Measurement of AC loss down to 25 K in a REBCO racetrack coil for electrical aircraft motor.

The development of full superconducting motors for electric distributed aircraft propulsion requires to test the stator coils at the operation temperature, usually between 20 and 40 K. Here, we study the AC loss of a test racetrack coil made of REBCO tape. We developed a measurement system within a non-metallic cryostat where a cryocooler cools the test coil in combination with liquid or solid nitrogen. We present transport AC loss measurements by electrical means down to 25 K for current amplitudes up to 140 A and frequency 18-576 Hz. The AC loss increased with second power with current, and did not depend on frequency or temperature. Later, we measured the AC parallel magnetization loss in a stack of tapes made of the same material as the coil, and in a stack of tapes without superconducting layer. The results in both samples is almost identical and presents the same behavior as the coil. We conclude that the main contribution to the AC loss in the tape stack and in the coil was from the magnetism of the Hastelloy substrate or buffer layers. Therefore, researchers need to take this into account in tape production and in superconducting motor design.

Aberrantly low STAT3 and STAT5 responses are associated with poor outcome and an inflammatory gene expression signature in pediatric acute myeloid leukemia

The relapse rate for children with acute myeloid leukemia is nearly 40% despite aggressive chemotherapy and often stem cell transplant. We sought to understand how environment-induced signaling responses are associated with clinical response to treatment. We previously reported that patients whose AML cells showed low G-CSF-induced STAT3 activation had inferior event-free survival compared to patients with stronger STAT3 responses. Here, we expanded the paradigm to evaluate multiple signaling parameters induced by a more physiological stimulus. We measured STAT3, STAT5 and ERK1/2 responses to G-CSF and to stromal cell-conditioned medium for 113 patients enrolled on COG trials AAML03P1 and AAML0531. Low inducible STAT3 activity was independently associated with inferior event-free survival in multivariate analyses. For inducible STAT5 activity, those with the lowest and highest responses had inferior event-free survival, compared to patients with intermediate STAT5 responses. Using existing RNA-sequencing data, we compared gene expression profiles for patients with low inducible STAT3/5 activation with those for patients with higher inducible STAT3/5 signaling. Genes encoding hematopoietic factors and mitochondrial respiratory chain subunits were overexpressed in the low STAT3/5 response groups, implicating inflammatory and metabolic pathways as potential mechanisms of chemotherapy resistance. We validated the prognostic relevance of individual genes from the low STAT3/5 response signature in a large independent cohort of pediatric AML patients. These findings provide novel insights into interactions between AML cells and the microenvironment that are associated with treatment failure and could be targeted for therapeutic interventions (AU)

Aberrantly low STAT3 and STAT5 responses are associated with poor outcome and an inflammatory gene expression signature in pediatric acute myeloid leukemia.

The relapse rate for children with acute myeloid leukemia is nearly 40% despite aggressive chemotherapy and often stem cell transplant. We sought to understand how environment-induced signaling responses are associated with clinical response to treatment. We previously reported that patients whose AML cells showed low G-CSF-induced STAT3 activation had inferior event-free survival compared to patients with stronger STAT3 responses. Here, we expanded the paradigm to evaluate multiple signaling parameters induced by a more physiological stimulus. We measured STAT3, STAT5 and ERK1/2 responses to G-CSF and to stromal cell-conditioned medium for 113 patients enrolled on COG trials AAML03P1 and AAML0531. Low inducible STAT3 activity was independently associated with inferior event-free survival in multivariate analyses. For inducible STAT5 activity, those with the lowest and highest responses had inferior event-free survival, compared to patients with intermediate STAT5 responses. Using existing RNA-sequencing data, we compared gene expression profiles for patients with low inducible STAT3/5 activation with those for patients with higher inducible STAT3/5 signaling. Genes encoding hematopoietic factors and mitochondrial respiratory chain subunits were overexpressed in the low STAT3/5 response groups, implicating inflammatory and metabolic pathways as potential mechanisms of chemotherapy resistance. We validated the prognostic relevance of individual genes from the low STAT3/5 response signature in a large independent cohort of pediatric AML patients. These findings provide novel insights into interactions between AML cells and the microenvironment that are associated with treatment failure and could be targeted for therapeutic interventions.

Inhibition of the miR-17-92 Cluster Separates Stages of Palatogenesis.

The role that noncoding regions of the genome play in the etiology of cleft palate is not well studied. A novel method of microRNA (miR) inhibition that allows for specific miR knockdown in vivo has been developed by our laboratory. To further understand the role of miRs in palatogenesis, we used a new mouse model to inhibit specific miRs within the miR-17-92 cluster. Transgenic mice expressing inhibitory complexes for miR-17 and miR-18 manifested a clefting phenotype that was distinct from that observed in mice carrying inhibitory complexes for miR-17, miR-18, miR-19, and miR-92. An in silico candidate gene analysis and bioinformatics review led us to identify TGFBR2 as a likely target of miR-17 and miR-19 family members. Reverse transcription polymerase chain reaction (RT-PCR) experiments showed that TGFBR1 and TGFBR2 expression levels were elevated in the palates of these miR transgenic embryos at embryonic day 15.5. RT-PCR data also showed that the expression of mature miRs from the miR-17-92 cluster was significantly decreased in the transgenic embryos. Decreased expression of TGFB pathway signaling ligands was also observed. Experiments in cells showed that inhibition of miR-17 and miR-18 was sufficient to induce increases in expression of TGFB receptors, while a concomitant decrease in TGFB signaling ligands was not observed. RT-PCR of mature miR-17-92 in cells demonstrated the selectivity and specificity of inhibitory complexes. While this study builds on previous studies that have implicated miR-17-92 in the regulation of important molecular components of the TGFB signaling pathway, it is likely that interactions remain to be elucidated between miR-17-92 and as-of-yet unidentified molecules important for the control of palatogenesis. The differential regulation of palatogenesis by members of the miR-17-92 cluster indicates that several gene combinations regulate palate elevation and extension during development.

Heparin-binding epidermal growth factor-like growth factor: a component in chromaffin granules which promotes the survival of nigrostriatal dopaminergic neurones in vitro and in vivo.

Chromaffin cells can restore function to the damaged nigrostriatal dopaminergic system in animal models of Parkinson's disease. It has been reported that a protein which is released from chromaffin granules can promote the survival of dopaminergic neurones in vitro and protect them against N-methylpyridinium ion toxicity. This neurotrophic effect has been found to be mediated by astroglial cells and blocked by inhibitors of the epidermal growth factor (EGF) receptor signal transduction pathway. Here we report the identification of bovine heparin-binding EGF-like growth factor (HB-EGF) in chromaffin granules and the cloning of the respective cDNA from bovine-derived adrenal gland. Protein extracts from bovine chromaffin granules were found to promote the survival of embryonic dopaminergic neurones in culture, to the same extent as recombinant human HB-EGF. Furthermore, the neurotrophic action of the chromaffin granule extract could be abolished by antiserum to recombinant human HB-EGF. We also show that intracerebral injection of recombinant human HB-EGF protected the nigrostriatal dopaminergic system in an in vivo adult rat model of Parkinson's disease. Intracerebral administration of this protein at the same time as a 6-hydroxydopamine lesion of the medial forebrain bundle was found to spare dopamine levels in the striatum and tyrosine hydroxylase-immunopositive neurones in the midbrain. This study has found that the main component in chromaffin granules responsible for their neurotrophic effect on dopaminergic neurones is HB-EGF. Furthermore, HB-EGF has significant protective effects on nigrostriatal dopaminergic neurones in vivo, making it a potential candidate for use in the treatment of Parkinson's disease.

[Growth and differentiation factor 5 (GDF-5) composite improves the healing of necrosis of the femoral head in a sheep model. Analysis of an animal model]. / Das Wachstumsfaktorkomposit aus GDF-5 und mineralisiertem Kollagen verbessert die Ausheilung einer Hüftkopfnekrose. Eine Untersuchung im Tiermodell.

MATERIALS AND METHODS: After creation of necrosis in 23 sheep, the composites were implanted in half of the animals. The animals were sacrificed 6 and 12 weeks after implantation and the femora were harvested. The specimens were investigated by microradiography, computed tomography, and histologically. RESULTS: The GDF-5 composites were effective in the necrosis model. Osseous regeneration of the necrosis and the drill track were accelerated and enhanced by the composites. In treated animals the necrosis was nearly healed and the drill track was filled with bone after 12 weeks. In the control group the track was partially filled with fibrous tissue and necrotic lesions were still present. Specific side effects of the growth factor or the matrix were not documented. This was documented by histological scoring and CT investigation. DISCUSSION: The application of an absorbable GDF-5 composite in combination with a core decompression procedure may enhance the healing of devitalized bone defects and is a promising approach for further studies.

Use of psychiatric emergency services and enrollment status in a public managed mental health care plan.

OBJECTIVE: This study examined the sociodemographic and clinical characteristics of acute-care psychiatric patients who visited the emergency department at a large public hospital in terms of the patients' enrollment status in the region's public managed mental health care plan. The results of the analyses were expected to provide information about the degree and types of access to care for individuals who are and are not enrolled in the plan. METHODS: Data were collected over a seven-month period for 2,419 patients who visited a large, inner-city crisis triage unit. Patients were grouped according to whether they were currently enrolled, previously enrolled, or never enrolled in the public managed mental health care plan. Univariate and logistic regression models were used to determine differences between the three groups. RESULTS: In general, patients who were currently enrolled in the plan had a higher rate of functional psychosis, past use of psychiatric services, and functional disability and lower rates of substance use and homelessness. Previously enrolled patients had a more moderate rate of psychosis but a higher rate of substance use, functional disability, and homelessness. The never-enrolled patients had a lower rate of psychosis, functional disability, and past use of psychiatric services, and moderate substance use. CONCLUSIONS: The region's public health plan appeared to be succeeding in engaging and keeping the most psychiatrically impaired patients in treatment; however, individuals with moderate psychiatric symptoms and high levels of substance abuse may never have been enrolled in the plan because of Medicaid ineligibility or because they dropped out of treatment. Problematic behavior and history of hospitalization were the best predictors of enrollment status.

Bone morphogenetic protein-2 and growth and differentiation factor-5 enhance the healing of necrotic bone in a sheep model.

INTRODUCTION: Osteotropic growth factors enhance bone repair, but their efficacy in an area of necrotic bone is not known. The purpose of this study was to investigate the effects and potential side effects of an intraosseous application of absorbable bone morphogenetic protein-2 (BMP-2) and growth and differentiation factor-5 (GDF-5) composites in a sheep model for partial necrosis of the femoral head. MATERIALS AND METHODS: The direct injection of ethanol under fluoroscopy into the superior centre of the right femoral head produced histologically documentable necrosis of the central region of the head in a previous study of ten sheep. Another 27 sheep constituted the sample to study the effects of BMP-2 and GDF-5. Necrosis was produced in the same fashion in these animals. Four weeks later nine sheep received 300 microg recombinant BMP-2 and nine sheep 300 microg recombinant GDF-5 on an absorbable carrier by surgical implantation. Nine sheep received the carrier alone (control group). The animals were sacrificed at 3, 6, and 12 weeks after implantation and both femora were harvested. RESULTS: Bone density analysis and microscopic examination indicated that bone formation was noticeably induced as early as 3 weeks postoperatively in the growth factor treated animals. Bone regeneration was enhanced by growth factor composites. This was documented by histological scoring and histomorphometric analysis. No severe local side effects secondary to the growth factors, such as heterotopic ossification or inflammation, were observed in either group. DISCUSSION: The application of an absorbable growth factor composite in combination with established surgical techniques is a promising approach, that may enhance the healing of devitalised bone defects. Based on these results, further studies regarding biodegradation, dosage of the protein and surgical technique are required.

Reliability and clinical utility of DSM-IV substance-induced psychiatric disorders in acute psychiatric inpatients.

The goal of his study was to evaluate in 1,951 acute psychiatric inpatients the reliability, construct, convergent, and predictive validity of substance-induced psychiatric syndrome ratings made by clinical attending pschiatrists. The primary admitting condition for each subject was categorically rated by clinical attendings as not, mildly, moderately, or mostly substance-induced at both admission and discharge. Individual substance categories were associated with characteristic demographic, clinical treatment response, and length of stay, findings indicating good construct, predictive validity, and clinical utility. A linear dimensional approach to rating substance-induced syndromes in acute clinical populations may be preferable to the simple dichotomous approach used in DSM-IV.

Contraceptive progestins. Various 11-substituents combined with four 17-substituents: 17alpha-ethynyl, five- and six-membered spiromethylene ethers or six-membered spiromethylene lactones.

Norethisterone (NET) is a 19-nortestosterone derivative with progestagenic and some androgenic activity, which was used in the first generation of contraceptives. NET was succeeded by levonorgestrel (LNG) and later on by desogestrel (DSG) and gestodene (GSD). Although these latter two progestins had increased potency, there was still androgenicity with gestodene and to a lesser extent with desogestrel. New progestins were synthesized in order to further enhance progestagenic and to reduce androgenic activity. Four different chemical moieties were introduced in position 17 of 19-nortestosterone, viz. 17alpha-ethynyl, five- and six-membered spiromethylene ethers, and a six-membered-spiromethylene lactone. In combination with these structures seven different substituents were added at position 11, i.e. methylene, methyl, ethyl, ethenyl, ethynyl, 2-propenyl and 1-propynyl. All substituents except for methylene occupied the 11beta-position. All these 32 compounds were synthesized and analysed in vitro and in vivo against etonogestrel (ETG, 3-keto-desogestrel), the biologically active metabolite of desogestrel. Their relative binding potency to progesterone (PR), androgen (AR) and estrogen (ER) receptors were determined in cell lysates of human breast tumor MCF-7 cells and to glucocorticoid (GR) receptors in that of human leukemic IM-9 cells. Moreover, their relative agonistic activities were assessed in Chinese hamster ovary cell-based transactivation assays. All in vivo activities were determined in McPhail (progestagenic), ovulation inhibition (progestagenic and estrogenic), Hershberger (androgenic), hormone screening (glucocorticoid and estrogen) and Allen-Doisy (estrogenic) tests after oral and for the McPhail test also after subcutaneous administration. The progestagenic binding and transactivation potencies of all compounds in the three 17-spiro series were higher than those of the corresponding analogues in the 17alpha-ethynyl series. None of the compounds showed estrogenic or clear androgenic binding and transactivation potential except for a six-membered-spiromethylene lactone with a propynyl group. This compound showed strong androgenic binding. The glucocorticoid binding and transactivation were very low for the compounds with the 17alpha-ethynyl and the five-membered-spiromethylene ether groups, whereas both six-membered-spiro series showed, clearly with methyl and ethynyl substituents, and less pronounced with methylene and ethenyl, higher binding and transactivation values. For the 17alpha-ethynyl series, the McPhail test showed high potencies with methylene, methyl and ethenyl substituents after oral treatment or with propenyl after subcutaneous administration. The introduction of the spiro substituents in position 17 led to high potencies for other 11-substituents as well. Besides methyl, also ethyl, ethynyl and propynyl were potent substituents. With ovulation inhibition tests, the ethyl, ethenyl and ethynyl substituents were the more potent compounds in all four series. However, compounds with methyl or ethynyl additions appeared to be glucocorticoidal in the hormone screening test irrespective of the 17-substituent, while with the three spiro series even methylene and ethenyl groups became active. Androgenicity was only observed at dose levels at or above 5 mg/kg, which is 2.5-fold weaker than ETG. Moreover, estrogenicity appeared negligible with the three spiro series, while with the 17alpha-ethynyl series methyl, ethyl, ethenyl and ethynyl substituents, a very high estrogenic potential was assessed. Based on the high efficacy and low side-effects, the following compounds show a high selectivity: 17alpha-ethynyl with ethyl, ethenyl and 2-propenyl substituents, six-membered spiromethylene ether with ethyl and six-membered-spiromethylene lactone with ethyl, 2-propenyl or 1-propynyl substituents. (ABSTRACT TRUNCATED)

Reliability and validity of screening instruments for drug and alcohol abuse in adults seeking evaluation for attention-deficit/hyperactivity disorder.

A growing number of adults are seeking evaluation for Attention-Deficit/Hyperactivity Disorder (ADHD). Screening for substance use disorders should be included as part of any comprehensive ADHD evaluation. We describe the validity and reliability of the Drug Abuse Screening Test (DAST) and the Alcohol Use Disorders Identification Test (AUDIT) in adults seeking evaluation for ADHD. Internal reliability estimates were excellent for both instruments. Scores on the DAST and AUDIT were higher among patients with a DSM-IV diagnosis of current drug abuse or dependence or current alcohol abuse or dependence, respectively. A cutoff score of 6 or above appears to be optimal for identifying individuals who are current drug abusers. A cutoff score of 6 or above on the AUDIT is suggested for detection of current alcohol abuse in this population. Comparable rates of substance use disorders were observed in ADHD and non-ADHD patients. Both measures are valid and reliable instruments for screening for alcohol and drug abuse among adults seeking evaluation for ADHD.

Nefazodone treatment of major depression in alcohol-dependent patients: a double-blind, placebo-controlled trial.

Depression is the most common comorbid psychiatric illness in patients with alcohol dependence. This double-blind study tested the efficacy of nefazodone versus placebo for the treatment of depression in actively drinking alcohol-dependent patients who were also participating in weekly group treatment for alcoholism. Sixty-four subjects with major depression disorder and alcohol dependence with a history of at least one prior episode of depression when not drinking were randomly assigned to receive 12 weeks of either nefazodone or placebo and participated in a weekly psychoeducational group on alcoholism. Subjects were assessed every 2 weeks for depression, anxiety, side effects, and drinking frequency. Subjects taking nefazodone were significantly more likely to complete the study (62%) than those taking placebo (34%). Analyses of covariance using drinks per week as a time-dependent covariate showed lower Hamilton Rating Scale for Depression scores at week 8 for end-point analysis and at weeks 8 and 12 for completers. The endpoint analysis demonstrated a significantly greater response in the nefazodone group (48%) than in the placebo group (16%). Both groups showed a similarly significant decrease in the average number of alcoholic drinks consumed per day over the course of the study. Although the number of adverse effects was significantly greater for the nefazodone group, there were no severe adverse events, and nefazodone was well tolerated. Nefazodone is a safe and effective antidepressant to use in a population of alcohol-dependent patients with depression who have a high degree of comorbidity. Nefazodone treatment was superior to placebo in alleviating depression in these patients but did not add any advantage over the psychoeducational group in terms of drinking outcomes.

Shorter hospital stays and more rapid improvement among patients with schizophrenia and substance disorders.

OBJECTIVE: Length of stay and treatment response of inpatients with acute schizophrenia were examined to determine whether differences existed between those with and without comorbid substance-related problems. METHODS: The sample comprised 608 patients with a diagnosis of schizophrenia or schizoaffective disorder treated on hospital units with integrated dual diagnosis treatment. They were rated on admission and discharge by a psychiatrist using a structured clinical instrument. Patients with no substance-related problems were compared with those with moderate to severe problems using t tests, chi square tests, and analysis of variance. RESULTS: When analyses controlled for age, gender, and other clinical variables, dually diagnosed patients were found to have improved markedly faster compared with patients without a dual diagnosis. Their hospital stays were 30 percent shorter on both voluntary and involuntary units. They also showed somewhat greater symptomatic improvement and no increase in 18-month readmission rates. On admission the dual diagnosis group was more likely to be younger, male, and homeless and more likely to be a danger to self and others. Severity of psychosis was the same at admission for the two groups, but the dually diagnosed patients were rated as less psychotic at discharge. CONCLUSIONS: Dually diagnosed patients with schizophrenia appear to stabilize faster during acute hospitalization than those without a dual diagnosis. The authors hypothesize that substance abuse may temporarily amplify symptoms or that these patients may have a higher prevalence of better-prognosis schizophrenia. The availability of integrated dual-focus inpatient treatment and a well-developed outpatient system may also have helped these patients recover more rapidly.

Alcohol problems in women admitted to a level I trauma center: a gender-based comparison.

BACKGROUND: Male patients constitute such a large proportion of trauma patients that most studies of alcohol problems in trauma patients have been carried out with clinical data largely or totally contributed by male patients. It may be incorrect to assume that the nature of alcoholism in women and men is identical, or that the size of the problem among women is small, eliminating the need to specifically study female patients. The purpose of this study was to perform a gender-based comparison of alcohol problems in trauma patients. METHODS: Admitted injured patients underwent routine screening, including a blood alcohol concentration, serum gamma-glutamyl transpeptidase, and the Short Michigan Alcohol Screening Test. A random sample of screen positive women and men underwent a comprehensive alcohol use and psychosocial assessment, and the results were compared by gender. RESULTS: The screen-positive rate was higher for men, 51% versus 34% (p < 0.01). However, screen-positive women and men had similar problem severity as reflected by mean blood alcohol concentration (162 mg/dL vs. 142 mg/dL, p = 0.16) and Short Michigan Alcohol Screening Test scores (4.6 vs. 5.0, p = 0.32). The Alcohol Use Disorders Identification Test, NIMH-DIS, and Severity of Alcohol Dependence Data form showed that female trauma patients with alcohol problems have the same severity of dependence symptoms as men. However, women were significantly more likely to have liver dysfunction, depression, psychological distress, and recent physical, emotional, or sexual abuse. CONCLUSION: Alcohol problems are more common in male trauma patients, but women with alcohol problems are just as severely impaired, have at least as many adverse consequences of alcohol use as their male counterparts, and have more evidence of alcohol-related physical and psychological harm.

Hormonal properties of norethisterone, 7alpha-methyl-norethisterone and their derivatives.

Norethisterone (NET) is a progestagenic compound with very weak androgenicity and estrogenicity. These low androgenic and estrogenic activities may be attributed to NET itself or induced by metabolites of NET. In order to improve the bioactivity of NET, the effects of a 7alpha-methyl substitution were studied. Thus this study has two objectives: first the comparison between biological activities of NET and 7alpha-methyl-NET (MeNET), and second the biological activity of tentative metabolites of NET and those of MeNET. The metabolites consist of a 3-keto-, 3alpha- or 3beta-hydroxy-group located next to a carbon 4 to 5 double bond (Delta(4)) or a 5alpha-hydrogen atom. The 7alpha-methyl substitution was of special interest as it prevents 5alpha-reduction. The biological activities of NET, MeNET and their potential metabolites were assessed by in vitro binding, transactivation and proliferation assays on progesterone (PR), androgen (AR), estrogen (ER) and glucocorticoid (GR) receptors and by in vivo progestagenic McPhail, androgenic Hershberger, estrogenic Allen-Doisy tests and combined estrogenic and progestagenic ovulation inhibition tests. NET is a compound with five- to eight-fold weaker PR binding and transactivation activities than the reference compound Org 2058 (100%) and two-fold stronger than progesterone. Binding and transactivation activities of NET for AR (DHT=100%) are 3.2 and 1.1%, respectively, for ER none (E2=100%) and for GR below 1% (DEX=100%). MeNET is 1.5- to two-fold less progestagenic and ten- to 20-fold more androgenic than NET, while it does not show activity for ER and GR. The relative binding affinity of 5alpha-NET was seven-fold lower for PR and 1.5-fold higher for AR than for NET, while in transactivation assays 5alpha-NET was only active at levels below 1% for all tested receptors. 3beta-Hydroxy-(5alpha-reduced)-metabolites showed clear ER binding and transactivation activities, while 3alpha-hydroxy-(5alpha-reduced)-metabolites did hardly possess these characteristics. These hydroxy metabolites did not bind or activate other receptors. Substitution of 7alpha-methyl to NET metabolites led to similar characteristics, but with higher activities for AR and ER and weaker activity for PR. The outcome of in vivo tests showed a remarkable effect for MeNET. Progestagenic activity in rabbits appeared for NET equipotent to or eight-fold higher than for MeNET, after subcutaneous or oral treatment, respectively. On the other hand, MeNET showed in rats a ten-fold higher androgenicity and eight-fold higher estrogenicity than NET. Ovulation inhibition was induced at very low oral or subcutaneous dose levels, being 120- or ten-fold lower than for NET, respectively. The estrogenicity can also be induced by 3alpha- or 3beta-hydroxy metabolites of MeNET, which are 15 or even more than 40-fold stronger than those of NET, respectively. In conclusion, after the introduction of a 7alpha-methyl substituent to NET an increased estrogenicity and androgenicity and a reduced progestagenic activity was found. The in vivo estrogenicity is mainly due to 3beta-hydroxy-MeNET and to a lesser extent to 3alpha-hydroxy-MeNET, while the androgenicity and progestagenicity are most likely caused by MeNET itself. Since the 7alpha-methyl substituent inhibits 5alpha-reductase, 5alpha-reduced MeNET metabolites can be excluded from biological activities. As MeNET is a very effective ovulation inhibitor, due to its mixed progestagenic and estrogenic profile, a further reduction of androgenicity of MeNET may yield new contraceptives with an attractive profile for contraception.

Localization of activin beta(A)-, beta(B)-, and beta(C)-subunits in humanprostate and evidence for formation of new activin heterodimers of beta(C)-subunit.

Activin ligands are formed by dimerization of activin ss(A)- and/or ss(B)-subunits to produce activins A, AB, or B. These ligands are members of the transforming growth factor-ss superfamily and act as growth and differentiation factors in many cells and tissues. New additions to this family include activin ss(C)-, ss(D)-, and ss(E)-subunits. The aim of this investigation was to examine the localization of and dimerization among activin subunits; the results demonstrate that activin ss(C) can form dimers with activin ss(A) and ss(B) in vitro, but not with the inhibin alpha-subunit. Using a specific antibody, activin ss(C) protein was localized to human liver and prostate and colocalized with ss(A)- and ss(B)-subunits to specific cell types in benign and malignant prostate tissues. Activin C did not alter DNA synthesis of the prostate tumor cell line, LNCaP, or the liver tumor cell line, HepG2, in vitro when added alone or with activin A. Therefore, the capacity to form novel activin heterodimers (but not inhibin C) resides in the human liver and prostate. Activin A, AB, and B have diverse actions in many tissues, including liver and prostate, but there is no known biological activity for activin C. Thus, the evidence of formation of activin AC or BC heterodimers may have significant implications in the regulation of levels and/or biological activity of other activins in these tissues.

Detection of acute alcohol intoxication and chronic alcohol dependence by trauma center staff.

BACKGROUND: Trauma patients with acute alcohol intoxication or chronic alcohol dependence are at greater risk for morbidity and mortality. We hypothesized that relying on clinical suspicion to detect acute alcohol intoxication and chronic alcohol dependence in trauma patients is inaccurate, influenced by injury factors, and biased by race, gender, age, and socioeconomic status. METHODS: Trauma patients were screened with a blood alcohol concentration and with the Short Michigan Alcohol Screening Test and CAGE questionnaire. Before screening, physicians and emergency department nurses were asked whether the patient was acutely intoxicated (blood alcohol concentration > 100 mg/ dL) or had a chronic alcohol problem. Sensitivity, specificity, positive, and negative predictive values were determined by comparing responses with blood alcohol concentration, Short Michigan Alcohol Screening Test, and CAGE questionnaire results, stratified by injury and demographic factors. RESULTS: Clinical evaluations were obtained on 462 patients. Overall, 23% of acutely intoxicated patients were not identified by physicians. The miss rate increased to one third in severely injured, chemically paralyzed, or intubated patients. Specificity was also poor. Patients with a negative blood alcohol concentration were more likely to be falsely suspected of intoxication if they were either young, male, perceived as disheveled, uninsured, or having a low income (p < 0.05). Staff identified < 50% of patients with a positive Short Michigan Alcohol Screening Test or CAGE, and falsely identified 26% of patients as alcoholic. CONCLUSIONS: Formal alcohol screening should be routine because clinical detection of acute alcohol intoxication and dependence is inaccurate. Screening should also be routine to avoid discriminatory bias attributable to patient characteristics.

Alcohol interventions in a trauma center as a means of reducing the risk of injury recurrence.

OBJECTIVE: Alcoholism is the leading risk factor for injury. The authors hypothesized that providing brief alcohol interventions as a routine component of trauma care would significantly reduce alcohol consumption and would decrease the rate of trauma recidivism. METHODS: This study was a randomized, prospective controlled trial in a level 1 trauma center. Patients were screened using a blood alcohol concentration, gamma glutamyl transpeptidase level, and short Michigan Alcoholism Screening Test (SMAST). Those with positive results were randomized to a brief intervention or control group. Reinjury was detected by a computerized search of emergency department and statewide hospital discharge records, and 6- and 12-month interviews were conducted to assess alcohol use. RESULTS: A total of 2524 patients were screened; 1153 screened positive (46%). Three hundred sixty-six were randomized to the intervention group, and 396 to controls. At 12 months, the intervention group decreased alcohol consumption by 21.8+/-3.7 drinks per week; in the control group, the decrease was 6.7+/-5.8 (p = 0.03). The reduction was most apparent in patients with mild to moderate alcohol problems (SMAST score 3 to 8); they had 21.6+/-4.2 fewer drinks per week, compared to an increase of 2.3+/-8.3 drinks per week in controls (p < 0.01). There was a 47% reduction in injuries requiring either emergency department or trauma center admission (hazard ratio 0.53, 95% confidence interval 0.26 to 1.07, p = 0.07) and a 48% reduction in injuries requiring hospital admission (3 years follow-up). CONCLUSION: Alcohol interventions are associated with a reduction in alcohol intake and a reduced risk of trauma recidivism. Given the prevalence of alcohol problems in trauma centers, screening, intervention, and counseling for alcohol problems should be routine.

Treatment satisfaction compared with outcome in severe dual disorders.

This paper examines patient (N = 75) ratings of treatment satisfaction and outcome for severely mentally ill dually diagnosed outpatients participating in long-term integrated dual focus treatment. In addition, it compares these ratings with case manager ratings of patient outcome over a one year period. Satisfaction ratings ranged from very good to excellent. Combined means of several outcomes ratings indicated that most patients rated themselves as improved. Satisfaction with over-all care and with case management was significantly, though weakly (r = .3 and .31, respectively, p < .05), related to patient ratings of overall outcome. While most patients rated that they had improved, satisfaction with treatment was only weakly related to either patient or case manager rated clinical outcomes. These findings indicate the relatively independent relationship of satisfaction with treatment outcome and caution against over generalizing the meaning of treatment satisfaction measures.