected for analysis. Normal structures, whole pelvic BM, PTV contours, and IMRT objects were standardized. Two whole pelvis Tomotherapy plans were created for each patient, one standard plan, and one with the addition of a BM sparing (BMS) constraint (V10 <85%, V20 < 80%). Data were calculated from multiple points with regard to BM dose, normal structure dose, and PTV coverage. Differences in dose distributions between the two sets of plans were analyzed using a paired t-test. The addition of a BMS planning constraint resulted in significant decreases in pelvic BM dose at the following dosimetric points: V5, V10, V15, V20, V30, V40, V50, and mean dose (p < 0.05 for all points). There were no significant differences in dose to small bowel, bladder or rectum, with the exception of one data point (small bowel V30, p = 0.004) between the two sets of plans. There was no sacrifice of PTV coverage or loss of homogeneity with the addition of a BMS planning constraint. BMS-IMRT significantly reduces radiation dose to the pelvic BM while maintaining the ability to spare dose to the small bowel, bladder and rectum. The planning constraints were met without violation of study criteria, and without sacrifice of PTV coverage. Further investigation is warranted to determine if rates of hematologic toxicity improve with utilization of Tomotherapy based BMS-IMRT.

Outcomes following surgery and adjuvant radiation in stage II endometrial adenocarcinoma.

PURPOSE: To evaluate locoregional control, disease free survival, and overall survival in patients treated with surgery and adjuvant radiation for stage II adenocarcinoma of the endometrium. Secondary goals include identification of prognostic factors and the comparison of toxicity profiles after vaginal cuff brachytherapy (VB) alone or combined with pelvic external beam radiation therapy (EXT). MATERIALS AND METHODS: All patients receiving adjuvant radiation at the University of Wisconsin following surgery for FIGO stage II adenocarcinoma of the endometrium between January 1991 and December 2006 were retrospectively reviewed. RESULTS: Between January 1991 and December 2006, 71 patients with FIGO stage II adenocarcinoma of the endometrium (23 stage IIA, 48 stage IIB) received adjuvant radiation at the University of Wisconsin. Fifty patients were treated with EXT and VB, twenty with VB alone, and one with EXT alone. At a mean follow-up of 5.1 years (range, 0.5-16.8 years), 5-year overall and disease-free survival were both 82%. Factors associated with an increased risk for recurrence include depth of myometrial invasion (p=0.005) and lymphovascular invasion (p=0.02). Receiving EXT was significantly associated with increased depth of myometrial invasion (p=0.007), higher grade (p=0.003), and less extensive surgery (p=0.01). Of the nine recurrences, three were initially local and six were distant recurrences alone. Grade 2 or greater acute and late side effects were significantly greater with EXT therapy compared to VB alone (p<0.0001 and p=0.02, respectively), although severe toxicities (grade 3 or greater) were limited with either modality. DISCUSSION: Local recurrence rates remain low after surgery and adjuvant radiation therapy for stage II endometrial cancer using a combination of VB and EXT tailored to the surgical and pathologic features. VB alone resulted in fewer toxicities without an increased recurrence risk compared to the combination of EXT and VB, suggesting that VB without EXT is sufficient for patients with low-risk histopathologic features and comprehensive surgical staging with complete lymphadenectomy.

Identification of the cellular receptor for anthrax toxin.

The tripartite toxin secreted by Bacillus anthracis, the causative agent of anthrax, helps the bacterium evade the immune system and can kill the host during a systemic infection. Two components of the toxin enzymatically modify substrates within the cytosol of mammalian cells: oedema factor (OF) is an adenylate cyclase that impairs host defences through a variety of mechanisms including inhibiting phagocytosis; lethal factor (LF) is a zinc-dependent protease that cleaves mitogen-activated protein kinase kinase and causes lysis of macrophages. Protective antigen (PA), the third component, binds to a cellular receptor and mediates delivery of the enzymatic components to the cytosol. Here we describe the cloning of the human PA receptor using a genetic complementation approach. The receptor, termed ATR (anthrax toxin receptor), is a type I membrane protein with an extracellular von Willebrand factor A domain that binds directly to PA. In addition, a soluble version of this domain can protect cells from the action of the toxin.

Variations on the CAGE alcohol screening questionnaire: strengths and limitations in VA general medical patients.

BACKGROUND: Several variations on the CAGE alcohol screening questionnaire have been recommended. This report evaluates modifications and additions to the CAGE. METHODS: Alcohol screening questionnaires were evaluated in male VA general medicine patients (n = 227; mean age, 65.8). Mailed questionnaires included two scoring options for the CAGE (standard and last-year time frames), questions about quantity and frequency of drinking, two questions about episodic heavy drinking, and the question "Have you ever had a drinking problem?" Main analyses compared alcohol screening questions, at various cut-points, to a gold standard of hazardous drinking during the past year (> or =14 drinks/week or > or =5 drinks on an occasion) and/or DSM-III-R alcohol abuse or dependence, based on standardized interviews. RESULTS: The CAGE questionnaire with a past-year time frame was much less sensitive (0.57 vs. 0.77) but more specific (0.82 vs. 0.59) than the standard CAGE for detecting hazardous drinking during the past year and/or DSM-III-R alcohol abuse or dependence. An eight-item questionnaire that included the standard CAGE was most sensitive (0.92) but had low specificity (0.50). A single question about the frequency of drinking > or =6 drinks on an occasion, included in the eight-item questionnaire, was both relatively sensitive (0.77) and specific (0.83). CONCLUSION: The CAGE questionnaire with a past-year time frame was an insensitive alcohol-screening test. An eight-item augmented version of the standard CAGE was the most sensitive. A question about the frequency of drinking > or =6 drinks on an occasion performed better than the standard CAGE, which made it the optimal brief screening test for at-risk drinking.

Binge drinking among female Veterans Affairs patients: prevalence and associated risks.

This study evaluated the prevalence and associated risks of binge drinking, defined as having > or = 4 drinks on an occasion in the past year, in a female patient population. Of 1,259 female Veterans Affairs patients surveyed, 780 reported drinking alcohol in the past year, and 305 (24% of respondents, 39% of drinkers) reported binge drinking in the past year; 84 (11% of drinkers) had done so monthly or more often. Age-adjusted logistic regression analyses indicated that women who reported past-year binge drinking monthly or more often reported significantly increased odds of morning drinking (odds ratio [OR] = 40.3), others worrying about their drinking (OR = 38.6), arguments after drinking (OR = 13.5), hepatitis or cirrhosis (OR = 3.1), frequent injuries (OR = 2.6), smoking (OR = 3.7), drug use (OR = 22.2), and multiple sexual partners (OR = 4.6).

The relationship between alcohol screening questionnaires and mortality among male veteran outpatients.

OBJECTIVE: This study evaluated whether responses to alcohol screening questionnaires predicted mortality in a Department of Veterans Affairs (VA) primary care population. METHOD: This study involved 5,703 male outpatients (mean age = 64) who were enrolled in General Internal Medicine clinics at three Veterans Affairs (VA) medical centers and returned mailed questionnaires in 1993-94. The two questionnaires included the CAGE and Alcohol Use Disorders Identification Test (AUDIT) alcohol screening tests. Mortality was ascertained using the VA Beneficiary Identification and Record Locator System. Five-year crude and adjusted mortality rates were calculated for patients who screened positive and patients who screened negative on each alcohol screening test. RESULTS: The risk of mortality was increased among drinkers who scored > or = 8 on the full AUDIT (hazard ratio: 1.47; 95% confidence interval [CI]: 1.08-2.00) or the three AUDIT consumption questions (1.58; 1.11-2.27), after adjusting for age, smoking, sociodemographic characteristics and chronic illnesses. The risk of mortality was also increased among drinkers who reported drinking > or = 3 drinks daily (1.69; 1.28-2.22) or prior alcohol treatment (1.66; 1.27-2.17), in "fully adjusted" models. A positive CAGE score (> or = 2) was associated with significantly increased risk of mortality among drinkers in a model adjusted only for age and smoking (1.27; 1.02-1.58). Among nondrinkers, neither a positive CAGE score (> or = 2) nor report of prior alcohol treatment was associated with increased risk of mortality. CONCLUSIONS: VA outpatients who reported drinking during the previous year and who had a positive result on an alcohol screening test experienced higher mortality over the subsequent 5 years than did patients who screened negative.

A physician survey of the effect of drug sample availability on physicians' behavior.

OBJECTIVE: Pharmaceutical companies often use drug samples as a marketing strategy in the ambulatory care setting. Little is known about how the availability of drug samples affects physicians' prescribing practices. Our goal was to assess: (1) under what circumstances and why physicians dispense drug samples, (2) if drug samples lead physicians to use medications other than their preferred drug choice, and (3) the physician characteristics that are associated with drug sample use. DESIGN: Cross-sectional survey. SETTING: University-based clinics at one academic medical center. PARTICIPANTS: 154 general medicine and family physicians. MEASUREMENTS AND MAIN RESULTS: Physicians' self-reported prescribing patterns for 3 clinical scenarios, including their preferred drug choice, whether they would use a drug sample and subsequently prescribe the sampled medication, and the importance of factors involved in the decision to dispense a drug sample. A total of 131 (85%) of 154 physicians responded. When presented with an insured woman with an uncomplicated lower urinary tract infection, 22 (17%) respondents reported that they would dispense a drug sample; 21 (95%) of 22 sample users stated that they would dispense a drug sample that differed from their preferred drug choice. For an uninsured man with hypertension, 35 (27%) respondents reported that they would dispense a drug sample; 32 (91%) of 35 sample users indicated that they would dispense a drug sample instead of their preferred drug choice. For an uninsured woman with depression, 108 (82%) respondents reported that they would dispense a drug sample; 53 (49%) of 108 sample users indicated that they would dispense a drug sample that differed from their preferred drug choice. Avoiding cost to the patient was the most consistent motivator for dispensing a drug sample for all 3 scenarios. For 2 scenarios, residents were more likely to report using drug samples than attendings (P <.05). When respondents who chose a drug sample for 2 or 3 scenarios were compared to those who never chose to use a drug sample, or chose a drug sample for only one scenario, only younger age was independently associated with drug sample use. CONCLUSION: In self-reports, the availability of drug samples led physicians to dispense and subsequently prescribe drugs that differ from their preferred drug choice. Physicians most often report using drug samples to avoid cost to the patient.

The AUDIT alcohol consumption questions: reliability, validity, and responsiveness to change in older male primary care patients.

OBJECTIVES: To determine the reliability, validity, and responsiveness to change of AUDIT (Alcohol Use Disorders Identification Test) questions 1 to 3 about alcohol consumption in a primary care setting. PATIENTS: Randomly selected, male general medical patients (n = 441) from three VA Medical Centers, who had 5 or more drinks containing alcohol in the past year and were willing to be interviewed about their health habits. MEASURES: Three self-administered AUDIT consumption questions were compared with a telephone-administered version of the trilevel World Health Organization interview about alcohol consumption. RESULTS: Of 393 eligible patients, 264 (67%) completed interviews. Test-retest reliability--Correlations between baseline and repeat measures 3 months later for four dimensions of consumption according to the AUDIT, ranged from 0.65 to 0.85, among patients who indicated they had not changed their drinking (Kendall's Tau-b). Criterion validity--Correlations between AUDIT and interview for four dimensions of alcohol consumption ranged from 0.47 to 0.66 (Kendall's Tau-b). Discriminative validity--The AUDIT questions were specific (90 to 93%), but only moderately sensitive (54 to 79%), for corresponding criteria for heavy drinking. Responsiveness to change--The AUDIT consumption questions had a Guyatt responsiveness statistic of 1.04 for detecting a change of 7 drinks/week, suggesting excellent responsiveness to change. CONCLUSIONS: AUDIT questions 1 to 3 demonstrate moderate to good validity, but excellent reliability and responsiveness to change. Although they often underestimate heavy alcohol consumption according to interview, they performed adequately to be used as a proxy measure of consumption in a clinical trial of heavy drinkers in this population.

Medical risks for women who drink alcohol.

OBJECTIVE: To summarize for clinicians recent epidemiologic evidence regarding medical risks of alcohol use for women. METHODS: MEDLINE and PsychINFO, 1990 through 1996, were searched using key words "women" or "woman," and "alcohol." MEDLINE was also searched for other specific topics and authors from 1980 through 1996. Data were extracted and reviewed regarding levels of alcohol consumption associated with mortality, cardiovascular disease, alcohol-related liver disease, injury, osteoporosis, neurologic symptoms, psychiatric comorbidity, fetal alcohol syndrome, spontaneous abortion, infertility, menstrual symptoms, breast cancer, and gynecologic malignancies. Gender-specific data from cohort studies of general population or large clinical samples are primarily reviewed. MAIN RESULTS: Women develop many alcohol-related medical problems at lower levels of consumption than men, probably reflecting women's lower total body water, gender differences in alcohol metabolism, and effects of alcohol on postmenopausal estrogen levels. Mortality and breast cancer are increased in women who report drinking more than two drinks daily. Higher levels of alcohol consumption by women are associated with increased menstrual symptoms, hypertension, and stroke. Women who drink heavily also appear to have increased infertility and spontaneous abortion. Adverse fetal effects occur after variable amounts of alcohol consumption, making any alcohol use during pregnancy potentially harmful. CONCLUSIONS: In general, advising nonpregnant women who drink alcohol to have fewer than two drinks daily is strongly supported by the epidemiologic literature, although specific recommendations for a particular woman should depend on her medical history and risk factors.

The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test.

OBJECTIVE: To evaluate the 3 alcohol consumption questions from the Alcohol Use Disorders Identification Test (AUDIT-C) as a brief screening test for heavy drinking and/or active alcohol abuse or dependence. METHODS: Patients from 3 Veterans Affairs general medical clinics were mailed questionnaires. A random, weighted sample of Health History Questionnaire respondents, who had 5 or more drinks over the past year, were eligible for telephone interviews (N = 447). Heavy drinkers were oversampled 2:1. Patients were excluded if they could not be contacted by telephone, were too ill for interviews, or were female (n = 54). Areas under receiver operating characteristic curves (AUROCs) were used to compare mailed alcohol screening questionnaires (AUDIT-C and full AUDIT) with 3 comparison standards based on telephone interviews: (1) past year heavy drinking (>14 drinks/week or > or =5 drinks/ occasion); (2) active alcohol abuse or dependence according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, criteria; and (3) either. RESULTS: Of 393 eligible patients, 243 (62%) completed AUDIT-C and interviews. For detecting heavy drinking, AUDIT-C had a higher AUROC than the full AUDIT (0.891 vs 0.881; P = .03). Although the full AUDIT performed better than AUDIT-C for detecting active alcohol abuse or dependence (0.811 vs 0.786; P<.001), the 2 questionnaires performed similarly for detecting heavy drinking and/or active abuse or dependence (0.880 vs 0.881). CONCLUSIONS: Three questions about alcohol consumption (AUDIT-C) appear to be a practical, valid primary care screening test for heavy drinking and/or active alcohol abuse or dependence.

Screening for problem drinking: comparison of CAGE and AUDIT. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test.

OBJECTIVE: To compare self-administered versions of three questionnaires for detecting heavy and problem drinking: the CAGE, the Alcohol Use Disorders Identification Test (AUDIT), and an augmented version of the CAGE. DESIGN: Cross-sectional surveys. SETTING: Three Department of Veterans Affairs general medical clinics. PATIENTS: Random sample of consenting male outpatients who consumed at least 5 drinks over the past year ("drinkers"). Heavy drinkers were oversampled. MEASUREMENTS: An augmented version of the CAGE was included in a questionnaire mailed to all patients. The AUDIT was subsequently mailed to "drinkers." Comparison standards, based on the tri-level World Health Organization alcohol consumption interview and the Diagnostic Interview Schedule, included heavy drinking (> 14 drinks per week typically or > or = 5 drinks per day at least monthly) and active DSM-IIIR alcohol abuse or dependence (positive diagnosis and at least one alcohol-related symptom in the past year). Areas under receiver operating characteristic curves (AUROCs) were used to compare screening questionnaires. MAIN RESULTS: Of 393 eligible patients, 261 (66%) returned the AUDIT and completed interviews. For detection of active alcohol abuse or dependence, the CAGE augmented with three more questions (AUROC 0.871) performed better than either the CAGE alone or AUDIT (AUROCs 0.820 and 0.777, respectively). For identification of heavy-drinking patients, however, the AUDIT performed best (AUROC 0.870). To identify both heavy drinking and active alcohol abuse or dependence, the augmented CAGE and AUDIT both performed well, but the AUDIT was superior (AUROC 0.861). CONCLUSIONS: For identification of patients with heavy drinking or active alcohol abuse or dependence, the self-administered AUDIT was superior to the CAGE in this population.

Alcohol screening questionnaires in women: a critical review.

OBJECTIVE: To describe the performance of alcohol screening questionnaires in female patients. DATA SOURCES: We searched MEDLINE from 1966 to July 1997 for alcoholism or alcohol-drinking and for CAGE, AUDIT, BMAST, TWEAK, T-ACE, MAST, SMAST, or SAAST; Citations Indexes for newer screening questionnaires and those without acronyms; and MEDLINE from 1996 to July 1997 for alcoholism or alcohol-drinking and screening. STUDY SELECTION AND DATA EXTRACTION: Reviewed studies presented data for women comparing brief alcohol screening questionnaires with valid criterion standards for heavy drinking (> or =2 drinks per day) or alcohol abuse or dependence in US general clinical populations. Sensitivities, specificities, and areas under receiver operating characteristic curves (AUROCs) were extracted. DATA SYNTHESIS: Thirteen articles (9 studies) were reviewed. The CAGE questionnaire had AUROCs of 0.84 to 0.92 for alcohol abuse and dependence in predominantly black populations of women, but using the traditional cut point of 2 or more resulted in low sensitivities (38%-50%) in predominantly white female populations. The TWEAK and Alcohol Use Disorders Identification Test (AUDIT) questionnaires had high AUROCs (0.87-0.93) for past-year alcohol abuse or dependence in black or white women, but had sensitivities less than 80% at traditional cut points. For detecting heavy drinking, the AUDIT questionnaire had AUROCs of at least 0.87 in female primary care patients. The TWEAK and T-ACE questionnaires had higher AUROCs (0.84-0.87) than the CAGE questionnaire (0.76-0.78) for detecting heavy drinking before pregnancy was recognized in black obstetric patients. CONCLUSIONS: The CAGE questionnaire was relatively insensitive in predominantly white female populations. The TWEAK and AUDIT questionnaires have performed adequately in black or white women, using lower cut points than usual.

Screening for problem drinking : Comparison of CAGE and AUDIT.

OBJECTIVE: To compare self-administered versions of three questionnaires for detecting heavy and problem drinking: the CAGE, the Alcohol Use Disorders Identification Test (AUDIT), and an augmented version of the CAGE. DESIGN: Cross-sectional surveys. SETTING: Three Department of Veterans Affairs general medical clinics. PATIENTS: Random sample of consenting male outpatients who consumed at least 5 drinks over the past year ("drinkers"). Heavy drinkers were oversampled. MEASUREMENTS: An augmented version of the CAGE was included in a questionnaire mailed to all patients. The AUDIT was subsequently mailed to "drinkers." Comparison standards, based on the tri-level World Health Organization alcohol consumption interview and the Diagnostic Interview Schedule, included heavy drinking (>14 drinks per week typically or >/=5 drinks per day at least monthly) and active DSM-IIIR alcohol abuse or dependence (positive diagnosis and at least one alcohol-related symptom in the past year). Areas under receiver operating characteristic curves (AUROCs) were used to compare screening questionnaires. MAIN RESULTS: Of 393 eligible patients, 261 (66%) returned the AUDIT and completed interviews. For detection of active alcohol abuse or dependence, the CAGE augmented with three more questions (AUROC 0.871) performed better than either the CAGE alone or AUDIT (AUROCs 0.820 and 0.777, respectively). For identification of heavy-drinking patients, however, the AUDIT performed best (AUROC 0.870). To identify both heavy drinking and active alcohol abuse or dependence, the augmented CAGE and AUDIT both performed well, but the AUDIT was superior (AUROC 0.861). CONCLUSIONS: For identification of patients with heavy drinking or active alcohol abuse or dependence, the self-administered AUDIT was superior to the CAGE in this population.

Enterobactin biosynthesis in Escherichia coli: isochorismate lyase (EntB) is a bifunctional enzyme that is phosphopantetheinylated by EntD and then acylated by EntE using ATP and 2,3-dihydroxybenzoate.

In Escherichia coli, the siderophore molecule enterobactin is synthesized in response to iron deprivation by formation of an amide bond between 2,3-dihydroxybenzoate (2,3-DHB) and l-serine and formation of ester linkages between three such N-acylated serine residues. We show that EntB, previously described as the isochorismate lyase required for production of 2,3-DHB, is a bifunctional protein that also serves as an aryl carrier protein (ArCP) with a role in enterobactin assembly. EntB is phosphopantetheinylated near the C terminus in a reaction catalyzed by EntD with a kcat of 5 min-1 and a Km for apo-EntB of 6.5 microM. This holo-EntB is then acylated with 2,3-DHB in a reaction catalyzed by EntE, previously described as the 2,3-DHB-AMP ligase, with a kcat of 100 min-1 and a Km of <<1 microM for holo-EntB. The N-terminal 187 amino acids of EntB (isochorismate lyase domain) are not needed for reaction of EntB with either EntD or EntE as demonstrated by the equivalent catalytic efficiencies of the full-length EntB (residues 1-285) and the C-terminal EntB ArCP domain (residues 188-285) as substrates for both EntD and EntE.